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CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY ISBN 0-323-02262-6 of Mosby, Inc.
Copyright © 2005, Mosby, Inc.
NOTICE
Knowledge and best practice in this field are constantly changing. As new research
and experience broaden our knowledge, changes in practice, treatment and drug
therapy may become necessary or appropriate. Readers are advised to check the
most current information provided (i) on procedures featured or (ii) by the
manufacturer of each product to be administered, to verify the recommended dose
or formula, the method and duration of administration, and contraindications. It is
the responsibility of the practitioner, relying on their own experience and
knowledge of the patient, to make diagnoses, to determine dosages and the best
treatment for each individual patient, and to take all appropriate safety
precautions. To the fullest extent of the law, neither the Publisher nor the Editors
assumes any liability for any injury and/or damage to persons or property arising
out or related to any use of the material contained in this book.
J. E. Szalados, M.D.
I wish this work to honor the many teachers, students, residents, and fellows
who over the years have made me think and grow in the subject of critical care.
I especially wish to honor the contributions of two great teachers: the late
Dr. Thomas Iberti M.D. who taught me to ask the key question of clinical
medicine, “why?”; and Prof. Dr. Lachmann who made me into a scientist.
To truly balance one’s life we need love and support, and without the great love
of my wife Susan and son Yanni I would not be able to find my inner strength.
And to my father who taught and guided me that with hard work you always
win, a special thanks. Also to my friends Allan Ross and Anne Snyder at Elsevier
who supported me in this and many other projects, we did it again.
P. J. Papadakos, M.D.
Contributors
vii
viii CONTRIBUTORS
Judit Szolnoki, MD
Assistant Professor of Anesthesiology and Critical Care
Department of Anesthesiology
Upstate Medical University
Syracuse, New York
Attending Anesthesiologist
VA Hospital of Syracuse and University Hospital
in Syracuse
Syracuse, New York
Preface
It is an incontrovertible fact that anesthesiology is the surgery is best positioned to understand the preopera-
practice of medicine. Therefore, anesthesiologists must tive and postoperative issues. Every preoperative patient
be fluent in the theories and techniques of preoperative requires that the anesthesiologist perform a careful and
medical assessment, intraoperative cardiopulmonary life detailed assessment of their medical condition including
support, and postoperative critical care intervention. coexisting illnesses, physical limitations, and their gen-
Anesthesiology is the synthesis of the basic medical eral fitness for anesthesia and surgery. It is a seldom-
sciences, including anatomy, physiology, biochemistry, voiced tacit understanding among anesthesiologists that
pharmacology, and epidemiology; and is a bridge that each and every patient who undergoes elective surgery
spans the disciplines of medicine and all its subspecial- becomes critically ill, albeit perhaps only for a limited
ties, surgery, and obstetrics. The making of an anesthesi- time period. Of course, those patients who come to the
ologist is therefore the culmination of premedical and operating room in the setting of severe trauma, over-
medical schooling, a four-year intense postgraduate whelming organ dysfunction due to illness, or patients
clinical residency program, and possibly thereafter a who present with severe comorbidities for emergency
subspecialized fellowship. Most importantly, there then surgery are de facto critically ill and are likely to remain
follows a lifetime commitment to learning and further so for some time postoperatively. There was once a time
honing of technical skills. when patients could be deemed “too sick for surgery.”
It is likely that no person will ever trust anyone else However, this adage is seldom employed today and anes-
to the extent that they trust their anesthesiologist. The thesiologists, surgeons, as well as patients and their fam-
patient undergoing surgery will depend on the anesthe- ilies in weighing the risks against the potential benefits
siologist for safety and comfort during a time when their often determine that the short and intense stress of
body is subjected to extreme stress. It is a remarkable surgery compares favorably to the alternative. Patients
fact that most patients accept the risks of anesthesia come to the operating room in septic shock for the con-
without questions, are incognizant of the fact that they trol of their septic source, following an acute myocardial
will fully be on “life support” for the duration of their infarction for emergency coronary revascularization, in
operation, and most do not remember the experience or multiple organ failure and end-stage liver disease for liver
even the name of their anesthesiologist. That the public transplantation, and after massive trauma; each patient’s
at large can have such trust and high expectations from condition can be further complicated by systemic dis-
medical professionals who will only be transiently eases such as chronic lung disease, severe athero-
involved in their care is a testament to the training, pro- sclerotic coronary and vascular disease, renal failure,
fessionalism, and skill of anesthesiologists as well as a diabetes mellitus, malnutrition, and others. Therefore,
reflection of the many technological advances in medical anesthesiology is unique in that there is no other spe-
science which have made modern anesthesiology a safer cialty of medicine where every single patient encounter
experience. requires both knowledge and application of advanced
In order for the anesthesiologist to provide the level life-support skills. All these patient groups will require
of medical care that will result in the best outcome for elements of mechanical ventilation, sedation and
the patient, the anesthesiologist must be comfortable in analgesia, neuromuscular blockade, intravascular volume
the role of a “perioperative physician.” That physician replacement, management of electrolytes, hemo-
who cares for patients as they undergo the stress of dynamic support and monitoring, monitoring of and
xi
xii PREFACE
replacement of blood and coagulation factors, as well as operating room. Therefore, new advances in modes of
related monitoring and interventions directed at mini- mechanical ventilation, new understanding regarding
mizing secondary injuries. optimization of oxygen delivery to tissues, new perspec-
It is because anesthesiology is also the practice of tives on the evaluation and management of severe
critical care medicine that this textbook summarizes for comorbidities, as well as preparedness for emerging
anesthesiologists the state-of-the-art and the standard of threats such as biological and chemical terrorism are
care for the management of critically ill patients. matters of interest to all anesthesiologists. Finally, for
It is incumbent on anesthesiologists to understand and those physicians who also practice in the intensive care
apply the principles of critical care medicine that are unit, this book is intended to highlight established
relevant to the management of intraoperative patients as principles, evolving standards of care, and new
well as their continued postoperative care. We recog- opportunities to provide excellence in patient care.
nize that not all anesthesiologists will participate in the
care of patients in the intensive care unit. However, all Peter J. Papadakos, M.D.
anesthesiologists will use critical care principles in the James E. Szalados, M.D.
1
CHAPTER Sepsis: The Systemic
Inflammatory Response
JEAN-LOUIS VINCENT, M.D., Ph.D
Definition and Diagnosis increasing as the size of the problem increases. This
Pathophysiology chapter briefly considers some of the basic features and
Inflammatory Mediators the latest developments in this critically important field
Pro-inflammatory Cytokines of sepsis in terms of diagnosis, pathophysiology, and
Anti-inflammatory Cytokines management.
Other Mediators
Coagulation and Inflammation
Management of Sepsis DEFINITION AND DIAGNOSIS
Hemodynamic Stabilization
Immunomodulating Therapy For many years definitions of sepsis have relied on
Conclusion those proposed by the ACCP/SCCM consensus confer-
ence published back in 1992. This conference intro-
Sepsis, the inflammatory response to infection, is duced the systemic inflammatory response syndrome
perhaps the most common disease encountered by the (SIRS) concept, whereby a patient was said to have SIRS
critical care physician, complicating some 30 to 40% of if they met two or more of the following conditions:
intensive care unit (ICU) admissions and accounting for temperature greater than 38°C or less than 36°C, tachy-
considerable morbidity and mortality. The exact inci- cardia, tachypnea, white blood cell count greater than
dence of sepsis is difficult to determine because of dif- 12,000 cells/mm3 or less than 4000 cells/mm3. Sepsis was
ferences in definitions and populations. An international then defined as infection plus SIRS, severe sepsis as sep-
study across eight countries involving 14,364 ICU patients sis plus organ dysfunction, and septic shock as severe
reported that there were 3034 infectious episodes giving sepsis with hypotension despite adequate fluid resusci-
a crude incidence of infections of 21.1%. Interestingly, tation and evidence of perfusion abnormalities. However,
one-fifth of these infections did not fit into any of the def- the SIRS criteria are very sensitive, and are met by most
inition categories proposed by the ACCP/SCCM classifi- ICU patients and many general ward patients, making
cation, which has been widely used in studies of sepsis. them of little practical value in identifying the patient
The mortality rate in patients with repeated infectious with sepsis.
episodes was 53.6% compared to 16.9% in non-infected Recently, a sepsis definitions conference involving
patients. A recent study, the Sepsis Occurrence in 29 physicians from Europe and North America was held
Acutely Ill Patients (SOAP), involving 3147 patients in in Washington, DC, to improve and standardize defini-
24 European countries, reported that 37.4% of patients tions in the field of sepsis. The conference participants
were infected at some point during their ICU stay. agreed with the 1992 definitions in that sepsis should be
Interestingly, the occurrence of sepsis ranged from 17.5 to defined as infection plus signs of systemic inflammation,
72.5% between countries. Importantly, the incidence of but felt that the SIRS criteria were too non-specific and
sepsis seems to be increasing with one study reporting proposed rather a much longer list of possible signs of
an annual increase of 8.7% in the USA, from 82.7 cases sepsis (Table 1-1). Unfortunately, as yet, no individual
per 100,000 population in 1979 to 240.4 per 100,000 sign is specific for sepsis and clinical diagnosis relies on
population in 2000. Thus, although the risk of death per the combined presence of several signs and symptoms that
individual case may be falling, overall mortality rates are together confirm the likelihood of sepsis as the diagnosis.
3
4 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Clinical Laboratory
signs and symptoms and to the degree of elevation of, The PIRO system is newly developed and each item
for example, white cell count, C-reactive protein, pro- requires weighting and validation in septic patients.
calcitonin, etc. Importantly, initial suggestions that sep- However, one could envisage patients receiving a PIRO
sis was simply an uncontrolled inflammatory response stage, e.g., P2I2R1O3, which would help determine prog-
and could be treated by blocking or removing any or sev- nosis and direct treatment. This is an important advance
eral of the inflammatory cytokines have been supplanted in this field and, in addition to characterizing individual
by the realization that the inflammatory response is a patients, will facilitate comparison of patient popula-
normal and necessary response to infection, and inter- tions for clinical trial purposes, and help focus clinical
rupting that response at any point may do more harm research. Importantly, as new developments are made in
than good. Indeed, the early hyperinflammatory phase of gene mapping, or new markers of disease presence and
sepsis is soon replaced by a hypoinflammatory state. severity are identified, the relevant component of the
Each individual will mount a different response pattern PIRO system would need to be modified accordingly.
depending on various factors including those outlined in
the predisposing factors and insult sections above, and
patients who die from sepsis often have a prolonged
hypoimmune stage (Figure 1-1). This differentiation is PATHOPHYSIOLOGY
important in therapeutic terms, as anti-inflammatory
therapies may be harmful if given to a patient who is Inflammatory Mediators
already in the hypoinflammatory phase; such a patient The pathophysiology of sepsis is complex and
may benefit rather from a pro-inflammatory therapy to although huge advances have been made, many facets
boost their immune system. remain unclear; indeed, while each new discovery pro-
Organ dysfunction – Organ dysfunction can be mea- vides new understanding, it also reveals new intricacies
sured using scores such as the sequential organ failure requiring further clarification. Essentially, the sepsis
assessment (SOFA; Table 1-3). This system uses parameters response is initiated directly by an invading organism,
that are routinely available in all ICUs to assess the or by particular products or features of the organism,
degree of dysfunction for six organ systems, respiratory, such as endotoxin (Gram-negative), peptidoglycan,
cardiovascular, renal, coagulation, neurologic, and hepatic, and lipotiechoic acid (Gram-positive). These microbial
with a scale of 0 (no dysfunction) to 4 for each organ. products stimulate endothelial damage, the release of
Importantly, organ dysfunction can be recorded for each cytokines, the generation of complement, the activation
organ separately or a composite score can be calculated. of coagulation, and a range of other effects, both directly
Thus with repeated scores, a dynamic picture of the effects and via so-called mediators of sepsis. The activities and
of sepsis on individual or global organ dysfunction can be identities of many of the mediators of sepsis have been
developed and followed. Sequential assessment of SOFA widely studied, but many features of the response remain
during the first few days of ICU admission has been shown unclear. Initiation occurs as microbial components are
to be a good indicator of prognosis, with an increase in recognized by soluble or cell-bound pattern recognition
SOFA score during the first 48 hours in the ICU predicting molecules or receptors, such as CD14 and TLRs. For
a mortality rate of at least 50%. Gram-negative organisms, endotoxin (lipopolysaccharide,
LPS) binds to a specific LPS-binding protein (LPB) in
the plasma, which carries the LPS to a macrophage mem-
brane receptor, CD14. The LPS/CD14 complex then
Degree of interacts with a signal-transducing receptor in the mem-
activation brane, TLR4, and MD-2. Activation of TLR4 induces the
Hyper-reactivity transcription of inflammatory and immune response genes
via a nuclear factor-κB (NF-κB)-mediated mechanism,
resulting in the release of cytokines. Pro-inflammatory
Adequate cytokine release then attracts further macrophages and
response monocytes and the cycle repeats. The LPS/LBP complex
Normal can also bind to a soluble CD14 receptor present in the
baseline level serum that promotes LPS binding to endothelial cells,
Hypo-reactivity
again via TLRs. For Gram-positive and fungal organisms,
the sequence is probably similar with cell-wall compo-
nents such as lipoteichoic acid or peptidoglycan binding
Time to CD14, which then binds to TLR2, again stimulating
Insult
Figure 1-1 Graph shows prolonged hypoimmune stage cytokine release. Bacterial components can also act directly
response. to stimulate the coagulation (see below) and complement
Table 1-3 The Sequential Organ Failure Assessment (SOFA) Score
SOFA score 0 1 2 3 4
Respiration
PaO2/FIO2, mmHg >400 ≤400 ≤ 300 ≤ 200 (with respiratory support) ≤ 100 (with respiratory support)
Coagulation
Platelets × 103/mm3 >150 ≤150 ≤100 ≤ 50 ≤ 20
Liver
Bilirubin, mg/dL (μmol/L) <1.2 (<20) 1.2–1.9 (20–32) 2.0–5.9 (33–101) 6.0–11.9 (102–204) >12.0 (>204)
Cardiovascular
Hypotension No hypotension MAP <70 mmHg Dopamine ≤5 or Dopamine >5 or epinephrine ≤0.1 Dopamine >15 or epinephrine >0.1
dobutamine (any dose)* or norepinephrine ≤0.1* or norepinephrine >0.1*
Central nervous system
Glasgow coma score 15 13–14 10–12 6–9 <6
Renal
Creatinine, mg/dL (μmol/L) <1.2 (<110) 1.2–1.9 (110–170) 2.0–3.4 (171–299) 3.5–4.9 (300–440) > 5.0 (> 440)
or urine output or < 500 ml/d or < 200 ml/d
* Adrenergic agents administered for at least one hour (doses given are in μg/kg/min).
Sepsis: The Systemic Inflammatory Response 7
systems; the overall host response is thus a complex key agents are platelet activating factor (PAF), interferon
interaction between multiple factors. (IFN)-γ, IL-4, macrophage inhibitory factor, high mobility
group (HMG) proteins, transforming growth factor
Pro-inflammatory Cytokines (TGF)-β, arachidonic acid metabolites, reactive oxygen
Cytokines are produced by a variety of cell types species, nitric oxide, and cell adhesion molecules.
under normal and pathological conditions, and have sys-
temic and local effects. They are commonly divided into
pro- or anti-inflammatory cytokines although some may Coagulation and Inflammation
have both effects at different times or on different cells One of the key concepts that has changed our view,
or tissues. Some of the key pro-inflammatory cytokines and indeed management, of sepsis is new understanding
are TNF and IL-1, -6, and -8. of the interaction of inflammation, coagulation, and
The TNF family is primarily involved in the regulation fibrinolysis. The imbalance in hemostatic mechanisms
of cell proliferation and apoptosis, but TNF-α also recruits may manifest as disseminated intravascular coagulopathy
and activates neutrophils, macrophages, and lympho- (DIC) and microvascular thrombosis and could be a key
cytes, and stimulates the release of other pro-inflammatory factor in the development of organ dysfunction, ultimately
cytokines and acute-phase proteins. TNF-α exerts its leading to multiple organ failure and death.
actions by binding to two distinct TNF receptors (TNFR1 Essentially, the cycle starts with early endothelial
and TNFR2). TNFR1 stimulation leads to classic TNF damage initiated both directly by endotoxins and other
effects, while TNFR2 stimulation facilitates binding of infectious products, and indirectly by the initial compo-
TNF-α to the TNFR1 receptor. nents of the inflammatory response to the invading
IL-1 includes two related proteins, IL-1α and IL-1β, microorganism, including TNF-α and IL-1. Subendothelial
which activate the same receptors and thus have similar structures are exposed and collagenases are released.
biological actions. The spectrum of activity of IL-1 is sim- Exposed tissue factor triggers the extrinsic coagulation
ilar to that of TNF-α, although it generally produces less cascade and accelerates the production of thrombin. At
severe effects; these two cytokines work synergistically the same time, the endothelial damage further exacerbates
to give a greater effect than stimulation of either alone. inflammation, with neutrophil activation, neutrophil–
IL-6 is released largely under the influence of TNF-α endothelial cell adhesion, and continued elaboration of
and IL-1, and is involved in stimulating the release of inflammatory cytokines, which in turn produce more
acute-phase proteins, such as C-reactive protein (CRP), endothelial damage, compromising microvascular func-
by the liver. It also induces B-cell growth and T-cell dif- tion. Endogenous modulators of homeostasis, such as
ferentiation, and has been implicated in the myocardial protein C and antithrombin, are consumed as the body
depression seen in septic shock. IL-6 levels correlate attempts to return to a normal functional state. Under nor-
more closely than other cytokines with the severity and mal conditions, the endothelial surface proteins, throm-
outcome of septic shock. bomodulin and endothelial protein C receptor (EPCR),
IL-8 is released predominantly on stimulation by TNF-α activate protein C and its modulating effects; however,
and IL-1. Its major role is as a chemokine, i.e., it recruits in sepsis the endothelial damage impairs this function of
inflammatory cells to the site of injury. It promotes recruit- thrombomodulin and EPCR, thereby contributing to the
ment and activation of leukocytes, upregulates expression loss of control. In addition to activated coagulation, fibri-
of adhesion molecules, and enhances degranulation. nolysis is suppressed, with increased levels of two of the
key inhibitors of fibrinolysis: plasminogen activator
Anti-inflammatory Cytokines inhibitor 1 (PAI-1) and thrombin activatable fibrinolysis
Anti-inflammatory cytokines are released alongside inhibitor (TAFI). There is thus a cascade of inflammation
the pro-inflammatory cytokines to modulate the inflam- and coagulopathy that drives the sepsis response, lead-
matory response. IL-10 is synthesized by monocytes, ing to multiple organ failure and death for many patients.
macrophages, T cells and B cells. IL-10 inhibits the
release of TNF, IL-1, and IL-6, and suppresses monocyte
procoagulant activity. Soluble TNF receptors are present
in septic patients and bind to TNF, thus acting to limit MANAGEMENT OF SEPSIS
TNF activity. IL-1 receptor antagonist (IL-1ra) is a com-
petitive inhibitor of the IL-1 receptor and is produced by Hemodynamic Stabilization
sepsis-activated monocytes and polymorphonuclear cells. The basic management of sepsis involves appropriate
and rapid antimicrobial therapy, surgical removal of any
Other Mediators infectious nidus, and hemodynamic stabilization follow-
Many other sepsis mediators are involved in the prop- ing the VIP (ventilate, infuse, pump) principles. The opti-
agation or control of the septic response; some of the mal hemodynamic management of septic shock has been
8 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
the subject of some debate, in particular regarding the in favor of one agent or another, with dopamine and nor-
choice of fluid and vasoactive agents. Patients with sep- epinephrine both valid choices as first-line agents.
tic shock can be successfully resuscitated with crystal- One of the key features of hemodynamic stabilization
loid or colloid, and when crystalloids and colloids are in septic patients is that it should be done early. Early
titrated to the same level of filling pressure they restore goal-directed therapy in patients with severe sepsis
tissue perfusion to the same degree. However, because and septic shock improves mortality rates compared to
of their propensity for leakage into the extravascular standard therapy.
space, to achieve the same effect approximately three
times greater volume of crystalloid is required than col-
loid, and slightly longer infusion periods may be necessary Immunomodulating Therapy
to achieve comparable hemodynamic endpoints. The The recognition of the important interaction between
choice of fluid is probably less important than the quan- the coagulation system and the inflammatory response
tity given, with cardiac output and systemic oxygen deliv- outlined above led to the development of the first
ery increasing in proportion to the degree of intravascular immunomodulating therapy to be shown to reduce mor-
volume expansion achieved. Repeated fluid challenges, in tality in patients with severe sepsis. A recombinant form
which a predefined amount of fluid is infused over a set of activated protein C, known as drotrecogin-alfa (acti-
time and the chosen clinical endpoints and pressure safety vated), given at a dose of 24 μg/kg/hour for 96 hours
limits monitored, can be conducted to assess the ade- improves organ dysfunction and decreases mortality in
quacy of fluid resuscitation (Table 1-4). patients with severe sepsis and septic shock. The mech-
Colloid solutions are much more expensive than crys- anisms of action of this drug are still uncertain, but com-
talloid solutions, even when taking into account the bine anticoagulant properties and direct effects on the
reduced volumes required. Crystalloids are often regarded inflammatory response. Activated protein C can reduce
as first-line fluids for the hemodynamically stable patient LPS-induced TNF release, inhibit leukocyte adhesion,
and colloids are administered in addition to rather than decrease leukocyte activation, inhibit NF-κB formation,
in lieu of crystalloids. However, when the patient is and inhibit induction of inducible nitric oxide synthase
hemodynamically compromised many clinicians prefer (iNOS), all key factors in the systemic inflammatory
colloids. With several recent studies suggesting that response to sepsis. Activated protein C also has anti-
new generation hydroxyethyl starches may reduce the apoptotic effects. As expected, drotrecogin alfa (acti-
inflammatory response and directly improve tissue oxy- vated) administration is associated with an increase in
genation, the precise choice of fluid may become more the risk of bleeding, although this is mostly associated
important; however, further study is needed to confirm with use of invasive procedures. It is therefore con-
these observations. traindicated in patients with active internal bleeding,
The choice of vasoactive agent similarly has been the recent hemorrhagic stroke, intracranial or intraspinal
subject of some debate, with a keen search to determine surgery, severe head trauma, presence of an epidural
which agent, if any, has direct beneficial effects on the catheter, intracranial neoplasm, or evidence of cerebral
microcirculation. However, there remains no evidence herniation (Table 1-5). Care should be taken in other
MAP 65 70 75 65
CVP 12 14 15 OR 15
Urine output 0 20 20 0
Skin Mottled OK OK Mottled
Action Continue Stop Stop
Sepsis: The Systemic Inflammatory Response 9
CONTRAINDICATIONS
SELECTED READING
Active internal bleeding
Trauma with risk of life-threatening bleeding (spleen, liver, Alberti C, Brun-Buisson C, Burchardi H et al: Epidemiology of
retroperitoneal, etc.) sepsis and infection in ICU patients from an international
Central nervous system (CNS) multicentre cohort study. Intensive Care Med 28:108–121,
Recent hemorrhagic stroke (3 months) 2002.
Recent CNS surgery or head trauma (2 months)
Intracranial mass Angus DC, Linde-Zwirble WT, Clermont G et al: Cost-effectiveness
Epidural catheter of drotrecogin alfa (activated) in the treatment of severe
sepsis. Crit Care Med 31:1–11, 2003.
CAUTIONS
Annane D, Sebille V, Charpentier C et al: Effect of treatment
Abnormal coagulation
with low doses of hydrocortisone and fludrocortisone on
Bleeding diathesis
mortality in patients with septic shock. JAMA 288:
Platelet count < 30,000/mm3
Very prolonged INR 862–871, 2002.
Full heparin therapy Appoloni O, Dupont E, Andrien M et al: Association of TNF2, a
Recent thrombolytic therapy TNFα promoter polymorphism, with plasma TNFα levels
Significant risk of bleeding and mortality in septic shock. Am J Med 110:486–488, 2001.
Polytrauma
Active ulcer Bernard GR, Vincent JL, Laterre PF et al: Recombinant human
Esophageal varices protein C Worldwide Evaluation in Severe Sepsis (PROWESS)
Recent ischemic stroke (3 months) study group. Efficacy and safety of recombinant human acti-
vated protein C for severe sepsis. N Engl J Med 344:699–709,
2001.
Bossink AW, Groeneveld J, Hack CE et al: Prediction of mortality
groups of patients at high risk of bleeding, and infusion in febrile medical patients: How useful are systemic inflam-
should be interrupted for surgery or invasive inter- matory response syndrome and sepsis criteria? Chest
ventions. Although costly, its cost-effectiveness ratio 113:1533–1541, 1998.
compares well with other widely used healthcare Eachempati SR, Hydo L, Barie PS: Gender-based differences
strategies. in outcome in patients with sepsis. Arch Surg 134:
Another strategy that has been shown to be beneficial 1342–1347, 1999.
in patients with septic shock is the administration of Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL: Serial evalu-
moderate doses of corticosteroids. In patients with septic ation of the SOFA score to predict outcome in critically ill
shock the adrenal response may be insufficient, and in patients. JAMA 286:1754–1758, 2001.
such patients moderate doses of corticosteroids (50 mg Hotchkiss RS, Karl IE: Pathophysiology and treatment of sepsis.
IV hydrocortisone every 6 hours) have been shown to N Engl J Med 348:138–150, 2003.
improve survival rates. Similarly, septic shock is associ- Joyce DE, Grinnell BW: Recombinant human activated protein C
ated with a relative deficiency of vasopressin and admin- attenuates the inflammatory response in endothelium and
istration of low doses of vasopressin may be beneficial monocytes by modulating nuclear factor-κB. Crit Care Med
although this has yet to undergo randomized clinical trials, 30:S288–S293, 2002.
and thus cannot be recommended for routine use. Levy MM, Fink MP, Marshall JC et al: 2001 SCCM/ESICM/
ACCP/ATS/SIS International Sepsis Definitions Conference.
Crit Care Med 31:1250–1256, 2003.
CONCLUSION Martin GS, Mannino DM, Eaton S et al: The epidemiology of
sepsis in the United States from 1979 through 2000. N Engl
Severe sepsis and septic shock are common causes of J Med 348:1546–1554, 2003.
morbidity and mortality, and their incidence is increasing. Members of the American College of Chest Physicians/Society
Improved understanding of the pathophysiology of the of Critical Care Medicine Consensus Conference Meeting:
sepsis response, in particular regarding the interaction Definitions for sepsis and organ failure and guidelines for
between inflammation and coagulation, has seen a major the use of innovative therapies in sepsis. Crit Care Med
advance in the treatment options with the development 20:864–874, 1992.
of drotrecogin alfa (activated). Importantly, as other Rivers E, Nguyen B, Havstad S et al: Early Goal-Directed
effective immunomodulatory strategies become available, Therapy Collaborative Group. Early goal-directed therapy
10 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
in the treatment of severe sepsis and septic shock. N Engl Intensive Care Medicine. Intensive Care Med 22:707–710,
J Med 345:1368–1377, 2001. 1996.
Vincent JL, Moreno R, Takala J et al: The SOFA (Sepsis-related Wichmann MW, Inthorn D, Andress HJ et al: Incidence and
Organ Failure Assessment) score to describe organ dys- mortality of severe sepsis in surgical intensive care
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Sepsis-Related Problems of the European Society of and outcome. Intensive Care Med 26:167–172, 2000.
2
CHAPTER Acute Respiratory
Failure
MICHAEL J. APOSTOLAKOS, M.D.
11
12 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
. .
where VE equals total minute
Table 2-2 Type 1 Respiratory Failure Mechanisms, . ventilation, VD equals dead-
space minute. ventilation, VA equals alveolar minute ven-
Responsiveness to Supplemental O2, .
tilation, and VCO2 equals CO2 production. Normally VD
and Presence of A-a Gradient .
and VA represent 30% and 70% respectively of total ven-
.
tilation. Also, as k is a constant and VCO2 can generally be
Responds Increased
Mechanism to Added O2 A-a PO2 Gradient .considered constant,. PaCO2 is inversely proportional to
VA (i.e., PaCO2 ~ 1/ VA). This will become important to
Decreased FIO2 Yes No understand when adjusting ventilator settings.
Hypoventilation Yes No When assessing hypoxemia it is important to under-
Shunt No Yes stand the normal physiology of the lung (Figure 2-1A).
V/Q Mismatch Yes Yes
Diffusion Limitation Yes Yes
The pulmonary artery is the only artery in the body that
delivers unoxygenated blood. A normal blood gas
obtained from the pulmonary artery is pH 7.35/PCO2 =
45 mmHg/PO2 = 40 mmHg/O2 sat = 75%. The alveolar PO2
is approximately 110 mmHg (obtained from the alveolar-
An example of the usefulness of calculating an A-a PO2
arterial gas equation), and alveolar PCO2 is 40 mmHg.
gradient is demonstrated by this case. A 21-year-old patient
A perfectly matched alveolar capillary unit will produce
is admitted from the emergency department (ED) with a
pulmonary venous blood with a pH of 7.4/PCO2 =
drug (narcotic) overdose. On presentation to the ED the
40 mmHg/PO2 = 110 mmHg, and O2 sat = 100%. However,
patient’s respiratory rate is 4 breaths per minute. Initial ABG
a “normal” arterial blood gas obtained peripherally will
is pH 7.1, PaCO2 = 80 mmHg, PaO2 = 40 mmHg, O2 sat =
yield something like: pH = 7.4/PaCO2 = 40 mmHg/PaO2 =
70%. The patient is intubated and transferred to the ICU.
95 mmHg/O2 sat = 98%. The difference between the pul-
The A-a PO2 gradient calculated from the equation above is:
monary venous blood and the arterial blood gas is due to
A-a PO2 gradient = 0.21(747 − 47) − (80/0.8) − 40 = 147 − 100 − 40 anatomic shunt. Approximately 2% of venous return
= 7 (i.e., ≤10 on room air) from the systemic circulation is returned to the left side
The normal A-a PO2 gradient supports the fact that of the circulation without going through the pulmonary
this patient’s hypoxemia is due solely to hypoventilation circulation. Two major contributors to this shunt are the
and that no other cause of hypoxemia, such as pneumo- bronchial circulation and the thebesian veins of the
nia, needs to be implicated. The normal A-a PO2 gradient heart. A combination of 98% of pulmonary venous blood
separates this category of hypoxemia from the other and 2% anatomic shunt (systemic venous) blood yields
three categories. the. “normal” peripheral ABG.
.
Diffusion limitation is a very rare cause of hypoxemia V/ Q mismatch leads to hypoxemia when perfused
in the ICU. The alveolar capillary unit has about 1 second alveolar units have reduced oxygen levels in the alveolar
in which to exchange carbon dioxide for oxygen. This space due to reduced ventilation. This reduced ventila-
normally occurs within the first 0.3 seconds. This leaves tion is generally due to some obstruction (bronchiolar
approximately 0.7 seconds as a buffer. This protects edema or mucus related.to. infection, bronchospasm sec-
against hypoxemia during exercise (which increases ondary to asthma, etc.). V/ Q mismatch, however, may be
overcome with additional
cardiac output and hence decreases available time for . . FIO2 (Figure 2-1B). Shunt is
gas exchange) and/or to overcome diseases which cause simply the extreme of V/Q mismatch where there is no
diffusion limitation. Except for severe end-stage lung dis- ventilation but perfusion persists. (Remember ventila-
ease (e.g., fibrosis, emphysema), this is a very rare occur- tion without perfusion is deadspace ventilation.) Shunt
rence and, hence, a very rare cause of acute hypoxemia. will not be overcome by additional FIO2 (Figure 2-1C).
Diffusion limitation, in general, is something that is handled
by .the. pulmonary specialist over a long period of time.
V/ Q mismatch is the most common cause of hypox- HYPOXEMIA: MANAGEMENT
emia. With reference to hypoxemia, only perfusion with
reduced or absent ventilation leads to hypoxemia. Quite simply there are two major ways to improve
Ventilation without perfusion is simply deadspace venti- oxygenation: (i) increase FIO2 and (ii) increase mean air-
lation and by itself does not lead to hypoxemia. If severe, way pressure.
it may lead to CO2 retention. Increasing FIO2 is simple and can only be done one
To understand this completely, one needs to call to way. Increasing mean airway pressure can be done by a
mind the following equations: multitude of ways. Increasing mean airway pressure
. . . improves oxygenation by recruiting partially or fully col-
VE = VD + VA lapsed alveoli, thus better matching ventilation to perfu-
. .
PaCO2 = k × VCO2/VA sion and reducing shunt. Mean airway pressure may be
Acute Respiratory Failure 13
C
Figure 2-1 Physiology of oxygenation in the lung under normal circumstances (A), during V/Q
mismatch (B), and shunt (C). See text for details. (Adapted from Apostolakos MJ: The critically ill
patient: overview of respiratory failure and oxygen delivery. In Apostolakos MJ, Papadakos PJ,
editors: The Intensive Care Manual, New York: McGraw-Hill, 2001, pp 1–13.)
14 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
increased either invasively or non-invasively. Non-invasive (ARDS). At times, deadspace ventilation may approach
means include the use of continuous positive airway pres- 70% or more of total ventilation. If this occurs, the rela-
sure ventilation (CPAP). CPAP utilizes a tightfitted nasal tive amount of alveolar ventilation is reduced and total
or naso-oral mask (to reduce leaks). The CPAP machine ventilation must be increased if PCO2 is to be maintained
provides a continuous pressure to the airway to assist constant. When this demand cannot be met, hyper-
in recruiting alveoli and improving oxygenation. Usual capnia ensues. Abnormalities of the airways or alveoli
starting pressures are 3–8 cmH2O and may be titrated to as described above increase the demand as well as
10–15 cmH2O to improve oxygenation. Issues of comfort increased
. . metabolic rate or elevated respiratory quotient
limit the pressure that can be used. Contraindications to (VCO2 /VO2) (Table 2-1).
the use of CPAP include poor mental status or patients The other side of the supply/demand equation that
with increased risk of aspiration (such as those patients can lead to hypercapnia is when the supply side is
with ileus or bowel obstruction). adversely affected. The supply side is made up of the
Another way to increase mean airway pressure is neuromuscular system. Normally the respiratory system
through invasive mechanical ventilation which utilizes can sustain approximately half of the maximum volun-
an endotracheal tube. The easiest way to increase mean tary ventilation (MVV). This is called the maximal sus-
airway pressure for a patient on invasive mechanical tainable ventilation (MSV). A 70-kg adult under basal
ventilation is to increase positive end expiratory pres- conditions has a minute ventilation of approximately
sure (PEEP). This is the back pressure that the ventilator 6 l/min, MSV of 80 l/min, and MVV of 160 l/min. When
provides during the exhalation phase to prevent alveolar certain conditions intervene (Table 2-1) the body’s abil-
collapse. Inverse ratio ventilation (IRV) is another ity to supply increases in ventilation are compromised
maneuver that increases mean airway pressure by and therefore hypercapnia can ensue. This may lead to
increasing the normal inspiratory/expiratory ratio from respiratory failure.
1:2 to 1:1 or 2:1. This change keeps the positive pressure Abnormalities of the central nervous system, peripheral
in the chest for longer periods of time. Some believe that nervous system, chest wall, airways, or alveoli can all lead
this technique simply adds to the PEEP by not allowing to hypercapnic respiratory failure. Narcotic overdose,
enough time for exhalation. This has led to the term meningoencephalitis, vascular abnormalities, or strokes
“sneaky PEEP” being used in reference to IRV. High- affecting medullary control centers can lead to hypoventi-
frequency JET ventilation and oscillating ventilation are lation and subsequently to hypercapnic respiratory failure.
“high tech” ways of increasing mean airway pressure A wide variety of disorders that affect peripheral
and oxygenation. Two less commonly used ways to nerves, neuromuscular junction, and chest wall are asso-
improve oxygenation, prone positioning and inhaled ciated with weakness and ineffective ventilation and
. .
nitric oxide, work by improving V/ Q matching. thus with hypercapnic respiratory failure. Guillain-Barré
syndrome, myasthenia gravis, polymyositis, muscular
dystrophies, and metabolic disorders are the most com-
HYPERCAPNIA mon neuromuscular causes of hypercapnic respiratory
failure.
Besides oxygenation, the other major function of the Primary disorders of the chest wall constitute another
respiratory system is ventilation (CO important category of neuromuscular respiratory failure.
. 2 removal). At a con-
stant rate of CO2 production ( VCO2), PaCO2 is deter- These conditions include severe kyphoscoliosis, flail
mined by the level of alveolar ventilation. The relationship chest, extensive thoracoplasty, morbid obesity, and mas-
between alveolar ventilation, rate of CO2 production, sive abdominal distention secondary to distended loops
and PaCO2 is: of bowel or ascites. These conditions place respiratory
. . muscles at mechanical disadvantage and tidal volume
VA = K × VCO2/PaCO2
. drops. Despite increases in respiratory rate, alveolar ven-
where V.A = alveolar minute ventilation, K = a . con- tilation drops and hypercapnia ensues.
stant, and VCO2 = rate of CO2 production. When VCO2 Obstructed airways are another common cause of
is constant. a patient’s PaCO2 will be inversely propor- hypercapnia. Causes of obstruction include aspirated
tional to VA in a linear fashion. foreign objects, tracheal tumor, COPD, and asthma. The
. . .
that VE = VD + VA, where
. One also needs to remember . airway narrowing leads to greater transthoracic pres-
VE = total minute ventilation, VD = deadspace minute venti- sure gradient required for inspiratory flow. The resistive
.
lation, and VA = alveolar minute ventilation. Normally component of the work of breathing is increased, and
deadspace ventilation represents approximately 30% of the increase is associated with increased oxygen con-
total ventilation. This, however, can increase in certain sumption. In addition tidal volume falls and deadspace
conditions such as chronic obstructive pulmonary dis- ventilation increases. Respiratory muscle fatigue and
ease (COPD) or acute respiratory distress syndrome hypercapnia develops.
Acute Respiratory Failure 15
When hypercapnia occurs ventilatory demand out- Acute respiratory failure is divided into type 1 hypox-
strips supply. Therefore choices of treatment are in two emic respiratory failure and type 2 hypercapnic respira-
categories: augment ventilatory capacity (supply) or tory failure. Type 1 hypoxemic respiratory failure is
decrease workload (demand). subdivided into four major categories that have unique
If airway obstruction is an issue such as it is in COPD characteristics with respect to the presence of A-a PO2
or asthma, bronchodilators (e.g., beta agonists), anti- gradient and response to supplemental oxygen. Type 2
inflammatories (e.g., steroids), and secretion elimination hypercapnic respiratory failure occurs when ventilatory
are effective in decreasing airway resistance and hence supply is outstripped by demand.
the workload. Thus, demand on ventilation is reduced. Treatment of respiratory failure focuses on reversing
Correcting electrolyte disturbances (e.g., hypokalemia, the underlying cause of respiratory failure. Barring that,
hypocalcemia, hypomagnesemia, and hypophosphatemia) supportive measures incude increasing FIO2 and mean
may improve respiratory pump function and thus augment airway pressure to improve oxygenation and the use of
ventilatory supply. Improving nutritional parameters can BiPAP or invasive ventilation to reduce PCO2.
have similar effects.
16
Vascular Access and Hemodynamic Monitoring 17
pressure of oxygen (PaO2) of 60 torr (or mmHg); and an jugular venous bulb oximetry, is used as an indicator of
SpO2 of 75% corresponds to a PaO2 of 40 torr. The SpO2 global oxygen kinetics in the brain. A fiber-optic catheter
as displayed by most pulse oximeters in clinical use can be containing fiber-optic sensors is passed retrograde via
expected to be within 2% of the value for oxyhemoglobin the jugular vein to the point of the jugular venous bulb
concentration of blood determined using a co-oximeter. where it continuously measures the saturation of ambi-
Therefore, there is an approximately 2% error associated ent blood. When the saturation of blood falls, there is
with pulse oximetry measurements. Anemia, as long as increased oxygen utilization in the brain and the data
the hematocrit is above 15%, does not interfere with the can be used to estimate the cerebral oxygen extraction
accuracy of pulse oximetry. Clinically detectable cyanosis ratio. This technology is commonly employed in neuro-
generally occurs at an SpO2 of 80%, which correlates with surgical and trauma ICUs to guide therapy.
a deoxyhemoglobin concentration of 5 g-%. However, the
reliability of most pulse oximeters in clinical use deteri-
orates very rapidly when the saturation value is < 75%. CAPNOGRAPHY
Therefore, there is very little physiologic meaning
attached to clinical documentation of saturations signifi- Capnography and capnometery refer to the monitor-
cantly below 75%. ing of CO2 concentration in exhaled gases. Capnometery
SpO2 values that are obtained in the absence of a refers to the determination of a simple numerical value
plethysmographic waveform are unreliable – the heart for CO2 concentration in expired gas. Capnography pro-
rate by the oximeter must correlate with the heart rate vides exhaled CO2 concentrations as a continuous wave-
as displayed by the ECG. Therefore, the use of pulse form display in addition to a numerical value for end-tidal
oximetry is limited in patients with severe peripheral CO2 (ETCO2) concentration. Reliable CO2 determination
vasoconstriction, since there is frequently inadequate in exhaled gas generally requires a closed ventilator
peripheral perfusion to obtain a reliable plethysmographic circuit. However, the use of capnography as a general
waveform. In the setting of profound peripheral vaso- monitor of respiration, e.g., during sedation when a patient
constriction, alternative sites for measurement of pulse is receiving oxygen by nasal cannulae, is widely accepted
oximetry are available such as the earlobe, tongue, or and encouraged as long as the associated limitations are
cheek. Additionally, warming the extremity is frequently understood. The concentration of CO2 in exhaled gas is
effective. Pulse oximeters are also prone to failure under measured using either an infrared analyzer or by mass
some ambient light conditions as well as in the presence spectrometry. The infrared analyzer determines CO2
of certain colors of fingernail polish (e.g., dark blue). concentration using infrared light absorption and is
Finally, pulse oximeters may be unreliable during periods more readily available, less costly, and allows for real-
of tachycardia and other arrhythmias. New technology, time sampling. The mass spectrometer is more complex
by MasimoR for example, allows computer-assisted extrac- and costly, is not portable, but is more accurate. Since
tion of pulse oximeter signals from ambient noise and capnography provides significantly more information, it
increases reliability and accuracy. has displaced capnometery as a standard for CO2 monitor-
Since carboxyhemoglobin and oxyhemoglobin both ing. Capnography thus allows for (1) real-time assessment
absorb light at identical frequencies, 660 nm, pulse of the adequacy of alveolar ventilation, (2) an indirect
oximeters that compare only two wavelengths of light assessment of pulmonary perfusion, (3) early detection of
will provide falsely high readings of SpO2 in patients ventilator malfunction or systems disconnections, and
with carbon monoxide poisoning. In these cases, a (4) waveform analysis that correlates with conditions
co-oximeter is necessary to determine SpO2 accurately such as bronchospasm. CO2 detection in expired gases is
(Figure 3-1). On the other hand, met-hemoglobin essential to document correct endotracheal tube place-
absorbs light and red and infrared wavelengths with ment following endotracheal intubation. Ordinarily, single-
the same absorption coefficient; this results in a 1:1 breath detection devices are used for this purpose;
absorption ratio which then corresponds to an SpO2 however, under some circumstances (such as ambient air
reading of 85%. Met-hemoglobinemia causes falsely low insufflation into the stomach, or recent consumption of
saturations when the actual arterial saturation is >85% carbonated beverages) single-breath detection is mislead-
and causes falsely elevated SpO2 readings when the ing. Note that while continuous capnography can reliably
actual arterial saturation is <85%. Met-hemoglobinemia detect esophageal intubation or verify airway intubation,
occurs in patients with severe septic shock due to it cannot detect endobronchial intubation.
increased nitric oxide production and it is also common The early return of CO2 in expired gases during resus-
following excessive topical administration of benzocaine citation from cardiac arrest correlates with outcome.
spray. Additionally, patients who are receiving sedation with-
The use of pulse oximetry to determine the saturation out a secure airway may become apneic for prolonged
of mixed venous blood return from the brain, known as periods of time during which pulse oximetry values do
Vascular Access and Hemodynamic Monitoring 19
not show hypoxemia; therefore, exhaled CO2 monitor- blood pressure measurements are relatively inaccurate
ing should be considered in all patients prone to apnea. measures of diastolic blood pressure. Also, oscillometric
When ETCO2 values are used in conjunction with blood pressure measurement is very difficult to use in
arterial PaCO2 estimation of the deadspace ventilation patients with arrhythmias or severe bradycardia.
fraction is also possible. The deadspace to tidal volume Furthermore, blood pressure measurements which rely
ratio can be calculated from the Bohr equation: on cuff bladders are subject to error based on relative
cuff-arm sizing, the conical anatomy of obese extremi-
VD PaCO2 − PECO2
+ ties, and alterations in the blood volume of the ipsilateral
VT PaCO2 extremity induced by repeated cuff inflation. Generally,
a cuff that is 20% wider than the diameter of the limb
where PaCO2 is the partial pressure of CO2 in arte-
must be used to obtain reliable noninvasive cuff blood
rial blood and PECO2 is the partial pressure of CO2 in
pressures, and this is not always feasible. Blood pres-
expired gas.
sures measured by automated cuffs are most reliable
Note that ETCO2 is not in itself an accurate indicator
with respect to systolic blood pressure and MAP,
of PaCO2. However, once an individual patient’s ETCO2
whereas invasively obtained blood pressures are more
to PaCO2 has been determined, under relatively stable
reliable with respect to MAP as well as the diastolic
physiologic conditions, the relationship should be rela-
blood pressure.
tively constant and therefore ETCO2 can be used as a
Doppler measurements of blood pressure are usually
substitute for arterial blood gas monitoring to assess the
obtained as an adjunct to sphygmomanometry during
adequacy of ventilation. In most patients the normal
profound hypotension or to auscultate specifically
arterial–ETCO2 gradient is 2–5 torr.
flow properties within an artery. The Doppler principle
creates a sound wave by applying electrical potential to
a crystal. When the sound wave passes through tissue
NONINVASIVE BLOOD and encounters a moving object, such as blood, the
PRESSURE MONITORING frequency of the reflected sound is altered in a manner
proportionate to the velocity of the reflecting material.
Arterial blood pressure can be measured using auscul- Therefore, “hissing” arterial pressures can be easily
tation (the Riva-Rocci method) whereby a compressed differentiated from venous “hums.” Additionally, amplifi-
artery is auscultated using a stethoscope and the turbu- cation of the Doppler signal allows the determination
lent flow within the blood vessel walls causes character- of flow which cannot be otherwise auscultated during
istic Korotkoff sounds. Korotkoff sounds cannot be heard periods of hypotension.
during the range of cuff deflation between systolic and
diastolic pressures; this is known as the “auscultatory gap.”
Typically, a sphygmomanometer is used to inflate a cuff GENERAL PROCEDURAL PRINCIPLES
to a set pressure and then slowly deflate the cuff while
ausculating for Korotkoff sounds. Visual–auscultatory Each year in the USA more than 150 million intravas-
correlation of the sounds with the pressure in the cuff cular devices such as peripheral venous catheters, arterial
(manometry) allows bedside determination of systolic and catheters, dialysis catheters, and central venous catheters
diastolic pressures. Although auscultated blood pressure (CVCs) are inserted. Of these, more than 5 million are
measure is now relatively seldom used, it plays a very CVCs. Therefore, these statistics underscore the depend-
important role in the rapid verification of blood pressures ence of modern inpatient medical care on intravenous
when automated methods fail. access.
Noninvasive blood pressure (NIBP) measurements are
more typically obtained using automated cuffs which rely
on the oscillometric technique. The DINAMAP (device Credentialing
for indirect noninvasive automatic mean arterial blood Procedural credentialing is generally accepted to be
pressure) is the most commonly used NIBP system. The specialty- as well as institution-specific. Providers who
oscillometric technique for determining blood pressure are not credentialed to perform a procedure independ-
either uses two cuffs placed in series, one includes the ently must be supervised. The level of supervision of
artery proximally, while the other detects the onset of non-credentialed providers that is typically required is
pulsations; or, as in the DINAMAP system, a single cuff is “immediately available,” a legal term which is commonly
alternately rapidly inflated and deflated. Oscillometry interpreted to mean that the supervisor is gowned,
actually measures mean arterial pressure, MAP, which gloved, and ready to assume redirection or the full com-
corresponds to the point of maximal cuff deflation. pletion of the procedure at an instant’s notice. The super-
Despite its common usage, noninvasive oscillometric vising or teaching physician assumes full responsibility
20 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
for all and any complications. There is a presumption that the risks, benefits, and alternatives to the proposed pro-
providers credentialed to perform independently a pro- cedures; and second, clear acceptance or denial of per-
cedure be able to recognize and treat or obtain immedi- mission by a decision-maker after careful consideration.
ate back-up in treating the more common complications Patients who have received psychoactive medications,
associated with the procedure. have an organic brain syndrome, or are confused due to
their underlying disease cannot give their valid informed
consent and they are considered to lack capacity. In
Justification such situations the healthcare proxy or surrogate decision-
No critically ill patient should be without secure and maker must give their consent on behalf of the patient,
functional intravenous access. Intravenous access is expressing the patient’s wishes as they understand them
required for the therapeutic administration of medica- to be. Even so, medical providers must be careful to
tions, fluids, blood or blood products, and for diagnostic avoid the use of jargon and technical language that may
monitoring. On the other hand, arterial blood pressure not be clearly understood during the consent process; a
monitoring is indicated for specific reasons in unstable clear concise presentation decreases the possibility of
patients. Every invasive procedure has an associated misunderstanding and confusion. Consent must always
risk–benefit analysis associated with its use. Therefore, be documented in writing. The documentation of
justification requires that the potential benefit to the consent may be limited to a brief note in the patient
patient be weighed against the short- and long-term risks chart relating the informed consent discussions, the
to the patient. Risk–benefit analysis is not the same as issues considered, and the outcome or decision and
cost–benefit analysis which has no role in emergency plan. However, a simple signed standard consent form
procedural justification. The justification or indication for placed within the body of the chart is traditionally
a given intervention or procedure should be documented acceptable, but less adequate. Frequently, during the
in the patient chart together with the procedural consent. care of unstable patients in the ICU, time pressures in
the setting of life-threatening illness, non-communicative
patients, or unavailability of proxy decision-makers, limit
Preparation practitioners’ ability to obtain informed consent and
Prior to considering any elective invasive procedure, ‘implied consent’ may temporarily suffice. In such
the provider must be intimately acquainted with the instances, the inability to obtain consent should be doc-
patient’s anatomy and physiology. Anatomic considera- umented. In some instances, consent may be obtained
tions include any lesions at or near the proposed opera- by telephone, these versions of verbal consents should
tive site, prior surgery, or positioning contraindications. always be verified and witnessed, and similarly docu-
For example, CVCs should not be placed near sites of mented in the record.
active infection, adjacent to arterial reconstructions,
or near prior hardware placement. Physiologic considera-
tions might include pre-existing coagulopathy, or cardiac Analgesia and Sedation
conduction abnormalities such as a left bundle branch Patient comfort during procedures is important for
block (LBBB). Where there is a pre-existing coagulopathy, both humanistic as well as practical purposes. A history
such as in the setting of active anticoagulant therapy, liver of allergies or reactions should be determined prior to
disease, uremia, or thrombocytopenia, vessels that can administering any medication. Local anesthesia or sys-
easily be compressed with external pressure (internal temic analgesia and/or anxiolysis may be appropriate.
jugular, femoral) should be chosen for access over those When local anesthesia is used it may be used copiously
that cannot be externally controlled if a hemorrhage as long as it does not distort the surrounding anatomy.
occurs (subclavian). Additionally, since irritation of the Note that 10 cm3 of 2% plain lidocaine that is inadver-
right heart by catheter, or by the guide wire during place- tently administered intravenously will have minimal
ment, can precipitate right-sided conduction abnormali- cardiovascular effects under normal circumstances.
ties and complete heart block or asystole, temporary Infiltration with local anesthesia must involve both
pacing may be required in patients with LBBB. superficial and deep structures; however, the majority of
pain receptors will be in the subcutaneous tissues.
Lidocaine 1–2% is typically used for infiltration. In some
Informed Consent instances epinephrine in a concentration of 1:100,000 or
Patients and/or their surrogate decision-makers have the 1:200,000 may be used to decrease cutaneous bleeding.
right to consent to or refuse treatment. Treatment without However, local anesthetics containing epinephrine
consent may represent assault and/or battery. Informed must never be injected in the proximity of arteries,
consent has two components: first, an explanation of especially end-arteries, because of the risk of vasospasm
Vascular Access and Hemodynamic Monitoring 21
and distal ischemia. Therefore, providers must person- the catheter is open, air can be entrained at the rate of
ally verify that the local anesthetic used for radial arterial 100 cm3 per second and is capable of producing a fatal
line placement does not contain epinephrine. air embolus within one second in an adult. The air that
In critically ill patients sedation needs to be considered enters the central venous system will pass through the
carefully; in particular, bolus dosing of sedatives can pre- right heart and cause an acute right ventricular outflow
cipitate hemodynamic compromise because all sedatives tract obstruction. Smaller amounts of air may pass
decrease autonomic tone. Bolus doses are more likely through a patent foramen ovale, and precipitate a stroke
than infusions to result in high plasma concentrations and in patients with this abnormality. The Trendelenburg
resulting side effects. In those patients who are maintain- position is also indicated for every removal of indwelling
ing cardiovascular homeostasis through an endogenous vascular catheters for the same reasons; central catheters
catecholamine release, even small doses of systemic must never be removed while the patient is in the
sedation may acutely cause significant cardiovascular upright or sitting position.
depression. Procedural sedation with fentanyl alone or
small doses of intravenous etomidate are likely to provide
the most sedation with the least hemodynamic compro- Infectious Complications
mise. Dexmetomidine provides hypnosis and analgesia Implanted foreign bodies are especially predisposed
but does not suppress respirations and only minimally to bacterial infection. More than 200,000 nosocomial
alters cardiovascular status and is an excellent alternative. bloodstream infections occur each year in the USA, with
Patient immobility during delicate procedures is important most of these being related to intravascular access devices.
for technical efficiency as well as for patient safety. The case-fatality rate of catheter-related sepsis ranges from
14 to 19%. The mortality rate for Streptococcus aureus-
related sepsis alone is 8.2%. Infected foreign bodies
Sterile Technique cannot be sterilized and must be removed. Indwelling
Sterile technique is fundamental to procedural medi- vascular cannulae have been shown to develop a thin
cine. The components of sterile technique are hand- biofilm coating shortly after intravascular insertion. The
washing, sterile attire (gowns, gloves, mask, hat), sterile biofilm is composed of thrombin and fibrin which serves
field containment, and recognition of breaches in sterile as a nidus for microthrombus formation and clot propa-
technique. The importance of handwashing in the ICU gation, as well as for bacterial colonization. Therefore,
cannot be over-emphasized. The cost of using sterile increasingly, catheters are impregnated with heparin,
technique is minimal compared to the cost of iatrogenic antibiotics, or both to decrease the microfilm coating
infection. In the ICU all invasive procedures should be and minimize the possibility of catheter colonization or
performed using sterile technique, as opposed to simpler infection.
aseptic techniques, because of the propensity of ICUs Catheters may be infected hematogenously during
to harbor ubiquitous pathogenic organisms. In most septicemia or episodes of bacteremia. Typically, follow-
instances a breach in sterile technique is easier to correct ing hematogenous colonization or infection, bacterial
by re-gloving, for example, than to have to address an cultures reveal enteric organisms such as enterococ-
infectious complication later. cus or Enterobacter; pulmonary organisms such as
Pseudomonas, S. pneumoniae, or Haemophilus; or
genitourinary organisms such as E. coli or Proteus.
Procedural Positioning Fungal catheter colonization is increasingly common in
Central veins must be cannulated with the patient in ICU patients but very difficult to detect on routine blood
at least 15 degree Trendelenburg (head-down) position and catheter cultures.
because when veins are open to air above the level of Most catheters are infected by cutaneous organisms
the phlebostatic axis (the level of the right atrium) there which translocate through the catheter insertion tract.
is an increased risk for venous air entrainment and These organisms, such as S. epidermidis and S. aureus
venous air embolism (VAE). The Trendelenburg position are the most common organisms isolated from catheter
during CVC placement both decreases the incidence of tip cultures. Catheters intended for long-term use are
VAE and also facilitates line placement because of usually tunneled subcutaneously prior to intravenous
venous engorgement. insertion, a technique that decreases the incidence of
The risk of VAE is especially great in those patients infection from cutaneous sources.
who are hypovolemic, breathing spontaneously, and The gut motor hypothesis proposes that bacterial
generating significant intrathoracic pressure, or when translocation occurs across the intestinal mucosal barrier
large-bore catheters are used. When the intrathoracic during periods of splanchnic hypoperfusion, as occurs
pressure is negative relative to atmospheric pressure and during shock. Bacteria have been identified in the
22 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Percutaneous exposure to latex is unlikely to trigger a sys- polyethylene, or siliconized polypropylene. Most catheters
temic anaphylactic reaction, but such an adverse reaction in common use are made radio-opaque by impregnation
should be recognized and treated immediately. Therefore, with barium or tungsten salts to facilitate their intravascu-
a high index of suspicion is important. In patients with a lar localization by radiography. Typically, radiographic
history of latex allergy or where there is a high proba- confirmation is used to verify the positioning of centrally
bility of prior subsidization, alternatives to latex barriers placed venous catheters, endotracheal tubes, and feeding
and tourniquets should be used. The treatment of any and nasogastric tubes.
allergic reaction includes rapid initiation of intravascular Although the radiation exposure from portable x-ray
volume resuscitation, airway support, epinephrine, machines is greater than that of fixed x-ray machines,
inhaled bronchodilators, systemic steroids, an intravenous the beam is less concentrated, there is significantly
antihistamine such as diphenhydramine, and an H-2 antag- greater scatter of radiation, and therefore the total or
onist such as ranitidine. focused exposure may be less significant. The scatter of
radiation from portable x-ray machines increases expo-
nentially at distances of greater than 6 ft from the source.
Needlestick Injuries However, radiographs are routinely performed in ICUs
Barriers such as gloves, masks, eye shields, and gowns and therefore providers receive potentially higher levels
that are used during “sterile technique” also protect the of cumulative exposure than staff outside the ICU. When
operator from percutaneous exposure to body fluids. indicated, maintaining a safe distance, lead shielding, or
However, obviously sharp objects will penetrate most of dosimeter monitoring may be considered. When there is
these barriers, and, since vascular access cannot presently a possibility of pregnancy in either the patient or the
be performed without sharp cannulae, providers must use provider, appropriate lead shielding is encouraged.
special precautions in the use and disposal of sharp Malposition of CVCs occurs in as many as 15% of cases,
objects. At least 20 different pathogens have been con- even when inserted by experienced clinicians. Therefore,
clusively shown to be transmitted by needlestick injuries. a chest radiograph is indicated to check for catheter
These include HIV, human T cell lymphotropic virus positioning as well as to rule out complications. Catheters
(HTLV), hepatitis, Creutzfeldt–Jakob, and cytomegalovirus placed via the internal jugular (IJ) approach are statisti-
(CMV). The risk of transmission of HIV infection is esti- cally less likely to be malpositioned than those placed by
mated to be approximately 0.4% per single percutaneous the subclavian route. Examples of malpositioned CVCs
exposure to body fluids from an HIV-infected patient. are those that are placed arterially or subcutaneously,
However, it is unethical for healthcare providers to within the cardiac chambers, or subclavian lines that
decline to perform necessary procedures on patients inadvertently pass retrograde into the internal jugular vein.
infected with HIV or hepatitis. ICU radiographs for central line placement are usually
The provider who is performing the procedure is AP films. Since upright expiratory films decrease relative
responsible for the proper disposal of all contaminated lung volume, they are most useful to exclude a small
objects. The premise behind the use of “universal precau- pneumothorax. Pneumothorax is air within the pleural
tions” is that any patient may be an unrecognized carrier of space. A pneumothorax is not always located at the lung
latent infection. Although the risk of transmission of blood- apex and this is especially true when supine chest x-rays
borne pathogens through percutaneous exposure or by are used. A pneumothorax may not be immediately evi-
needlestick injury is relatively low, the implications for dent following pleural injury and may take 24–48 hours
healthcare workers are potentially devastating. Inadvertent to become sufficiently large as to be clearly visualized.
needlestick injuries are thought to occur in as many as 80% The size of a pneumothorax will develop much more
of cases of inexperienced practitioners performing inva- rapidly when pleural injury occurs in patients receiving
sive procedures. However, it is estimated that less than positive pressure ventilation. When there are clinical
25% of injuries are documented. Documentation of inad- signs of a significant pneumothorax, or tension pneu-
vertent exposure to infectious agents is important for the mothorax, occurring in the setting of clinical index of sus-
management of occupational health risks, early initiation picion, the diagnosis should never await chest x-ray
of appropriate treatment, and support for future disability. confirmation prior to treatment. The emergency treatment
The CDC has guidelines regarding testing and prophylaxis for tension pneumothorax is the insertion of a large-bore
following inadvertent needlestick injury. Hospital policies catheter, such as a 16- or 14-gauge IV, into the second
should also be consulted and followed. intercostal space, above the rib, in the anterior midclavic-
ular line. Thereafter, following evacuation of the tension, a
tube thoracostomy can be placed semi-electively.
Radiologic Verification The CVC tip should lie within the superior vena cava.
Vascular catheters are typically constructed of polymers When the catheter tip is in a subclavian vein, the risk of
such as polyurethane, polytetrafluoroethylene (Teflon), thrombus formation or vessel occlusion is increased.
24 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Furthermore, when the catheter tip is within the right blood pressure. Continuous beat-to-beat blood pressure
atrium, or within the cardiac silhouette on the chest radio- monitoring is essential in patients with rapidly changing
graph, there is increased risk of right atrial perforation and hemodynamic status and patients receiving rapidly acting
cardiac tamponade and arrhythmias. In some instances, cardiovascular agents. Under some circumstances, such
usually following left subclavian catheterization, a catheter as extreme obesity, arterial blood pressure monitoring
tip will be seen to abut the wall of the superior vena cava. may necessarily and appropriately take the place of non-
A catheter tip left in this position can erode and perforate invasive pressure monitoring. Arterial cannulation is also
the vena cava causing death by acute hemothorax. indicated when there is a need for frequent blood bio-
chemical analyses, especially arterial blood gas analysis.
It is generally accepted that if a patient will require more
Catheters and Thrombosis than six arterial punctures over their admission, conven-
Stasis predisposes to coagulation. By definition, the ience and safety favor an indwelling cannula.
blood flow in cannulated vessels is diminished because The primary sites for arterial cannulation for blood
of the decreased effective luminal size. Therefore, intra- pressure monitoring are the radial artery, the femoral
vascular catheters must be flushed regularly with sterile artery, and the dorsalis pedis artery. However, the radial
fluids or anticoagulant solution to maintain catheter and artery is the most common site for percutaneous arterial
luminal patency. Typically, pressure transducers infuse a cannulation because it is superficial, technically easy to
flushing solution at the rate of 3 cm3/hour. Although access, and is well collateralized. The ulnar artery is a
dilute heparin (100 units/ml) has been used ubiquitously dominant artery to the hand in up to 90% of patients.
to prevent the clotting of catheters, frequent or repeated Under some circumstances the axillary artery may also be
exposure to heparin may precipitate heparin-induced used as an alternative. However, the risk of thrombotic
thrombocytopenia (HIT), or heparin-associated thrombo- or air embolic stroke during flushing of the catheter is
cytopenia (HAT), through platelet sensitization. HIT is significantly greater with axillary artery lines because
a devastating complication and practitioners should have the tip of the cannula is very close to the carotid artery.
a high index of suspicion for HIT when the platelet End-arteries are never cannulated, since in the absence
count acutely drops following heparin exposure. of collateral flow tissue distal to the end-artery will
Furthermore, the incidence of HIT in the general popu- become ischemic. Surgical arterial cutdown should be
lation is increasing rapidly as more patients are sensi- used only in extreme circumstances because of the need
tized to heparin and are returning for repeat episodes for distal ligation and the high incidence of thrombosis
of medical care. and infection.
An acceptable alternative to heparin is the use of The Allen test is used to evaluate collateral flow to the
sodium citrate in catheter flushes. Since citrate binds cal- hand when the radial artery is occluded; it is therefore a
cium, it prevents completion of the coagulation cascade. test for the patency of the ulnar artery. Under normal
Sodium citrate is the anticoagulant used to prevent clotting circumstances blanching following release of the ulnar
of banked blood. The key advantage of sodium citrate is artery during the Allen test should resolve in approxi-
that it does not produce HIT. Furthermore, the negligible mately 7–10 seconds. Although universally recommended,
amount of citrate does not usually contribute to the the Allen test does not have any proven validity.
development of metabolic alkalosis. Insertion technique is an important determination of
Patients with underlying malignancies tend to be complications. Typically, a 20-gauge catheter is inserted
hypercoagulable at baseline and therefore are at increased using the Seldinger technique under aseptic, and prefer-
risk for catheter-related thrombosis. Thrombosis of the ably sterile, conditions. Repeated attempts to cannulate
subclavian vein should be considered whenever there is the artery may cause vasospasm, laceration, or thrombo-
unilateral upper extremity edema which may be related sis and even permanent occlusion. Arterial occlusion has
to an indwelling vascular catheter. been documented in up to 25% of arterial cannulations
Polytetrafluoroethylene (Teflon) catheters are signifi- and the occlusion may be permanent in up to 3% of
cantly less thrombogenic than are catheters made of these cases. Ischemic necrosis of the digits is extremely
polypropylene, polyvinyl chloride, or polyethylene. rare, but since the thumb is at risk, closed monitoring of
Therefore, the choice of catheter material may also distal perfusion is important. Therefore, arterial cannula-
influence complication rates. tion is not a benign procedure. Pre-existing arterial dis-
ease may be a risk factor for distal ischemia. Due to the
right-handed dominance of the majority of patients, the
ARTERIAL CANNULATION left hand may be the preferred site for radial cannulation
if the patient’s “handedness” is unknown. It is estimated
Percutaneous arterial cannulation is most often per- that the critical wrist circumference to safely accommo-
formed for the purpose of continuous monitoring of date a 20-gauge radial arterial catheter is 15 cm; smaller
Vascular Access and Hemodynamic Monitoring 25
The fallacy of blood pressure Normally, there is little or no variation in the amplitude
Pressure = Flow x Resistance
of arterial waves. However, respiratory variation, usually a
decrease in the amplitude of arterial waves with inspira-
Blood pressure = Cardiac output x Systemic resistance
tion (pulsus alternans), correlates well with hypovolemia.
When arterial catheters are flushed manually after
Central sympathetic sampling, heparinized fluid is infused into the artery
Preload
Afterload outflow under high pressure (250–300 torr). During flushing, the
Contractility Adrenergic release area supplied by the artery is frequently observed to
Heart rate Alpha-1 receptors
Facilitators blanch visibly. However, there is also retrograde flow of
Glucocorticoids flush solution and with continued flushing, saline, air
Vasopressin bubbles, and debris can be flushed into the central arte-
BP = CO x TPR rial circulation. This is an important consideration with
Figure 3-3 The fallacy of blood pressure. See text for details. axillary arterial catheters but can be significant even
with radial or femoral arterial lines. Flushing of arterial
catheters is an extremely important consideration in
pediatric patients both with respect to flush volume as
while the TPR drops and CO increases. In both the
well as the possibility of cerebral embolization.
scenarios global tissue perfusion can be severely com-
The presence of an indwelling arterial catheter is inde-
promised in the face of a normal MAP.
pendently correlated with the frequency of blood work
The mean arterial blood pressure can be determined
drawn from any one particular patient. Therefore, arterial
electronically by integrating the area under the arterial
catheters correlate with the cost of ICU care. Biochemical
pressure waveform and dividing by the duration of the
laboratory analyses are frequently most easily drawn from
cardiac cycle; MAP can also be estimated as diastolic
arterial catheters. Routine monitoring of blood chemistries
pressure is one-third of the pulse pressure. Mean arterial
may phlebotomize an adult ICU patient at the rate of one
blood pressure is the driving pressure for peripheral
unit of packed red blood cells per week. Whenever possi-
blood flow and a key determinant of tissue perfusion
ble adult ICU patients should have all their blood work
(Box 3-1). The MAP represents the standing pressure
drawn in pediatric tubes. Arterial cannulation should be
in the arterial circuit, “averaging” the phasic nature of
avoided for blood sampling purposes alone and the use of
systolic and diastolic variations. Mathematically it is
venous blood gases coupled with pulse oximetry should
given by:
be used to monitor oxygenation and ventilation status.
SBP + (2 × DBP ) Finally, arterial catheters must be clearly labeled to mini-
MAP = mize the possibility that vasoconstrictive substances be
3
inadvertently injected or infused.
Pulse pressure is the difference between the systolic
and diastolic pressures and reflects both cardiac stroke vol-
ume and vascular compliance. Pulse pressure narrowing, CENTRAL VENOUS CANNULATION
less than 30 torr, is associated with tachycardia, constric-
tive pericarditis, pleural effusions, and aortic stenosis. Overview
Widening of the pulse pressure is associated with aortic
regurgitation, patent ductus arteriosus, arteriovenous CVCs are essential for the management of critically ill
shunting, coarctation of the aorta, and thyrotoxicosis. patients. A large variety of catheters are available for
venous access and the choice of catheter must be based
on its intended purpose. CVCs are used for the infusion
of vasoactive substances, intravascular volume replace-
Box 3-1 Examples Where MAP Reflects
ment, total parenteral nutrition (TPN), hemodialysis, and
Driving Pressure for Perfusion
hemodynamic monitoring. CVCs are routinely placed in
many clinical settings; however, they are probably more
1. Cerebral Perfusion Pressure: frequent in operating rooms and ICUs. Large-bore single-
CPP = MAP − ICP lumen catheters are best suited for rapid infusion of fluid,
(ICP is the intracranial pressure) whereas multi-lumen catheters are important when
2. Coronary Perfusion Pressure:
multiple infusions of a potentially incompatible nature
CPP = MAP − LVEDP
must be administered simultaneously. It is estimated that at
(LVEDP is the left ventricular end-diastolic pressure)
MAP = mean arterial blood pressure. least 8–12% of hospitalized patients receive percutaneous
central venous cannulation.
Vascular Access and Hemodynamic Monitoring 27
Vasoactive drugs should always be infused via secure short-term CVCs. Therefore, PICC lines have important
CVCs since inadvertent infiltration of vasoactive advantages in those instances where the need for central
substances subcutaneously or into deep tissue spaces access is based on medication infusions, TPN, or even
will cause vasospasm, severe tissue necrosis, and even intravenous therapy in the home care setting. PICC lines
loss of limb or limb function. The insertion of catheters do retain their favorable comparison to other CVCs with
into central veins, because of their larger size and more respect to the incidence of venous thrombosis. PICC
rapid vascular flow, is also indicated for the administration lines are completely inadequate for monitoring or for
of hyperosmotic substances such as for chemotherapy or acute intravascular volume expansion.
TPN. Hyperosmotic substances irritate small vessels and However, the maximum fluid infusion rate is deter-
predispose to thrombophlebitis (venous inflammation) mined by the size of the catheter and not by the size of the
and phlebothrombosis (intravascular clotting). vein that is cannulated. For example, the maximum flow
Peripherally inserted central catheters (PICC lines) rate through a 9-French introducer sheath is approxi-
are increasingly used for intravenous access in hospitals. mately 247 cm3/minute, through 14-gauge peripheral IV
PICC lines are long catheters that are used for the basilic the maximum flow rate is 195 cm3/minute, and through
or cephalic vein at the antecubital fossa. Generally, the the 16-gauge port of a typical triple-lumen catheter the
basilic vein (medial) is preferred because it follows maximum flow rate is only 54 cm3/minute. In reality, the
a straighter course into the thorax and is less likely to most important limitation of flow rate through a 9-French
have venous valvular obstruction (Figure 3-4). PICC lines introducer is the diameter and length of the IV tubing and
have lower nosocomial infection rates than do other not the catheter itself. The Advanced Cardiac Life Support
protocol of the American Heart Association advocates
venous cannulation of the antecubital veins for cardiac
resuscitation as the preferred IV access site.
The rate of flow through a cylinder such as a catheter
or tube is described mathematically by the Poiseuille–
Hagen formula which states that flow is directly propor-
tional to the fourth power of the radius and inversely
proportional to the length of the catheter and the
viscosity of the fluid. This formula is expressed as:
πr 4
Q=
Cephalic vein 8ηL
Basilic vein where Q is the rate of flow, r is the internal radius of the
catheter, η is the viscosity of the fluid or gas flowing
through the catheter or tube, and L is the catheter
length. Therefore, for the purpose of rapid infusion
of volume, because of length considerations, a short
peripheral catheter is a better choice than an identical
gauge longer centrally inserted catheter such as a PICC
line. Alternatively, a large-bore CVC such as an 8.5 or 9 Fr
Radial artery
percutaneous introducer sheath, which is both of short
length and of large gauge, is the access of choice for
rapid intravascular volume expansion. Furthermore, the
relationship also makes it clear that viscous fluids such
Ulnar artery
as packed red blood cells will infuse more rapidly if
diluted with a crystalloid to decrease viscosity. Of note,
packed red blood cells transfused through catheters of
Palmar arch
20-gauge or smaller, especially when transfused under
pressure, are extremely likely to hemolyze on infusion.
Additional considerations regarding catheter size are
related to other specific indications for catheter place-
Figure 3-4 The vascular anatomy of the arm and forearm. The
cephalic vein runs medial to the basilica vein in the arm. The radial
ment. An introducer sheath is necessary for a pulmonary
and ulnar arteries together provide the blood supply to the hand artery catheter placement, and a different type of intro-
via the palmar arches. ducer is required for passage of a temporary transvenous
28 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
pacemaker wire. Hemodialysis catheters are typically method that is typical to vascular access and other inva-
large-bore catheters that have two ports to facilitate sive procedures. Typically, the guide wire has both a
high-volume flow during hemodialysis. straight tip, and a flexible “J-wire” tip which is inserted
Central venous lines directly administer fluid and med- intravascularly to prevent vascular injury.
ications to the right heart. Catheterization of the femoral Cannulation of the central circulation, which typically
vein is not technically central venous cannulation refers to the great veins within the thorax, is usually
because it infuses fluid and medications into the inferior accomplished via the internal jugular (IJ) or subclavian
vena cava, which is far removed from the right heart. vein (SV) approaches (Figure 3-5).
Additionally, femoral venous access during cardiac arrest The IJ vein can be cannulated via at least three differ-
and external thoracic compressions is notoriously ineffec- ent approaches: (1) the anterior approach, anterior to
tive for the delivery of vasoactive substances to the heart. the lateral belly of the sternocleidomastoid muscle
Moreover, in trauma patients infusion of substances (SCM); (2) the posterior approach, posterior to the lat-
through a femoral venous catheter may be ineffective in eral belly of the SCM; and (3) a supraclavicular approach
the setting of inferior vena cava disruption or hepatic at the midpoint of the anterior triangle immediately
trauma. Finally, central venous pressure (CVP) cannot be above the clavicle. The two heads of the SCM and the
reliably measured via a femoral venous catheter. clavicle form the three sides of triangle which contains
Cannulation of the external jugular (EJ) vein is not IJ vein, the carotid artery, and the vagus nerve. In almost
considered an appropriate approach for CVC placement any patient, except the extremely obese or edematous,
in ICU patients because the vein is technically difficult the IJ vein can be located using a 25-gauge “finder”
to catheterize and therefore does not represent secure needle. The IJ runs deep to the lateral or posterior head
access, venous valves prevent successful catheter pas- of the SCM in a direction parallel to a line drawn
sage in most instances, and the catheter often does not between the mastoid process and the ipsilateral nipple
pass into the thorax past the level of the clavicle. Venous when the neck is turned slightly (30°) to the opposite
valves are also prone to injury during EJ cannulation. side. The large introducer needle should never be used
Catheters sizes are expressed in either gauge or for initial localization. If a paresthesia is obtained in an
French units which are measures of external diameter. awake patient, the needle is injuring the cervical seg-
The largest catheter diameters are those with the small- ment of the brachial plexus and needle location is too far
est gauge designation but with the largest French size. posterior. The carotid artery runs close and medial to the IJ.
Mathematically, French size is defined as the outside Moreover, “cutting-tip” needles should never be reposi-
catheter diameter in millimeters multiplied by three. tioned subcutaneously because of the risk of lacerating
vital structures; successive attempts requiring redirec-
tion of the needle tip must always be initiated at the
Central Venous Catheter Placement level of the skin. Recently, the use of bedside ultrasound
Procedure technology such as the Site-RiteR can help better locate
CVCs are typically placed using the Seldinger tech- the IJ vein, decrease the incidence of pneumothorax and
nique, which refers to a “catheter-over-guide wire” arterial puncture, and also improve patient comfort.
However, such bedside ultrasound technology is rarely catheter insertion because the acute angulation from the
available in emergencies and therefore practitioners right subclavian vein makes PAC passage into the right
should be able to place reliably CVCs without the aid of atrium technically more difficult.
such a device. When the possibility of a carotid arterial Typically, the CVC should be passed to a depth of
puncture is suspected, the needle or catheter should 15–16 cm via the right IJ approach, 13–15 cm via the
either be transduced, or blood should be drawn for a right subclavian approach, 15–16 cm via the left sub-
comparison in color to an arterial sample. Acute embolic clavian approach, and 16–17 cm via the left IJ approach.
cerebrovascular accidents (CVAs) have been reported Radiographic verification is used to confirm proper
with a single carotid puncture with a 25-gauge finder catheter tip location and to exclude pneumothorax or
needle. Acute CVAs are rare, however, and every hemothorax. Data suggest that the incidence of pneu-
attempt must be made to ascertain venous location prior mothorax is not different between the IJ and subclavian
to passing subsequently the larger-bore catheters via the approaches. The tip of the pleura, the cupula of the
Seldinger technique. CVC kits usually contain both a soft lung, extends approximately 2.5–3 cm above the clavicle
plastic catheter and a larger steel needle, either of which into the anterior triangle. Therefore, lower approaches,
can be used to pass the J-wire. The catheter may be more especially when the needle is misdirected posteriorly,
appropriate for the IJ approach, since it can be inserted may puncture the pleura. However, inadvertent arterial
with minimal trauma and is more easily secured prior to cannulation is slightly more likely with the anterior IJ
guide wire placement. On the other hand, the catheter approach, because the carotid artery runs immediately
will bend and kink under the clavicle and therefore only medial to the IJ vein higher in the neck. The left-sided IJ
the steel needle should be used for the subclavian approach carries an increased risk for thoracic duct
approach. Following insertion of the guide wire, with injury, since the duct is anatomically located underneath
the J-tip leading, the introducer needle or catheter is the left IJ vein.
withdrawn and a dilator is inserted. A scalpel is used to The femoral vein runs medial to the femoral artery
cut the skin at the insertion site and facilitate passage of within the femoral sheath. The femoral vein is a direct
the dilator and, ultimately, the catheter. The smaller the continuation of the popliteal vein and becomes the
cut, the smaller the chance of lacerating the EJ vein, or external iliac vein at the level of the inguinal ligament.
cutting into the IJ vein. The scalpel tip should always be The femoral vein is cannulated inferior to the inguinal
aimed laterally so that the chance of carotid puncture ligament, and is usually located 1–2 cm medial to the
with the scalpel tip is minimized. If the dilator does not palpated femoral artery pulsation.
pass easily, it must not be forced since the possibility of
lacerating a thin-walled vein exists. Thereafter, the CVC
should be passed to an appropriate depth. Central Venous Pressure Monitoring
The SV is most often cannulated via an infraclavicular Vascular accesses are also used for monitoring pur-
approach. Supraclavicular approaches are only more poses, and CVCs allow for the measurement of venous
likely to cause a pneumothorax when attempted by inex- pressure within the thorax. Preload is defined by the
perienced operators. The SV begins at the outer aspect of volume of blood in the cardiac ventricle just prior to
the first rib as a continuation of the axillary vein, passes contraction and represents the sum of venous filling and
anterior to the scalenus anterior muscle and its insertion residual volume following the previous contraction. CVP
point on the first rib, then passes caudally and anteriorly correlates with jugular venous distention and jugular
to join the IJ to form the brachial cephalic trunk. As the venous pulsation on bedside clinical examination. The
SV passes over the first rib, it is anterior to the subclavian CVP, like the arterial waveform, must be measured at
artery and brachial plexus and only separated from the level of the right atrium, or the phlebostatic axis. The
them by the thin scalenus anterior muscle. In general, in phlebostatic axis is defined as the only point within
order to access the SV, the insertion site should be at least the cardiovascular system where intravascular pressure
2 cm in and inferior to the clavicle in order to optimize reaches zero.
the angle approach and minimize the possibility of passing A typical CVP waveform consists of three positive
inferior to the vein. A frequent choice for initial needle deflections (a, c, v waves) and two descents (x and y)
placement is at the level of the clavicular notch, the point (Figure 3-6). The a wave represents the increasing
at which the clavicle turns posteriorly. The clavicular venous pressure generated by each atrial contraction. The
notch lies at the junction of the outer one-third and the c wave is generated when the tricuspid valve is displaced
medial two-thirds of the clavicle. This point also generally into the right atrium during initial ventricular contraction.
coincides with the insertion point of the SCM on the The v wave is produced by the increasing atrial pressure
clavicle. The direction in which the needle is pointed is which occurs when venous return continues despite
directly toward the sternal notch. The left SV is anatom- closure of the tricuspid valve. The x descent is the rapid
ically preferable to the right SV for pulmonary artery decrease in CVP which corresponds to the period of
30 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
CVP x
(mmHg y ([Hb])(1.34)(SaO2) + (PaO2)(0.0031) x (Stroke volume index)(HR)
or Torr) c
a v
Preload (LVEDV)
Afterload x HR
Contractility (dP/dt)
Atrial Ventricular Distole
systole systole Figure 3-7 The determinants of oxygen delivery, DO2.
Figure 3-6 Correlation of CVP waveform monitoring with the
electrocardiogram. See text for details.
Therefore, hypovolemic shock reflects a low cardiac
ventricular ejection. The y descent occurs when the output state which can be treated with intravascular vol-
tricuspid valve opens at the end of ventricular contrac- ume expansion. Since oxygen delivery is most effectively
tion and blood again enters the ventricle. The impor- improved by increasing cardiac output, clinical strategies to
tance of these waveforms is in their correlation with monitor and improve cardiac output must be implemented.
pathophysiologic processes. An absence of the a wave Therefore, hemodynamic monitoring is necessary to
is characteristic of atrial fibrillation, where the x descent determine the pathophysiologic basis of the shock state.
is also often absent. Amplified, or “cannon,” a waves Hypovolemic shock is treated by improving venous
occur in the presence of mitral stenosis. Finally, both return, CVP, pulmonary capillary wedge pressure (PCWP),
the x and y descents are frequently exaggerated in the and cardiac preload. Cardiogenic shock is treated by
presence of constrictive pericarditis whereas cardiac optimizing, often decreasing, cardiac preload to prevent
tamponade magnifies the x descent and abolishes the ventricular overdistention and through the use of inotropic
y descent.
III
Index of II
cardiac
function I
Afterload
Figure 3-9 The relationship between cardiac function and
afterload. Curve III represents a normal ventricular response to Figure 3-11 Sequential waveform changes during advancement
increasing afterload. Following an initial period of compensation, of the pulmonary artery catheter from the superior vena cava (SVC)
there is progressive decrease in left ventricular performance. through the right atrium (RA), to the right ventricle (RV), into the
Curve II represents a failing ventricle or it can also represent a nor- pulmonary artery (PA), and finally into the “wedge position”
mal right ventricular curve. Curve I represents a failed ventricle. (PCWP). Note that catheter migration from the RV into the PA is
Decreasing afterload improves cardiac performance. heralded by a change in diastolic pressure.
32 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
A pseudo-wedge tracing also resembles an “over- without accounting for compliance. Furthermore, the
wedged” catheter tip with an elevated pressure reading. assumption that the PCWP is directly related to LVEDP
Since there is no blood flow past the tip of the PAC, the is flawed since pressures are measured across the pul-
pressure transducer at the tip of the catheter distal to the monary circuit, the left atrium, and the left ventricle.
balloon will transduce pressure from a theoretically
CVP ∝ RVEDP ∝ PCWP ∝ LAP ∝ LVEDP ∝ LVEDV
static column of blood extending from that particular
pulmonary arteriole through to the left atrium. During dias- Contractility can be improved using inotropic
tole, when the mitral valve is open, the pressure transduced agents. Examples of inotropic agents include β-1 agonists
by the PAC tip may approximate the left ventricular end- such as epinephrine, dopamine, or dobutamine;
diastolic pressure (LVEDP). Therefore, the measured pres- phosphodiesterase-III inhibitors such as milrinone; or
sure is known as the pulmonary artery occlusion pressure more general inotropes such as digoxin or calcium. When
(PAOP), or, more commonly, the PCWP. contractility is improved, the cardiac function at any given
The information obtained through the use of a PAC is level of preload is increased.
complex and includes differential cardiac chamber pres- Tachycardia is often seen in hypovolemic states in
sure information, transduced waveforms, measures of physiologic effort to maintain cardiac output, a response
cardiac output, and the oximetry-derived saturation of mediated by endogenous catecholamine release. Also,
venous blood. β-1 agonists have chronotropic action in addition to their
The PAC directly measures right heart pressures, ther- inotropic effects. Tachycardia may not be desirable
modilution, right heart cardiac output, and mixed venous because it increases myocardial oxygen demand and
oxygen saturation. The utility of the PAC is that it allows consumption and also may compromise cardiac output
for bedside construction of serial ventricular function due to a rate-related impairment of diastolic ventricular
(“Starling”) curves. The ventricular function curve relates filling. Patients with either fixed coronary obstruction or
indices of cardiac function as dependent variables to those with dynamic left ventricular outflow tract obstruc-
indices of estimated preload. tion do not tolerate tachycardia well. Additionally, patients
Derived indices of cardiac function include CO, cardiac who are receiving beta-blocker therapy may not mani-
index (CI), stroke volume (SV), ejection fraction (EF), fest a compensatory tachycardia in hypovolemic states;
or ventricular stroke work index. Measured indices these patients will instead retain a controlled slower heart
of estimated preload include CVP or PAOP or PCWP. The rate and the only sign of hypovolemia may be progressive
cardiac index is the cardiac output divided by the body hypotension.
surface area: CI = CO/BSA; the units are l/minute/m2. Cardiac output was at one time determined using indi-
It is important to realize that in physiologic terms, cator dye methods (Fick principle) or manual thermo-
preload is actually a volume, which causes stretching of dilution measurements using iced saline. Most catheters
cardiac sarcomeres to various points of contractility. currently in use have instead a heater-coil which allows
More accurately, preload is a wall tension that results continuous automated cardiac output determination
from the LVEDV, which causes myofibril stretch. without the variability introduced by manual injections.
Optimal pre-contraction sarcomere length is 2.2 times The principle of thermodilution remains founded on a
the resting sarcomere length. When the sarcomeres are temperature gradient between the heater-coil and a
stretched beyond 3.0 times their resting length, they are more distally placed temperature sensor. The greater the
overstretched and cardiac contractility is impaired; this cardiac output, the faster the blood flow around the
may account for the negative slope of the ventricular catheter, and the less and more transient the change in
function curve during volume overload. However, it is blood temperature (Figure 3-12).
very difficult to obtain clinically accurate bedside It is important to realize that the SVR is not measured
measurements of ventricular volumes. Therefore, pres- but is calculated. Additionally, it is calculated using the
sures are measured and these pressures are used to cardiac output, to which the SVR is inversely related by
estimate preload. Pressure and volume are related the formula SVR = [(MAP − CVP)/CO] × 80. The term
mathematically through compliance (C = ΔV/ΔP). Where “SVR” is frequently and erroneously used to refer to the
preload acutely exceeds the ability of cardiac contractil- total peripheral resistance (TPR) in the vascular circuit,
ity to move the blood forward, the excessive preload which is related to a quantity different from the calcu-
precipitates signs and symptoms of heart failure. lated SVR. Moreover, SVR does not in itself describe
However, the causes of pulmonary edema are many. “afterload” which is a more specific term referring to the
The CVP measures right-sided cardiac pressures, and impedance to forward cardiac output.
the PCWP extrapolates LVEDP by measuring the back Complications that are relatively unique to PAC use
pressure at the point of right heart pulmonary capillaries include catheter knotting and pulmonary artery rupture.
via a catheter lodged in the right heart. Therefore, The inadvertent knotting of a PAC occurs when the
volume is estimated from pressure measurements catheter does not pass easily through the cardiac
Vascular Access and Hemodynamic Monitoring 33
within zone III that the reliability of the PCWP is greatest. oxyhemoglobin into the tissues follows a concentration
Only in zone III is there a constant, uninterrupted column gradient, tissues with greater metabolic rates utilize
of blood between the catheter tip, through the pulmonary more oxygen and blood flowing from these tissues is
capillary circuit, through to the left heart. However, zone more “desaturated.” Additionally, blood that is flowing at
distributions change with patient positioning changes. lower rates, as in low cardiac output states, is more likely
Zone III is gravitationally defined so that it is in the to be “desaturated.” Therefore, the oxyhemoglobin
dependent lung, for whatever position in which the saturation of “desaturated” blood accurately reflects the
patient is placed. Note that lung zones cannot be actu- combined effects of peripheral tissue extraction and
ally determined by chest radiography and catheter tip cardiac output (flow).
positioning is instead determined physiologically. Normally, peripheral oxygen consumption, or uptake,
Zone I is especially vulnerable to high airway pres- is independent of oxygen delivery. Peripheral oxygen
sures. When positive end-expiratory pressure (PEEP) is extraction is linearly related to oxygen delivery.
applied then there is a greater likelihood that the PCWP The oxygen extraction ratio, O2 ER, is a calculation
will be falsely elevated by the airway pressures when the that determines global oxygen utilization based on the
catheter tip is in zone I. Since many patients who have difference between the oxygen that is delivered to tissues
required PAC placement in the past have also required in the oxygen concentration in mixed venous blood:
mechanical ventilation with higher airway pressure O2 ER = VO2/DO2
and PEEP, the PCWP may have inadvertently been mis-
interpreted. The relationship between PEEP and PCEP The pulmonary artery catheter has recently fallen into
is not linear but can be estimated by: disfavor. Outcome studies are ambivalent regarding the
benefit of the PAC in critically ill patients. Perhaps an
PCWP = PCWPM − 0.5(PEEP − 10)
important response to the skepticism is that repeated
where PCWPM is the PCWP measured at any level studies demonstrate that many clinical practitioners
of PEEP. have a flawed or incomplete understanding of the physi-
In order for the PAC to provide meaningful measure- ology and the assumptions involved in PAC placement
ments of PCWP, the PCWP must always be measured at and data interpretation. Furthermore, practitioners fre-
end-expiration in the respiratory cycle. Intrathoracic quently treat absolute numbers such as the wedge pres-
pressure variations differ between spontaneously breath- sure or the CVP in isolation from the cardiac output, and
ing and mechanically ventilated patients (Figure 3-14). in isolation of the rest of the clinical picture. The key
The saturation of the blood within the pulmonary assumptions, that right heart function and compliance,
capillaries, immediately prior to reoxygenation in the that the catheter tip is reliably placed within lung zone
alveolar capillaries, is known as the mixed venous oxy- II or III, that transpulmonary pressures are linearly
gen saturation SVO2. Since the diffusion of oxygen from related to the PCWP, and that left-sided volumes can be
reliably estimated by using right-sided pressures, must be
accounted for within the global clinical context.
Situations where the PCWP is likely to be significantly
greater than LVEDP include mitral stenosis, pulmonary
End expiration
venous instruction or hypertension, left atrial myxoma,
or elevated pulmonary alveolar pressure. Situations
Spontaneous ventilation
where the PCWP is likely to be significantly less than
LVEDP include instances of diminished left ventricular
PCWP
ECHOCARDIOGRAPHY
extremely useful to image blood flow. In perioperative Branson PK, McCoy RA, Phillips BA, Clifton GD: Efficacy of 1.4
liver transplantation patients TEE can also easily image percent sodium citrate in maintaining arterial catheter
hepatic blood flow and serve as a useful adjunct to clin- patency in patients in a medical ICU. Chest 103(3):882–885,
ical and laboratory data regarding graft patency. 1993.
TEE is extremely useful in the direct visualization of Calvert N, Hind D, McWilliams RG et al. The effectiveness and
cardiac chamber size and dynamic contractility. In cost-effectiveness of ultrasound locating devices for central
patients with hypovolemia the end-systolic volume venous access: a systematic review and economic evalua-
tion. Health Technol Assess 7(12):1–84, 2003.
(ESV) and the end-diastolic volume (EDV) can be easily
visualized with TEE to guide diagnosis and therapy. In Connors AF, Speroff T, Dawson NV et al: The effectiveness of right
hypovolemia the left ventricle contracts down upon heart catheterization in the initial care of critically ill patients.
JAMA 276:889, 1996; Crit Care Med 28(8):2812–2818, 2000.
itself almost completely. Computer-assisted TEE imaging
allows for reliable determination of cardiac ejection frac- Davis N, Pohlman A, Gehlbach B et al: Improving the process
tion by comparison of EDV and ESV. However, the deter- of informed consent in the critically ill. JAMA
289(15):1963–1968, 2003.
mination of cardiac ejection fraction based on chamber
size comparisons alone is unreliable if there are associ- Denault AY, Couture P, McKenty S et al: Perioperative use of
ated valvular abnormalities or intracardiac shunts. transesophageal echocardiography by anesthesiologists:
impact in noncardiac surgery and in the intensive care unit.
In patients with impaired contractility dynamic imag-
Can J Anaesth 49(3):287, 2002.
ing will clearly reveal areas of wall motion abnormality,
segmental wall motion defects (SWMAs). The SWMA will Domino KB, Bowdle TA, Posner KL et al: Injuries and liability
related to central vascular catheters: a closed claims analy-
correlate with the anatomic distribution of ischemia and
sis. Anesthesiology 100(6):1411–1418, 2004.
frequently will demonstrate reversibility with therapy.
Since SWMAs are much earlier and more sensitive indi- Hind D, Calvert N, McWilliams R et al: Ultrasonic locating
devices for central venous cannulation: meta-analysis. BMJ
cators of cardiac ischemia than are either the PAC or the
327(7411): 361, 2003.
ECG, TEE is an important clinical monitor.
TEE can also help visualize anatomic abnormalities Huttemann E, Schelenz C, Kara F, Chatzinikolaou K, Reinhart K:
The use and safety of transoesophageal echocardiography
such as valvular abnormalities and function, tumor or
in the general ICU – a mini review. Acta Anaesthesiol Scand
clot within the cardiac chambers, or aortic pathology.
48(7):827–836, 2004.
Pulsed Doppler ultrasound is especially useful when
Iberti TJ, Fischer EP, Liebowitz AB et al: A multicenter study of
examining cardiac valves to look for valvular gradient
physicians’ knowledge of the pulmonary artery catheter.
abnormalities, prosthetic valve dysfunction or perivalvu-
JAA 264:2928, 1990.
lar leak, regurgitant ejection fraction, and pulmonary
Knutstad K, Hager B, Hauser M: Radiologic diagnosis and man-
blood flow; this is known as color-flow mapping. When
agement of complications related to central venous access.
Doppler technology is combined with rapid ejection of
Acta Radiol 44(5):508–516, 2003.
agitated saline or agitated albumin the microbubbles
Mermel LA, Farr BM, Sherertz RJ et al; Infectious Diseases
can help delineate intracardiac shunting; which may be
Society of America; American College of Critical Care
more sensitive than Doppler technology alone. TEE can
Medicine; Society for Healthcare Epidemiology of America:
also help visualize valvular endocarditis lesions. Pulsed Guidelines for the management of intravascular catheter-
Doppler evaluation of aortic blood flow velocity is an related infections. Clin Infect Dis 32(9):1249–1272, 2001.
important adjunctive evaluation of cardiac function.
Porembka DT, Hoit BD: Transesophageal echocardiography in
Important limitations regarding the use of TEE in ICU the intensive care patient. Crit Care Med 19:826, 1991.
patients include a secure airway, coagulopathy, hiatal
Taylor RW, Ahrens T, Bennet ED et al: Pulmonary artery catheter
hernia, esophageal variceal disease, or recent esophago-
consensus conference: consensus statement. Crit Care Med
gastric surgery. 25:910–925, 1997.
Teichgraber UK, Gebauer B, Benter T, Wagner HJ: Central venous
access catheters: radiological management of complications.
SELECTED READING Cardiovasc Intervent Radiol 26(4):321–333, 2003.
Bellomo R, Uchino S: Cardiovascular monitoring tools: use and Williams G, Grounds M, Rhodes A: Pulmonary artery catheter.
misuse. Curr Opin Crit Care 9(3):225–229, 2003. Curr Opin Crit Care 8(3):251–256, 2002.
4
CHAPTER Modern Acid–Base
Physiology
JOHN A. KELLUM, M.D., F.A.C.P., F.C.C.P.
RINALDO BELLOMO, M.D., F.R.A.C.P., F.C.C.P.
DAVID STORY, M.D., F.A.N.Z.C.A.
Historical Background of the Acid–Base disinterest was due mainly to the fact that the approach,
Physiology Debate while conceptually simple and elegant, is operationally
Fundamental Principles of Hydrogen Ion complicated and unwieldy. Most clinicians feel quite
Regulation comfortable with the traditional approach to acid–base
Biochemistry of Aqueous Solutions physiology and few can be easily convinced that
Strong Ion Difference, pCO2, and Total Weak Acid “re-learning” this area is worthwhile. However, for
Concentration patients in the intensive care unit (ICU), extreme
Clinical Applications derangements in physiology are common and traditional
Quantification of Acid–Base Disorders methods are often inadequate to explain the severe
Chloride: the “Forgotten Electrolyte” acid–base disorders present in some of these patients.
Other Anions Although the Stewart approach is based on the same
Treatment of Acidosis and/or Acidemia physical chemical principles on which more traditional
Other Mechanisms of Lactic Acidosis approaches are based, this new approach is vastly dif-
The Artificial Kidney and Lactate ferent. The most important difference is that, in this
Effects of Plasma Proteins view of the biological universe, hydrogen ions and
Conclusion bicarbonate ions are not independent variables but are
instead determined by other factors. Changes in pH are
Significant advances in medicine, like other fields of not the result of the generation or removal of these ions
science, are the products of multiple individual discov- per se, but rather are the result of changes in other
eries, usually by many different people, often over many variables. In this universe, it is the Earth rather than the
years. Furthermore, pivotal advances, those that alter Sun that moves.
the very way we look at a particular issue, occur only The Stewart approach has now been found very
very rarely given the thousands of individual investiga- robust in a wide variety of patient types and experimen-
tors who contribute to the collective literature of tal conditions. Recently, it has been shown that quanti-
science and medicine. These paradigm shifts are often tatively this approach is compatible with the more
met with great resistance in part because they require traditional approaches; the difference lies in the under-
us to unlearn the old way as much as they require us to standing of the mechanisms involved. The observation
learn something new. When it was first reported that that metabolic acidosis is associated with a decrease in
peptic ulcer disease was due to H. pylori infection, the plasma bicarbonate and base excess remains valid.
scientific community reacted slowly and then with However, the implication that these changes cause the
skepticism. acidosis is not. Some might argue that such a conceptual
Little more than 20 years ago Peter Stewart published change makes little difference. If one can measure the
his revolutionary physical chemical analysis of acid–base size and origin (respiratory vs. metabolic) of a change in
physiology. Stewart’s approach to acid–base was praised acid–base status, does the average clinician really need
by some and criticized by others, but mostly it was to understand how it occurs? Of course, this was the
ignored. Indeed, there has been very little interest in this same argument facing Galileo when he insisted that the
approach until quite recently. It would seem that the Earth was not the center of the universe. Even without
37
38 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
CURRENT CONTROVERSY
[H CO ]
[H ]
+
=k×
[
2
HCO3−
3
]
What is a buffer? Why use pH? The same issues
related to the definition of an acid pertain to the
definition of a buffer. Sodium lactate is a “buffer” in
conventional acid–base physiology. However, if enough
where k is a constant. sodium lactate is given fast enough, hyperlactatemia
Over the next 20 years several developments came occurs and the base excess falls. Is this because lactate
from Denmark. A new definition of an acid was devel- is not transformed into CO2 (conventional explanation)
oped by Brønsted: an acid is a substance that donates by the liver or because the SID has decreased due to
hydrogen ions in solution. Brønsted noted that an the rapid infusion of a solution with a SID of 0 (Stewart
explanation)? It is not possible to tell. Equally, is the
Englishman, Lowry, had developed a similar definition.
use of pH helpful to clinicians to appreciate changes in
This became the Brønsted–Lowry definition, still the
acid–base balance more than the actual hydrogen ion
dominant definition of an acid. The operative and sci- activity in nmol/l? We doubt it. In our opinion, the use
entific superiority in the biological field of this later of pH in modern medicine appears unnecessary and
definition of acid over Arrhenius’s concept is neither potentially misleading.
obvious nor proven.
Modern Acid–Base Physiology 39
Over the next 50 years acid–base physiology centered of hydrogen ions in the Stewart approach is the dissoci-
on the Henderson–Hasselbalch equation. The partial ation of water molecules. Important underlying factors
pressure of carbon dioxide was substituted for carbonic are the temperature-dependent dissociation constants of
acid. The non-volatile, or metabolic, component was weak acids, including carbonic acid, and the dissociation
interpreted as being due to the body controlling plasma constant of water.
bicarbonate concentration. One difficulty in clinical appli-
cation was that changes in bicarbonate had to be inter-
preted while allowing for changes in the partial pressure
CLINICAL CAVEAT
of carbon dioxide. To deal with this problem, Schwartz
and Relman, Boston physicians, produced “rules of What is the source of hydrogen ions? The source of
thumb.” The rules of thumb were equations to deter- hydrogen ions is plasma water not “acid” generation by
mine whether the simultaneous changes in bicarbonate cells. One liter of water contains approximately 55 ×
and carbon dioxide were a single process, such as meta- 6.022 × 1023 hydrogen ions. The quantity of hydrogen
ions that is released from water depends on the
bolic acidosis with compensation, or mixed processes.
independent variables described by Stewart. Normally,
In the 1960s Siggard-Anderson, a Danish physician,
at 25°C, one in 1014 molecules of water is dissociated.
introduced “base excess” as a measure of the metabolic To put it another way, in a solution of distilled water,
acid–base status. Using base excess did not require cal- not all of the water is water. Some of it is dissociated
culating the rules of thumb. Base excess assumes a par- into hydroxyl ions and hydrogen ions. The glass
tial pressure of carbon dioxide of 40 mmHg and includes electrode measures free hydrogen ions and, of course,
the plasma bicarbonate concentration in the calculation. ignores free hydroxyl ions. The more water is
The subsequent controversy between Boston and dissociated, the greater the amount of free hydrogen
Copenhagen over the merits of the rules of thumb ver- ions and the lower the pH.
sus base excess was known as the “Great Transatlantic
Debate.” It continues to this day.
In the late 1970s and early 1980s, in several papers
and a book, Peter Stewart, a Canadian-American physiol- For several reasons Stewart’s work provoked, and
ogist working at Brown University, introduced a new continues to provoke, strong adverse reaction from those
approach to acid–base physiology and disorders. While committed to the Henderson–Hasselbalch approach.
using the partial pressure of carbon dioxide, Stewart First, he rejected bicarbonate as a vital controlling factor.
used two other variables, the strong ion difference and Second, he emphasized the vital role of strong ions; he
the total weak acid concentration, instead of bicarbonate. saw hydrochloric acid as acidifying not because it has
Stewart based his work on several chemical principles, hydrogen ions but because it has strong anions, chloride,
particularly electroneutrality, conservation of mass, and without strong cations. Third, he rejected the notion of
dissociation of electrolytes. Unfortunately for the ongoing buffers, and instead talked of weak acids. Fourth, he
debate, Stewart died in 1993. rejected pH in favor of a return to hydrogen ion concen-
The main principles of Stewart’s approach are that tration. Last, he returned to the acid definition of
there are three important independent factors control- Arrhenius: a substance that when added to a solution
ling the acid–base status of a physiological solution: the increases the hydrogen ion concentration. This defini-
partial pressure of carbon dioxide, the strong ion differ- tion accommodates both carbon dioxide and strong
ence, and the total weak acid concentration. The role of anions.
carbon dioxide, controlled by the lungs, is similar to that Many groups have continued Stewart’s work: in clini-
in the Henderson–Hasselbalch approach. Strong ions are cal work (particularly critical care), in exercise physiol-
ions that are completely dissociated in solution. The ogy, and in veterinary work.
most important strong ions are sodium, potassium, and
chloride. The important factor is the difference between
the strong ions rather than the absolute concentrations FUNDAMENTAL PRINCIPLES OF
of the ions. As the strong ion difference falls the hydro- HYDROGEN ION REGULATION
gen ion concentration increases. Lactate is treated as a
strong ion because with a pKa of 3.4 it is almost com- Before we examine this area it is first necessary to
pletely dissociated at a pH of 7.40. The most important review the basic principles of H+ regulation. Large living
weak acids in plasma are albumin and, to a lesser extent, organisms seek to maintain plasma pH within strict toler-
phosphate. Stewart emphasized that the three independ- ance limits. In fact, the free H+ concentration is maintained
ent factors must be considered simultaneously. These inde- within the nmol/l range (36–43 nmol/l). By contrast,
pendent factors will control dependent factors including most other ions are regulated in the mmol/l range. One
bicarbonate, hydroxyl ions, and hydrogen ions. The source reason H+ concentration is so closely regulated is that
40 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
these ions have very high charge densities and conse- ill patients. Of note, neither H+ nor HCO3− is a strong ion.
quently very large electric fields. Furthermore, the The pCO2 is an independent variable assuming that the
strength of H+ bonds (ubiquitous in biologic systems) is system is open (i.e., ventilation is present). Finally, the
very sensitive to local H+ concentration. Biochemical weak acids (A−), which are mostly proteins and phos-
reactions as well as interactions of hormones and drugs phates, contribute the remaining charges to satisfy the
with plasma proteins and cell surface receptors are also principle of electroneutrality. A−, however, is not an
influenced by changes in H+ concentration. In addition, independent variable because it changes with alterations
fluctuations in intracellular H+ concentration have major in SID and pCO2. ATOT (AH + A−) is the third independent
effects on cellular performance presumably by altering variable because its value is not determined by any
protein charge, thereby affecting structure and enzy- other. The essence of the Stewart approach (and indeed
matic function. Obviously then, in order to understand what is revolutionary) is the understanding that only
how the body regulates plasma H+ concentration, we these three variables are important. Neither H+ nor
must first understand the physicochemical determinants HCO3− can change unless one or more of these three
of H+ concentration. variables change. The principle of conservation of mass
makes this point more than semantics. Strong ions can-
not be created or destroyed to satisfy electroneutrality
Biochemistry of Aqueous Solutions but H+ ions are generated or consumed by changes in
Virtually all solutions in human biology contain water water dissociation. Hence, in order to understand how
and aqueous solutions provide a virtually inexhaustible the body regulates pH we need only ask how it regulates
source of H+. In these solutions, H+ concentration is these three independent variables (SID, pCO2, and ATOT).
determined by the dissociation of water into H+ and OH−
ions. In other words, changes in H+ concentration occur
not as a result of how much H+ is added or removed but CLINICAL APPLICATIONS
as a consequence of water dissociation. The factors that
determine the dissociation of water are the laws of phys- This “new” approach changes nothing about the mea-
ical chemistry. Two in particular apply here, electroneu- surement or classification of acid–base disorders. All of the
trality (which dictates that, in aqueous solutions, the careful observations that have been made over the years
sum of all positively charged ions must equal the sum of are no less valid under this approach. What does change
all negatively charged ions) and conservation of mass is the interpretation of these observations. The Sun still
(which means that the amount of a substance remains sets in the west and rises in the east, but now it is the
constant unless it is added or generated, or removed or Earth that moves.
destroyed). In pure water, according to the principle of
electroneutrality, the concentration of H+ must always
equal the concentration of OH−. In more complex solu- Quantification of Acid–Base Disorders
tions we have to consider other determinants of water While the understanding of how an acid–base dis-
dissociation, but still the source of H+ remains water. order occurs is now quite different, it is important to
Fortunately, even in a solution as complex as blood emphasize that not only does the traditional approach to
plasma, the determinants of H+ concentration can be quantifying an acid–base disorder still “work,” but that
reduced to three. If we know the value of these three it is entirely complementary to this physical chemical
determinants, the H+ concentration can be predicted analysis. In fact the standard base excess (SBE) can be
under any conditions. These three determinants are the used to quantify the amount of change in SID that has
strong ion difference (SID), pCO2, and total weak acid occurred from baseline. The SBE can be thought of as
concentration (ATOT). the amount of change in the SID that is required in order
to restore the pH to 7.40, given a PCO2 of 40 mmHg (a
negative SBE refers to the amount the SID must increase).
Strong Ion Difference, pCO2, and Total This is because the SID is essentially equal to the buffer
Weak Acid Concentration base of Singer and Hastings and base excess (BE) quanti-
The SID is the net charge balance of all strong ions fies the change in buffer base. SBE is superior to BE
present, where a “strong” ion is one that is completely because the former has been “standardized” to account
(or near-completely) dissociated. For practical purposes for the difference between CO2 equilibration in vitro
this means (Na+ + K+ + Ca2+ + Mg2+) − (Cl− + lactate−). compared to in vivo. Although SBE is not strictly com-
This is often referred to as the “apparent” SID (SIDa) with parable to the change in SID because it deals with whole
the understanding that some “unmeasured” ions might blood as opposed to plasma, the two are generally close
also be present. In healthy humans this value is 40–42 enough for most clinical circumstances. Thus, SBE pro-
mEq/l, although it is often quite different in critically vides an estimate of the amount of strong anion that
Modern Acid–Base Physiology 41
needs to be removed or strong cation added in order Next, consider the treatment for a hypochloremic meta-
to normalize the pH. For example, in order to change bolic alkalosis. Aside from preventing further Cl− loss,
the SBE from −20 to −10 mEq/l by adding NaHCO3, the the therapy is to give back Cl−. Saline works in this
serum Na+ concentration would need to be increased by regard because even though one is giving equal amounts
10 mEq/l. of Na+ and Cl−, the plasma Cl− concentration is always
Recently, Schlichtig and co-workers described the much lower than the plasma Na+ concentration and thus
changes in SBE that occur with acute and chronic disor- Cl− increases more than Na+ when large amounts of
ders of PaCO2. The SBE does not change with acute saline are administered. KCl works better for this indica-
changes in PaCO2. During chronic respiratory acidosis tion because, with a metabolic alkalosis, much of the K+
or alkalosis the change in the SBE is equal to 0.4 × goes intracellular leaving much of the Cl− in the plasma
(PaCO2 − 40). Similarly, the expected change in PaCO2 to decrease the SID.
for a given abnormality in SBE is as follows: for acidosis From the example above, one can easily understand
the decrease in PaCO2 is equal to the change in SBE; for not only how administration of 0.9% saline can correct a
alkalosis the increase in PaCO2 is equal to 0.6 × SBE. hypochloremic metabolic alkalosis but also how massive
amounts would lead to a decreased plasma SID and thus
a hyperchloremic metabolic acidosis. This particular
Chloride: The “Forgotten Electrolyte” issue has been the focus of two recent studies, one in
One of the most important implications of the Stewart animals with experimental sepsis the other in humans
analysis is the role of chloride in acid–base homeostasis. undergoing surgery.
If the body is to alter the SID, its primary tools are Na+
and Cl−. An increase in Na+ relative to Cl− (or a decrease
in Cl− relative to Na+) increases the SID and hence the
pH. The opposite effects, a decrease in the SID and a fall CURRENT CONTROVERSY
in the pH, occur when Na+ and Cl− concentrations move What is the cause of so-called dilutional acidosis?
closer together. Since Na+ concentration is tightly regu- The conventional view of this phenomenon is that the
lated by the body to control tonicity, Cl− emerges as the “buffers” are diluted by the administration of fluids.
body’s foremost tool for adjusting the SID and hence the The Stewart explanation is simple. If one adds solutions
plasma pH. Furthermore, acid–base abnormalities are with a SID of 0, the SID of plasma will fall and water
frequently the result of disorders in chloride homeosta- will be more dissociated with a greater release of
sis. For example, a common form of metabolic alkalosis hydrogen ions.
seen in the ICU is caused by the loss of gastric secre-
tions. The loss of HCl from the stomach results in a
hypochloremic metabolic alkalosis sometimes severe
enough to require therapy. Of course this is the loss of In the first study we administered E. coli endotoxin to
H+, but H+ is also lost with every molecule of water dogs and then volume resuscitated with 0.9% saline.
removed from the body. Moreover, gastric secretions Over a 3 hour period, each animal received an average
may reach a pH of 1.0, or a H+ concentration of 108 nmol/l. of 1.8 liters of saline and the pH decreased from 7.32 to
If one liter of gastric fluid is lost, this would mean that 7.11 ( p < 0.01) while CO2 and lactate were unchanged.
108 nmol (0.1 mol!) of H+ would be removed. If one con- Using the SID it was possible to calculate the amount of
siders that plasma H+ concentration is 40 nmol/l (or 4 × acidosis that was attributable to saline. Although the
10−8 mol/l), and if the majority of body fluids are at or serum Na+ concentration did not change, the serum Cl−
near this concentration, one sees that the amount of total concentration increased by almost 10 mmol/l. It was
body free H+ is only about 1.6 × 10−7 mol. If physiology concluded that saline alone was responsible for 42% of
were just simple accounting, a patient with a 200 ml the total acid load experienced by these animals. In the
emesis would entirely deplete the H+ stores of the body second study, Scheingraber and colleagues randomized
and die of severe alkalemia in minutes. Of course this is patients undergoing major gynecologic surgery to
not what happens and in reality the H+ concentration receive either 0.9% saline or lactated Ringer’s solution.
decreases by a much smaller amount. The reason it Patients receiving saline exhibited a decrease in their
decreases at all is because the plasma SID is increased and arterial pH from 7.41 to 7.28 while no change occurred
this is because Cl− (a strong anion) is lost without loss of in the lactated Ringer’s group. These investigators also
a strong cation. This increased SID forces a decrease in used the SID to calculate the expected change in pH
the amount of water dissociation and hence a decrease in with saline and found that the acidosis was entirely
the plasma H+ concentration. When H+ is “lost” as water explained by chloride administration.
rather than HCl, there is virtually no change in the SID Although dilutional acidosis was first described over
and hence no change in the plasma H+ concentration. 40 years ago, it has more recently been likened to Lewis
42 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Carroll’s Cheshire cat in that it is more imaginary than anion gap (AG), which is a measure of missing charge,
real. In healthy animals large doses of NaCl have been does not change. However, when other anions are pres-
demonstrated to produce only a minor hyperchloremic ent, the AG increases. Unfortunately, the accuracy of the
acidosis. These studies have been interpreted to show AG is questionable in certain clinical situations, particu-
that if dilutional acidosis occurs it is only in the extreme larly in critically ill patients who are frequently hypoalbu-
case and even then it is only mild. This line of reasoning minemic and acidotic. This has prompted some authors to
cannot be applied to many critically ill patients for two adjust the “normal range” for the AG by the patient’s
reasons. First, large-volume resuscitation is commonly albumin or even phosphate concentration. Each g/dl of
required in patients with sepsis and trauma. These albumin has a charge of 2.8 mEq/l at pH 7.4 (2.3 mEq/l at
patients may receive crystalloid infusions of 5–10 times 7.0 and 3.0 mEq/l at 7.6) and each mg/dl of phosphate has
their plasma volumes in a single day. The second prob- a charge of 0.59 mEq/l at pH 7.4 (0.55 mEq/l at 7.0 and
lem with this line of reasoning is that it fails to consider 0.61 mEq/l at 7.6). Except in cases of abnormal parapro-
the fact that critically ill patients are frequently not in teins, globulin does not contribute to the AG. Thus a con-
normal acid–base balance to begin with. These patients venient way to estimate the “normal range” of the AG for
may have lactic acidosis or renal insufficiency. a given patient is by use of the following formula:
Furthermore, critically ill patients might not be able to “Normal” AG = 2(albumin g/dl) + 0.5(phosphate mg/dl)
compensate normally by increasing ventilation and may
have abnormal buffer capacity owing to hypoalbumin- Or for international units:
emia. In patients, as well as in animals with experimental “Normal” AG = 0.2(albumin g/l) + 1.5(phosphate mmol/l)
sepsis, dilutional acidosis does occur and can produce
significant acid–base derangements. Figge et al. have shown that in the majority of criti-
The clinical implication for management of patients in cally ill patients the “normal” AG can be estimated by
the ICU is that when large volumes of fluid are used for using 2.5 times the albumin concentration in g/dl (or
resuscitation they should be more physiologic than saline. 0.25 for albumin in g/l). However, if the serum phos-
phate concentration is significantly abnormal this esti-
mate will be inaccurate.
CLINICAL CAVEAT
How can one avoid “dilutional” acidosis? Dilutional
acidosis can be avoided by administering “balanced
CLINICAL CAVEAT
solutions” which have a SID close to the normal SID of
plasma. Lactate Ringer’s solution is such a fluid. It is With regards albumin and the anion gap, the anion
important to realize that if large amounts of this fluid gap must always be adjusted for the effect of
are given to critically ill patients, hyperlactemia might hypoalbuminemia. In a critically ill patient with an
be induced. Such hyperlactemia is usually mild to albumin of 1.5 g/dl a normal unadjusted anion gap can
moderate and should not be misunderstood as a sign of coexist with a lactate of 6 mmol/l!
clinical deterioration.
One alternative is lactated Ringer’s solution. This fluid The etiology of anions other than Cl− varies depend-
contains a more physiologic difference between Na+ and ing on the population studied. Ketones, organic acids
Cl− and thus the SID is closer to normal (roughly 28 mEq/l accumulating in renal failure, and toxins are important
compared to saline which has an SID of 0 mEq/l). Of course causes in appropriate patient groups. In critically ill
this assumes that the lactate in lactated Ringer’s is metabo- patients lactate is a particularly important cause. Lactate
lized, which may take several minutes. Until the lactate is is a strong ion by virtue of the fact that at pH within the
removed the effect of lactated Ringer’s is identical to saline physiologic range, it is almost completely dissociated (i.e.,
since one strong anion (i.e., lactate) is as good as another the pK of lactate is 3.9; at a pH of 7.4, 3162 ions are disso-
(i.e., Cl−). Therefore, massive doses of sodium lactate, for ciated for every one that is not). Because the body can pro-
example given as replacement fluid for hemofiltration, may duce and dispose of lactate rapidly, it functions as one of
transiently result in acidosis as the SID decreases. the most dynamic components of the SID. Lactate there-
fore can produce significant acidemia. However, often crit-
ically ill patients have hyperlactatemia that is much greater
Other Anions than the amount of acidosis seen. Physical chemistry
When the SID decreases, metabolic acidosis ensues. also allows us to understand how hyperlactatemia may
When this occurs as a result of increased Cl−, the exist without metabolic acidosis. First, acid is not being
Modern Acid–Base Physiology 43
“generated” apart from lactate such as through “unreversed long-term sequelae. By contrast, hyperlactatemia in the
ATP hydrolysis” as some have suggested. Phosphate is a critically ill is an important predictor of mortality. One of
weak acid and does not contribute substantially to meta- the major controversies associated with hyperlactatemia
bolic acidosis even under extreme circumstances. and associated acidosis or indeed acidemia concerns its
Furthermore, the H+ concentration is not determined by treatment.
how much H+ is produced or removed from the plasma but
rather by changes in one of the three independent variables
(SID, pCO2, or ATOT). Virtually anywhere in the body, pH is Treatment of Acidosis and/or Acidemia
above 6.0 and lactate behaves as a strong ion. Its generation Whether induced by the accumulation of the lactate
will then decrease the SID and result in increased water dis- anion or by the accumulation of other anions (chloride,
sociation and thus increased H+ concentration. ketones, exogenous acids, acids associated with renal
How then might the plasma lactate concentration be failure), severe acidosis may be associated with inade-
increased and the H+ concentration not? There are two quate physiological compensation and lead to acidemia.
possible answers. First, if lactate is added to the plasma, Although it is agreed by all that treatment of such
not as lactic acid but rather as the salt of a strong acid acidemia/acidosis should first and foremost involve cor-
(i.e., sodium lactate), there will be little change in the rection of its cause, it is controversial whether some or all
SID. This is because a strong cation (Na+) is being added of these patients should also receive alkalinizing solutions
along with a strong anion. In fact, as lactate is then such as sodium bicarbonate. The biologic rationale for
removed by metabolism, the remaining Na+ will increase administering sodium bicarbonate rests on three major
the SID resulting in metabolic alkalosis. Hence it would considerations: (1) a low pH impairs myocardial contrac-
be possible to give enough lactate to increase the plasma tility, (2) IV sodium bicarbonate can increase pH, and
lactate concentration without any change in H+ con- (3) any adverse effects of sodium bicarbonate are out-
centration. However, the amount of exogenous lactate
weighed by its benefits. However, concerning point
required would be very large. This is because normal
(1), evidence that a low pH decreases myocardial con-
metabolism results in the turnover of approximately
tractility is mostly based on data from isolated animal
1500–4500 mmol of lactic acid per day. Thus, only very
heart muscle preparations. In whole-animal preparations
large amounts of lactate infused rapidly will result in
the effects of acidosis on contractility are much more dif-
appreciable increases in the plasma lactate concentra-
ficult to document. In humans data from patients with
tion. In this setting, a mild acidosis may occur until the
permissive hypercapnia or with diabetic ketoacidosis sup-
lactate is metabolized (usually within several minutes). port the view that there is marked tolerance to a low pH
Levraut et al. infused 1 mmol/kg of lactate over 15 minutes without major adverse effects. Furthermore, there is a
in 10 patients with acute renal failure on continuous renal body of data to suggest that acidosis may protect cells
replacement therapy. Their mean plasma lactate con- from anoxia, chemical hypoxia, and reperfusion injury.
centration increased from 1.4 to 4.8 mmol/l after the With regard to point (2), clinical studies show that the
infusion but normalized rapidly. Under such conditions effect of up to 2 mmol/kg of sodium bicarbonate on pH is
it is possible (if transiently) to produce hyperlactatemia small with increments in the range 0.05–0.014 in humans.
without acidemia. Unfortunately, these authors do not
In addition, sodium bicarbonate fails to predictably
report the acid–base status of their patients. However, in
increase intracellular pH and often appears to induce a
another recent study, Morgera et al. showed that lactate-
decrease instead. Changes in blood pH may also decrease
based hemofiltration resulted in increased plasma
oxygen delivery to tissues by changing the dissociation
HCO3− concentration and pH as well as hyperlactatemia.
curve of hemoglobin. Thus the efficacy of sodium bicar-
A more important mechanism whereby hyperlactatemia
bonate in lowering pH where it matters is unclear. The
exists without acidemia (or with less acidemia than
hemodynamic effects of IV sodium bicarbonate have been
expected) is where the SID is corrected by the elimina-
studied in humans. They were indistinguishable from
tion of another strong anion from the plasma. This was
those of an equivalent amount of sodium delivered as
demonstrated by Madias et al. In the setting of sustained
saline. In uncontrolled studies of patients with diabetic
lactic acidosis induced by lactic acid infusion, these
ketoacidosis no benefits could be seen and delayed
investigators found that Cl− moves out of the plasma
clearance of ketones and lactate were documented.
space to normalize pH. Under these conditions hyper-
Bicarbonate also lowers ionized calcium concentrations
lactatemia may persist but BE may be normalized by
and PaO2 in animals and non-acidemic patients with con-
compensatory mechanisms to restore the SID. gestive cardiac failure. Thus the safety of IV bicarbonate
The meaning of hyperlactatemia is very different remains untested. Other alkalinizing preparations exist:
depending on the patient population being considered.
Healthy humans can achieve plasma lactate concentra- 1. Carbicarb (equimolar mixture of sodium carbonate
tions with exercise in excess of 25 mmol/l without any and sodium bicarbonate)
44 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
2. Dichloroacetate (an agent that stimulates pyruvate molecular weight of lactate. Assuming a small molecular
dehydrogenase and lowers lactate levels) clearance of 200 ml/minute, lactate clearance during
dialysis would reach approximately 20% of endogenous
3. Tris-hydroxymethyl aminomethane (THAM)
clearance. The impact of such clearance on lactate lev-
Carbicarb has also undergone limited studies in els, however, has not been studied. Lactate has not been
humans and its role is unclear. Dichloroacetate has been traditionally used as a buffer for intermittent hemodialy-
tested in a large randomized controlled trial in patients sis, and therefore there is little specific information on
with lactic acidosis. In this trial it was found efficacious the use of lactate-buffered dialysate on lactate levels and
in lowering lactate levels and increasing bicarbonate acid–base balance in dialysis patients.
concentration and pH. However, it did not achieve any When intermittent hemofiltration is used, however, and
changes in hemodynamics or clinical outcomes. THAM lactate-based replacement fluid is administered at high
appears to improve contractility in isolated rabbit heart rates (approximately 200 mmol/hour), a significant
preparations. However, no controlled studies are avail- increase in plasma lactate levels can be easily demon-
able to support its use in humans with acidemia and the strated. Although the clinical significance of such increases
side effects of hyperkalemia, hypoglycemia, extravasation- in lactate levels is unknown, this iatrogenic phenomenon
related tissue necrosis, and neonatal hepatic necrosis needs to be appreciated in order to avoid misdiagnosis.
demand great caution in its utilization. Also, the magnitude of this phenomenon (average peak
increase of 3 mmol/l at 3 hours) needs to be understood
to separate it from other factors, which may simultane-
ously be operative in determining the patient’s lactate
CURRENT CONTROVERSY levels.
A similar phenomenon has been described during
The administration of IV sodium bicarbonate in
continuous renal replacement therapy (CRRT), but the
patients with acidemia remains one of the most passion-
increment in lactate levels was less due to the lower rate
laden areas of anesthetic and critical care practice. Like
other similar areas of controversy, the intensity of of lactate administration. However, it is important to
opinion is inversely proportional to the quality and note that increments in lactate levels in patients on
amount of evidence available. There are insufficient data CRRT are not simply dependent on the rate of lactate
to support the use of IV sodium bicarbonate in patients administration but also on the body’s ability to handle a
with acidemia. There are also insufficient data to given lactate load. Thus, the administration of up to
proscribe the use of sodium bicarbonate in these 200 mmol/hour of lactate may lead to modest changes in
patients. If a decision is made to administer IV sodium lactate levels and pH. However, the administration of the
bicarbonate, we recommend that it should occur with same amount or even less in a patient with pre-treatment
close hemodynamic and biochemical monitoring and lactate intolerance (liver failure, severe septic shock) will
that the agent be administered in the presence of a
induce a dramatic increase in lactate concentration and
physician.
a profound acidosis. Under such circumstances, lactate-
buffered replacement solutions should be avoided.
Furthermore, in patients with lactic acidosis and acute
renal failure receiving CRRT, the administration of
bicarbonate-based replacement fluids is an effective way
Other Mechanisms of Lactic Acidosis of avoiding any exacerbation of hyperlactatemia and of
Although lactic acidosis is associated with major physio- restoring acid–base homeostasis. Some investigators
logical stress in all patients and with shock in most, some have suggested that lactate removal during CRRT may
particular situations occur where neither may be at work. lower plasma lactate levels and participate in the cor-
A unique situation that requires separate discussion is that rection of acidosis seen during bicarbonate-based CRRT.
of the patient receiving artificial kidney support. In response to this hypothesis, Levraut and colleagues
conducted a careful analysis of lactate clearance during
CRRT and compared it to endogenous clearance. They
The Artificial Kidney and Lactate found that the median endogenous lactate clearance
The use of the artificial kidney also has a clinically sig- was 1379 ml/minute, while the median filter lactate
nificant impact on lactate balance and on plasma lactate clearance was 24.2 ml/minute. Thus, CRRT-based lactate
concentrations. This impact may derive from lactate clearance accounted for <3% of total lactate removal.
removal as well as lactate administration. Lactate clear- It may appear surprising that increases in plasma lac-
ance during intermittent hemodialysis or intermittent tate concentration of up to 8 mmol/l would not induce
hemofiltration has not been formally studied but is likely a pronounced degree of acidification. It should do so by
to be similar to that of other small molecules given the increasing the concentration of anions in plasma and
Modern Acid–Base Physiology 45
thus decreasing the SID and its effect on the dissociation acidosis seen in patients with critical illness. The presence
of plasma water into hydrogen ion. In fact some prelim- of unexplained anions in the blood of both patients with
inary observations suggest that several complex events sepsis and liver disease was investigated further in an ani-
occur during the onset of such rapid iatrogenic hyper- mal model of sepsis using endotoxemia. In this study it was
lactatemia. In particular, a marked decrease in chloride found that during control conditions the liver cleared
appears to occur despite the administration of chloride- unmeasured anions from the circulation (mean flux
rich replacement fluid. This change in chloride is likely −0.34 mEq/minute). With early endotoxemia, however,
to be secondary to a shift into cells similar to that seen in the liver switched to release of anions (0.12 mEq/minute,
venous blood when the CO2 rises (Hamburger shift). p < 0.005). These data suggest that the liver has a role in
Such a shift in chloride rapidly attenuates the impact of systemic acid–base balance by way of regulating anion
hyperlactatemia on pH and prevents the development of fluxes apart from metabolism of lactate.
a progressive and sustained acidemia.
Finally, it must be emphasized that the view of lactate as
representative of so-called “anaerobic glycolysis” is not EFFECTS OF PLASMA PROTEINS
supported by the data available. The hyperlactatemia of
septic shock, for example, appears most likely secondary Considerable controversy has developed over the
to accelerated glycolytic flux, where glucose breakdown past decade as to how to classify acid–base derange-
into pyruvate is proceeding faster than pyruvate can be ments occurring as a result of abnormalities in the weak
channeled into the citric acid cycle via acetyl coenzyme A. acids, ATOT. A sudden decrease in ATOT produces alkalo-
sis while an increase is acidifying. Some have advocated
a third classification for this effect, perhaps termed
CURRENT CONTROVERSY “proteinaceous acidosis or alkalosis,” to be added to
“metabolic” (SID) and “respiratory” (pCO2). Others have
What is the meaning of hyperlactatemia? There is no
strenuously objected. The debate may actually prove
evidence to indicate that hyperlactatemia is due to
anaerobic glycolysis in critically ill patients and much
moot in light of more recent evidence. When the SID of
evidence to suggest that it occurs in the setting of full critically ill patients was compared to SBE the intercept
intracellular oxygenation and in the presence of for SBE = 0 was found to be 30–35 mEq/l rather than
elevated levels of pyruvate. As fast glycolysis occurs in 40–42 mEq/l as for healthy individuals. Thus, in these
the liver and glucose is the preferred fuel of stress, it critically ill patients, many of whom had a decreased
appears likely that peripheral lactate generation allows ATOT secondary to hypoalbuminemia, the SID was
rapid fuel supply for glycolysis (lactate from muscle to reduced even when there was no apparent acid–base
liver, in liver to pyruvate for gluconeogenesis (Cori disorder. The reason for this is obvious from a physical
cycle), then glucose use for energy generation: the chemical perspective. As a patient’s albumin decreases
lactate shuttle). Alternatively, glucose breakdown is so so does ATOT and thus A−. This decrease in weak acid has
fast under stress that pyruvate is generated faster than
a slightly alkalinizing effect. The body could adapt to this
it can be taken up by mitochondria, and thus it
becomes lactate and is recycled.
change by retaining CO2 but it appears to reserve this
adaptation for changes in SID. Instead, the body adapts
to a decreased ATOT by decreasing the SID. While one
might be tempted classify this adaptation as a mixed
It is important to note that not all anions appearing in the acid–base disorder, a hypoalbuminemic alkalosis with a
blood of the critically ill can be explained. The SID can be compensatory metabolic acidosis, it does not appear to
used to detect unexplained anions because the apparent be a disorder at all. Indeed, a patient who failed to
SID (SIDa) calculated from the measurable ions should be reduce their SID in response to a decreased ATOT should
equal to the effective SID (SIDe) derived from the remain- be considered to have a metabolic alkalosis as conse-
ing charges attributable to CO2 and A−. If a difference exists quence of failed renal homeostatic mechanisms (e.g.,
between the SIDa and SIDe, then unmeasured anions must secondary to hypovolemia), not a proteinacious alkalosis
be present. This difference has been termed the strong ion secondary to hypoalbuminemia. The findings of Wilkes
gap (SIG) to distinguish it from the AG. Unlike the AG, the in critically ill patients and Wooten in mathematical
SIG is normally zero and does not change with changes in simulations appear to support this assertion. Both
pH or albumin concentration as does the AG. However, it authors have demonstrated that the “set point” for the
should be noted that this “gap” need not be filled by SID to achieve a normal pH given a normal pCO2
strong ions. Weak acids may also play a role. changes with changes in ATOT. Furthermore, although
In recent years unmeasured anions have been reported the loss of weak acid from the plasma space is an
in the blood of patients with sepsis and liver disease. These alkalinizing process, there is no evidence that the body
anions may be the source of much of the unexplained regulates ATOT to maintain acid–base balance and there is
46 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
no evidence that clinicians should treat hypoalbumin- by the removal of strong anions without strong cations
emia as an acid–base disorder. (e.g., gastric suctioning).
This “new” understanding has considerable impact on
how we think about gastric suction alkalosis, dilutional aci-
CASE STUDY dosis, and lactic acidosis as well as how we approach the
treatment of these disorders. Our understanding of many
A 77-year-old man has cardiopulmonary bypass other medical conditions (e.g., renal tubular acidosis)
(CPB). On admission to the ICU he has a pH of 7.24, relies on a paradigm of acid–base regulation that is incon-
CO2 of 47, bicarbonate of 19 mmol/l, and BE of −7 mEq/l. sistent with established physical chemistry principles.
He is receiving a low-dose epinephrine infusion at
In this “post-Copernican” era, we will need to rethink
3 μg/minute for a poor cardiac output following
separation from the pump. His urea and electrolytes
our-approach to these areas in the light of this fact.
show a sodium of 140 mmol/l, chloride of 110 mmol/l,
potassium of 6 mmol/l, and urea of 6 mmol/l (BUN of
SELECTED READING
16.5 mg/dl). His anion gap is 11 (normal). Does this
man have a lactic acidosis? What acid–base disorders Figge J, Jabor A, Kazda A, Fencl V: Anion gap and
does this man have? A normal anion gap would suggest hypoalbuminemia. Crit Care Med. 26:1807–1810, 1998.
that this man does not have a lactic acidosis. However, Figge J, Mydosh T, Fencl V: Serum proteins and acid–base
the anion gap is not corrected for the serum albumin. equilibria: a follow-up. J Lab Clin Med 120:713–719, 1992.
This man had a crystalloid pump prime, which was
saline based. He now has iatrogenic hyperchloremia Kellum JA, Bellomo R, Kramer DJ, Pinsky MR: Etiology of
with a low SID which is responsible for a degree of metabolic acidosis during saline resuscitation in endotox-
acidosis. The acidemia might have contributed to emia. Shock 9:364–368, 1998.
hyperkalemia which will have an alkalinizing effect on Kellum JA, Bellomo R, Kramer DJ, Pinksy MR: Hepatic anion
the SID. But he is also likely to have dilutional flux during acute endotoxemia. J Appl Physiol 78:
hypoalbuminemia, which would cause an alkalosis. 2212–2217, 1995.
When measured, the albumin concentration was in fact Kellum JA, Bellomo R, Kramer DJ, Pinsky MR: Splanchnic
1.5 g/dl. Thus the normal anion gap (assuming a normal buffering of metabolic acid during early endotoxemia.
phosphate) should actually be about 4.5–5 mEq/l. J Crit Care 12:7–12, 1997.
The fact that it is 11 mEq/l indicates that there are
Kellum JA, Kramer DJ, Pinsky MR: Strong ion gap: a methodol-
approximately 6–7 mEq/l of unmeasured anions, which
ogy for exploring unexplained anions. J Crit Care
of course could be due to lactate. The lactate was
10:51–55, 1995.
indeed measured. It was 6.3 mmol/l. This man had
iatrogenic hyperchloremic acidosis, iatrogenic Leblanc M, Kellum JA: Biochemical and biophysical principles
hypoalbuminemic alkalosis, a mild hyperkalemic of hydrogen ion regulation. In Ronco C, Bellomo R, editors:
alkalosis, a mild respiratory acidosis, and a moderate Critical Care Nephrology, Dordrecht, The Netherlands:
lactic acidosis. No obvious cause for his lactic acidosis Kluwer Academic, 1998, pp 261–277.
was found. Epinephrine was suspected as being Levraut J, Ciebiera JP, Jambou P, Ichai C, Labib Y, Grimaud D:
responsible for it. His epinephrine was changed to Effect of continuous venovenous hemofiltration with dialy-
milrinone. Within 6 hours his lactate level was down sis on lactate clearance in critically ill patients. Crit Care
to 2.3 mmol/l and his cardiac index was preserved at Med 25:58–62, 1997.
2.4 l/m2/minute. Madias NE, Homer SM, Johns CA, Cohen JJ: Hypochloremia as
a consequence of anion gap metabolic acidosis. J Lab Clin
Med 104:15–23, 1984.
Magder S: Pathophysiology of metabolic acid–base disturbances
CONCLUSION in patients with critical illness. In Ronco C, Bellomo R,
editors: Critical Care Nephrology, Dordrecht, The
In order to understand the causes of the acid–base Netherlands: Kluwer Academic, 1998, pp 279–296.
derangements, many of which are common in the ICU, Salem MM, Mujais SK: Gaps in the anion gap. Arch Intern Med
we need only look at three independent variables (SID, 152:1625–1629, 1992.
pCO2, and ATOT). Metabolic acidemia results from a Scheingraber S, Rehm M, Sehmisch C, Finsterer U: Rapid saline
decrease in the plasma SID usually brought about by the infusion produces hyperchloremic acidosis in patients
addition of strong anions (lactate, Cl −, other “unknown” undergoing gynecologic surgery. Anesthesiology 90:
anions). Conversely, metabolic alkalemia occurs when 1265–1270, 1999.
the plasma SID is increased either as a result of the addition Stewart PA: Modern quantitative acid–base chemistry. Can J
of strong cations without strong anions (e.g., NaHCO3) or Physiol Pharmacol 61:1444–1461, 1983.
5
CHAPTER Metabolic
Derangements
CARLOS J. LOPEZ III, M.D.
JUDIT SZOLNOKI, M.D.
Sodium Derangements
Hyponatremia SODIUM DERANGEMENTS
Hypernatremia
Potassium Derangements Hyponatremia
Hypokalemia
Hyponatremia is defined as a [Na+] < 135 mEq/l.
Hyperkalemia
Symptoms and signs are a factor of sodium concentra-
Calcium Derangements
tion and rapidity of onset. They typically begin to occur
Hypocalcemia
at levels <130 mEq/l, primarily with neurologic symp-
Hypercalcemia
toms such as headache, lethargy, and confusion. The
Magnesium Derangements
more severe symptoms such as stupor, seizures, and
Hypomagnesemia
coma generally do not occur until [Na+] < 120 mEq/l.
Hypermagnesemia
The biggest danger is the brain edema that occurs from
Phosphorus
movement of water from the extracellular fluid (ECF) to
Hypophosphatemia
the intracellular fluid (ICF) compartments. The rapidity
Hyperphosphatemia
at which hyponatremia occurs will also play a role in
Thermal Derangements
development of the clinical picture. Patients with
Hyperthermia
chronic hyponatremia will often be asymptomatic in
Heat Stroke
spite of having remarkably low levels. There are dangers
Drug-Induced Hyperthermias
to an overly rapid correction of hyponatremia.
Malignant Hyperthermia
Approaches to treating the hyponatremic patient must
Neuroleptic Malignant Syndrome
be tempered by the level, associated symptoms, and
Serotonin Syndrome
chronicity.
Sympathomimetic Poisoning Syndrome
Causes of hyponatremia can be described by the osmo-
Anticholinergic Syndrome
lality of the ECF. The osmolality is the solute or particle
Hypothermia
concentration of a fluid. Box 5-1 presents the osmolality
Perioperative Hypothermia
calculation for plasma.
Summary
The differential diagnosis includes (1) hypo-osmolar
hyponatremia, (2) normo-osmolar hyponatremia, and
Metabolic derangements can present with mild (3) hyperosmolar hyponatremia.
alterations in signs and symptoms or as life-threatening Hypo-osmolar hyponatremia is the most common.
situations. Rapid recognition and understanding of the In general it is caused by either sodium loss or primary
physiology involved allows a more directed approach to water gain. Because the ECF volume reflects total body
their management. In this chapter we review some com- sodium, the volume status of the patient is used
mon abnormalities in electrolyte homeostasis and briefly to further subdivide hypo-osmolar hyponatremia into
explore derangements in temperature regulation. decreased, normal, and increased ECF volume.
47
48 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Decreased ECF volume is due to renal or extrarenal Hyperosmolar hyponatremia is usually due to
losses of sodium such as sodium wasting nephropathies, increases in nonsodium solutes that remain mostly in the
hypoaldosteronism, diuretics, and vomiting. These ECF. Hyperglycemia and mannitol use are common
losses are often replaced with hypotonic fluids. The causes of this condition. The sodium in hyperglycemia is
decreased arterial volume can also contribute by stimu- corrected by adding 1.6 mmol/l to the sodium for every
lating thirst and vasopressin release and impairing the 100 mg/dl rise in glucose. Other solutes such as ethanol,
ability of the kidneys to excrete a dilute urine. Diuretics methanol, and ethylene glycol which occur from intoxi-
and vomiting can also result in a large potassium loss cations may also be implicated.
which through transcellular ion exchange causes further
hyponatremia. A UNa+ > 20 mmol/l in the face of a
hyponatremic, hypovolemic state suggests a renal cause, CLINICAL CAVEAT
while UNa+ < 10 mmol/l is consistent with extrarenal Hyponatremia
losses. Hypo-osmolar: most common – sodium loss or primary
Normal ECF volume can present with SIADH which water gain
is the most common cause of normovolemic hypo- ● Decreased ECF – nephropathies, hypoaldosteronism,
natremia. It is associated with an impaired excretion of diuretics, and vomiting
renal free water due to nonphysiologic release of antidi- ● Normal ECF – SIADH, steroids, hypothyroidism,
uretic hormone (ADH) or vasopressin. Malignant tumors, CRF, drugs, and primary polydipsia
● Increased ECF – CHF, cirrhosis, nephritic syndrome,
pulmonary diseases, central nervous system (CNS) dis-
and ARF
orders, and drugs are causes of SIADH. It is characterized Normo-osmolar: most commonly pseudohyponatremia
by (1) hypo-osmotic, hyponatremia, (2) euvolemia, ● Hyperlipidemia and hyperproteinemia
(3) no renal, adrenal thyroid dysfunction, or diuretic Hyperosmolar: excess nonsodium solutes
use, (4) UNa+ > 20 mmol/l, and (5) a less than maximally ● Hyperglycemia and mannitol
dilute urine UOSM > 300 mOsm/l. These patients are
treated with water restriction, democycline, and treat-
ment of underlying disorders. Other causes not related
to SIADH are glucocorticoid deficiency, hypothyroidism, Treatment of hyponatremia depends on the sodium
chronic renal failure, drugs, and primary polydipsia. concentration, symptoms, and the ECF volume status.
Increased ECF volume tends to have an increased Mild asymptomatic hyponatremia requires no treatment.
total body sodium, but there is a much larger increase in Patients with underlying chronic hyponatremia that
total body water. It is usually a consequence of condi- have mild symptoms are treated gently with the goal of
tions associated with edema, congestive heart failure returning sodium levels to 125 mEq/l. Those patients
(CHF), cirrhosis, nephrotic syndrome, and acute renal with stupor, seizures, and coma, however, are treated
failure. These conditions result in a decrease in arterial aggressively with 3% NS in order to reach a sodium goal
blood volume, which leads to increased thirst and vaso- of 125–130 mEq/l. This must not be done too rapidly
pressin levels. Diagnosis is made by a UNa+ ≤ 20 mmol/l because of the risk of an osmotic demyelination syn-
for CHF and cirrhosis, and UNa+ > 20 mmol/l for acute drome called central pontine demyelination (CPM).
renal failure. These patients may develop flaccid paralysis, dysarthria,
Normo-osmolar hyponatremia is commonly due and dysphagia. The diagnosis is confirmed by magnetic
to a pseudohyponatremia resulting from hyperlipidemia resonance imaging (MRI). To avoid this one does not
and hyperproteinemia. Plasma is composed of water and correct sodium at greater than 0.5 mEq/l/hour and one
nonaqueous plasma proteins and lipid. If proteins or corrects to a sodium of 125–130 mEq/l. Mild sympto-
lipids are elevated, the sodium concentration measured matic hyponatremia is treated with NS and occasionally
is less than its true concentration. These patients have 3% NS, while avoiding too rapid a correction. Patients
both a normal plasma sodium and plasma osmolality. with normal ECF volume may have pseudohyponatremia
Elevations in solutes other than sodium, like glucose and and not require treatment. Those with mild symptoms
mannitol, can also result in a similar picture. are treated with furosemide diuresis or isotonic saline.
Metabolic Derangements 49
In patients with increased ECF volume, fluid restriction are treated with hypotonic fluids to replace water
and hypertonic saline are useful. Fluid restriction is deficits. This group also includes those with DI. Specific
particularly useful in patients with SIADH, renal failure, treatment using DDAVP along with water deficit replace-
or primary polydipsia. ment is used for central DI. In nephrogenic DI the
concentrating defect may be reversed by removing the
offending drug, restricting sodium and water intake, and
Hypernatremia administering thiazides. This strategy results in increased
Hypernatremia is defined as a [Na+] > 145 mEq/l. fluid reabsorption in the proximal tubules by decreasing
Symptoms and signs are typically seen with levels > 150 ECF volume. Hypervolemic patients are sodium over-
mEq/l. Neurologically these patients may present at first loaded. They respond to increasing sodium excretion
with neuromuscular irritability, ataxia, lethargy and with loop diuretics and replacement of water deficit
progress to confusion, coma, and seizures as the sodium with hypotonic fluids.
approaches 180 mEq/l. They may complain of increased
thirst and have evidence of hypovolemia. They may have
evidence of decreased urinary concentrating ability, POTASSIUM DERANGEMENTS
renal insufficiency, and occasionally progress to acute
renal failure. Potassium is the major intracellular cation. While
Hypernatremia is typically caused by either a water normal plasma potassium is 3.5–5.0 mEq/l, normal intra-
loss or a primary sodium gain. Hypernatremia due to cellular concentration is 150 mEq/l. The concentration
water losses is due to either renal or nonrenal causes. gradient between ICF and ECF is kept fairly constant.
Renal losses are the most common and are either from Since the ICF volume is much greater than ECF volume,
diabetes insipidus or osmotic diuresis. Nonrenal losses the vast majority of potassium stores are intracellular.
are from the gastrointestinal (GI) tract and from insensi- Therefore plasma potassium is a poor indicator of total
ble losses. Hypernatremia due to sodium gain occurs potassium stores. Potassium concentrations are main-
much less frequently. Hypertonic saline, sodium bicar- tained by the Na-K-ATPase pump, which actively trans-
bonate, and iatrogenic causes of sodium administration ports potassium into the cell and sodium out of the cell.
account for the majority of these patients. Less com- It is the quantitative passive diffusion of potassium out of
monly hypernatremia can occur because of a decreased the cell that helps establish a resting membrane poten-
ability to take in PO fluids. Infants, patients with an tial and generates action potentials. Therefore keeping
altered mental status, and intubated patients may potassium concentrations within normal range is impor-
develop hypernatremia. tant for the proper functioning of skeletal and smooth
The treatment of hypernatremia requires the assess- muscle, and for CNS function.
ment of water deficit and ECF volume status. Box 5-2
presents the calculation for water deficit. Although use-
ful in initiating therapy, this assessment tends to under- CLINICAL CAVEAT
estimate the free water loss in those patients with Potassium
hypotonic fluid losses. Half the deficit is replaced over ● An intracellular cation – serum levels do not reflect
the first 24 hours and the remainder over the next 24–48 stores
hours. Overly rapid correction of [Na+], however, can ● Requires repeated dosing to correct low levels
result in seizures, coma, and brain edema. Therefore a
reasonable goal should be to limit the decline in [Na+] to
1–2 mEq/l/hour.
The specific therapy will depend on ECF volume
status. Hypovolemic patients should be treated first with Hypokalemia
volume resuscitation using NS. The hypernatremia can Symptoms and signs include myalgias, fatigue, ileus,
subsequently be corrected with hypotonic fluid admin- constipation, and weakness which can progress to paralysis
istration either PO or intravenously. Euvolemic patients in severe cases. EKG changes with T-wave flattening,
Free water deficit (liters) = (TBW) × [(plasma [Na+] − 140)/140], where TBW = 0.6 × BW in kilograms.
50 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
U waves, ST-segment depression; and cardiac arrhyth- [K+] < 6.0 mEq/l. EKG changes and cardiac arrhythmias
mias such as APCs, PVCs, ventricular tachycardia, and account for the most severe presentations. When the
ventricular fibrillation can occur. Severe hypokalemia can plasma potassium is above 6.0 mEq/l the patient’s EKG
also result in decreased renal concentrating activity with begins to show tall narrow T waves, blunted P waves,
polyuria and development of alkalosis. prolonged PR intervals, which progress until the P wave
Hypokalemia results from either a shift of potassium disappears and eventually QRS widening and cardiac
into the cells or by potassium depletion. The shifts can asystole. Neuromuscular symptoms and signs can occur
occur due to the increased activity of Na-K-ATPase pump at plasma levels of [K+] around 7.0 mEq/l, with proximal
by β-agonists, insulin, carbohydrate loading, or by alkalo- muscle weakness, flaccid paralysis, and even respiratory
sis which causes a potassium–hydrogen exchange across failure occurring in severe cases.
the cellular membrane. Potassium depletion is due pre- Hyperkalemia can result from pseudohyperkalemia
dominantly to renal losses but extrarenal losses can due to hemolysis during venipuncture, prolonged
occur. Renal losses have UK+ > 30 mEq/l. They can be cat- tourniquet use, and marked leukocytosis. Hyperkalemia
egorized on the basis of their acid–base status. They can can also occur due to redistribution of potassium from
have a serum bicarbonate less than 24 mEq/l such as in ICF to ECF and increased total body potassium stores.
patients with renal tubular acidosis type I (distal) and Redistribution of potassium is seen in acidosis, hypo-
type II (proximal). Others with metabolic acidosis insulinemia, and digoxin toxicity. Destruction of cellular
include patients with diarrhea, chronic laxative abuse, membranes due to rhabdomyolysis and hemolysis also
and diabetic ketoacidosis (DKA). Patients with serum results in the release of potassium into the ECF. Reduced
bicarbonate greater than 24 mEq/l can be differentiated renal excretion and exogenous administration account
by their urine [Cl+] levels. For those with [Cl+] > 10 mEq/l for the rest of the causes. Reduced renal excretion occurs
the etiology may be due to diuretics, hyperaldosteronism, in severe renal failure with a GFR less than 10 ml/min,
steroids, and low magnesium levels. Cases with [Cl+] adrenal insufficiency, potassium-sparing diuretics,
< 10 mEq/l are caused by vomiting, nasogastric suction- angiotensin-converting enzyme (ACE) inhibitors, and
ing, and hyperventilation. Extrarenal causes of potassium nonsteroidal anti-inflammatory drugs (NSAIDs). These
depletion include diarrhea, villous adenoma, vasoactive patients have a reduced urine [K+] < 30 mEq/l.
intestinal peptide tumors, chronic laxative abuse, and Exogenous causes include diets rich in potassium, iatro-
profuse sweating. Inadequate intake of potassium by genic administration and blood transfusions. These
itself is rarely a cause of hypokalemia because the kidneys patients have urine [K+] > 30 mEq/l.
can effectively reduce potassium excretion.
The treatment depends on the potassium level and
the clinical picture. Although a serum potassium level DRUG INTERACTIONS
greater than 3.5 mEq/l is considered normal, one aims Exogenous Potassium
for a level of 4.0 mEq/l in the critically ill patient. A [K+] ● Examine closely medication list for exogenous
of 3.0 mEq/l in a patient with a normal acid–base status sources of potassium
correlates with a 200–400 mEq deficit. For nonlife- ● Do not forget diet as a contributor
threatening hypokalemia oral KCl is given at 10–40 mEq
PO qd to bid depending on the level. In patients who are
critically ill or who are not eating, KCl IV at 10 mEq/l
peripherally or 20 mEq/l centrally is administered at a Treatment depends on the level. Removal of all
rate no more than 10–20 mEq/hour to avoid hyper- exogenous causes is the first step in mild hyperkalemia.
kalemic complications. If more rapid replacement is Kayexelate (polystyrene sulfonate), a cation-exchange
required because of very low plasma levels and signs of resin, removes potassium through the GI tract and is
hypokalemia, continuous EKG monitoring and frequent given as 30 g in 100 cm3 20% sorbitol every 3 to 4 hours
[K+] checks should be used. One should avoid glucose- orally or 50 g in 200 cm3 20% sorbitol as a retention
containing solutions, insulin, β-agonists, and other agents enema. Lasix by enhancing renal excretion is also useful.
that may shift potassium intracellularly. The underlying Life-threatening cases, however, require more aggressive
cause of hypokalemia should be diagnosed and treated. therapy. Treatment to minimize membrane repolariza-
Potassium-sparing diuretics should be considered for tion, to decrease quickly plasma potassium levels, and to
those with continuing losses. decrease total body stores needs to be instituted. Calcium
gluconate 10% at 10 cm3 over 3 minutes is given to antag-
onize membrane hyperexcitability. Glucose as 50 cm3
Hyperkalemia D50 and regular insulin at 10 units is given to promote
Hyperkalemia is typically defined as a [K+] > 5.0 mEq/l, an intracellular shift of potassium. This effect lasts
although patients are generally asymptomatic at approximately 15 to 30 minutes and can be repeated.
Metabolic Derangements 51
Sodium bicarbonate by alkalinizing the plasma will also apnea; and psychiatric presentations with anxiety, irri-
cause a transcellular shift and is given either as one tability, and depression.
50 cm3 ampule over 5 minutes and repeated in 10 minutes The causes of hypocalcemia are varied. Decreased
as needed, or as a drip by placing 3 ampules in 1 liter of parathyroid hormone (PTH) secretion due to hypoparathy-
D5W. Patients with chronic renal failure respond poorly roidism, hypomagnesemia, hypermagnesemia, or surgi-
to this intervention. Nebulized albuterol at 2.5 mg can cal damage can result in hypocalcemia. Hypocalcemia
also be used and lasts approximately 2 to 4 hours. Care will occur 24–36 hours postoperatively following sur-
in patients with tachycardia needs to be observed. gery on the parathyroid glands and on the thyroid gland
Decrease in potassium stores, however, does not occur if all four parathyroid glands are removed. Alkalosis
unless kayexelate and lasix are used. Hemodialysis which results in increased calcium binding to albumin
which removes 70–150mEq of potassium is usually can cause a precipitous fall in plasma calcium. Massive
reserved for very severe cases which are complicated by blood transfusions, especially in patients with hepatic
unresponsiveness to treatment, volume overload, and and renal failure where citrate clearance is reduced, can
acidosis. develop hemodynamically significant hypocalcemia due
to the chelation effect of citrate. Other causes include
reduced intestinal absorption of calcium from vitamin D
CALCIUM DERANGEMENTS deficiency, renal insufficiency, hyperphosphatemia, and
liver disease; drugs such as lasix and aminoglycosides;
Normal total serum calcium in plasma is 8.5– sepsis; and pancreatitis.
10.2 mg/dl, while normal ionized calcium is 4.8–7.2 mg/dl Aggressive treatment should be limited to ionized
or 1.1–1.3 mmol/l. Ionized calcium is the physiologically calcium levels below 0.8 mmol/l or to symptomatic
active form of calcium. The total serum calcium as com- patients. Replacement should be initiated with 1 amp IV
monly measured is not. Therefore ionized calcium should calcium chloride and continued with an IV infusion to
be measured instead. Total serum calcium is dependent keep the level between 0.8 and 1.0 mmol/l. A drip at
on albumin level, acid–base status, and chelators. A low 1 mg/kg/hour can be used to keep levels replaced as cal-
total serum calcium, which commonly occurs in critically cium diffuses into tissues and is eliminated in the urine.
ill patients due to a low albumin, is generally associated Special attention needs to be given to certain conditions.
with a normal ionized calcium level. These patients may For instance rhabdomyolysis and tumor lysis syndrome
not truly be hypocalcemic. If ionized calcium cannot be can result in a hyperphosphatemic hypocalcemia.
measured, the total serum calcium is often adjusted Treating these patients with calcium may cause calcium
upward by 0.8 mg/dl for every 1 mg/dl decrease in albu- precipitation, which can lead to organ injury. These
min below 4.0 mg/dl. Calcium is responsible for normal patients are treated by lowering phosphorus levels. This
neuromuscular function and bone formation. Alterations can be accomplished with phosphorus binders, dialysis,
in calcium levels will affect normal muscle, cardiac, res- and diuresis. Severe hypomagnesemia can inhibit PTH
piratory, neurologic, and psychiatric function. production and action. Replacement of magnesium gen-
erally corrects the ionized calcium level by stimulating
PTH secretion.
CLINICAL CAVEAT
Calcium
● Ionized calcium is a more accurate measure of DRUG INTERACTIONS
calcium homeostasis Calcium
● Ionized calcium is the physiologically active form of ● Rhabdomyolysis and tumor lysis syndrome can
calcium result in hyperphosphatemic hypocalcemia
● Ionized calcium is affected by albumin level, ● Treatment with calcium may cause calcium
acid–base status, and chelators precipitation with organ injury
● Treat by lowering phosphorus with phosphorus
binders, dialysis, and diuresis
Hypocalcemia
Manifestations of hypocalcemia include neuromuscular
excitability such as paresthesia, cramps, hyperreflexia, Hypercalcemia
spasms, tetany, and Chvostek’s and Trousseau’s signs; The signs and symptoms of hypercalcemia are often
cardiovascular signs such as peripheral vasodilatation, described by the constellation of symptoms referred to
hypotension, ventricular tachycardia, and prolonged QT as “bones, stones, psychic moans, and abdominal groans.”
interval; respiratory signs including laryngospasm and The symptoms and signs include weakness, hypotonia,
52 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
hyporeflexia, and seizures; confusion, psychosis, and 25 μg/kg over 6 hours, is a cytotoxic agent that inhibits
coma; anorexia, vomiting, and constipation; polyuria bone resorption. Due to its side effects of thrombo-
and nephrocalcinosis; fractures, osteopenia, and ectopic cytopenia, coagulopathy, and hepatic and renal failure it
calcification; hypovolemia and hypotension; and QT is rarely used.
shortening, cardiac arrhythmias, and heart block. Causes Hydrocortisone, 200–300 mg qd for 3 days, lowers
of hypercalcemia include primary hyperparathyroidism, plasma calcium by lowering cytokine release, inhibiting
the most common cause in outpatient setting. However, intestinal reabsorption, and increasing urinary calcium
malignancies such as squamous cell cancer of the lung, excretion. It is particularly effective in patients with lym-
head and neck tumors, metastatic disease from breast phatic malignancies, multiple myeloma, granulomas, and
cancer, multiple myeloma, and lymphoma are the most vitamin D intoxication. Hyperparathyroidism and other
common in hospitalized patients. Other etiologies tumors causing metastasis rarely respond. Phosphorus
include sarcoidosis, hyperthyroidism, immobilization, administration with Neutraphos at 0.5–1.0 g bid to qid
thiazide diuretics, aluminum intoxification in renal fail- may be useful because it inhibits calcium absorption and
ure patients, and vitamin A and D intoxication. increases calcium deposition in bone. Use should be lim-
ited to patients with low phosphate levels because of the
CLINICAL CAVEAT potential for soft tissue calcification. Dialysis can be
done as a last resort prior to surgery. In patients with
Hypercalcemia hyperparathyroidism due to an adenoma or hyperplastic
● “Bones, stones, psychic moans, and abdominal thyroid tissue surgical removal is undertaken. Malignancies
groans”
may require chemotherapy, radiation therapy, and surgery.
● Hyperparathyroidism most common cause in
outpatient setting
● Malignancies most common cause in hospitalized
MAGNESIUM DERANGEMENTS
patients
Magnesium is important for neuromuscular function,
Hypercalcemia is defined as a [Ca+] > 1.3 mmol/l, or cardiac conduction, and many metabolic pathways. The
serum calcium level > 10.5 mg/dl. Patients are asympto- physiologically active form of magnesium is ionized and
matic or with mild symptoms until the serum calcium normal levels are generally expressed as 1.6–2.6 mEq/l.
levels are above 11.5 mg/dl. Moderate symptoms then In the critically ill patient, however, the goal for
occur with the more severe presentations occurring at replacement is 2.0 mEq/l. Only 1% of total magnesium
levels of greater than 13 mg/dl. Management requires stores are in the ECF, the majority is in bone, muscles,
efforts to lower directly the calcium and treatment of and cells. Serum magnesium levels are therefore a poor
the underlying disease. Drugs that may elevate calcium reflection of total body stores.
levels are removed. Normal saline at 250–500 cm3/hour
is given to correct volume depletion, dilute the ionized Hypomagnesemia
calcium, and inhibit calcium reabsorption by increasing
Hypomagnesemia can present with neurologic mani-
sodium excretion by the kidneys. After volume replace-
festations such as parathesias, fasciculations, spasms,
ment is complete, a loop diuretic such as furosemide
tetany, hyperreflexia, and seizures; cardiac signs such as
40–100 mg IV every 2 hours is given to further enhance
APCs, PVCs, prolonged PR and QT intervals, atrial fibril-
calcium excretion. Calcitonin, 4–8 IU/kg IM or SC q12
lation, SVTs, and ventricular arrhythmias including
hours × 2, inhibits bone resorption and increases calcium
torsades de pointes; CNS symptoms such as confusion,
excretion. It is most effective in patients with increased
ataxia, and coma; and metabolic abnormalities such
bone resorption. It begins to lower calcium within 2 hours,
as refractory hypokalemia and hypocalcemia. Digoxin
with a peak effect at 6 to 10 hours. Due to tachyphylaxis
toxicity is exacerbated by hypomagnesemia.
it lasts only a few days. An added benefit appears to be
its potent analgesic activity in patients with bone metas-
tasis. It is associated with allergic reactions and skin test- CLINICAL CAVEAT
ing should be done before its use. Pamidronate, a
Magnesium
biphosphonate, is used at 60 mg IV over 4 hours for mild
● Serum magnesium is a poor indicator of total body
cases of hypercalcemia and 90 mg IV over 24 hours
stores
for severe cases. Bone resorption is decreased because ● Optimal level in critically ill patients is 2.0 mEq/l
of its inhibitory effect on osteoclasts. Another biphos- ● Check [Mg+] and [K+] in the critically ill patient with
phonate, etidronate disodium, 7.5 mg/kg over 4 hours arrhythmias
for 3–7 days, is also useful. Its use is limited because of ● Consider digoxin toxicity with arrhythmias
diarrhea and nephrotoxicity. Mithramycin (Plicamycin),
Metabolic Derangements 53
Etiologies are decreased intestinal absorption or Elimination of magnesium may require hemodialysis in
increased renal excretion. Malabsorption, malnutrition, patients with acute renal failure. Supportive care with
alcoholism, diarrhea, and gastric aspiration are common mechanical ventilation or temporary pacemaker may be
for decreased absorption. Renal losses result from needed.
osmotic diuresis, hypercalcemia, aminoglycosides,
amphotericin B, and cyclosporin.
Treatment depends on the level and clinical signs. PHOSPHORUS
Because magnesium is essentially only eliminated by the
kidneys, replacement in patients with renal insufficiency Phosphorus is important for cellular energy metabo-
is done carefully. Chronic or mild hypomagnesemia is lism, the maintenance of acid–base balance, and bone
treated with magnesium oxide, 400 mg PO qid to bid. formation. It is difficult to assess exactly the ion concen-
Magnesium sulfate IV is used in critically ill patients with tration and so it is measured in mg/dl with a normal
symptoms or low levels. One gram of magnesium sulfate range of 2.5–4.5 mg/dl. Bone accounts for 85% of total
is approximately 4 mmol or 8.0 mEq of elemental mag- body stores, followed by cells with 14% and ECF at 1%.
nesium. Generally 2 g are given over 1 hour and repeated Serum phosphorus levels like potassium and magnesium
several times depending on the level. Severe hypomag- are poor indicators of total deficit.
nesemia with serum levels less than 1.0 mEq/l can be
treated with magnesium sulfate, 2 g IV over 30 minutes,
followed by 6 g in 250 cm3 NS over 6 hours. In life- Hypophosphatemia
threatening hypomagnesemia with seizures and arrhyth- Symptoms and signs do not usually present unless
mias, 2 g IV over 2 minutes is given, and followed with the level is less than 1.0 mg/dl. There can be muscular,
6 g in 250 cm3 NS infused over 3 hours. These patients respiratory, cardiac, neurologic, hematologic, and bone
will require further aggressive replacement over the involvement. Patients may complain of weakness;
next several days due to the large body deficits. develop impaired diaphragmatic function, and respiratory
and cardiac failure; progress to rhabdomyolysis; manifest
confusion, stupor, and seizures; show hemolysis and
Hypermagnesemia thrombocytopenia; and develop osteomalacia and rickets.
The manifestations of hypermagnesemia occur when Hypophosphatemia results from decreased intestinal
serum magnesium is greater than 4 mEq/l. Neurologic absorption, increased urinary excretion, and redistribu-
and cardiac dysfunction predominates. Weakness, lethargy, tion into the intracellular space. Decreased absorption
and paralysis can occur, with progressive areflexia often is seen in malabsorption, malnutrition, starvation, and
present as the magnesium concentration increases. administration of phosphate binders. Increased urinary
Cardiac signs include hypotension, bradycardia, pro- excretion can result from hyperparathyroidism, diuretics,
longed PR, QRS, and QT, complete heart block, and polyuric phase of ATN, postobstructive diuresis, DKA,
asystole. The loss of tendon reflexes occurs as the RTAs, and renal transplantation. Redistribution occurs
level approaches 6 mEq/l, with respiratory paralysis at with glucose, insulin, β-agonists, respiratory alkalosis,
12–15 mEq/l, then cardiac block and subsequently car- alcohol withdrawal, and recovery phase of starvation.
diac arrest at levels above 15 mEq/l. Patients with aggressive overfeeding poststarvation, alco-
The causes are few, because any excess magnesium is hol abuse and withdrawal, hyperalimentation, DKA, and
rapidly excreted by the kidneys. Acute renal insuffi- burns are at high risk for very low phosphate levels of
ciency or renal failure especially when combined with less than 1.0 mg/dl.
magnesium-containing antacids, laxatives, and IV mag- Treatment depends on the level and clinical picture.
nesium is the most common cause of hypermagnesemia. Mild hypophosphatemia, in healthy patients tolerating
It can occur with the large amounts of exogenous mag- PO, can be replaced with Neutraphos, 250–500 mg PO
nesium used in patients with pre-eclampsia and eclamp- q 6 hours. In moderate hypophosphatemia, 1.0–2.0 mg/dl,
sia. Patients with rhabdomyolysis and hemolysis can also elemental phosphate 0.08–0.16 mmol/kg in 100 NS IV
develop hypermagnesemia. over 6 hours can be used safely. Elemental phosphate
Treatment involves eliminating exogenous adminis- comes as potassium phosphate which contains 3 mmol
tration, antagonizing the chemical–electrical effects, and PO4 with 4.4 mEq potassium per cm3, and sodium phos-
removing magnesium from the body. Calcium gluconate phate which is 3 mmol PO4 with 4 mEq sodium per cm3.
10%, 10–20 cm3 IV (1–2 g) over 10 minutes, temporarily Severe hypophosphatemia is treated aggressively with
antagonizes the effects. If renal function is not impaired elemental phosphate, 0.16–0.25 mmol/kg over 4–8 hours.
severely and the patient makes urine, excretion of Continued phosphate replacement will be required for
magnesium can be enhanced by providing 2 g of calcium several days due to depleted phosphate stores. Hypo-
gluconate 10% in 1 liter NS at 150–200 cm3/hour. magnesemia and hypokalemia often occur concurrently
54 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
and must be addressed. Extreme care should be taken in When the elevation in the body temperature occurs
treating patients with DKA, as the level often improves without alteration in the hypothalamic set point we talk
significantly with treatment of acidosis. about hyperthermia. In this case the underlying process
is either excessive heat production or inadequate heat
dissipation or both. Hyperthermic syndromes include
Hyperphosphatemia heat stroke and endocrinopathies, which are described
Patients are generally asymptomatic until the level is elsewhere, and the drug-induced hyperthermias. The
>5.0 mg/dl. The clinical picture is due to hypocalcemia drug-induced hyperthermias are malignant hyperther-
and ectopic calcification. Ectopic calcification occurs as mia, neuroleptic malignant syndrome, serotonin syn-
the calcium × phosphorus product goes over 60. Heart drome, sympathomimetic poisoning syndrome, and
block is a life-threatening complication for which one anticholinergic syndrome.
should monitor.
A common etiology is renal failure, but it also occurs
due to cellular damage caused by trauma, acidosis, Heat Stroke
rhabdomyolysis, and tumor lysis syndrome. Hypopara- Heat stroke is an acute breakdown of the body’s ther-
thyroidism and exogenous phosphate syndrome are also moregulatory mechanism in warm environments result-
frequently implicated as causes of hyperphosphatemia. ing in severe hyperthermia with core temperatures
Management requires eliminating the cause; restrict- >40°C. There are actually two forms of heat stroke.
ing dietary phosphate; increasing urinary excretion with Exertional heat stroke occurs typically in young individ-
normal saline and acetazolamide, 500 mg q 6 hours; and uals who engage in strenuous physical activity for a
increasing GI losses with phosphate binders such as alu- prolonged period in a hot environment, while classic
minum hydroxide, 30–45 cm3 q 6 hours. Patients with nonexertional heat stroke occurs in sedentary elderly
renal failure or ectopic calcification will benefit from individuals, in persons who are chronically ill, and in the
dialysis. Associated hypocalcemia may also need to be very young. This latter form is more prevalent during
treated, but care must be taken to keep the calcium × environmental heat waves. Both types are associated
phosphorus product less than 60. with high morbidity and mortality especially when diag-
nosis is delayed.
Increased heat production, impaired heat loss, and
THERMAL DERANGEMENTS decreased ability to sweat effectively are important in
the pathogenesis of the syndrome. High-risk groups include
Maintaining a normal body temperature despite the elderly, patients with schizophrenia, Parkinson’s dis-
environmental variations creates a stable milieu for the ease, alcoholics, and paraplegics and quadriplegics. The
hundreds of heat-sensitive enzymes to function and to pathophysiology involves muscle degeneration and
maintain homeostasis within normal ranges. There exists necrosis resulting in rhabdomyolysis; increased cardiac
a 24-hour circadian temperature rhythm with a morning output, with decreased systemic vascular resistance;
nadir and an afternoon peak that can be as much as direct thermal injury to brain and spinal cord resulting in
0.5–1°C. In ovulating women there is an additional edema and hemorrhage; acute renal failure due to dehy-
increase in the baseline body temperature of approxi- dration and myoglobinuria; hepatic necrosis leading to
mately 0.5°C in the second half of the menstruating death; coagulopathy; and multiple electrolyte abnormal-
cycle. Other physiologic states that can affect baseline ities. The diagnostic criteria include a compatible
temperatures are postprandial state, pregnancy, and age. history, core temperature >40°C, anhidrosis, elevated
creatine kinase level, and depressed mental status.
Treatment with aggressive cooling is initiated by
HYPERTHERMIA using evaporative cooling techniques such as wetting
skin, cool water spray, and electric fans; direct careful
Hyperthermia describes the state when body temper- external cooling by ice packs or cold water immer-
ature is above normal. Normothermia is generally sion; and occasionally when very severe hyperthermia
accepted to exist between 36 and 37.5°C measured at is present by performing gastric lavage or peritoneal
the body surface. When an elevated body temperature lavage with iced saline, or even hemodialysis. Aggressive
exists because of a change that occurs in the thermoreg- hemodynamic monitoring and supportive care is insti-
ulatory center at the anterior hypothalamus we talk about tuted in an intensive care unit (ICU). Hypotension is
fever. Substances that cause fever are called pyrogens. common and is treated with warm IV fluids initially.
Pyrogens can be further divided to endogenous and Dopaminergic and alpha agents should be avoided
exogenous pyrogens. because they may enhance vasoconstriction and instead
Metabolic Derangements 55
bladder and bowel incontinence, and nausea and vomiting Neuromuscular irritability is reflected mostly in the
are frequently seen. Laboratory tests are generally non- lower extremities with tremors, myoclonus, and muscle
specific and reflect organ involvement. Elevations in cre- rigidity. The autonomic instability is characterized by
atine kinase due to rhabdomyolysis from hyperthermia diaphoresis, dilated reactive pupils, labile blood pres-
and muscle rigidity, elevations in blood urea nitrogen sure, arrhythmias, and vomiting. Hyperthermia is com-
and creatinine due to pre-renal azotemia and myo- mon and can reach 40°C. Laboratory abnormalities are
globinuria, leukocytosis from the stress response, and minimal and nonspecific, but in severe cases leukocyto-
multiple electrolyte and acid–base abnormalities are sis, metabolic acidosis, renal failure, rhabdomyolysis,
frequently seen. and DIC may occur.
Treatment includes discontinuation of the neurolep- Treatment includes immediate withdrawal of the
tic agent. General measures to lower body temperature offending drug, aggressive supportive care and monitor-
such as removal of excess clothing and cool water spray ing in an ICU, rapid cooling, and the use of benzodi-
with air circulation should start immediately. In mild azepines for the treatment of neuromuscular irritability.
cases supportive care may be sufficient. In moderate to The serotonin antagonist cyproheptadine, at 4–8 mg
severe NMS aggressive monitoring and support in an ICU repeated every 4 hours to a total daily dose of 32 mg,
setting is necessary. Dantrolene which reduces thermo- has been reported to shorten the course of serotonin
genesis by reducing muscle contraction is given at syndrome. Methysergide, another nonspecific serotonin
1.0–2.5 mg/kg IV q6 hours until a dose of 100–300 receptor blocker, has had mixed results. Fatalities do
mg/day PO can be given. Neuromuscular blockade may occur, but recovery is expected in most patients.
be useful initially to reduce the metabolic rate and
muscle contraction. Specific drug therapy to lower core
temperature and reduce extrapyramidal side effects is Sympathomimetic Poisoning Syndrome
initiated. Dopamine agonists such as bromocryptine, Sympathomimetic poisoning syndrome results from
amantadine, and levo-carbidopa combination are recom- an increase central sympathetic activity due to both ther-
mended. Bromocryptine 5–20 mg/day given in divided apeutic and recreational drugs. Over the counter cold
doses has been shown to decrease the course of NMS. It remedies, appetite suppressants, and frequently abused
is continued at 2.5 mg PO tid for 1 week or longer drugs such as cocaine, amphetamines, LSD, and PCP are
depending on the rate of elimination of the offending known causes. Increased ambient temperature is an
drug. Recurrence can occur if dopamine agonists are associated predisposing factor.
prematurely discontinued. Mean recovery time is Patients are usually referred to the emergency depart-
approximately 9 days. ment because they are delirious, agitated, and combat-
ive. Tremors, hyperreflexia, rigidity, and occasionally
seizures occur. On physical examination patients are
Serotonin Syndrome diaphoretic with dilated but reactive pupils, and are
Serotonin syndrome results from increased central hypertensive and tachycardic. Hyperthermia as a marker
serotonin receptor activity which produces a clinical of moderate to severe poisoning is associated with many
picture of encephalopathy, neuromuscular hyperactivity, complications involving organ damage. Rhabdomyolysis,
and autonomic dysfunction. Initially described in associ- acute renal failure, metabolic acidosis, DIC, and liver fail-
ation with monoamine oxidase inhibitors, serotonin ure similar to the other drug-induced hyperthermias may
uptake inhibitors are more commonly implicated reflect- occur. The diagnosis is suggested in those patients with
ing their increased use. It typically occurs from the use previous drug use and confirmed by a positive toxicol-
of two or more drugs with serotonergic activity, or ogy screen.
from the overdose of a single agent. Increased serotonin Treatment requires aggressive cooling including pos-
synthesis from L-tryptophan; decreased metabolism of sibly neuromuscular blockade and benzodiazepines to
serotonin due to MAOIs; serotonin receptor agonists treat delirium, agitation, and seizures. Nitroprusside or
busripone, lithium, LSD; increased serotonin release labetolol may be needed to treat the hypertensive mani-
caused by amphetamines, amphetamine derivatives, and festations of the syndrome. Aggressive monitoring and
cocaine; nonselective serotonin reuptake inhibitors like supportive care, including mechanical ventilation, may
TCAs, cocaine, amphetamines, meperidine, dextro- be needed for several days.
methorphan, and selective inhibitors such as sertaline,
fluoxetine, and nefazodone are all mechanisms that can
interact to cause a serotonin overload. Anticholinergic Syndrome
Signs and symptoms are acute, within 24 hours of a Anticholinergic syndrome results from the blockade
precipitating event. Altered sensorium with hyperactivity, of central and peripheral muscarinic receptors. Many
agitation, delirium, and occasionally seizures occur. drugs including over the counter medications and some
Metabolic Derangements 57
plants are known to precipitate this syndrome. blankets, and immersion in warm baths. Severe
Medications such as atropine, scopolamine, belladonna hypothermia requires active core rewarming with
extracts, TCAs, oxybutynin, antihistamines including humidified warmed oxygen, gastric lavage, peritoneal or
diphenhydramine and meclizine, phenothiazines, pleural lavage, and may include cardiopulmonary
antiparkinsonian agents, and the antiarrhythmics quini- bypass. Cardiac medications are typically not effective.
dine, procanamide, and dispyramide can be causes of However, bretrylium for arrhythmias and dopamine for
the syndrome. ionotropic support have been shown to be effective.
Presentation is usually due to an altered fluctuating Electrical defibrillation may be ineffective until the core
mental status. Patients can manifest a depressed senso- temperature is >30°C. Although hypothermic patients
rium including unresponsiveness and even coma, or an may be brought into the emergency department without
agitated, hyperactive, delirious state which may result in a blood pressure or rhythm, they cannot be pronounced
seizures. Dry mouth, dry skin, blurry vision with dilated dead until they are at 37°C.
unreactive or slightly reactive pupils, hypoactive bowel
sounds, and hyperthermia characterize the syndrome.
The hyperthermia is only seen in a quarter of patients, PERIOPERATIVE HYPOTHERMIA
and can be mild to severe.
Treatment is mostly supportive. Aggressive cooling Anesthesia and surgery commonly cause substantial
and monitoring are necessary. Physostigmine, an acetyl- thermal perturbations. Hypothermia, the typical alter-
cholinesterase inhibitor that increases the concentration ation, results from a combination of anesthetic-induced
of acetylcholine and overcomes the muscarinic block, is impairment of thermoregulatory control, a cool operat-
sometimes used. Physostigmine, however, is associated ing room environment, and factors unique to surgery
with serious adverse effects such as bradycardia, asys- that promote excessive heat loss. Hypothermia develops
tole, salivation, bronchorrhea, and seizures. Therefore it with a characteristic pattern. An initial decrease of the
is reserved for severe cases presenting with seizures, core temperature by 1–1.5°C over the first hour is fol-
severe delirium, cardiovascular collapse, or life-threaten- lowed by a slower linear decrease, which finally leads to
ing hyperthermia in the absence of sweating. a plateau phase during which the temperature remains
Physostigmine 1–4 mg IV is given slowly while monitor- constant. Data suggest much more hypothermia results
ing the heart rate. The effect is quick, but lasts less than from altered distribution of body heat rather than from a
60 minutes. The dose may need to be repeated. systemic imbalance between metabolic heat production
and heat loss.
Since intra- and postoperative hypothermia carries
HYPOTHERMIA many disadvantages (including increased blood loss sec-
ondary to impaired coagulation and reduced platelet
Hypothermia is characterized by a core body temper- function, myocardial ischemia secondary to the
ature < 35°C. It can be classified as mild hypothermia, increased oxygen consumption associated with shiver-
32–35°C; moderate hypothermia, 30–32°C, and severe, ing, decreased drug metabolism, and of course patient
< 32°C. Predisposing factors are advanced age, exposure discomfort), all patients should be protected from it.
to cold, drug use (especially alcohol), trauma, CNS dys- Patients especially susceptible to hypothermia are those
function, SCI, endocrine dysfunction, and iatrogenic in extremes of age.
causes. Signs and symptoms are characterized by a In neurosurgical procedures, however, mild systemic
depressed level of consciousness. Mental status can hypothermia carries the advantage of cerebral protec-
range from stuporous or confused at temperatures tion due to decreased cerebral metabolic rate. This
< 35°C to coma when the temperature is < 27°C. Other neuroprotective effect of decreased body temperature
physiologic affects of hypothermia include cardiac dys- also seems to be useful at the initial resuscitation phase
function with decreased cardiac output, bradycardia and in closed head injured trauma patients as long as the
cardiac irritability at < 33°C, ventricular fibrillation at degree of hypothermia does not jeopardize other vital
< 28°C, and hypotension at < 25°C; hematologic abnor- functions.
malities with coagulopathy, and decreased oxygen deliv-
ery; and endocrine dysfunction with decreased insulin
release and insulin resistance. SUMMARY
Treatment with rewarming is initiated at 2°C/hour
depending on the degree of hypothermia. Mild exposure Metabolic abnormalities are extremely common in
requires passive external warming with blankets, cloth- the critically ill patient. Maintaining electrolytes at nor-
ing, and warm IV fluids. Moderate exposure requires mal levels is important for the proper functioning of the
active rewarming with hot blankets, circulating warm air electrochemical reactions of the body. Failure to do so
58 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
will result in abnormalities in neuromuscular, cardiac, calcium precipitation with organ injury. Similarly
and metabolic pathways. For instance, calcium and hypothermia and hyperthermia require an appreciation
phosphorus which are very closely interrelated are of the interrelationship between the physiology and the
important in neuromuscular function, cellular metabo- pharmacologic actions of both recreational and thera-
lism, maintenance of acid–base balance, and bone for- peutic drugs. Recognizing the syndrome, avoiding inad-
mation. A poor understanding of this relationship may vertent interactions, selecting medications to counter
result in the inappropriate replacement of calcium in the the deleterious effects, and aggressive supportive care
hyperphosphatemic, hypocalcemia patient, rather than are essential for proper care.
the correct treatment with phosphate binders and cause
SELECTED READING
Boucharma A, Knochel J: Heat stroke. N Engl J Med
346:1978–1988, 2002.
CASE STUDY Braunwald E et al: Harrison’s Principles of Internal Medicine,
An 18-year-old male is admitted to the ICU early ed 15, McGraw Hill, 2001.
Monday morning after being brought to the ER because Carbone JR: The neuroleptic malignant and serotonin syn-
of delirium, tremors and high fever. According to his dromes. Emerg Med Clin North Am 18:317–325, 2000.
girlfriend who called 911, he had returned late Sunday Goldman L et al: Cecil Textbook of Medicine, ed 21, W.B.
evening after attending a weekend concert with his Saunders, 2000.
friends. He is agitated, confused, hallucinating,
tremulous, and notably hot to touch. On exam, his Hopkins PM: Malignant hyperthermia: advances in clinical mana-
blood pressure is 199/115, heart rate 160 and regular, gement and diagnosis. B J Anesth 85(1):118–128, 2000.
respiratory rate 30–40, and his temperature is 40°C. Longnecker D et al: Principles and Practice of Anesthesiology,
Since arrival to the ER 4 hours before, he has made 10 cc ed 2, Mosby, 1998.
of dark colored urine, and his lab work has returned MacLennan DH: Ca2+ signalling and muscle disease. Eur J Biochem
with a K 6.9 meq/l, HCO3 12 meq/l, BUN 65 mg/dl, 267:5291–5297, 2000.
creatinine 2.6 mg/dl and a PO4 of 9.9 mg/dl.
Murray M et al; ASCCA: Critical Care Medicine: Perioperative
QUESTIONS Management, ed 2, Lippincott Williams and Wilkins,
1. What further information would you like from his 2002.
girlfriend? Sambuughin N: North American malignant hyperthermia pop-
2. What is your differential diagnosis? ulation. Anesth 95:594–599, 2001.
3. How would you explain the signs and symptoms?
Sessler DI: Perioperative heat balance. Anesth 92(2):578–596,
4. What is your initial treatment plan?
2000.
5. What are the potential pitfalls during treatment?
Simon HB: Hyperthermia. N Engl J Med 329:483–487, 1993.
CHAPTER Fluid, Electrolyte,
Normal Body Fluid and Electrolyte Composition determines cardiac function, measured as cardiac output
Fluid Compartments or ejection fraction (Figure 6-1). Cardiac output is a key
Electrolyte Distribution determinant of tissue and organ perfusion. Diminished
Fluid and Electrolyte Loss and Redistribution in organ perfusion is associated with decreased oxygen and
Pathologic States nutrient delivery, removal of metabolic by-products, and
Electrolyte Deficit and Excess in the case of the kidneys decreased filtration pressure
Glucose and waste elimination in urine output. Tissue hypoper-
Sodium and Water fusion, and even transient ischemia, triggers metabolic
Potassium alterations such as a shift from oxidative phosphoryla-
Chloride tion to anaerobic glycolysis with ensuing lactate and
Magnesium hydrogen ion production, and alterations in cellular
Calcium water, sodium, and calcium flux. Cellular metabolic
Phosphate alterations are the trigger for activation of the cellular
Acid–Base Physiology and humoral inflammatory response which perpetuates
Acidosis the cycle of ischemia, cell death, tissue necrosis, and
Alkalosis systemic inflammatory response.
Crystalloids The electrolytes, water, and protein content of body
Colloids fluids are regulated within a narrow range; however
Blood and Blood Products
Red Cell Transfusion
Platelet Transfusion
Fresh Frozen Plasma
Cryoprecipitate
Measure of cardiac function
59
60 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
PEARLS
● Hypovolemia is decreased effective intravascular Interstitial fluid: ISF Plasma volume: PV
volume. Cardiac signs of hypovolemia are decreased 15% body weight 5% body weight
preload (low CVP, pulmonary artery occlusion 75% ECF 25% ECF
10.5 L 3.5 L
pressure, or diminished end-systolic ventricular
chamber volumes on echocardiography), Figure 6-2 Distribution of body water.
tachycardia, and decreased cardiac output (oliguria,
vasoconstriction, acidosis, lactate accumulation, and
altered mental status).
body water and of body weight. The ECF is divided
● The Starling curve depicts the effect of incremental between blood volume (8% body weight), plasma (5%
changes in preload on cardiac function. See Figure 6-1. body weight), and interstitial fluid (ISF; 15% body
● Decreased oxygen delivery to tissues resulting from weight). Intracellular fluid (ICF) comprises two-thirds of
diminished cardiac output defines the state known total body water and about 40% of body weight.
as “shock.”
● Empiric therapy based on the clinical presentation
may suffice; however, if there is no response or a PEARLS
continued deterioration, then invasive monitoring is
necessary to determine intravascular volume and ● Total body water = 0.6 × wt (kg) in males; and
cardiac output, and to guide resuscitation. 0.5 × wt (kg) in females
● Serum osmolarity = (2 × [Na]) + [glucose]/18 +
[BUN]/2.8. Normal serum osmolarity =
290 mOsm/kg H2O.
● The fractional excretion of sodium (FEN) is
NORMAL BODY FLUID AND extremely useful in the management of oliguria
ELECTROLYTE COMPOSITION (TABLE 6-1) (FENa = [NaUrine/NaSerum]/[CrUrine/CrSerum]). A FENa of
less than 1% is an excellent indicator of prerenal
Fluid Compartments oliguria in the absence of diuretic therapy, renal
Total body water is distributed across semipermeable failure, or osmotic load.
membranes into fluid compartments as outlined in ● The Starling–Landis equation (transcapillary fluid flux)
is: F = k[(PH − PISF) − δ (COPV − COPISF)], where k is the
Figure 6-2.
ultrafiltration coefficient of fluid; PH is the intravascular
For an average adult male, body weight is comprised hydrostatic pressure; PISF is the hydrostatic pressure of
of 60% water, 7% minerals, 18% protein, and 15% fat. intravascular fluid; δ is the reflection coefficient; COPV
Females have a slightly increased body fat content and is the intravascular oncotic pressure; and COPISF is the
a correspondingly decreased water content of 50%. oncotic pressure of the interstitial fluid.
Extracellular fluid (ECF) comprises one-third of total
Table 6-1 Average Electrolyte Content and Daily Volumes of Body Fluids and Secretions
Adult Volume
Fluid Na (mEq/l) K (mEq/l) H (mEq/l) Cl (mEq/l) HCO3 (mEq/l) (ml/day)
Saliva 60 20 0 15 50 1500
Gastric 20-120 15 60 130 0 2500
Pancreatic 140 5 0 70 70 1000
Biliary 140 5 0 140 44 600
Ileostomy 120 20 0 100 40 3000
Diarrhea 100 20 0 100 40 –
Fluid, Electrolyte, Blood, and Blood Product Management 61
Plasma volume is the first ECF space. The normal hypoglycemia can precipitate a myocardial infarction or
ISF space is the second ECF space. A pathologically encephalopathy. Tissues may be starved for glucose either
expanded ISF space is a third ECF space, increased pri- due to absolute hypoglycemia (low serum glucose levels),
marily at the expense of plasma volume referred to as a or relative cellular hypoglycemia (insulin resistance, defec-
“third space” loss. Tissue edema is one type of third space tive glycolysis or oxidative phosphorylation). Patients at
fluid loss. Third space losses can constitute tremendous risk for fasting hypoglycemia include those with depleted
plasma volume loss: 1 mm of diffuse peritoneal edema glycogen stores or impaired glycogenolysis, such as
in an adult represents approximately 20 liters of fluid. patients with malnutrition, cirrhosis, renal failure, alco-
Failure to replace lost intravascular fluid results in dimin- holic ketoacidosis, or patients with inborn errors of metab-
ished cardiac output and tissue perfusion, and ischemic olism. Medications that can lead to hypoglycemia include
tissue injury. Third space losses occur in the setting of ethanol, oral hypoglycemic agents, insulin, pentamidine,
injury and inflammation and do not equilibrate with moxifloxacin, salicylates, haloperidol, and trimethoprim-
other fluid compartments. Third space fluid cannot be sulfamethoxazole. Hypoglycemia of endocrine origin is
mobilized and removed by changing the volume of other seen with glucocorticoid deficiency, hypopituitarism, and
fluid compartments. Third space fluid mobilizes sponta- glycogen storage diseases.
neously when inflammation subsides and the fluid
moves from the abnormal interstitial compartment to Hyperglycemia
the plasma volume. Hyperglycemia is most often seen in the setting of dia-
betes, insulin resistance, diabetic ketoacidosis, or nonke-
totic hyperosmolar states. Hyperglycemia may also result
Electrolyte Deficit and Excess from overfeeding, stress, or medications. Patients with
Glucose renal failure typically have insulin resistance and hyper-
Blood or serum glucose levels must be closely moni- glycemia. Hyperglycemia in critically ill patients has been
tored in critically ill patients since both hyperglycemia shown to increase morbidity due to hospital-acquired infec-
and hypoglycemia have important therapeutic ramifica- tions, and also increase overall mortality. Relative insulin
tions. Sources of glucose include endogenous synthetic resistance occurs in the setting of glucocorticoid or cate-
processes, such as gluconeogenesis and glycogenolysis, cholamine administration. Hyperglycemia causes a relative
and exogenous sources, such as enteral or parenteral hyperosmolar state and can thereby precipitate an osmotic
nutrition and intravenous fluids. It is important to realize diuresis, which can lead to dehydration and electrolyte
that glucose is present in intravenous fluids either to cre- imbalances (hypokalemia, hypernatremia) due to diuresis
ate a fluid which is isotonic for safe intravascular adminis- of a very dilute urine. Hyperglycemia has also been shown
tration (without precipitating hemolysis), or with the to detrimentally affect neurologic outcome after cardiac
specific intent of glucose administration. Glucose admin- arrest, presumably by increasing the level of intraneural
istered intravenously is rapidly metabolized and the fluid lactic acidosis in the setting of cerebral ischemia. Thus,
in which it was contained then becomes hypotonic and insulin is an important adjunct therapy for most critically
behaves as “free water.” Thus, dextrose-containing solu- ill patients and is most appropriately administered intra-
tions such as D5W represent a major source of free water venously, especially in instances where there is peripheral
and should not be administered to patients with head edema or anasarca which impairs the absorption of sub-
injury or after recent neurosurgery where there is a risk cutaneous insulin.
for the development of cerebral edema, or in those patients
with pre-existing hyponatremia. The administration of
intravenous glucose does not have any measurable “pro- CLINICAL CAVEAT
tein-sparing effect” in catabolic states. Furthermore, the
metabolism of glucose will typically result in some level of Infusion of Free Water
hypokalemia as glucose and potassium are co-transported Free water should never be infused in patients with
head injury or those undergoing neurosurgery because
into cells.
it exacerbates cerebral edema. Normal saline is the
fluid of choice in these patients.
Hypoglycemia
Glucose is an important metabolic substrate.
Hypoglycemia should be considered as a potential cause of
any acute deterioration, such as mental status change or Sodium and Water
cardiac arrest, in critically ill patients. Hypoglycemia is an A minimal urine output of 500 cm3/24° is required for
important cause of agitation, somnolence, or seizures. solute excretion in a normal adult. In the adult ICU
Early symptoms of hypoglycemia include tremulousness, patient, oliguria is defined as a urine output of < 0.5 cm3/
diaphoresis, palpitations, and nausea; however, profound kg/hour over two consecutive hours. Adult maintenance
Fluid, Electrolyte, Blood, and Blood Product Management 63
Extrarenal loss Renal loss Extrarenal loss Renal loss Cushing’s syndrome,
hyperaldosteronism
Perspiration Osmotic diuresis Insensible losses Diabetes insipidus NaHCO3−; NaCl dialysis
(respiratory, skin)
Hypertonic urine Iso- or hypertonic Hypertonic urine Variable urine Iso- or hypertonic urine
urine tonicity
Urine Na+ < 10 mEq/l Urine Na+ > 20 mEq/l Variable urine Na+ Variable urine Na+ Urine Na+ mEq/l
Hypertonic saline Water replacement Diuretics + water
fluid requirements are approximately 2500 ml/day under water deficit = 0.6(M) or 0.5(F) × Wt(kg) × ([Na+] −
normal conditions. Serial body weight and daily 140/140) or water deficit = 0.6(M) or 0.5(F) × Wt(kg) ×
intake/output measurements are important to follow [plasma Na+/140 − 1] × 10. Males (M) have slightly
total body water status. Normal plasma or serum sodium higher total body water content than do females (F).
concentration ranges from 135 to 145 mEq/l. Serum
osmolarity (mOsm/kg) = total solute (mOsm)/ total body
water (kg). Sodium is the main determinant of plasma CLINICAL CAVEAT
(serum) osmolarity. The disorders of sodium balance are Correction of Hypernatremia
summarized in Tables 6-2 and 6-3. ● Hypernatremia that is corrected too rapidly may
result in acute cerebral edema.
Hypernatremia ● Urine osmolality less than that of plasma suggests
Symptoms of hypernatremia include lethargy, irri- central (antidiuretic hormone (ADH)-deficient) or
tability, seizures, and coma. The in-hospital mortality nephrogenic (ADH-resistant) diabetes insipidus.
associated with severe hypernatremia exceeds 50%. The ● Urine sodium is low in the setting of water loss and
diagnosis of hypernatremia relies on the measurement of high with salt ingestion.
urine sodium and/or osmolarity. ● The water restriction test is helpful in hypernatremic
states to diagnose central diabetes insipidus: water
Hypernatremia (plasma sodium > 145 mEq/l) may be
intake is stopped to stimulate ADH release; if no
a result either of hypertonic fluid gain (sodium infusion), response occurs then 1-deamino-8-D-arginine
or more commonly a relative free water deficit. The differ- vasopressin (DDAVP) is administered. If the urine
ential diagnosis and treatment of hypernatremia depends osmolality rises the patient has central diabetes
on the estimated total body sodium (Table 6-2). Thirst insipidus.
occurs when serum sodium rises by 3–4 mEq/l. Calculated
Potassium
Hyperkalemia
CLINICAL CAVEAT Normal plasma or serum potassium concentration
Correction of Hyponatremia ranges from 3.5 to 5.5 mEq/l. Body potassium stores are
● The rate of serum sodium increase during the correc- primarily intracellular and total body potassium is
tion of hyponatremia should not exceed 0.5–2 approximately 50 mEq/kg or 3500 mEq in a 70 kg person.
mEq/l/hour (12–20 mEq/l) in the first 24 hours; and Of this total, 2% (70 mEq) are found in the ECF.
0.3–0.5 mEq/l/hour thereafter. In extreme emergen- Hypokalemia (<3.5 mEq/l) signals total body depletion of
cies a maximum of 20 mEq/l/day may be tolerated potassium stores, a deficit of approximately 250–300 mEq
but has significant associated risks which should not
in a 70 kg adult. This deficit must be replaced gradually.
outweigh benefits.
● Hyponatremia corrected too rapidly can produce
Hyperkalemia in the face of acidosis signals a significant
central pontine myelinolysis (osmotic demyelination) total body potassium deficit. Untreated hypokalemia can
syndrome which is an irreversible CNS injury related be expected to worsen as the pH rises. Acidosis pro-
to both rate and degree of Na+ correction. Imaging motes an efflux of potassium from the ICF compartment.
studies may not be positive for up to weeks. Sources of hyperkalemia include renal failure, hypo-
adrenocorticalism (Addison’s syndrome), hemolysis, rhab-
domyolysis, potassium supplements, and medications
such as penicillin-K, heparin, aldosterone antagonists,
In the setting of hypervolemia, a hypo-osmolar serum ACE inhibitors, and succinylcholine. Pseudohyperkalemia
and a urine sodium less than 10 mmol/l is usually associ- may result from leukocytosis (>100,000/mm3) or elevated
ated with congestive heart failure, nephritic syndrome, platelet count (>600,000/mm3).
hypothyroidism, malnutrition, and hypoalbuminemia, Hyperkalemia causes tall peaked T waves, widened QRS,
cirrhosis, or pregnancy. In the setting of hypovolemia, a and wide PR. These patients should be carefully monitored.
Fluid, Electrolyte, Blood, and Blood Product Management 65
Chloride
CLINICAL CAVEAT
Gastric secretions are a primary source of loss pro-
Treatment of Hyperkalemia ducing hypochloremic metabolic alkalosis. (See section
● Plasma or serum hyperkalemia can be reduced by on acid–base physiology below). Exogenous chloride
promoting alkalosis (hyperventilation, exogenous and renal failure are the primary causes of hyper-
bicarbonate), or increasing intracellular glucose by
chloremic metabolic acidosis.
the administration of glucose (0.5–1.0 g/kg) and
insulin (0.1 unit regular insulin/kg); beta2-agonist
(albuterol); maneuvers that move potassium from the Magnesium
ECF to the ICF compartment. Ten percent calcium glu- Since magnesium is primarily intracellular, serum mag-
conate 50 mg/kg IV or 10% calcium chloride nesium levels can be normal while total body magnesium
10 mg/kg IV transiently antagonize the effects of is severely depleted. Magnesium is a cofactor for many
hyperkalemia at excitable membranes. enzymatic reactions and therefore plays an important role
● Sodium polystyrene sulfonate in 20% sorbitol by mouth, in ATP mediated processes (N+–K+ ATPase) such as elec-
NG tube, or enema removes approximately 1 mEq/g trical membrane potentials, neurotransmitter release,
of K+, but simultaneously adds approximately 1.7 mEq
and smooth muscle contraction. Magnesium deficiency
of Na+/g.
● Hyperkalemia decreases the transmembrane electrical
predisposes to arrhythmias especially those arising from
potential and will arrest the heart in diastole. Intravenous QT and PR interval prolongation; and intravenous mag-
calcium administration preserves cardiac contractility nesium is the treatment for torsades de pointes.
and transiently antagonizes symptomatic hyperkalemia. Magnesium deficiency may also manifest as vertigo,
dysarthria, psychosis, weakness, tremor, paresthesias, and
seizures. Magnesium deficiency is extremely common
Hypokalemia and under-recognized. Losses are from the GI and renal
Hypokalemia is defined as a serum potassium concen- systems. Predisposing conditions include chronic alcohol
tration of less than 3.5 mEq/l and is due to either intracel- abuse, secretory diarrhea, diabetes mellitus, myocardial
lular potassium shift or total body potassium depletion infarction, and drug therapy (furosemide, aminoglyco-
(renal losses with diuresis, diarrhea). Urine potassium can sides, amphotericin, pentamidine, cyclosporine, digitalis).
help guide diagnosis. If urine potassium is less than 20 Gentamicin induces magnesuria. Alcoholics are particu-
mmol/l one should consider inadequate intake, diarrhea, larly likely to have magnesium depletion. In addition, mag-
biliary loss, or diuresis. If the urine potassium is greater nesium is a cofactor for thiamine action. There are no
than 20 mmol/l in a normotensive patient one should con- specific clinical manifestations of magnesium deficiency.
sider renal tubular acidosis, diabetic ketoacidosis. If the However, reactive CNS magnesium deficiency can
urine potassium is greater than 20 mmol/l in a hyperten- mimic a cerebrovascular accident (ataxia, dysarthria,
sive patient one should consider malignant hypertension seizures, obtundaton, and spasms).
or renal artery stenosis if the plasma renin activity is ele-
vated; otherwise one should consider mineralocorticoid
CLINICAL CAVEAT
use or Cushing’s syndrome. Clinical manifestations of
hypokalemia include muscle weakness, cardiac arrhyth- Magnesium Repletion
mias, cardiac U waves, flattened and inverted T waves, ● Magnesium repletion can be accomplished using
ileus, paresthesias, and prolongation of the QT interval. enteral or intravenous supplementation. Magnesium
sulfate delivers 8 mEq/g and may be given intra-
Severe hypokalemia can precipitate rhabdomyolysis.
venously over minutes to hours. A typical dose in a
Hypokalemia will also increase renal ammonia production
70 kg adult with moderate magnesium depletion
and worsen hepatic encephalopathy. Magnesium deple- would be in the range 2–4 g IV. Magnesium oxide
tion impairs potassium reabsorption across the renal delivers 20 mEq, 10 mmol, or 241 mg of elemental
tubules; therefore effective treatment of hypokalemia is magnesium per 400 mg tablet.
difficult in the setting of magnesium depletion. ● Magnesium is administered in obstetric patients in
large doses for severe eclampsia and pre-eclampsia
CLINICAL CAVEAT where the dose is titrated to diminished deep ten-
don reflexes (DTRs). DTRs are abolished above
Treatment of Hypokalemia
serum levels of 4 mEq/l; somnolence accompanies
● Potassium repletion can be accomplished using
levels of 7 mEq/l; and heart block and paralysis is
enteric or intravenous supplementation. Intravenous
likely at levels of 10 mEq/l or greater.
potassium repletion should never exceed 40 mEq/hour
in adults and administration of more than 10 mEq/hour
should be performed with telemetry monitoring.
● The average increase in serum potassium is Magnesium has also been used as an adjunct bron-
0.25 mmol/l per 20 mmol infused. chodilator in status asthmaticus. Magnesium accumula-
tion occurs in patients with impaired renal function and
66 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
supplementation should be with great care in these calcium administration in the presence of concomitant
patients. Hypermagnesemia also occurs with adrenal hypomagnesemia.
insufficiency, hyperparathyroidism, and lithium intoxi- Ionized calcium levels can decrease rapidly in the
cation. Clinical effects of hypermagnesemia include presence of pancreatitis, where fat necrosis binds cal-
diminished neuromuscular function and paralysis, cium in a process of saponification; and following mas-
vasodilation and hypotension, bradycardia, heart block, sive red cell transfusion where the anticoagulant citrate
respiratory depression, and coma. Hemolysis releases in transfused red blood cells binds plasma ionized cal-
magnesium from lysed erythrocytes. cium (especially with coexisting liver disease which
impairs citrate metabolism). Calcium is administered
intravenously as either 10% (100 mg/ml calcium salt) cal-
CLINICAL CAVEAT
cium chloride (0.1–0.2 ml/kg) or 10% calcium gluconate
Treatment of Elevated Magnesium (0.5–1.0 ml/kg). However, calcium chloride contains
● Neuromuscular and cardiac toxicity from hyper- three times as much elemental calcium (1.36 mEq/ml) as
magnesemia can be treated emergently but tran- calcium gluconate (0.46 mEq/ml). Ten milliliter amps
siently with calcium, 100–200 mg slow IV push. contain 272 mg compared to 90 mg of elemental cal-
● Forced diuresis will decrease serum magnesium in
cium, respectively. Intravenous calcium administration
patients with intact renal function.
can precipitate ventricular arrhythmias in patients receiv-
● Magnesium can be removed by dialysis
ing digoxin because calcium antagonizes potassium at
the cardiac muscle membrane. Calcium supplementa-
tion should be avoided in digoxin toxicity.
Calcium Hypercalcemia
Calcium is the most abundant electrolyte in the Hypercalcemia (>10.5 mmol/l) or ionized hypercal-
human body but 99% is bound in bone. Calcium is cemia (>1.3 mmol/l) is relatively rare, most commonly
mainly distributed in ECF where 50% is bound to plasma due to hyperparathyroidism, sarcoidosis, milk-alkali syn-
proteins. Albumin accounts for 80% of calcium binding drome, vitamin A or D intoxication, malignancy, thyro-
in plasma. Some 5–10% is chelated to sulfates and phos- toxicosis, or drugs (lithium, tamoxifen, thiazides).
phates. Calcium is important to blood clot formation, Hypercalcemia produces an osmotic diuresis resulting in
excitation–contraction coupling, neurotransmission, symptoms of polyuria and polydipsia. Clinical manifesta-
enzyme function, cell division and motility, and wound tions of hypercalcemia are nonspecific and include ileus,
healing. Only unbound, or ionized, plasma calcium is pancreatitis, nephrocalcinosis, confusion, and coma.
physiologically active. Electrocardiographic effects of hypercalcemia include
Normal total serum calcium ranges from 8.0 to 10.2 PR prolongation, QRS widening, ST shortening, and flat-
mg/dl or 2.2 to 2.5 mmol/l; and normal serum ionized tened T waves. Management of hypercalcemia is with
calcium ranges from 4.0 to 4.6 mg/dl or 1.0 to 1.5 mmol/l. saline infusion and diuretics to maintain a brisk diuresis.
Hypocalcemia Severe or symptomatic hypercalemia can be managed
Calcium must be corrected for plasma albumin levels. with calcitonin IM/SQ; hydrocortisone; pamidronate IV;
Corrected total Ca = measured total Ca + 0.8 × (4.0 − and mithramycin or plicamycin IV. Calcium salts are
albumin). The key clinical manifestations of hypo- deposited in tissues when a critical calcium–phosphate
calcemia are enhanced neuromuscular excitability and product is reached (>60). Administration of either salt in
reduced muscle contractility. Hypocalcemia is associ- the presence of high concentrations of the other must
ated with decreased parathormone (PTH) levels follow- be carried out with caution.
ing parathyroidectomy, tumor, or hemochromatosis.
Pseudohyoparathyroidism is end-organ unresponsive- Phosphate
ness to PTH and is often nephrogenic. Vitamin D defi- Phosphate is the most abundant intracellular anion
ciency due to inadequate dietary intake is rare. However, and is essential for energy storage and transport (ATP,
vitamin D deficiency due to malabsorption, hepatobil- cAMP, cGTP, CPK, etc.). Normal dietary phosphate
iary disease, renal disease, and alcoholism is a relatively accounts for 1 g/day. Most body phosphorus is in the
common cause of hypocalcemia. Classic but insensitive bony skeleton; the rest is bound in phospholipids and
clinical signs of hypocalcemia are Chvostek’s (facial phosphoproteins. The remaining 15% exists as inorganic
hyperreflexia) and Trousseau’s (carpopedal spasm) phosphorus which is primarily intracellular, mainly as
signs. Ionized hypocalcemia (<1.0 mmol/l) occurs in high-energy phosphates. Normal serum phosphate
the setting of alkalosis, magnesium depletion, renal ranges from 2.5 mg/dl (0.8 mmol/l) to 4.5 mg/dl (1.4
insufficiency, and sepsis, and with the use of medi- mmol/dl). Phosphorus is filtered at the glomerulus and
cations such as aminoglycosides, estrogen, dilantin, reabsorbed in the proximal tubules, regulated by
theophylline, and heparin. Hypocalcemia is refractory to PTH and vitamin D. Hypophosphatemia (<3 mg/dl) is
Fluid, Electrolyte, Blood, and Blood Product Management 67
common in hypermetabolic states (diabetic ketoacidosis, in pH. Pseudohypoxemia and pseudoacidosis can occur
alcohol withdrawal, refeeding syndrome, trauma, etc.). when increased oxygen consumption and CO2 production
However, even severe hypophosphatemia is usually occurs in the sample due to active metabolism in the set-
clinically silent. Phosphate depletion can also occur with ting of temperature, leukocytosis (>105/mm3), or throm-
medications such as aluminum- or calcium-containing bocytosis (>106/mm3). Pseudohypocarbia and false oxygen
antacids, sucralfate, diuretics, androgens, salicylates, PaO2 can occur in the setting of trapped air bubbles. Air
aminoglycoside and acetaminophen toxicity, and cisplatin bubbles can increase PO2 by >25 mmHg, but are unlikely
therapy. Clinical manifestations of hypophosphatemia to affect PCO2. The oxygen saturation of a blood gas spec-
may become evident with stress and include acute skele- imen is not measured but calculated from the PaO2 using a
tal myopathy, respiratory muscle dysfunction, cardiomy- normogram. The body temperature should be recorded at
opathy, decreased platelet adhesion and prolonged the time of ABG collection. Gas solubility decreases with
bleeding time, phagocytic impairment, and hemolysis. warming and “temperature correction” of PaO2 and PCO2
may be necessary. Venous blood gases have a higher PCO2
and lower PO2 than arterial blood. Venous blood gases may
CLINICAL CAVEAT be adequate indicators of acid–base and, when used with
Treatment of Hypophosphatemia oximetry, approximate arterial blood gases. In the ICU the
● Intravenous replacement therapy for hypophos- number of blood gas analyses correlates with the presence
phatemia is with either sodium (4.0 mEq/l Na) or or absence of an arterial cannula. Normal arterial pH varies
potassium (4.3 mEq/l K) phosphate. A dose of from 5.35 to 7.45. A pH less than 7.35 is a relative acidosis,
0.02–0.04 mmol/kg (15–30 mmol in a 70 kg patient) whereas a pH greater than 7.45 is a relative alkalosis.
over 1–4 hours is a typical starting dose. Phosphate
replacement should be slow and cautious in patients
with renal failure. Acidosis
● Enteral phosphate replacement with Neutra-Phos or Metabolic acidosis represents excess unbuffered H+
K-Phos is an alternative. ion concentration. Metabolic acidosis is usually partially
compensated by hyperventilation and a relative respira-
tory alkalosis. Bicarbonate is not measured during blood
PEARLS gas analysis; it is calculated from the pH and PCO2 using
a normogram derived from the Henderson–Hasselbach
● A decrease in plasma albumin affects primarily
equation. Directed automated determination of HCO3−
protein-bound calcium. Measured serum calcium is
(PCO2) is standard with electrolyte panels using the
low in hypoalbuminemia but the physiologically
active ionized calcium fragment may be unaffected. sequential multichannel analyzer (SMA). The bicarbonate
● Calcium chelates phosphorus; caution must be used (carbonic acid) buffer is quantitatively the most important
when administering either when the concentration plasma buffering system. In metabolic acidosis bicarbonate
of the other is high. is consumed and depleted. Bicarbonate compensation
occurs over 24–38 hours. Below a pH of 7.15 the con-
formation of catecholamine receptors is altered and
Hyperphosphatemia (>4.5 mg/dl) is common in renal there is a decreased responsiveness to endogenous and
failure and widespread tissue or cell lysis syndrome exogenous catecholamines. Acidemia also decreases
(tumor lysis, rhabdomyolysis). Calcium acetate, sucral- conduction in excitable tissues. Hyperkalemia in acido-
fate, or hemodialysis will lower serum phosphate. sis increases cardiac depression and arrhythmias.
Acidosis in the setting of excessive lactate production
(Type A) usually occurs in the setting of anaerobic gly-
ACID–BASE PHYSIOLOGY colysis in shock. Excess lactate production suggests an
imbalance in oxygen delivery and extraction (DO2 < VO2).
In general, mild acidosis is better tolerated physiologi- Type B lactic acidosis is differentiated into subtypes:
cally than alkalosis, because of improved oxygen kinetics B1 is due to underlying diseases such as liver disease,
in the setting of acidosis. With the exception of the malignancy, pheochromocytoma, and, most importantly,
pulmonary vasculature, all vascular beds vasodilate in thiamine deficiency; B2 is associated with medications
response to acidosis. Acidosis causes pulmonary vaso- or toxins such as biguanides, ethanol, methanol, salicylates,
constriction and bronchodilation. Acidosis increases acetaminophen, or propylene glycol; B3 occurs with
catecholamine release but severe acidosis impairs cate- inborn errors of metabolism such as glucose-6-phosphate
cholamine responsiveness. Proper arterial blood collection dehydrogenase deficiency, pyruvate dehydrogenase
technique is essential. If the specimen is not placed on deficiency, or fructose-1,6-diphosphatase deficiency.
ice PaCO2 rises 3–10 mmHg/hour with a concomitant fall The anion gap is given by (Na+ + K+) − (HCO3− + Cl−).
68 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
normal (1 gEq/l). NS is termed “normal” because it is iso- the vascular to the ISF space, diminishing volume expan-
tonic (actually slightly hypertonic at 308 mOsm/l) with sion and contributing to “third space” losses and diffuse
human ECF. edema. The intravascular half-life of colloids depends on
NS is acidic and unbuffered. Accumulation of chloride elimination and metabolism, molecular size, and the
with NS administration results in hyperchloremic meta- presence of capillary leak. Six percent Hetastarch in 0.9
bolic acidosis. Lactated Ringer’s solution, or Hartman’s normal saline (HespanR) is implicated in coagulopathy
solution, is a balanced-salt solution with a composition (alteration of platelet rheology and adhesion) at volumes
closely approximating human ECF. Under normal condi- exceeding 1.5 liters in a 70 kg patient and in hyper-
tions the infused lactate is extracted (primarily in the chloremic acidosis due to the chloride load inherent in
liver) and converted to bicarbonate and water. Solutions saline. Six percent Hetastarch in Ringer’s lactate
containing dextrose, acetate, or lactate (RL, D5W, (HextendR) is not presently implicated in either coagu-
D51/2NS, D51/4NS, Normosol, etc.) add to free water lopathy or hyperchloremic acidosis (Table 6-5).
load. Free water is contraindicated in head injury patients
and hyponatremia. Hypertonic saline (1.8%, 3%, or 5%)
expands intravascular volume transiently primarily
through its osmotic effects, drawing fluid from the inter-
BLOOD AND BLOOD PRODUCTS
stitial and intracellular spaces (Table 6-4).
Red Cell Transfusion
Anemia is frequently diagnosed in hospitalized patients,
COLLOIDS especially those with critical illness. Whereas acute ane-
mia, most commonly due to blood loss, may be life-threat-
Colloids maintain or increase oncotic pressure (COP). ening, anemia of gradual onset is usually well-tolerated
Normal plasma COP is 25–30 mmHg. COP cannot be due to cardiovascular compensation (increased cardiac
inferred from plasma protein concentrations – it must be output). Causes of anemia which are often overlooked
measured. Albumin accounts for most of the COP of include hemodilution, phlebotomy, or drug-induced
plasma. However, albumin also accounts for binding of hemolysis. The primary function of red blood cell transfu-
electrolytes, drugs, and other molecules, free radical sion is to maintain oxygen carrying capacity. Red blood
scavenging, toxin binding, and inhibition of platelet cell transfusion should never be used solely for intravascu-
aggregation. If plasma COP remains above 20 mmHg it is lar volume expansion. Although the transfusion of red
likely that plasma albumin concentration, in itself, is of blood cells to maintain an arbitary hematocrit level has
no significance in transmembrane fluid flux (Box 6-3). been a mainstay of ICU therapy, the practice of routine red
In the absence of pathologic capillary leak syndrome, blood cell transfusion is being increasingly challenged.
edema is favored by increased intravascular hydrostatic Transfusions have been shown to impair immune func-
pressure, increased interstitial oncotic pressure, or tion, to increase the risk of nosocomial infectious compli-
decreased intravascular oncotic pressure. Tissue edema cations, and also to promote the spread of tumor emboli
increases the diffusion distance for oxygen and can lead during cancer surgery. Moreover, critically ill patients are
to widespread relative cellular hypoxia. at risk of erythropoietin deficiency. Therefore, alternatives
Volume for volume, colloids increase threefold the to transfusion such as therapeutic erythropoietin supple-
effect of crystalloids on preload. In the setting of inflam- mentation, vitamin and mineral supplementation, and
mation “capillary leak” may allow colloids to leak from appropriate caloric intake are important adjuncts in both
acute and chronic care.
Patients at risk for hemorrhage should have at least
one catheter placed into a large vein. The Poisseuille–
Box 6-3 Starling–Landis Equation Hagen formula defines flow through catheters. Flow is
faster with short, wide-bore catheters, and with fluids of
The Starling–Landis equation defines transcapillary fluid low viscosity. As much as 750 cm3 of acute blood loss
flux: can be tolerated without hemodynamic derangements in
F = k[(PH − PISF) − δ (COPV − COPISF)] a typical adult. The first sign of acute hemorrhage is a
narrowing of pulse pressure which occurs with a Class
where k is the ultrafiltration coefficient of fluid; PH is
II (750–1000 cm3) hemorrhage. Tachycardia does not
the intravascular hydrostatic pressure; PISF is the
occur until late in Class II hemorrhage. Patients with
hydrostatic pressure of intravascular fluid; δ is the
reflection coefficient; COPV is the intravascular oncotic cardiomyopathy, medications that decrease or limit heart
pressure; and COPISF is the oncotic pressure of the rate (beta-blockers, calcium channel blockers, digitalis),
interstitial fluid. or patients with dysautonomia due to diabetes mellitus
may not show tachycardia despite severe hypovolemia.
70
saline
Ringer’s 130 109 4 0 28 0 0 3 0 6.7 273 9
lactate
D – 5 LR 130 109 4 50 28 0 0 3 0 6.7 525 170
D – 5% 0 0 0 50 0 0 0 0 0 5.0 253 170
water
D – 10% 0 0 0 100 0 0 0 0 0 4.9 505 340
water
D – 5% 77 77 0 50 0 0 0 0 0 4.9 407 170
1/2 N
saline
Normosol 140 98 5 0 0 23 27 0 3 7.4 295 0
3% NS 513 513 1025
5% NS 855 855 1710
Standard 47 35 23 100 0 0 36 12.5 12.5 880*
PPN
Standard 35 53 40 250 0 0 25 12.5 12.5 1825*
TPN
and is a pulmonary manifestation of systemic inflamma- Rh antigens. DDAVP (Desmopressin) 0.3–0.4 μg/kg tran-
tion in the setting of large-volume transfusions. siently improves platelet function in the setting of von
Infectious complications of transfusion persist despite Willebrand’s disease, uremia, aspirin ingestion, or post-
testing and include transmission of HIV, hepatitis A–E, cardiopulmonary bypass.
cytomegalovirus (CMV), West Nile virus, and prions.
Transfusions must be administered through filters which
filter microaggregates of fibrin, platelets, and cells rang- Fresh Frozen Plasma
ing in size from 20 to 170 μm. Hypothermia can compli- Fresh frozen plasma (FFP) contains antithrombin III
cate rapid infusion of unwarmed PRBCs stored at 4°C. and can be used to treat heparin resistance. A corollary
Acute hemolytic reactions have an incidence of 1/6000 is that FFP can increase the anticoagulant effect of
and are fatal in about 1/100,000 transfusions. The most heparin. The main indication for FFP is the rapid rever-
common cause of transfusion reaction is clerical error sal of coumadin-induced anticoagulation, replacement of
and therefore autologous blood is not significantly safer vitamin K-dependent coagulation factors (cirrhosis). FFP
than homologous blood transfusion. Acute hemolytic is indicated for replacement of factors II, V, VII, VIII, IX,
transfusion reactions are usually due to ABO erythrocyte X, XI, and XIII, and von Willebrand’s factor. Each milli-
surface antigen incompatibility between donor and recip- liter of transfused plasma contains only about 1 unit of
ient red cells. Acute hemolytic transfusion reactions are each factor, necessitating large volumes of plasma for
potentially life threatening. Morbidity is related to the vol- effective factor replacement. Allergic reactions to FFP
ume of cells infused. Recipient blood should be exam- are common because of platelets and leukocytes. FFP
ined for xanthochromia and free hemoglobin. A positive should be compatible with the recipient’s red blood
direct Coomb’s test confirms a hemolytic reaction; how- cells, but need not be compatible with the recipient’s
ever, a false negative direct Coomb’s test is seen when the plasma. FFP is not indicated for volume expansion and
majority of donor cells are already lysed. Serum LDH is should not be used as a colloid substitute.
usually elevated and serum haptoglobin decreased.
Cryoprecipitate
Platelet Transfusion Cryoprecipitate is a plasma concentrate pooled from
Thrombocytopenia is variably defined as a platelet multiple donors and contains primarily factor VIII and
count less than 100,000–150,000/mm3. In the absence fibrinogen. A unit of cryoprecipitate contains about 100
of risk factors, platelet counts as low as 5000/mm3 may units of factor VIII and 250 mg of fibrinogen. A typical
be tolerated without bleeding. Platelet counts below dose of cryoprecipitate is 8–10 units, which increases
5000/mm3 are associated with a high risk of sponta- factor VIII levels by an average of 2%. A thromboelasto-
neous hemorrhage. Platelet counts ≥ 50,000/mm3 are graph is a useful guide to platelet, FFP, or cryoprecipi-
sufficient to provide hemostasis for surgical procedures, tate replacement.
assuming the platelets are functional (absence of uremia,
NSAID, or aspirin therapy). Causes of thrombocytopenia SELECTED READING
include sepsis, disseminated intravascular coagulation,
thrombotic thrombocytopenic purpura, and heparin- Adrogue HJ, Madias NE: Management of life-threatening
associated thrombocytopenia (HAT). Thrombocytopenia acid–base disorders. N Engl J Med 338:26–34; 107–111, 1998.
may be the earliest hematologic abnormality in sepsis. Bugg NC, Jones JA: Hyposphosphatemia. Pathophysiology and
Dilutional thrombocytopenia can occur with large fluid management in the intensive care unit. Anaesthesia
volume or multiple packed cell infusions. The major 3:895–902, 1998.
complication of HAT is thrombosis, not bleeding. Fawcett WJ, Haxby EJ, Male DA: Magnesium: physiology and
Platelet dysfunction is most commonly due to renal pharmacology. Br J Anaesth 83:302–320, 1999.
insufficiency, cardiopulmonary bypass, or medications. Gennari FJ: Hypokalemia. N Engl J Med 339:451, 1998.
Platelets are stored at room temperature. Hypothermia Mizock BA, Falk JL: Lactic acidosis in critical illness. Crit Care
interferes with platelet thromboxane synthesis and clot- Med 20:80–92, 1992.
ting. Platelets are normally pooled from multiple donors, Palevsky PM: Hypernatremia. Semin Nephrol 18:20–30, 1998.
increasing the potential for infectious complications. Wagner BKJ, D’Amelio LF: Pharmacologic and clinical consid-
Each unit of platelets transfused is expected to increase erations in selecting crystalloid, colloidal, and oxygen-
the platelet count by 5000–10,000/mm3, unless destruc- carrying resuscitation fluids. Part I. Clin Pharm
tion or sequestration is ongoing. Platelets are usually 12:335–346, 1993.
administered as six-packs, which raise the platelet count Wagner BKJ, D’Amelio LF: Pharmacologic and clinical consid-
by 25,000–50,000/mm3. ABO compatible platelets are erations in selecting crystalloid, colloidal, and oxygen-
less likely to form antiplatelet antibodies and therefore carrying resuscitation fluids. Part II. Clin Pharm
survive longer post-transfusion. Platelets do not contain 12:415–428, 1993.
7
CHAPTER Arrhythmia
Management
SANJEEV V. CHHANGANI, M.D., M.B.A.
73
74 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
and drugs used in anesthesia and intensive care. In addi- and outward (potassium) currents, phase 3 results from
tion, the perioperative and critical care physician should the delayed activation of potassium channels, and in
be familiar with implantable devices used in the treat- some pacemaker cells (sinoatrial and atrioventricular)
ment of arrhythmias. This review summarizes recent phase 4 results in slow spontaneous depolarization lead-
advances in our understanding of arrhythmia mecha- ing to another action potential. This explains the auto-
nisms and management. maticity of the pacemaker cells. Phases 0 to 2 represent
depolarization and phase 3 repolarization of the car-
diac myocyes. The ECG records the electrical activity of
ELECTROPHYSIOLOGIC MECHANISMS the heart that triggers heart muscle to contract (Figure 7-2).
OF ARRHYTHMIA The sinoatrial (S-A) node signals the beginning of the
cardiac cycle with the P wave on the ECG due to atrial
Knowledge of the cardiac action potential is a pre- depolarization. Atrial repolarization is usually too small
requisite for a better understanding of the pathophysio- in amplitude to be detected on the ECG. Next, the elec-
logic mechanisms underlying arrhythmia formation. trical impulse travels through the atrioventricular (A-V)
The cardiac action potential represents the rapid flux node to reach the ventricular muscle cells. The QRS
of ions across the cardiomyocytes producing a wave- complex represents ventricular depolarization, and the
front of excitation. An electrocardiogram (ECG) is a ST-T complex represents ventricular repolarization. The
recording of the electrical activity of the heart from sur- J point is the junction between the end of the QRS com-
face electrodes. Figure 7-1 summarizes the action poten- plex and the beginning of the ST segment. The rapid
tial and ECG. The ventricular cell at baseline maintains a upstroke (phase 0) of the action potential corresponds
resting potential of −80 to −90 mV (polarized state) as a to the onset of QRS. The plateau (phase 2) corresponds
result of a high level of potassium conductance across to the isoelectric ST segment, and active repolarization
the cell membrane. The action potential is divided into (phase 3) to the beginning of the T wave.
four phases depending upon the channel activation and There are three fundamental electrophysiologic
changes in membrane potential. Phase 0 is the result of mechanisms that are responsible for arrhythmia formation.
activation of fast sodium channels producing an over-
shoot in membrane potential, phase 1 results from the
transient outward potassium currents and results in a Reentry
slight fall in membrane potential, phase 2 (plateau) Reentry is the most common mechanism underlying
results from a balance of inward (sodium and calcium) arrhythmia formation. Three conditions must be met for
the reentry mechanism to result in an arrhythmia: the
presence of a central area of inexcitable tissue separat-
+25 ing two pathways for conduction, unidirectional block
Transmembrane potential (mV)
1 2
in one of the two pathways, and slow conduction per-
0
mitting delay and recovery of excitability in the previ-
-25 ously blocked area. Pathologic substrate, as in the tissue
3 surrounding an infarct zone, or altered milieu, as in func-
-50
0 EAD tional alterations in conduction secondary to electrolyte
-75 DAD disturbance, or ischemia can predispose to reentry-
4 induced arrhythmia.
-100
Na Ca K Na K
Influx Influx Efflux Efflux Influx R
QRS P
J
T
ST ECG
Q S RRP
PR
Figure 7-1 Phases of ventricular action potential and ECG. ARP
Phase 0, overshoot is caused by rapid inward Na current; Phase 1,
transient potassium efflux; phase 2 (plateau), slow inward Ca cur-
rent; phase 3 (repolarization), outward K current; phase 4, resting
potential maintained by Na–K–ATPase pump. Specialized conduc- QT Interval
tion system tissue has spontaneous depolarization during phase 4. Figure 7-2 ECG cardiac cycle. ARP, absolute refractory period;
EAD, early after-depolarization; DAD, delayed after-depolarization. RRP, relative refractory period; J, J-point.
Arrhythmia Management 75
cause arrhythmias either by themselves or acting in con- noncardiac QT interval-prolonging drugs. These inter-
cert with the two risk factors discussed above (structural actions can be pharmacodynamic (both drugs affect
heart disease and altered milieu). cardiac electrophysiology), pharmacokinetic (one drug
affects clearance of the other), or mixed in nature.
Catecholamines Therefore, combination of QT interval-prolonging drugs
Through stimulation of β-adrenergic receptors, should be avoided.
endogenous (sympathetic activation) or exogenous cate-
cholamines can result in enhanced automaticity or trig- Drug Withdrawal
gered activity. Reentry may also be facilitated in the Beta-blockers are commonly used in the prophylaxis
presence of ischemia. and treatment of arrhythmias in the high-risk patient.
Beta-blocker withdrawal has been associated with post-
Volatile Anesthetics operative supraventricular arrhythmias. A state of increased
There is increasing evidence that volatile anesthetics catecholamine effect occurs because of chronic β-blocker
have potent electrophysiologic influences on arrhythmias associated up-regulation (higher density) of β-adrenergic
due to both altered impulse initiation and conduction. receptors.
Depression of inward Ca2+ currents by the volatile anes-
thetics contributes to largely antiarrhythmic actions on
mechanisms generating abnormal impulses as a result CLASSIFICATION, DIAGNOSIS, AND
of intracellular Ca2+ “overload” resulting from cate- MANAGEMENT OF ARRHYTHMIAS
cholamine exposure, digitalis intoxication, and ischemia.
On the other hand, the actions of volatile anesthetics in Cardiac arrhythmias may be simply classified as
combination with catecholamines depressing conduc- (1) those resulting in cardiac arrest, (2) bradyarrhythmias,
tion and altering refractoriness of the myocardium may (3) ventricular arrhythmias, and (4) supraventricular
potentially facilitate the induction of reentrant arrhyth- arrhythmias. This classification places an emphasis on
mias. The adverse interaction between volatile anesthet- the urgency of diagnosis and management. Table 7-3
ics and catecholamines remains a clinically relevant summarizes the classification of cardiac arrhythmias.
problem.
ECG criteria (Figure 7-3). There are no recognizable pharmacologic therapy is considered. Current pharma-
P, QRS, or T waves. The rate is difficult to determine. cologic therapy consists of intravenous epinephrine 1 mg
The rhythm is indeterminate with patterns of upstrokes every 3 to 5 minutes as an adrenergic stimulant to
and downstrokes. Ventricular fibrillation (VF) can be fine improve perfusion pressure of vital organs. Vasopressin,
(amplitude 1 to 5 mm) or coarse (amplitude 10 to 15 mm). administered as 40 units intravenous push single dose,
Clinical features. The patient becomes unconscious may be used as an alternative to epinephrine and is
without pulse. Respirations become agonal and apnea associated with less risk of postresuscitation tachy-
quickly ensues. This can result in sudden death. arrhythmias. Amiodarone (300 mg intravenous push) is
Etiology. Common etiologies of VF/pulseless ventric- considered next to prevent refibrillation after a shock
ular tachycardia (VT) include acute myocardial infarction causes defibrillation. If VF/VT recurs, administration of a
leading to areas of ischemic myocardium, untreated VT, second dose of Amiodarone 150 mg IV should be con-
primary or secondary QT interval prolongation, PVCs sidered, with a maximum cumulative dose of 2.2 g over
with R on T phenomenon, electrocution, and hypoxemia. 24 hours. Lidocaine and procainamide are considered of
Therapy. Early defibrillation (asynchronous DC coun- indeterminate class benefit for persistent VF/VT.
tershock) is the hallmark of treatment. Time to defibril- Correction of hypomagnesemia and acidosis is consid-
lation is the most important determinant of survival from ered using magnesium and sodium bicarbonate in pro-
cardiac arrest. Probability of successful resuscitation longed arrest situations.
declines by 2% to 10% per minute from the onset of
symptoms. In this respect the use of automatic external Pulseless Electrical Activity
defibrillators (AEDs) has gained popularity in a variety Pathophysiology. In this condition there is electrical
of settings, public and healthcare alike. After a sequence activity in the form of cardiac conduction impulses, but
of three rapid defibrillation shocks (200, 220, 360 J), this fails to produce myocardial contraction or ejection.
ECG criteria (Figure 7-4). There is organized electrical
activity with narrow (QRS < 0.10 ms) or wide (> 0.10 ms)
waves, and at a fast or slow heart rate.
Clinical features. Clinical manifestations are the same
as those of pulseless VT/VF.
Etiologies. Common causes of pulseless electrical
activity are often reversible and can be grouped under
“five H’s”: hypovolemia, hypoxia, acidosis (increased
hydrogen ion), hyperkalemia/hypokalemia, hypothermia;
Figure 7-3 Ventricular fibrillation. and “five T’s”: tablets (drug overdose, ingestions),
80 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Supraventricular Arrhythmias
Atrial Fibrillation/Atrial Flutter
Atrial fibrillation (AF) occurs in 0.5–1% of the general
population, especially in patients older than 60 years.
In postcardiac surgery patients AF is more frequent
(10–65%). The frequency of AF in noncardiac surgery
patients falls between the above two groups (2–10%).
AF is the most common arrhythmia in the surgical inten-
sive care unit (cardiac and noncardiac). Five independ-
ent risk factors were identified in a recent study of AF in
Figure 7-4 Pulseless electrical activity (PEA). Organized
rhythm without detectable pulse. surgical intensive care units. These were advanced age,
withdrawal of calcium channel blockers, blunt thoracic
trauma, shock, and use of a pulmonary artery catheter.
tamponade (cardiac), tension pneumothorax, thrombus Pathophysiology. AF is an example of reentry tachy-
(coronary), thromboembolism (pulmonary). arrhythmia. In AF the atria contract in a chaotic fashion
Therapy. Identification and treatment of reversible and impulses travel in a random pathway through the
causes is the mainstay of therapy. After establishment of atria. The multiple wavelet theory is most common in
airway, ventilation, and basic CPR, intravenous epineph- explaining the erratic electrical conduction occurring in
rine 1 mg or atropine 1 mg can be administered if heart most AF. Alterations in the atrial electrophysiologic con-
rate is < 60 beats per minute. ditions, such as decreased repolarization time, decreased
refractory periods, and variable refractory dispersion,
Asystole are favorable conditions to stimulate and maintain AF.
Pathophysiology. It usually represents a terminal These conditions promote development of multiple
rhythm. reentry circuits that perpetuate throughout the atria
ECG criteria (Figure 7-5). Classically asystole pres- and allow AF to sustain. Atrial flutter involves impulses
ents as a flat line. Asystole can be verified by checking traveling in a circular course around the atria.
the lead and cable connection, increasing monitor gain, ECG criteria (Figure 7-6). The classic pattern of AF is
and changing leads. There is no ventricular activity or at an irregular rhythm with varying RR interval. P wave and
a rate of <6 beats per minute. Occasionally P waves are PR interval is not defined. In atrial flutter a “sawtooth”
seen, but without R waves. pattern is classic. Unlike AF, ECG rhythm and ventricular
Clinical features. It presents as cardiac arrest with no response is regular in atrial flutter with 2 to 1 or 3 to 1
pulse or blood pressure, and agonal respirations. ratio depending upon A-V node conduction block.
Etiology. Usually indicates end of life. Reversible Clinical features. Signs and symptoms depend upon
causes such as the five H’s and five T’s should be sought the rate of ventricular response, with dyspnea, chest pain,
and corrected. Asystole can also be seen after massive acute pulmonary edema, congestive heart failure, and
electrical shock or postdefibrillatory shock.
Therapy. After establishment of an airway, ventilation,
and basic CPR, intravenous epinephrine 1 mg (every 3 to
5 minutes) and atropine 1 mg (total 2 mg) is adminis-
tered. If considered, transcutaneous pacing is performed
immediately. With respect to hospital admissions and
discharge, a recent study found vasopressin (40 U) to be
superior to epinephrine in patients with asystole. A
B
Figure 7-5 Asystole. Figure 7-6 Atrial fibrillation (A) and atrial flutter (B).
Arrhythmia Management 81
altered consciousness often occurring with rapid ven- The rate-controlling drugs are A-V nodal blockers, which
tricular response. Loss of “atrial kick” may result in a act by slowing down the rate. These include beta-blockers,
drop in cardiac output and blood pressure in patients calcium channel blockers, and digoxin. These drugs
with ventricular hypertrophy and aortic stenosis. should be avoided in patients with AF in association with
Etiology. Common etiologies of atrial flutter/fibrilla- Wolff–Parkinson–White (WPW) syndrome. Pharmacologic
tion include hypoxia (acute pulmonary embolism, agents used for heart rate control in AF are shown in
chronic obstructive pulmonary disease), enlargement of Table 7-5.
atria (mitral or tricuspid valve disease, fluid overload), Anticoagulation
acute coronary syndromes, hyperthyroidism, and drugs Patients with AF lasting longer than two days or of
such as digoxin and quinidine. unknown or intermittent duration should be anticoagu-
Therapy. The goals of AF/atrial flutter management lated with a therapeutic international normalized ratio
are hemodynamic stabilization, restoration and mainte- (INR) of 2–3 for at least 2–3 weeks before and after
nance of sinus rhythm, and prevention of thrombo- cardioversion. Screening for left atrial thrombus by
embolism. The therapeutic decisions are based on four echocardiography is an acceptable alternative to routine
factors: hemodynamic stability, cardiac function, presence pre-cardioversion anticoagulation. The risk of thrombo-
of pre-excitation on ECG, and duration (two days or more). embolic complications is higher in patients older than
Cardioversion 65 years, with valvular heart disease, history of congestive
Electrical or pharmacologic cardioversion must be heart failure, enlarged atrium, left ventricular dysfunction,
considered in patients with AF that presents with rapid and myocardial infarction.
ventricular rate with hemodynamic compromise. Early
cardioversion increases both the success of cardio- Wolff–Parkinson–White Syndrome
version and reduces the rate of recurrence, as well as the Pathophysiology. A prototypical pre-excitation syn-
need for anticoagulation. Current guidelines state that drome, WPW syndrome consists of an extra electrical
patients with AF of less than 2 days’ duration can be connection (accessory pathway) between the atria and
cardioverted without anticoagulation. Direct current the ventricles that allows the atrial impulse to bypass the
cardioversion usually is performed under sedation to A-V node. The majority of arrhythmias associated with
minimize patient discomfort. Adequate oxygenation WPW syndrome are reciprocating tachycardias which
and ventilation must be ensured during the procedure. may be narrow complex or wide complex.
A standard defibrillator is used to deliver a synchronized ECG criteria (Figure 7-7). When the accessory path-
shock at energies ranging from 100 to 300 J. The shock ways conduct impulses in an antegrade direction, there
electrode position can be either anterior–anterior (right is a fusion of activation of the ventricles by the bypass
sternal border and left lateral chest wall) or anterior– tract and the A-V nodal His-Purkinje system. This is rep-
posterior (precordial and interscapular). Atrial flutter resented on the ECG by a short PR interval (<120 ms) and
requires a lower energy for cardioversion. Newer defib- slurring of the initial component of the QRS complex
rillators with energy delivered in the form of biphasic (delta wave) giving it a widened appearance (>120 ms).
waveforms require less energy and provide greater suc- Secondary ST-T wave changes generally are directed
cess with cardioversion. Several drugs, including ibutilide, opposite to the major delta and QRS vector.
Amiodarone, procainamide, flecainide and propafenone, Clinical features. Patients with WPW syndrome may
have been used in the pharmacologic cardioversion of remain completely asymptomatic. Tachycardia may present
AF or atrial flutter. The caveats in the pharmacologic as palpitation, dyspnea, chest pain, or congestive heart fail-
cardioversion of AF include avoiding multiple QT- ure (CHF). Hereditary and male predisposition is common.
prolonging drugs, close watch for torsades de pointes, Etiology. The accessory pathway in WPW syndrome
and administration of magnesium. is a congenital malformation.
Therapy. Treatment of WPW syndrome is based on
the presence of hemodynamic instability, cardiac func-
CLINICAL CAVEAT tion impairment, or duration of AF with WPW syndrome.
In pharmacologic cardioversion of atrial fibrillation/ AF with rapid ventricular response is the life-threatening
atrial flutter: avoid multiple QT-prolonging drugs, arrhythmia in the patient with WPW syndrome and
watch for torsades de pointes, and give magnesium. should be treated with electric cardioversion. In the
patient with a normal heart the choice of antiarrhythmic
drugs include Amiodarone, flecainide, procainamide,
Rate Control propafenone, or sotalol. In the patient with impaired car-
For patients with AF or atrial flutter who present diac function cardioversion or Amiodarone can be used.
with rapid ventricular rate and stable condition, rate Anticoagulation is required for AF with WPW syndrome
control can be achieved using pharmacologic means. lasting more than two days.
82 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Table 7-5 Pharmacologic Agents for Heart Rate Control in Atrial Fibrillation
Loading
Drug Dose Infusion Onset Side Effects Comment
Diltiazem 0.25 mg/kg IV 5–15 mg/hour 2–7 minutes Hypotension, May be considered in
over 5–10 minutes heart block patients with low EF
Esmolol 0.5 mg/kg IV 0.05–0.2 mg/kg/ 2 minutes Hypotension, Caution in patients with
over 5–10 minutes minute heart block, asthma, low EF
bradycardia, CHF
Metoprolol 2.5–5 mg IV Not 5 minutes Hypotension, Well tolerated in patients
bolus over recommended heart block, with normal EF and
2 minutes; repeat wheezing, no history of asthma or
up to 4 doses bradycardia, CHF COPD
Multifocal Atrial Tachycardia (diltiazem) and Amiodarone are effective. Direct current
Pathophysiology. Mutifocal atrial tachycardia (MAT) cardioversion is not effective in the treatment of MAT.
results from areas of increased automaticity arising irreg-
ularly and rapidly in different areas of the atrium. Paroxysmal Supraventricular Tachycardia
ECG criteria (Figure 7-8A). Heart rate typically ranges Pathophysiology. Paroxysmal supraventricular tachy-
from 120 to 130 beats/minute. The rhythm is usually cardia (PSVT) is another example of reentry-mediated
irregular. There are three or more different morpholo- tachyarrhythmia. In patients with PSVT impulses arise
gies of P waves and PR interval is variable. QRS complex and perpetuate repeatedly in the A-V node because of
is usually narrow. areas of unidirectional block in the Purkinje fibers.
Etiology. The common causes of MAT include
chronic obstructive pulmonary disease (COPD), digoxin
toxicity, and acute coronary syndrome.
Therapy. Adenosine or vagal stimulation may be help-
ful if ECG diagnosis is unclear. In patients with preserved
heart function, beta-blockers can be used. In patients
at risk for wheezing (COPD, asthma) or in patients with
impaired heart function, calcium channel blockers
A
B
Figure 7-8 (A) Onset of supraventricular tachycardia (arrow).
Figure 7-7 Wolff–Parkinson–White (WPW) syndrome. Arrows (B) Mutlifocal atrial tachycardia (MAT). Arrows indicate multiple
indicate delta waves. P wave morphologies.
Arrhythmia Management 83
ECG criteria (Figure 7-8B). The heart rate varies ECG criteria (Figure 7-9A). Ventricular rate is typi-
between 150 and 250 beats/minute and the rhythm is cally 120–250 beats/minute, and the rhythm is regular
regular. P waves are absent or buried in T waves. QRS without atrial activity. QRS complexes are wide and
complex is usually narrow. “bizarre” (>0.12 ms). The presence of three or more
Clinical features. Palpitation, anxiety, low exercise PVCs qualifies as VT. If the duration is <30 seconds, it is
tolerance, dyspnea, and light-headedness are common nonsustained VT.
presenting features of PSVT. Clinical features. Monomorphic VT can be asympto-
Etiology. Many patients with PSVT have accessory matic. Symptoms of decreased cardiac output, such as
conduction pathway. Factors that are known to precipi- orthostasis, hypotension, or syncope, are present. If left
tate PSVT include caffeine, hypoxia, smoking, stress, untreated it can deteriorate into VF or unstable VT.
anxiety, and sleep deprivation. Etiology. Acute myocardial ischemia or infarction, occur-
Therapy. Vagal maneuver or adenosine may help rence of PVC during the relative refractory period (R-on-T
differentiate between PSVT and AF. DC cardioversion phenomenon), cardiomyopathy, or QT interval-prolonging
should be considered in the hemodynamically unstable drugs are some of the causes of monomorphic VT.
patient. The patient with preserved ventricular function Therapy. In patients with normal ventricular function,
will tolerate A-V nodal blockade using beta-blockers, cal- drugs like procainamide, lidocaine, sotatol, or amiodarone
cium channel blockers, procainamide, or digoxin. In the can be used. Lidocaine, amiodarone, or DC cardio-
patient with impaired ventricular function Amiodarone, version are recommended in patients with impaired ven-
diltiazem, or digoxin may be a better choice. tricular function. Electrolyte abnormalities (hypokalemia
and hypomagnesemia) must be corrected.
Junctional Tachycardia
Pathophysiology. This is an example of tachyarrythmia Polymorphic Ventricular Tachycardia
as a result of enhanced automatic impulse formation in Pathophysiology. Polymorphic VT also results from
the A-V node. Both antegrade and retrograde transmis- reentry phenomenon, with multiple areas of ventricle
sion of impulses occur. serving as the source of ectopic impulse formation.
ECG criteria. The rhythm is regular at a rate of ECG criteria (Figure 7-9B). The ventricular rate is
100–180 beats/minute. P waves are usually absent or typically 120–250 beats/minute, and the rhythm is regular.
inverted. QRS complexes are narrow in the absence of P waves and PR interval are not seen. QRS complexes
ventricular conduction delay. show marked variation and inconsistency. QT interval
Clinical features. CHF may occur as a result of loss of is classically prolonged in patients with Torsades de
sinus (atrial) “kick.” Symptoms of unstable tachycardia, pointes.
dyspnea, chest pain, or light-headedness may occur. Clinical features. The majority of patients show
Etiology. Acute coronary syndrome or digoxin toxicity symptoms of decreased cardiac output. It tends to dete-
are common causes of junctional tachycardia. riorate rapidly into VF.
Therapy. DC cardioversion is usually not recom-
mended. Beta-blockers, calcium channel blockers, or
Amiodarone have been used with success.
Ventricular Arrhythmias
Ventricular arrhythmias are classified as benign or
malignant based upon duration, absence or presence of
hemodynamic consequences, or significant structural
heart disease. Premature ventricular contractions (PVCs)
and nonsustained ventricular tachycardia rarely require
therapy in the absence of symptoms or structural heart A
disease.
used and provides several advantages over unipolar An example of a perioperative guide for patients with
leads. They are less susceptible to interference by electro- PPMs or ICDs is shown in Figure 7-11.
magnetic current and skeletal myopotential, thereby Use of a Magnet
there is less risk of inhibition by extraneous signals. Contrary to the traditional belief, application of a
A dual-chamber PPM (A-V) with rate-adaptive features magnet does not “turn-off” a PPM, but it allows the
allows preservation of A-V synchrony and “atrial kick,” pacemaker circuitry to be switched to asynchronous
and an increase in the heart rate in response to exercise. mode and reveal remaining battery life and pacing
threshold safety factors. At the same time, not all pace-
makers switch to asynchronous mode when a magnet is
Implantable Cardioverter Defibrillator placed on the generator. However, the response of an
Indications for an ICD are rapidly expanding. The ICD ICD to an externally applied magnet is different. ICDs
is indicated in patients with a known history of ventricular will be prevented from delivering a shock when a mag-
arrhythmias or those at high risk for ventricular arrhyth- net is placed over the generator for 20–30 seconds
mias, e.g., post-MI left ventricular ejection fraction (LV-EF) (Guidant devices signal a beeping tone). Placing the
of 30–40% and inducible sustained ventricular tachycardia, magnet over the generator again for 20–30 seconds can
LV-EF < 30% and QRS duration >120 ms, and patients with reactivate Guidant devices. The ICDs of other manufac-
hereditary arrhythmias such as long-QT syndrome and the turers will remain inactive as long as an external magnet
Brugada syndrome. The ICD consists of a generator, which remains over the generator. If the magnet is removed,
houses a microprocessor, complex electronic circuitry, the ICD becomes active. The pacemaker function of ICD
lithium battery and capacitor, and defibrillator electrodes. generators is not affected by application of a magnet.
The maximal output from an ICD is about 30 J (45 J in When in doubt, one must contact the manufacturer to
“high-energy” devices), whereas external defibrillators find each device’s response to a magnet.
deliver a maximal output of 360 J. Modern ICDs are also Monitoring
capable of functioning as pacemakers. In addition to basic monitoring, a five-lead ECG sys-
tem is helpful in analyzing the rhythm during periods of
interference from cautery. A pulse oximeter or arterial
Clinical Management catheter provides monitoring of beat-to-beat mechanical
In order to care safely for a patient with an activity of the heart and ensures perfusion during
implantable cardiac device in the perioperative and crit- periods of interference. If present, minute ventilation
ical care setting, careful attention must be given to the rate responsiveness is turned off before surgery.
following considerations. Electrocautery
Electrocoagulation (repeated bursts of current) and
Assessment of the Device electrocutting (sustained current) are commonly used
The routine history must include questions pertaining during surgical procedures. Electrosurgical units (ESUs)
to the presence of an implanted cardiac device, its type, may be unipolar or bipolar. With a unipolar ESU, current
manufacturer, and model, and indication for insertion. is passed over a large area before it is returned to the
A detailed cardiac history must be obtained. The patient’s pad. However, a bipolar ESU allows limited dispersion of
old medical record or wallet card may provide informa- current due to housing of both cathode and anode
tion about the type of the device as well as details on within the tip of cautery. Therefore, most pacemaker-
intrinsic rhythm, programming mode, and the rate. An related complications are likely to occur with unipolar
ECG may be helpful to determine the type of pacemaker and cutting systems. When using the unipolar system,
(atrial, ventricular, or dual chamber) and if the patient is short bursts are recommended. The cautery pad should
completely dependent on the pacemaker. ECG must be be in full contact with the patient’s skin and placed as
obtained without applying a magnet on the device, as close as possible to the site of surgery and as far as pos-
some ICDs may be permanently deactivated with magnet sible from the generator. Potential adverse consequences
placement. A roentgenogram of the chest can identify if of cautery device interference include bradycardia, asys-
the pacemaker is single chamber vs. dual chamber, and tole, tachyarrhythmia, and unintended delivery of shock,
with unipolar or bipolar leads. An ICD generator is usually impaired cardiac output, and endocardial injury.
larger than a pacemaker generator. Whenever feasible, a Effect of Drugs, Metabolic, and Electrolyte
competent authority must interrogate the PPM or ICD and Imbalance
a copy of this report placed in the patient’s chart. Common metabolic and electrolyte abnormalities such
as acidosis, alkalosis, myocardial ischemia, hyperkalemia,
Perioperative Care of the Patient and severe hyperglycemia may result in an increase in
As a rule, a means of providing backup pacing or pacing threshold and failure to pace. Many antiarrhyth-
defibrillation must be immediately available. mic drugs may potentially increase pacing threshold.
Arrhythmia Management 87
No
ICD response
Pacer effect (EKG), to magnet
First document known response to
patient response magnet then place magnet7 on
and BP with magnet device and observe EKG & clinical
placed is good9 response "Beep-o-gram"
(beep with QRS)8
Consultation remove magnet
No recommended immediately
1
"DEVICE" = pacemaker or ICD (Internal Cardioverter Defibrillator). ICDs defibrillate but may also have pacing capabilities.
2MANUFACTURER CONTACTS: MEDTRONIC: 800-462-7775 or 800-551-5544 (after hours page rep at 800-MEDTRONIC): GUIDANT: 800-
CARDIAC (medical records); ST JUDE: 888-756-2763 x 5802 (7-5 PST, after hours page rep at 800-PACE-ICD)
3EPS = Electrophysiology service of cardiology
4
Proper care includes device assessment or interrogation at least once a year.
5CONSULTATION = Consultation with either the patient's cardiologist, the manufacturer of the device, or the EPS service
6
ELECTROCAUTERY: You can minimize electrocautery impact on device function in most patients. Bipolar electrocautery is safest. Unipolar
electrocautery is safest when short burst (<1 sec) and distant from the device and its leads (not abdominal or thoracic). Other electromagnetic
sources (e.g. MRI, lithotripsy, ECT) can affect devices. The return pad (sometimes called grounding although it is not) should be placed furthest from
the device and its leads.
7
MAGNET placement over a pacer results in an asynchronous pacing rate of 80-100 and is usually tolerated unless patient requires optimal pacing
(e.g. atrial synchronization) for adequate hemodynamics. Electrocautery may reprogram a pacer to other rhythm which is usually safe. MAGNET on
an ICD disables defibrillating capability (sometimes indicated by a tone of 20-30 sec) as long as the magnet is over the device. ICDs with pacing
function do not have their pacing function disabled by a magnet, but can have their pacing function inhibited by electrocautery. Majority of patients
are not pacer dependent; pacer dependent patients paced with an ICD may require consultation and reprogramming of their ICD pacing function if
electrocautry will interfere with ICD pacing.
8
Beep-o-gram indicates that defibrillating capability will be disabled after 30 sec of exposure to magnetic field. Reprogramming will be necessary to
restore this function. Guidant beep may require stethoscope to be heard. No beep or beep-o-gram = consult recommended.
9
Some patients may not tolerate asynchronous pacing (e.g. they require AV synchrony to optimize atrial "kick")
10All patients should have their devices interrogated after surgery.
A
EMERGENT PROCEDURE: No time for consultation, perform quick check of 1) current rhythm, 2) pacer type & function, 3) effect of magnet,
4) minimize electrocautery, 5) consider preparing alternate means of pacing &/or defibrillating. Updated12 9 02
(Copyright pending Peter L Bailey, MD)
Figure 7-11 An example of a patient care guide for PPM or ICD. (Courtesy of Department of
Anesthesiology, University of Rochester.)
88 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Myopotentials resulting from skeletal muscle fascicula- Optimal management of cardiac arrhythmias requires a
tions secondary to succinylcholine may result in failure basic understanding of cardiac electrophysiology and
to pace due to pacemaker oversensing, especially of a pharmacology of antiarrhythmic drugs. Perioperative
unipolar system. period and critical illness present with unique meta-
External Defibrillation bolic, ischemic, and neurohumoral stressors that can
External synchronized cardioversion or defibrillation result in arrhythmia formation. The basic approaches
may potentially damage pacemaker circuitry and result to arrhythmia management include airway support, cor-
in increased pacing threshold. Therefore, before elective rect diagnosis, establishing urgency of treatment and
cardioversion the pacemaker threshold must be increased hemodynamic stability, and prevention of complica-
and the pacemaker appropriately reprogrammed after tions. It is important to remember that antiarrhythmic
shocks have been delivered. Minimally effective energy drugs can also be proarrhythmogenic. PPMs and ICDs
output is selected and paddles are positioned such that require unique considerations. Using care guides for
current is delivered perpendicular to the pacing system. patients with PPMs or ICDs and a means of providing
backup pacing or defibrillation will ensure safe patient care.
Special Circumstances
Magnetic resonance imaging (MRI) is known to cause
SELECTED READING
serious derangements in pacemaker activity and should
be avoided in pacemaker patients. When administered Al-Khatib SM, Allen LaPointe NM, Kramer JM, Califf RM: What
asynchronously, shock waves and electrical interference clinicians should know about the QT interval. JAMA
during lithotripsy can inhibit pacemaker output. 289:2120–2127, 2003.
Therefore, shock waves are synchronized with the QRS. Amar D: Perioperative atrial tachyarrhythmias. Anesthesiology
The rate-responsive feature of the pacemaker and anti- 97:1618–1623, 2002.
tachycardia feature of the ICD must be deactivated dur- Chaudhry GM, Haffajee C: Antiarrhythmic agents and pro-
ing lithotripsy. Radiation therapy may potentially arrhythmia. Crit Care Med 28(Suppl):N158–N164, 2000.
damage the silicon processor chip of the pacemaker. Guidelines 2000 for cardiopulmonary resuscitation and emer-
Cardiopulmonary resuscitation can be safely performed gency cardiovascular care. International consensus on
in patients with ICDs. science. Circulation 102:1–376, 2000.
Seguin P, Signouret T, Laviolle B, Branger B, Malledant Y:
Incidence and risk factors of atrial fibrillation in a surgical
SUMMARY intensive care unit. Crit Care Med 32:722–726, 2004.
Stone KR, McPherson CA: Assessment and management of
There have been tremendous advances in the diagnosis patients with pacemakers and implantable cardioverter
and management of arrhythmias over the last two decades. defibrillator. Crit Care Med 32(Suppl):S155–S165, 2004.
8
CHAPTER Critical Care
Pharmacologic
Principles: Vasoactive
Drugs
CURTIS E. HAAS, Pharm.D.
JACLYN M. LEBLANC, Pharm.D.
89
90 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
cardiac ischemia should be closely monitored or alterna- cortisol or insulin secretion. These effects may con-
tive vasopressors should be considered. tribute to the catabolic response of critical illness and
The most common reported adverse effects of DA are interfere with protein anabolism. In addition, DA has
related to its cardiovascular effects and include sinus been associated with suppression of dehydroepiandros-
tachycardia, arrhythmias, cardiac ischemia, and a risk of terone sulfate serum concentrations, an androgenic
excessive peripheral vasoconstriction leading to tissue hormone with immune stimulatory effects. Lastly, DA
necrosis. Extravasation of DA at the injection site can aggravates the pituitary blunting of LH pulse amplitude
cause local tissue necrosis and sloughing. The drug may observed in critically ill patients and may also decrease
also have adverse effects on pulmonary gas exchange. pulse frequency leading to iatrogenic suppression of the
DA has been consistently shown to increase pulmonary gonadal axis which delays the recovery of testosterone
shunt fraction, which may lead to a worsening of oxy- secretion in men. This may contribute to negative nitro-
genation in some patients. However, an increase in mixed gen balance, delayed anabolic response, and immune
venous oxygen saturation secondary to effects on cardiac suppression. An appreciation of the complex effects DA
output may offset the increased shunt fraction minimizing may have on neuroendocrine response, and the increas-
effects on arterial PaO2. The drug may also inhibit the cen- ing recognition of the importance of endocrine responses
trally mediated ventilatory response to hypercarbia. on outcome of critically ill patients raises several concerns
With an increased emphasis in recent years on the about the routine use of DA for hemodynamic support in
effects of vasopressors on regional perfusion as a marker the ICU.
of comparative efficacy and safety, several investigators In summary, DA effectively improves MAP in patients
have evaluated the effects of DA on splanchnic perfusion with refractory septic shock primarily by increasing
and oxygen utilization with mixed results. The use of cardiac index. In the SCCM Practice Parameters updated
low-dose DA in combination with fluids and norepi- in 2004 DA is recommended as a first line vasopressor for
nephrine in patients with septic shock has been associ- septic shock. In the absence of definitive data concern-
ated with variable effects on splanchnic perfusion. ing the drug of choice for the management of refractory
Splanchnic blood flow, O2 delivery (DO2), and O2 con- septic shock, DA remains a reasonable treatment alter-
sumption (VO2) were increased in patients with a nor- native. For other indications for vasopressor therapy
mal splanchnic DO2 at baseline, but not in patients with where the primary objective is to increase peripheral vas-
an increased splanchnic DO2. Despite increases in O2 cular resistance, DA should not be considered the first-
delivery and consumption, there was no change in gas- line agent.
tric intramucosal pH (pHi) or hepatic vein lactate con-
centrations raising concerns about the relevance of the Norepinephrine
observed increases in DO2 and VO2 or the possibility of Over the past decade there has been a renewed inter-
a direct metabolic effect of DA. In a randomized study est in the use of norepinephrine (NE) for the treatment
comparing norepinephrine and DA in septic shock, the of common shock states, especially hyperdynamic septic
group randomized to DA experienced a significant shock. At pharmacologic doses used for the treatment of
reduction of gastric pHi despite improvement in global shock, NE has a predominant agonist effect at α1-adrenergic
DO2 and VO2, suggesting that DA may increase splanch- receptors, with a lesser effect at β1-receptors, and rela-
nic oxygen debt due to increased splanchnic oxygen tively little effect at β2-receptors. The typical hemody-
utilization. Other investigators have found no important namic response to NE is an increase in diastolic, systolic,
effects on splanchnic blood flow. The importance these and pulse pressures, no change to a slight reduction in
variable effects on regional perfusion may have on clini- cardiac output, marked increases in peripheral vascular
cal outcome is unknown and requires additional study. resistance, and a reduction in heart rate with an increase
An under-appreciated potential risk of DA in critically in left ventricular stroke volume. NE has minimal effects
ill patients relates to its effects on anterior pituitary func- on measures of preload and pulmonary vascular resist-
tion. DA profoundly suppresses prolactin, thyroid- ance. In the setting of septic shock the major contribu-
stimulating hormone (TSH), and luteinizing hormone tion to the increase in MAP is vasoconstriction with
(LH) secretion from the anterior pituitary. Prolonged a rise in vascular resistance, while the β1 agonist effect
hypoprolactinemia in critically ill patients receiving DA appears to result in maintenance of cardiac output.
induces an impairment of the T-lymphocyte proliferative Unlike DA, NE behaves as a vasoconstrictor in the treat-
response, which may increase susceptibility to infectious ment of septic shock. Although sinus tachycardia and
complications. DA induces or aggravates the low-T3 syn- other tachyarrhythmias may be seen, especially at higher
drome of critical illness due to direct inhibition of TSH doses, it is usually less frequent than what is observed at
secretion. DA attenuates pulsatile growth hormone equally effective doses of DA.
secretion, and prolonged infusions are associated with Due to early observations of renal failure, bowel
low insulin-like growth factor-I, without influencing ischemia, metabolic acidosis, and severe peripheral
92 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
vasoconstriction with tissue necrosis when NE was concentrations are usually maintained or improved fol-
administered to patients with shock, for many years the lowing the initiation of NE, and, as mentioned above,
drug was relegated to a second- or third-line role in the renal blood flow and renal function are improved in
management of septic shock and was only used when patients that have an adequate hemodynamic response
the patient failed to respond to other agents. This has to NE. Since all of the regional perfusion data come from
been referred to as a “pharmacologic extreme unction” patients with septic shock, it is possible that patients
and NE picked up the nickname “leave-em-dead,” a play with hypotension due to other causes may experience
on the original trade name Levophed. Many textbooks decreases in renal and mesenteric blood flow similar to
still recommend maximal doses of 10–12 μg/minute in what has been observed in healthy volunteer studies,
the treatment of adult patients with shock, primarily presumably due to a generalized vasoconstriction observed
based upon these fears of potent vasoconstriction. with NE.
Multiple studies over the past 10–15 years have Increases in afterload, combined with an increase in
clearly demonstrated that NE can be safely used in the contractility and possibly heart rate, increase left ven-
hemodynamic management of septic shock provided the tricular stroke work and may precipitate myocardial
patient has been adequately fluid resuscitated. The doses ischemia and infarction. Like all catecholamines, NE
used in these trials have been higher by several orders of should be cautiously administered to patients with
magnitude than the prior arbitrarily chosen maximal known coronary artery disease or evidence of myocar-
doses. Mean doses have been 0.2–1.3 μg/kg/minute, dial ischemia.
with doses as high as 3.3 μg/kg/minute being used. Other common adverse effects of NE are predictable
Despite these high doses, improvement in GFR, urine extensions of its cardiovascular effects and include
output, and renal blood flow have been reported, and tachycardia, other tachyarrhythmias, marked increases
patients have not experienced worsening of metabolic in blood pressure, and severe peripheral vasoconstric-
acidosis or complications from severe peripheral vaso- tion with tissue necrosis. Ensuring the patient has an
constriction. The primary difference between the cur- adequate intravascular volume can minimize the risk of
rent and historical experiences with NE appears to be tachyarrhythmias and peripheral vasoconstriction. NE
the careful attention to adequate fluid resuscitation in has fewer “hormonal” effects than epinephrine, but at
the recent clinical reports, although there are no con- high doses may cause hyperglycemia. Extravasation at
trolled data supporting this assumption. the site of injection may cause local tissue necrosis and
In the setting of septic shock, high doses of NE are often sloughing.
required probably due to α-receptor downregulation and NE has emerged as a drug of choice for the manage-
possibly other factors that reduce vascular smooth muscle ment of refractory septic shock in the opinion of many
response to catecholamines. For patients receiving NE for experts. Recent clinical experience and published
the treatment of shock or hypotension due to other reports have dispelled many of the myths and fears sur-
causes, much lower NE infusion rates are typically rounding the use of this drug; however, a strong bias
required. NE should be started at rates of 0.03 against the routine use of NE persists in the minds and
–0.05 μg/kg/minute (2–5 μg/minute in adults) and titrated practices of many critical care practitioners. If NE is
to the desired hemodynamic response. In the management going to be used for the treatment of severe septic
of septic shock the dose should be titrated to the goal MAP shock, it should be used early in combination with
rather than a derived parameter like systemic vascular aggressive volume resuscitation and inotropic support as
resistance. There is no apparent reason to dictate a maxi- indicated, and not reserved as a second-line or late salvage
mal dose of NE in the treatment of septic shock provided therapy.
the patient’s intravascular volume status is adequately
maintained and the patient has not developed intolerable Epinephrine
adverse events (see later discussion of vasopressin in sep- Epinephrine (EPI) has potent agonist effects at both
tic shock). Doses greater than ~3 μg/kg/minute have not α- and β-adrenergic receptors. Due to its complex phar-
been previously reported. All patients receiving intra- macologic effects, the overall hemodynamic response to
venous infusions of NE should have their blood pressure an infusion of EPI is dose-dependent. At relatively low
and heart rate continuously monitored. doses, the β-receptor-mediated effects predominate lead-
Several studies have evaluated the impact of NE, either ing to an increase in cardiac output due to an increased
alone or in combination with low-dose dobutamine, on stroke volume and heart rate, and a reduction in afterload.
measures of regional perfusion and oxygen utilization. The net vasodilation and reduction in afterload is prima-
Although the results have been somewhat variable, the rily due to stimulation of β2-receptors, which are pre-
overall conclusions are that if cardiac output is maintained, dominantly present on the resistance arterioles of
splanchnic perfusion and oxygen utilization are main- skeletal muscle. The overall effects on MAP at low dose
tained or improved in patients with sepsis. Serum lactate are variable and dependent upon the patient’s baseline
Critical Care Pharmacologic Principles: Vasoactive Drugs 93
hemodynamic state and the net effects on cardiac output with other vasopressors. EPI also has important meta-
and vascular resistance. bolic adverse effects. Hyperglycemia secondary to inhi-
At higher infusion rates typically administered for the bition of insulin secretion, enhanced secretion of
treatment of shock or hypotension, the balance shifts glucagon, inhibition of glucose uptake by skeletal muscle
towards increased α-adrenergic effects leading to vaso- cells, and stimulation of glycogenolysis are commonly
constriction and increased peripheral resistance. Cardiac observed. EPI also stimulates K+ uptake into cells due to
effects will include an increase in heart rate and con- activation of β2-receptors. The resulting hypokalemia is
tractility. Cardiac output is typically increased, but may often exacerbated by treatment of EPI-induced hyper-
vary depending upon the effects on afterload. Due to the glycemia with insulin. EPI increases triglyceride lipase
nature of the distribution of α- and β2-receptors through- activity, which increases the breakdown of triglycerides
out the vasculature, the local effects of EPI on vascular to free fatty acids and glycerol, increases circulating con-
tone and blood flow will depend upon the tissue. centrations of free fatty acids, and has a significant calori-
Vasoconstriction may predominate in the arterioles and genic effect. Although some of these metabolic effects
precapillary sphincters of many tissues and organs includ- may be seen with high doses of NE, they are much more
ing the parenchymous organs such as the kidney, liver, and common during infusions of EPI.
lungs, the gut, cutaneous structures, and mucus mem- In summary, EPI effectively increases MAP during the
branes. A reduction in vascular resistance of the skeletal treatment of common shock states, but recent evidence
muscle vasculature is usually observed with the higher suggesting that EPI may have more adverse effects on
doses of EPI since the powerful β2-receptor-mediated regional perfusion and metabolism have led to recom-
effects are only partially countered by α1-receptor-mediated mendations that EPI not be considered a drug of choice
vasoconstriction. Understanding these variable local for the treatment of refractory septic shock. EPI has
effects of EPI may explain the observed differences in been commonly recommended for anaphylactic shock
regional perfusion and oxygen utilization between EPI due to its combined effects on cardiovascular, pulmonary,
and NE despite both agents being titrated to achieve a and inflammatory systems during allergic responses. In
similar target MAP during the treatment of septic shock. most common shock states EPI is not considered a drug
EPI effectively raises MAP in patients with septic of choice and is often reserved as a second-line agent for
shock that is refractory to volume resuscitation. The patients failing to respond to NE or DA.
hemodynamic responses leading to the increase in MAP
are an increase in cardiac output due primarily to increased Phenylephrine
stroke volume, combined with modest increases in vascu- Despite several decades of clinical use for the treat-
lar resistance and heart rate. Similar to DA, the predomi- ment of shock, there is relatively little published data on
nant effect in septic shock is the increase in cardiac the use of phenylephrine (PHE) and essentially no com-
output. The increase in contractility and heart rate parative studies with other catecholamines. PHE is a rel-
increases left ventricular stroke work and may precipi- atively selective α1-adrenergic receptor agonist, although
tate cardiac ischemia and infarction. at high concentrations it may also stimulate β-receptors.
Although EPI has shown consistent effects on improv- When administered to patients with septic shock follow-
ing global DO2 and VO2 in most clinical reports of patients ing fluid resuscitation there is typically an increase in
being treated for refractory septic shock, recent studies MAP primarily due to peripheral vasoconstriction, an
have indicated that these global effects may not predict increase in stroke volume index, a small to no reduction
regional oxygen utilization. EPI has been shown to in heart rate, and maintenance of cardiac output. The
decrease splanchnic blood flow, increase arterial, venous, increase in stroke volume suggests a positive inotropic
and hepatic venous lactate concentrations, and decrease response to PHE, which may be due to stimulation of
pHi, especially in the first 12 to 24 hours of treatment. The α-receptors present on the myocardium or some inher-
importance of these regional effects on clinical outcome ent β-adrenergic activity of PHE at the doses being used
have not been evaluated; however, since the overall goal for septic shock. Unlike other catecholamines, heart
of resuscitation is to improve tissue perfusion and oxy- rate typically remains relatively unchanged or decreased
gen utilization these observations have raised significant with the use of PHE as a vasopressor. In fact, sinus
concerns relative to the role of EPI in the treatment of bradycardia and slowed atrioventricular (AV) nodal
refractory septic shock. conduction may result from reflex vagal responses,
The most common adverse effects of EPI are pre- although this is more likely in normotensive patients
dictable and similar to other catecholamines. These receiving PHE.
include tachycardia, other tachyarrhythmias, cardiac Limited data evaluating the effects of PHE on global
ischemia, excessive increases in blood pressure, and oxygen utilization and regional perfusion during the
severe peripheral vasoconstriction. Reductions in renal treatment of septic patients indicate that DO2 and VO2
blood flow appear to be more pronounced with EPI than are maintained or increased, arterial lactate concentrations
94 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
are decreased or unchanged, and urine output increases. primarily at differences in global hemodynamic responses,
There is no comparative data with other catecholamines which were later followed by studies that included global
for these parameters. In the treatment of sepsis and DO2 and VO2 as primary endpoints or as components of a
refractory septic shock PHE is usually initiated at a dose composite endpoint. As it became evident that these global
of 0.5 μg/kg/minute and titrated to goal MAP. The surrogate endpoints were not predictive of survival, more
reported dose range has been 0.11–9.9 μg/kg/minute, recent studies have focused on measures of regional perfu-
which similar to NE is considerably higher than the sion and oxygen utilization, most commonly focused on the
traditionally quoted maximum dose of 200 μg/minute splanchnic circulation. This attention to the splanchnic cir-
for adult patients. These higher doses have been well culation has occurred for several reasons. First, it is thought
tolerated provided the patient is adequately volume that inadequate splanchnic perfusion and compromise of
resuscitated, suggesting that arbitrary maximum doses gastrointestinal mucosal integrity may play a central role in
for PHE are not appropriate in the management of septic the pathogenesis of multiple organ failure in the setting of
shock. For the treatment of hypotension secondary to sepsis and septic shock. Secondly, due to the countercur-
causes other than sepsis, or for elevation of MAP in rent flow in the splanchnic microcirculation the gut has a
normotensive patients (e.g., head trauma), a much lower higher critical DO2 than other organs and therefore may be
dose is typically required. more sensitive to changes in DO2 and VO2. Lastly, the gut is
Adverse effects of PHE are predicted by its pharma- generally more easily accessible than other major organ sys-
cology and include excessive increases in blood pres- tems, and therefore lends itself to study using relatively non-
sure, severe peripheral vasoconstriction, bradycardia, invasive means in the critical care setting. It is important to
cardiac ischemia, and local skin necrosis with extravasa- remember that despite the widespread attention to the
tion at the injection site. The risk of adverse events effects of catecholamine therapy on splanchnic perfusion
appears to be reduced by ensuring the patient’s intravas- and metabolism there is no current evidence that differ-
cular volume status is optimized and maintained. PHE ences in these intermediate endpoints translate directly into
may be advantageous in patients with baseline tachy- differences in clinical outcomes.
cardia, intolerance to other catecholamines secondary to Table 8-2 summarizes the comparative studies that have
excessive increases in heart rate, or coexisting chronic evaluated catecholamine treatments in the management of
or acute atrial fibrillation. Compared to other agents, the patients with hyperdynamic septic shock. The overall
role of PHE in the management of common shock states trend in these comparative studies is that NE with or
requires further comparative studies. without concomitant dobutamine is superior to DA and
EPI when evaluating either achievement of hemodynamic
and oxygen transport goals, or effects on regional per-
CLINICAL CAVEAT fusion and oxygenation. There are no comparative studies
involving PHE. Two recent reviews on the treatment of
Catecholamine Safety hyperdynamic septic shock have recommended NE as
The safe use of catecholamines for the treatment of the drug of choice when vasopressor therapy is indi-
hypotension is improved by:
cated (see Dellinger and Ruokonen et al. in Selected
● Ensuring the patient is adequately fluid resuscitated
Reading), and the SCCM Practice Parameters consider NE
based upon subtle clinical evidence of intravascular
volume overload; PAOP = 14–18 mmHg; or CVP =
8–14 mmHg.
● Using the lowest effective dose for the shortest
CURRENT CONTROVERSY
possible length of time – frequent and ongoing dose
titration. Norepinephrine is Drug of Choice for Septic
● Adding inotropic support (dobutamine) to NE or PHE Shock
with reduced cardiac output (CI < 3.0 l/minute/m2). ● Surrogate endpoints of regional perfusion more
consistently improved by NE compared to DA or EPI.
● Minimal tachycardia compared to DA and EPI.
● No alterations in neurohormonal response, unlike DA.
● More consistent achievement of global
Choice of Catecholamine
hemodynamic goals compared to DA.
Most of the literature and discussions on the choice of ● Contrary to traditional teaching, NE improves
catecholamine therapy have focused on the treatment of cardiac output, renal blood flow, and urine output
hyperdynamic septic shock. There are no comparative clin- in refractory septic shock.
ical trials with patient outcome or survival as a primary or ● Potential survival advantage compared to other
secondary endpoint. All of the comparative trials have vasopressor choices.
relied upon various surrogate endpoints. Early trials looked
Table 8-2 Comparative Studies of Catecholamines During Hyperdynamic Septic Shock
Martina DA 2.5–25 μg/kg/minute Prospective, DB, R Achieve and maintain goals for 6 hours: DA group – 5/16 (31%) achieved goals
(n = 16) vs. NE Refractory hyperdynamic SVRI > 1100 dynes/s/cm5·m2 or NE group – 15/16 (93%) achieved goals
0.5–5 μg/kg/minute septic shock patients MAP > 80 mmHg CI > 4 l/minute/m2 10/11 of DA failures responded to addition of NE
(n = 16) Crossover allowed for IDO2 > 550 ml/minute/m2
treatment failures IVO2 > 150 ml/minute/m2
Marikb DA (n = 10) vs. NE Prospective, R, 3 hour study Global hemodynamics No differences in global parameters except HR and CI
(n = 10) Hyperdynamic septic shock Global oxygen utilization (IDO2 and IVO2) (both greater with DA)
with MAP < 60 mmHg or Gastric pHi Gastric pHi increased with NE, but decreased with DA
SVRI < 1200 dynes/s/cm5·m2 Arterial lactate (p < 0.001)
despite fluid resuscitation
Infusions titrated to
MAP > 75 mmHg
No crossover permitted
Dayc DA 2.5–10 μg/kg/minute vs. Open, R, crossover study Global hemodynamic response EPI – resulted in increased lactate (infusion stopped in
EPI 0.1–0.5 μg/kg/minute Severe sepsis (n = 10) Acid–base balance 84%), decrease in arterial pH
using stepped infusions and severe malaria (n = 13) DA – small fall in arterial lactate and rise in arterial pH.
Infusion not stopped in any patient. DO2 and
VO2 increased with both drugs
Meier- EPI vs. NE + DOB Prospective, crossover study Global hemodynamics and oxygen utilization No difference in global parameters
Hellmannd Refractory hyperdynamic Splanchnic perfusion, and oxygen utilization Splanchnic blood flow and VO2 were lower,
septic shock (n = 8) 2 hour Gastric pHi arterial, hepatic, and venous lactate were higher,
infusions titrated to achieve and pHi was lower during EPI infusion
CI > 5.5 l/minute/m2 or
DO2 > 650 ml/minute, and
MAP ≥ 70 mmHg
Levye EPI vs. NE + fixed dose DOB Prospective, R study Global hemodynamics and oxygen utilization No differences in global parameters
(5 μg/kg/minute) Hyperdynamic, DA-resistant Blood lactate and pyruvate At 6 hours, lactate, lactate/pyruvate ratio, and pCO2
septic shock Gastric tonometry – pHi and pCO2 gap gap increased and arterial pH decreased in EPI
(n = 30) Measurements at 1, 6, 12, and 24 hours group. Return to baseline by 24 hours.
Infusions titrated to NE + DOB group had reduction in lactate, and
MAP > 80 mmHg normalization of tonometry values by 6 hours
Seguinf EPI vs. NE + fixed dose DOB Prospective, R study Global hemodynamics and No difference in global hemodynamic parameters,
(5 μg/kg/minute) Hyperdynamic septic oxygen utilization except EPI had greater CI, DO2, and gastric mucosal
shock (n = 22) Gastric mucosal blood flow (Doppler blood flow
Infusions titrated to MAP of flowmetry) No difference in ICG clearance
70–80 mmHg Hepatic function (ICG clearance)
Duranteaug EPI vs. NE vs. NE + fixed dose Prospective, R, crossover study Global hemodynamics EPI and NE + DOB increased CI and DO2 compared to
DOB (5 μg/kg/minute) DA-resistant septic shock (n = 12) Gastric mucosal perfusion NE alone
60-minute infusions (laser Doppler flowmetry) Increase in mucosal perfusion greater with EPI and
Infusions titrated to MAP Gastric tonometry (pHi and pCO2 gap) NE + DOB than NE. pHi and pCO2 gap better with
70–80 mmHg NE + DOB compared to EPI or NE alone
Continued
Table 8-2 Comparative Studies of Catecholamines During Hyperdynamic Septic Shock—Cont’d
DeBackerh DA vs. NE vs. EPI in moderate Prospective, R, crossover, open Evaluated effects on splanchnic circulation Moderate shock: NE and DA had similar HD effects,
septic shock label by: ICG clearance; hepatic vein oxygen EPI had greater increase of CI.
NE vs. EPI in severe septic Moderate shock (n = 10) saturation; gastric tonometry (pCO2) No differences in splanchnic blood flow or gastric
shock Severe, DA-resistant shock pCO2
(n = 10) Severe shock: EPI impaired splanchnic circulation
All agents titrated to compared to NE
MAP > 65 mmHg
CI, cardiac index; DA, dopamine; DB, double-blind; DOB, dobutamine; EPI, epinephrine; ICG, indocyanine green; IDO2, oxygen delivery index; IVO2, oxygen consumption index; MAP, mean arterial pressure;
NE, norepinephrine; pCO2 gap, difference between arterial pCO2 and gastric mucosal pCO2; pHi, intramucosal pH; R, randomized; SVRI, systemic vascular resistance index.
aMartin C, Papazian L, Perrin G et al: Norepinephrine or dopamine for treatment of hyperdynamic septic shock? Chest 103:1826–1831, 1993.
bMarik PE, Mohedin M: The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 272:1354–1357, 1994.
cDay NPJ, Phu NH, Bethell DP et al: The effects of dopamine and adrenaline infusions on acid–base balance and systemic haemodynamics in severe infection. Lancet 348:219–223, 1996.
dMeier-Hellman A, Reinhart K, Bredle DL et al: Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med 25:399–404, 1997.
eLevy B, Bollaert PE, Charpentier C et al : Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective,
a first line agent. Dobutamine should be added if the stimulation of vasopressin release, and increased catabo-
cardiac index is < 3.0 l/minute/m2. Although there are no lism of circulating vasopressin. The administration of
randomized, prospective trials evaluating the effects of the vasopressin at a rate of 0.01–0.04 Units/minute results
choice of catecholamine therapy on outcome, a recently in rapid and significant improvements in MAP, often
published prospective, observational, cohort study of 97 allowing significant dosage reductions for concomitant
adult patients with septic shock concluded that NE was catecholamines required for hemodynamic support.
significantly associated with a lower overall hospital mor- Although the initial studies are encouraging, the reports
tality rate than high-dose DA or EPI. Based upon these lim- to date have involved relatively small numbers of
ited data, NE appears to be the vasopressor of choice for patients, inadequate comparisons with conventional
hyperdynamic septic shock at the current time. therapy, and inadequate safety assessments to justify
The choice of vasopressor for other indications recommendations for the routine use of vasopressin for
besides septic shock is less clear. If the primary desired septic shock, especially as a first-line agent. Vasopressin
effect is an increase in vascular resistance, then NE or should be considered experimental and unproven until
PHE are preferred over DA or EPI. If the patient has ongoing, large controlled studies are completed. Most
baseline tachycardia, is at high risk for tachycardia, or is clinicians recommend that the addition of vasopressin
intolerant of other catecholamines due to tachycardia, be reserved for patients that are refractory to or requir-
then PHE may be considered. Due to the potential meta- ing high doses of catecholamines. This conservative
bolic adverse effects and the risk of decreased organ per- approach is supported by the recent report of ischemic
fusion, EPI should not be considered as a first-line skin lesions developing in 30.2% of patients receiving
vasopressor. vasopressin for catecholamine-resistant vasodilatory
shock. Patients with pre-existing peripheral artery dis-
ease and septic shock appear to be at greatest risk for
DRUG INTERACTIONS ischemic lesions.
Catecholamines If vasopressin is used for hemodynamic support of
May potentiate pressor or cardiac effects of refractory vasodilatory shock, the dose should be limited
catecholamines: to 0.01–0.04 Units/minute. Infusion rates greater than
● Tricyclic antidepressants. 0.04 Units/minute do not appear to increase the effec-
● Antihistamines (e.g., diphenhydramine, tiveness, and may increase the risk of adverse events
tripelennamine, dexchlorpheniramine). including myocardial and splanchnic ischemia. Once
● Ergot alkaloids.
vasopressin is started the existing catecholamine infu-
● MAO inhibitors (? clinical significance).
sion should be adjusted to the lowest dose necessary to
● Oxytocic drugs.
● Nonselective β-blockers (“unopposed maintain the desired MAP. The patient should be closely
α1-stimulation”). monitored for signs and symptoms of ischemic compli-
May antagonize pressor or cardiac response: cations including myocardial ischemia and necrotic skin
● β-Blockers (decreased inotropic and chronotropic or mucus membrane lesions.
response).
● Haloperidol, phenothiazines (α1-blocking effects).
May increase risk of cardiac arrhythmias: VASODILATORS
● General anesthetics (halogenated hydrocarbons and
cyclopropane). The most common indications for the use of par-
● Digoxin. enterally administered vasodilators in the critical care
setting include hypertensive crisis, cardiac ischemia,
acute postoperative hypertension, cardiogenic shock,
acute aortic dissection, and control of hypertension in a
patient unable to take oral medications. Less common
Vasopressin indications include pheochromocytoma and drug over-
Recent evidence suggests that low-dose vasopressin doses involving sympathomimetic agents or cocaine.
may have a role in the hemodynamic support of hyper- The agents used for the acute management of MAP come
dynamic septic shock and possibly other causes of from multiple pharmacologic categories including
vasodilatory shock which are resistant or relatively direct-acting vasodilators, nitrates, β-adrenergic antago-
refractory to catecholamines. Patients with septic shock nists, calcium channel blockers, angiotensin-converting
have significantly lower plasma vasopressin concentra- enzyme inhibitors, and dopamine agonists. From the
tions than patients with cardiogenic shock, possibly due perspective of pharmacologic effects, the vasodilators
to exhaustion of neurohypophyseal stores during pro- can be divided into agents that have predominant effects
longed hypotension, blunting of baroreflex-mediated on the arterial circulation, venous circulation, or mixed
98 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
in oxygenation and pH with venous hyperoxemia and enzymatic reaction releases nitric oxide, leading to
lactic acidosis. Other manifestations may include nausea, vasodilation via the guanyl cyclase–cyclic-GMP pathway.
vomiting, abdominal pain, increased salivation, and NTG exerts its anti-ischemic and antihypertensive effects
tachyphylaxis to the effects of SNP. The accumulation of primarily through marked relaxation of the veins, result-
cyanide and resulting toxicity can be prevented by ing in decreased ventricular preload and increased
co-administering sodium thiosulfate, typically in a 10:1 venous capacitance. Although venodilation with result-
ratio in the same infusion. Sodium thiosulfate provides ing reduction in preload is the predominant anti-ischemic
the necessary substrate to detoxify cyanide, does not inter- effect, NTG may also cause coronary vasodilation, reverse
fere with the antihypertensive effects of SNP, and is coronary vasospasm, improve myocardial collateral per-
inexpensive. Although this may increase thiocyanate fusion, and improve the epicardial to endocardial blood
accumulation and the risk of thiocyanate toxicity, this flow ratio. At higher doses, NTG also causes arterial
should not be a concern with short-term administration vasodilation leading to a reduction in afterload. NTG is
of SNP, and the adverse effects of thiocyanate are much the vasodilator of choice for the management of cardiac
less concerning than cyanide toxicity. ischemia, or for reducing MAP in a patient with underly-
ing cardiac ischemia. NTG may also be used for rapid
reduction of preload for patients with left ventricular dys-
function or cardiogenic shock who fail to respond to
diuretics. However, the drug should be administered cau-
tiously since excessive reductions in preload may lead to
CLINICAL CAVEAT
a reduction in cardiac output.
Sodium Nitroprusside – Preventing NTG is usually initiated at 5–10 μg/minute (0.075–
Cyanide Toxicity 0.15 μg/kg/minute) with the dose increased by 5–10 μg/
● Do not exceed infusion rates of 5 μg/kg/minute for minute every 3–5 minutes to achieve the desired clinical
more than a few minutes. response. Like SNP, NTG has a rapid onset and short
● Avoid prolonged infusions (>2 hours) using doses
duration of action making it attractive for the manage-
greater than 2.5 μg/kg/minute.
● Use alternative agents when high does of sodium
ment of acute elevations in blood pressure or cardiac
nitroprusside are required. ischemia in the ICU. Close monitoring of blood pressure
● Add sodium thiosulfate injection (10:1 ratio) to and heart rate during the initiation and titration of the
infusions of sodium nitroprusside. NTG infusion is recommended; however, invasive moni-
● Remain vigilant for common signs and symptoms of toring is not necessary.
cyanide toxicity – mental status changes, venous Tolerance to the vasodilatory effects of NTG develops
hyperoxemia, lactic acidosis. within 48–72 hours of starting an infusion. The develop-
All institutions using sodium nitroprusside should ment of tolerance is postulated to be secondary to
have a cyanide antidote kit readily available. baroreceptor- and hormonally mediated compensatory
mechanisms evoked in response to reductions in arterial
pressure, and from depletion of tissue sulfhydryl donors
necessary for the metabolism of nitrates to nitric oxide.
The most common side effects associated with NTG
SNP can result in the reversal of pulmonary hypoxic infusions are headache, hypotension, and reflex tachy-
vasoconstriction and worsen ventilation:perfusion match- cardia. The free nitrite ion can react with hemoglobin to
ing leading to increased hypoxemia. Potent vasodilators produce methemoglobinemia, which is of greatest con-
like SNP should be used cautiously in patients with com- cern with prolonged, high-dose infusions. When severe,
promised oxygenation due to chronic lung disease, acute methemoglobinemia can cause pseudocyanosis, tissue
respiratory distress syndrome, or severe pneumonia. hypoxia, and death. Patients with critical aortic stenosis
Nitroprusside may also cause an abrupt increase in intra- are preload-dependent and may tolerate NTG poorly;
cranial pressure (ICP) in patients with an elevated ICP therefore NTG should be avoided or used very cau-
and should be avoided in these patients. Abrupt discon- tiously in these patients. NTG has less effect on hypoxic
tinuation of SNP infusions carries a risk of rebound pulmonary vasoconstriction than SNP, and therefore
hypertension, and therefore should be tapered off may be better tolerated by the patient with hypoxemia.
slowly whenever possible.
Hydralazine
Nitroglycerin Hydralazine is a direct-acting arteriolar vasodilator lead-
Nitroglycerin (NTG) is denitrated in vascular smooth ing to a reduction in systemic vascular resistance (SVR),
muscle cells, releasing a free nitrite ion. A second with no effect on venous or epicardial coronary arteries.
100 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Following intravenous administration, hydralazine filling pressures remained unchanged or were slightly
reduces MAP, systolic and diastolic blood pressures, and increased. This suggests that in some clinical settings the
increases heart rate, cardiac output, and myocardial con- predominant effect on MAP is secondary to the non-
tractility. An observed increase in sympathetic activity is selective β-blockade effects on the heart; however, the
predominantly a result of baroreceptor-mediated reflex, α1-receptor antagonism appears to prevent an increase
as well as a drug-induced release of NE from sympathetic in SVR that is commonly observed following the admin-
nerve terminals. Hydralazine also directly increases car- istration of purely nonselective β-receptor antagonists.
diac contractility. Due to the effects on heart rate and Differences in hemodynamic response may be due to dif-
contractility, no increase in epicardial blood flow, and ferences in the severity of hypertension, or to the dose
the potential for “coronary steal” syndrome, hydralazine or method of administration of the drug.
has negative effects on myocardial oxygen balance and Labetalol reduces indicators of myocardial oxygen
may precipitate acute cardiac ischemia and infarction. demand while maintaining or improving indicators of
The initial dose of hydralazine should be 5–10 mg IV myocardial oxygen supply. This apparent beneficial effect
over 2 minutes, with additional doses used as needed. on myocardial metabolism may make labetalol a preferred
Single IV doses should not exceed 20 mg, and the dose agent in the setting of suspected or documented myocar-
is usually repeated every 6 hours due to its long duration dial ischemia. In addition, labetalol does not affect ICP or
of action. Intravenous hydralazine is contraindicated in cerebral blood flow, and is therefore an effective and
patients with known coronary artery disease or evidence safe agent for the control of blood pressure for neuro-
of cardiac ischemia, and should be used with caution surgery and neurotrauma patients.
in patients greater than 40 years of age. Although Onset of effect is within minutes following intra-
IV hydralazine has been widely used for many years in venous administration with peak effects observed within
the treatment of hypertension and heart failure in the 5–10 minutes following a single intravenous injection.
ICU, the drug should not be considered a first-line agent The drug has a long duration of action with an elimina-
due to its potential for adverse effects, long duration of tion half-life of up to 8 hours. Labetalol has been admin-
action, and the availability of safer options for achieving istered as individual bolus doses, by continuous infusion,
short-term hemodynamic goals. or as a combination of bolus and infusion therapy for the
management of acute hypertension. An initial dose of
10–20 mg administered over 2 minutes can be followed
Labetalol by increased doses of 20–80 mg every 10 minutes, until
Labetalol is a racemic mixture of four diastereomers the desired blood pressure goal is achieved. The patient
that all have unique effects at α1- and β-adrenergic recep- can receive subsequent bolus doses of labetalol if
tors, with a net effect of nonselective β-receptor and needed to maintain blood pressure within the desired
α1-receptor antagonism. The drug also demonstrates range. Alternatively, the drug may be infused at a rate
some β2-receptor agonism, which may contribute to of 0.5–4 mg/minute until the goal blood pressure is
vasodilatation, and inhibition of the neuronal uptake of achieved, and then should be stopped due to the long
NE (a cocaine-like effect). Following intravenous admin- duration of action. Supplemental bolus doses of 10–20 mg
istration, the potency for β-receptor blockade is about may be given every 10 minutes during the early period of
five to ten times that for α1-receptor blockade. Labetalol the infusion to achieve more rapid control of blood
is an attractive option for the management of acute pressure. Blood pressure should be carefully monitored
hypertension since it potentially combines vasodilata- during dose titration; however, invasive monitoring is
tion secondary to α1-receptor antagonism, reversing the generally not required. The US FDA approved maximum
increases in afterload observed during common hyper- dose is 300 mg over 24 hours; however, higher doses
tensive syndromes, with β-receptor blockade to prevent have been well tolerated provided the patient is properly
reflex tachycardia. In the setting of acute aortic dissec- monitored.
tion, labetalol lowers MAP, decreases left ventricular All of the usual precautions and contraindications for
contractility, and therefore the aortic wall is exposed to the use of a nonselective β-blocker should be observed.
reduced shear forces, meeting the primary objectives of Patients with impaired left ventricular function, defined
medical management for this condition. as an ejection fraction <40% or a cardiac index
A reduction in SVR is not universally observed with <2.5 l/minute/m2, should receive alternative agents for
labetalol therapy. Hemodynamic studies of labetalol for the treatment of acute hypertension. In addition,
acute postoperative hypertension have shown that the patients with bronchospastic lung disease, impaired
predominant effect of the drug is a reduction in systolic cardiac conduction, or resting bradycardia should not
and mean arterial pressure, heart rate, and cardiac output, receive intravenous labetalol. The most common adverse
with no significant change in SVR. Right ventricular effects associated with labetalol are hypotension, which
Critical Care Pharmacologic Principles: Vasoactive Drugs 101
can be precipitous, bradycardia, cardiac conduction staff administering IV nicardipine should be properly
delays, left ventricular dysfunction, bronchospasm, and instructed about the use of this drug, and orders should
rare skin rashes. clearly indicate the need to reduce the infusion rate
once blood pressure goals are achieved.
Adverse events have been reported in 7–38% of
Nicardipine patients participating in controlled clinical trials of IV
Intravenous nicardipine, a dihydropyridine class cal- nicardipine. These were generally mild and transient,
cium channel blocker, is the most widely studied cal- less common than with SNP, and usually did not require
cium channel blocker for the treatment of hypertensive discontinuation of the drug. The most common adverse
crises and acute postoperative hypertension. Like other effects were headache, hypotension, sinus tachycardia,
dihydropyridines, nicardipine is relatively selective for and nausea and vomiting.
vascular smooth muscle with little effect on cardiac con-
duction or inotropic activity in vivo. Therefore, the pre-
dominant hemodynamic effect of nicardipine is arterial Fenoldopam
vasodilation leading to a reduction in vascular resistance Fenoldopam is a selective dopamine-1 (DA1) receptor
and MAP. There are typically small increases in cardiac agonist approved for the short-term treatment of severe
output and heart rate with variable effects on preload. hypertension. The stimulation of vascular DA1 receptors
Nicardipine has beneficial effects on myocardial metab- results in relaxation of vascular smooth muscle via
olism with increases in coronary blood flow and time to a cyclic-AMP-dependent pathway. DA1 receptors are
the development of angina or ECG evidence of ischemia distributed throughout most arterial beds, but are pres-
during exercise. ent in highest density in renal and splanchnic arteries.
Nicardipine has been shown to effectively lower Stimulation of DA1 receptors present on renal tubular
blood pressure in multiple clinical trials involving cells produces a naturesis and increased urine flow
patients with severe hypertension or postoperative rate. The naturetic effect may be augmented by an
hypertension. It has been found to be equally effective increase in renal blood flow and GFR associated with
as SNP and NTG, and superior to placebo, with overall fenoldopam.
response rates of 86–98%. Compared to SNP, IV nicardi- The predominant hemodynamic effect of fenoldopam
pine demonstrated more consistent control of MAP is a reduction in SVR with decreases in MAP and systolic
necessitating fewer dose adjustments, and in some trials and diastolic blood pressure. Heart rate, cardiac output,
a shorter time to therapeutic response and fewer and left ventricular stroke volumes are increased, and
adverse effects necessitating discontinuation of the drug. there is no significant effect on preload. Unlike SNP,
The shorter time to therapeutic response and higher dis- fenoldopam does not significantly increase pulmonary
continuation rates may have been due to protocol design shunt fraction.
rather than true differences in efficacy or safety. Fenoldopam has been shown to be equivalent to SNP
The recommended regimen for IV nicardipine is an ini- for the treatment of severe hypertension with a similar
tial infusion of 5 mg/hour with increases of 2.5 mg/hour overall response rate and time to response. For the treat-
every 15 minutes to a maximum of 15 mg/hour or until ment of postoperative hypertension, fenoldopam has
target MAP is achieved. The infusion should then be been shown to be superior to placebo and equivalent to
decreased to a maintenance rate of 3 mg/hour and SNP and IV nifedipine. The drug should be initiated at a
adjusted by 1 to 2.5 mg/hour every 15 minutes to main- rate of 0.1 μg/kg/minute, then titrated by increments
tain target blood pressure. The controlled trials involving of 0.05–0.1 μg/kg/minute at 15–20 minute intervals to
patients with acute postoperative hypertension started achieve the goal blood pressure. The maximum recom-
the infusion at 10 mg/hour, with increases of 2.5 mg/hour mended infusion rate is 1.6 μg/kg/minute. The mean
every 5 minutes to a maximum of 15 mg/hour or until tar- time to therapeutic goal was 28 minutes in a placebo-
get blood pressure was achieved. A similar maintenance controlled trial, and 70% of cardiac surgery patients
infusion regimen was used. For acute postoperative had achieved goal blood pressure by 30 minutes after the
hypertension the mean time to therapeutic response start of treatment with fenoldopam. The time to thera-
was approximately 10–15 minutes, and the time to offset peutic response may have been affected by the protocol
of clinical effect after discontinuation of the infusion was design and rate of titration of the infusion. Due to its short
approximately 15–20 minutes. Due to differences in dose half-life of approximately 5–10 minutes the effects of
titration, the mean time to therapeutic response in the fenoldopam dissipate relatively quickly after cessation of
severe hypertension trials was approximately 60 minutes. an infusion, with about a 50% loss of effect by 15 minutes
The recommendation for a loading infusion followed by without evidence of rebound hypertension.
a reduced dose maintenance infusion may create an The effects of fenoldopam on renal blood flow and
opportunity for medication errors. Therefore, the clinical glomerular filtration pose a theoretical advantage for
102 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
fenoldopam in the treatment of severe hypertension perfusion pressure, which may be of some concern in
associated with compromised renal function. However, patients with evidence of myocardial ischemia.
there are no clinical data to support the supposition that Patients with congestive heart failure (CHF) adminis-
fenoldopam will improve the outcome of renal function tered intravenous enalaprilat experience a reduction in
when compared to other vasodilators. The most com- blood pressure, SVR, preload, and heart rate, with an
mon adverse effects with fenoldopam are hypotension, increase in stroke volume. These effects are similar to what
tachycardia, headache, flushing, dizziness, and brady- has been observed following oral administration of an ACEI.
cardia. Fenoldopam increases intraocular pressure, and The initial adult dose of IV enalaprilat should be
therefore should be avoided in patients with glaucoma 0.625–1.25 mg, administered over 5 minutes. The dose
or high intraocular pressure. Due to its potent naturetic can be repeated after 20–30 minutes if the patient has an
effects, intravascular volume depletion may occur and inadequate response. The effective dose is typically
urine output will not be a reliable clinical indicator of repeated every 6 hours, and may be continued until the
hypovolemia. Lastly, fenoldopam has been reported to patient is able to transition to oral therapy. Since
cause changes in T-wave morphology on the surface enalaprilat is cleared by the kidneys, the dose should be
ECG; however, these changes do not appear to repre- reduced in the setting of significant renal insufficiency.
sent myocardial ischemia. The major disadvantage of The potential adverse effects from ACEI therapy
fenoldopam when compared to other therapeutic include hypotension, which may be prolonged, acute
options is the high acquisition cost of this agent; how- decreases in renal function, hyperkalemia, and rare cases
ever, the recent loss of patent protection for this com- of angioedema. Patients with intravascular volume
pound is likely to lead to significant price erosion. depletion are at greatest risk for hypotension and acute
renal insufficiency, so careful attention should be paid to
volume status. Bilateral renal artery stenosis or severe
Enalaprilat renal dysfunction are considered relative contraindica-
Enalaprilat is the only intravenous angiotensin convert- tions to treatment with ACEIs. The long duration of
ing enzyme inhibitor (ACEI) approved for clinical use, and action of enalaprilat, while potentially advantageous
has been evaluated for the treatment of severe hyper- from the perspective of dose frequency, may be a disad-
tension, acute left ventricular failure, and perioperative vantage if the patient experiences significant hypoten-
hypertension. Enalaprilat is the active metabolite of the sion. For the treatment of severe hypertension in the
oral prodrug enalapril. ACEIs inhibit the enzyme respon- critical care setting, enalaprilat should be considered a
sible for the conversion of angiotensin I to angiotensin II, second-line agent.
and the metabolism of bradykinin to its inactive form.
The resultant pharmacodynamic effects include vaso-
dilation, decreased sympathetic response, renal efferent Nesiritide
arteriolar vasodilation, and decreased sodium retention. Nesiritide is a recombinant B-type naturetic peptide
Bradykinin may also contribute to systemic vasodilation. (BNP) approved for the management of acute, decom-
Hemodynamic effects include reductions in MAP, sys- pensated heart failure, and represents the first thera-
tolic and diastolic blood pressure, and preload, with a peutic advance in the treatment of severe CHF in over
variable effect on cardiac output. Reflex tachycardia is 10 years. Administration of nesiritide causes both arterial
not observed, and arterial oxygenation is not affected. and venous vasodilation with a reduction in preload
Intravenous enalaprilat has been shown to effectively (pulmonary artery occlusion pressure (PAOP) and right
lower blood pressure in small studies involving patients atrial pressure) and SVR, with an increase in stroke vol-
with moderate to severe hypertension. The maximal ume and cardiac index. The peptide also has naturetic
decrease in blood pressure is usually observed within effects with increases in urinary sodium excretion and
30 minutes, and the duration of response has been vari- urine output, and may be associated with increases
able depending upon the size of the dose administered. in GFR. Plasma aldosterone concentrations are also
Intravenous enalaprilat has also been evaluated in a ran- decreased following the administration of nesiritide.
domized, controlled trial for patients with hypertension Nesiritide is indicated for hospitalized patients with
following intracranial neurosurgery. Compared to the decompensated heart failure with signs and symptoms of
control group, enalaprilat effectively lowered blood volume overload over the past 72 hours. If a pulmonary
pressure, with an average onset of approximately artery catheter is inserted, the PAOP should be greater
15 minutes. The duration of response exceeded 4 hours than 18 mmHg. Patients with a history of significant
in this study. The effect was primarily due to a reduction valvular stenosis; hypertrophic, restrictive, or obstructive
in vascular resistance with no significant change in car- cardiomyopathy; constrictive pericarditis; primary pul-
diac output. There was a slight reduction in myocardial monary hypertension; biopsy-proven active myocarditis;
Critical Care Pharmacologic Principles: Vasoactive Drugs 103
Sodium 0.25–5 mg/kg/minute <1 minute 1–3 minutes Tachycardia, precipitous Requires continuous
nitroprusside (max.10 μg/kg/minute) reductions in blood invasive monitoring;
pressure, myocardial sodium thiosulfate
ischemia, cyanide and (10:1) prevents
thiocyanate toxicity, cyanide toxicity
pulmonary V/Q
mismatch, rebound
hypertension,
restlessness, nausea,
and vomiting
Nitroglycerin 5–300 μg/minute <1 minute 5–10 minutes Tachycardia, headache, Tolerance develops;
hypotension, nausea, good choice with
and vomiting myocardial ischemia
Labetalol Bolus: 10–20 mg, then <5–10 minutes 3–5 hours Bradycardia, Usual precautions
20–40 mg q bronchospasm LV for nonselective
10 minutes; infusion: dysfunction, prolonged β-blocker; good
0.5–4 mg/minute; hypotensive effect choice with
maximum dose = myocardial ischemia,
300 mg (?) aortic dissection, or
↑ ICP
Nicardipine Initiate: 5 mg/hour, 10–15 minutes 15–20 minutes Tachycardia, hypotension, Caution with loading
↑ by 2.5 mg/h q5–15 nausea, and vomiting infusion vs.
minutes to maximum maintenance infusion
of 15 mg/hour. dose. Good choice
Maintenance: start at with myocardial
3 mg/hour ischemia
Hydralazine 5–20 mg IV q6 hours 15–30 minutes 4–6 hours Tachycardia, hypotension, Not routinely
headache, nausea, recommended.
flushing, cardiac Contraindicated with
ischemia cardiac ischemia
Enalaprilat 0.625–5 mg IV every 15–20 minutes >4 hours Hypotension, renal Contraindicated with
6 hours dysfunction, bilateral renal artery
hyperkalemia, stenosis. Good choice
angioedema with congestive heart
failure
Fenoldopam Initial 0.1 μg/kg/minute, 20–40 minutes 15–30 minutes Hypotension, tachycardia, Avoid in patients with
increase by headache, flushing, glaucoma or high
0.05–0.1 μg/kg/minute dizziness, bradycardia, IOP. Theoretical good
q15–20 minutes. ECG changes, elevated choice with acute
Maximum of IOP renal failure
1.6 μg/kg/minute
ICP, intracranial pressure; IOP, intraocular pressure; LV, left ventricle; V/Q, pulmonary ventilation:perfusion ratio.
Energy and Macronutrients Used in Nutrition between nitrogen intake from protein and nitrogen of
Energy urine urea (NUU), calculated by accommodating urine
Carbohydrates for 24 hours.
Lipids Visceral protein status is determined by albumin and
Amino Acids transferin serum level. However, not all conditions cor-
Enteral Nutrition relate with nutritional status that affects albumin and
Parenteral Nutrition and Perioperative Nutrition transferin serum. Both these visceral proteins have a
Nutrition in Trauma long half-life.
Nutrition in Acute Respiratory Failure Retinol binding protein, transthretin, thyroxin binding
Nutrition in Septic Patients prealbumin (TBPA), fibronectin, and somatomedin C
Immunonutrition in Sepsis can be used as nutrition markers during enteral nutrition
Nutrition in Acute Renal Failure in the critically ill. Visceral protein status can also be
Nutrition in Acute Pancreatitis determined by an immune function test, such as total
Immunonutrition in the Intensive Care Unit leukocyte count and skin hypersensitivity; however, the
N-3 Fatty Acid interpretation should be made carefully in patients with
Glutamine infection.
Arginine Somatic protein status can be determined by creati-
Nucleotides nine height index, because creatinine is released from
muscle tissue at relatively constant speed, and so the
The comprehensive evaluation of nutritional status amount of urine creatinine is proportional to muscle
includes intake analysis, physical and anthropometric tissue. 3-Methyl histidine (3-MH) secretion through urine
examination, laboratory examination, and radiology. is another alternative for measuring somatic protein
Patient history is taken and physical examination is per- status. 3-MH is a metabolic result from muscles, and thus
formed to identify the mechanisms underlying the occur- its value can be used to identify turnover from the muscle
rence of depletion or over-nutrition, such as inadequate which is proportional to somatic protein reserves.
intake or absorption, impeded utilization, and increasing The nutrition risk index (NRI) takes into account body
nutrient loss. mass variation and serum albumin. NRI < 83.5 indicates
Anthropometric examination provides information severely malnourished patients for whom nutritional
on the reserves of muscle mass and fat mass which support is required.
describe the reserves of energy and protein mass.
Normal examinations include body weight, body height,
skin fold thickness, and the circumference of various
body organs. ENERGY AND MACRONUTRIENTS
Energy balance can be determined by comparing USED IN NUTRITION
direct energy with that obtained indirectly with
calorimetry, or calculating the need using the Harris Energy
Benedict formula, which is compared with intake. The energy expenditure of most hospitalized patients
Nitrogen balance can be determined by the balance is often lower than values obtained from classic equations
106
Nutrition in the Intensive Care Unit 107
During acute illness and convalescence intakes of smaller feeding tubes if enteral nutrition is well tolerated
1.2–1.5 g/kg are desirable and have proved beneficial. In and expected to last for more than 10 days. After place-
some diseases protein intake must be controlled, e.g., ment of the nasoenteric tube, an abdominal x-ray should
acute liver failure when the intake has to be restricted in be performed to verify its proper placement.
order to avoid hepatic coma and uremia, during which Hospital kitchen-prepared feeding solutions can
the capacity to excrete nitrogenous end products is cause numerous potential complications, such as nutri-
limited. In the dietary management of uremia, an intake tionally unbalanced solutions, water and electrolyte dis-
of 0.5 g protein/kg allows the patient to resist inter- orders, diarrhea, and severe nosocomial infection due to
current infections better than for an earlier recommen- bacterial contamination. These problems have led to the
dation of 0.25 g/kg. development of standardized, industrially prepared feed-
ing solutions. The most commonly used feeding solution
is the iso-osmotic solution (±300 mOsm/l).
ENTERAL NUTRITION Standard feeding solutions are polymeric, being made
up of substrates similar to those found in normal feeds.
Enteral nutrition is the preferred method of nutri- Recent studies suggest that polymeric solutions should
tional support in the critically ill with an intact function- be considered as the first line of enteral nutrition, while
ing gastrointestinal tract. In general, enteral nutrition semi-elemental solutions should be considered in
should be started within 48 hours of ICU admission with patients with severe small bowel disease or extensive
an aim of stimulating gut function and trophicity. There intestinal resection.
is some evidence that this goal can be attained with only Adding fibers to enteral feeding solutions is benefi-
minimal amounts of enteral nutrition. cial, as insoluble fibers (cellulose, lignin) absorb water,
Optimal timing of the onset of enteral nutrition is which leads to the improved regulation of intestinal
crucial. Unnecessary delay due to regurgitation caused transit and reduced incidence of diarrhea. Soluble fibers
by decreased gastroduodenal motility may prolong nega- (pectin, gums, mucilages) are degraded into short-chain
tive nitrogen balance. fatty acids, which enhance water and electrolyte absorp-
The amounts of enteral nutrition are based on nutri- tion, and provide nutrition for colonicyte.
tional assessment, energy requirements, patient history, Enteral nutrition can be administered by gravity or
and medical condition. In patients with severe catabolic with a constant delivery pump. The former is simple and
illness and/or poorly functioning gut, parenteral nutrition cheaper, but less precise than the pump technique, and
should be started concomitantly, in order to meet protein may cause accidental bolus administration, which
and energy requirements and minimize excessive muscle increases the risk of gastroesophageal reflux and
wasting. In patients with persistent gastroparesis and bronchoaspiration. Improved tolerance and a reduced
intolerance to gastric feeding despite adequate prokinetic incidence of diarrhea have been documented with
treatment, endoscopic placement of a nasoduodenal tube continuous compared to bolus feeding.
should be the next step, while nasojejunal tubes should Critically ill patients very often present with delayed
be used only as a last resort, since they are technically the gastric emptying and impaired gastroduodenal motility,
most difficult to place, and do not protect from aspiration which often cause incomplete delivery of the prescribed
or duodenogastric reflux. daily feed. Measuring gastric residuals by aspiration is
Percutaneous gastronomy has become a preferable often used as a monitoring tool.
route when long-term (≥4–6 weeks) enteral nutrition An arbitrary value above which enteral nutrition is
support is required. Although the risk of aspiration is usually given at a slower rate or discontinued is 150 ml
decreased when the latter is administered in the and may lead to underfeeding. Prokinetic drugs may be
jejunum, airway protective measures such as inclination administered to help to lessen the gastric residuals.
of the torso 30° above the horizontal plane, endotra- Diarrhea is a frequent problem in ICU patients receiv-
cheal intubation, or tracheostomy should be considered. ing enteral nutrition, and has often been associated with
The most comfortable tubes for patients are silicone the osmolarity. Most standard polymeric industrial feeds
or polyurethane small-diameter (6–12 F) tubes, the have osmolarity of ≤380 mOsm/kg. There are many fac-
length of which depends on the location of feeding. tors that determine the etiology of diarrhea in enterally
When higher viscosity solutions such as fiber-enriched fed patients, among which are factors related to the
solutions are used, administration through smaller diam- nutrition itself, antibiotics and other medications,
eter tubes might be more difficult unless a constant infu- Clostridium difficile colitis, hypoalbuminemia, sepsis,
sion pump is applied. Since gastric aspiration is often and fever.
required in ICU patients, it is preferable to use the latter Mild symptoms of intolerance are managed with
in the early period of an ICU stay, and to switch to the observation by physical examination at the time of onset
Nutrition in the Intensive Care Unit 109
and within 6 hours, with the current rate of feeding effects of disease and surgery-related malnutrition on body
being maintained. For moderate distention, tube feeds composition, organ function, and subsequent patient per-
are stopped and the patient is assessed for evidence of formance. Available trials concluded that the routine use
small bowel obstruction. If distention remains mod- of perioperative parenteral nutrition in unselected surgi-
erate, an elemental formula is begun. Moderate diarrhea cal patients was unjustified, but might be helpful in high-
(3–4 times/shift) is managed by maintaining the current risk patients.
feeding rate and repeating the examination in 6 hours. Approximately 40% of candidates to general and vas-
Severe distention is managed by stopping all tube feeds, cular surgery present with malnutrition. Postoperative
increasing IV fluid administration, and evaluating the outcome influenced by malnutrition may occur in major
possibility of nonocclusive bowel necrosis. For severe surgery and particularly in elderly patients. The severity
diarrhea, tube feeds are reduced by 50%, antidiarrheal of postoperative complications is related to the degree
medications are added, and the patient is evaluated for of preoperative malnutrition. Malnutrition most often
possible Clostridium difficile infection. Vomiting is reflects the severity of underlying disease and the occur-
managed by ensuring adequate gastric decompression rence of underlying disease complications.
and decreasing the infusion rate by half. High nasogas- Among anthropometric parameters, body weight loss
tric output is treated by verifying postpyloric placement is the most useful. A weight loss ≥20% clearly indicates
of the tube and checking the nasogastric aspirate. poor postoperative outcome, while a weight loss ≥10%
within a six-month period or a weight loss ≥5 kg during
the three preoperative months indicates higher inci-
PARENTERAL NUTRITION dence of major postoperative complications.
AND PERIOPERATIVE NUTRITION Protein malnutrition is the best predictor of compli-
cations both in surgical and nonsurgical patients. Among
Currently, total parenteral nutrition is used in a wide 15 tested variables, it was shown that serum albumin
variety of patients when the enteral route cannot be <35 g/l, transferrin <1.74 g/l, and prealbumin <0.12 g/l
used. Parenteral nutrition in the ICU is also being used had the highest predictive values of postoperative
commonly together with enteral nutrition. complications.
Parenteral nutrition may be achieved using a periph- Nutrient metabolism during surgery depends on pre-
eral venous catheter, but it is difficult to administer ade- operative patient condition and surgery-induced meta-
quate caloric, protein, and electrolytes, and thus central bolic changes. In normal subjects endocrine and metabolic
venous access should be used. In the absence of a pre- adaptation will tolerate prolonged starvation without
existing line, either the subclavian or internal jugular site compromising survival. After 2 to 3 days of starvation, glu-
is preferred. The former has lower infection risk and cose needs are mainly satisfied by gluconeogenesis from
dressing care is easier, while the risk of pneumothorax amino acids released by protein degradation (approxi-
or subclavian artery puncture is higher, both complica- mately 75 g of protein/day, i.e., 300 g of muscle). Then,
tions having potentially devastating effects in unstable an increase in fat utilization and ketogenesis are associ-
ICU patients. In severely ill ICU patients a central venous ated with a decrease in gluconeogenesis, and proteolysis
line must be used solely for the purpose of parenteral falls at 20 to 30 g/day. Surgical stress markedly impairs
nutrition. those adaptations and increases protein loss. Thus, toler-
Subcutaneously tunneled catheters should be reserved ance to starvation depends on preoperative nutritional
for long-term parenteral support (>3–4 weeks), such as status, length of perioperative starvation, and intensity of
in bone marrow transplantation associated with multiple aggression. Preoperative feeding can be altered by under-
intensive intravenous therapy. lying disease, hospitalization, and preoperative investiga-
A recent meta-analysis of perioperative feeding con- tions. In non-malnourished patients, during elective and
cluded that there was no benefit, and indeed possible noncomplicated surgery, starvation of 7 to 14 days will
harm, from the routine use of short periods of postoper- not affect the outcome.
ative parenteral nutrition. There appeared to be some Major surgery induces a systemic inflammatory
benefit when this was given perioperatively to patients response of varying intensity. Mobilization of fuel stores
with severe antecedent malnutrition. and gluconeogenesis are stimulated by the release of cat-
Malnutrition in surgical patients is associated with echolamines, cortisol, glucagons, and growth hormone,
delayed wound healing and increased risk of morbidity as well as by insulin resistance. Interleukin-1 (IL-1) and
and mortality. The main goals of perioperative nutrition tumor necrosis factor (TNF) are responsible for an
are to reduce the incidence of postoperative complica- increase in muscle protein catabolism and a decrease in
tions, the length of postoperative hospitalization, and protein synthesis, while IL-6 is responsible for acute-
operative mortality. An additional goal is to decrease the phase protein synthesis in the liver.
110 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Endocrine changes in stress conditions are characterized appear to be better utilized and do not produce the
by a downregulation of hypothalamus–pituitary–thyroid hyperglycemia associated with TPN.
axis and low plasma T3 concentrations. Cytokines suppress TEN prevents gut mucosal atrophy, attenuates the stress
prealbumin synthesis reducing retinol-binding protein. response, maintains immunocompetence, and preserves
The subsequent release of increased amounts of thyroxine gut flora. In addition, to prevent acute protein malnutri-
and retinol in free form strengthens the effect of cyto- tion, early TEN with immune-enhancing diets also promote
kines. Thyroxine-binding globulin, corticosteroid-binding normal gut function and enhance systemic immune
globulin, and IGF-binding protein-3 degradation allow the responses, thereby preventing nosocomial infections.
occurrence of peak endocrine and mitogenic influences To achieve adequate amounts of early TEN, it is best
at the site of inflammation. This mechanism is associated delivered into the proximal small intestine. Enteral
with hyperthermia, weight loss, and hypoalbuminemia. feeding access should be obtained at the time of initial
Increased protein catabolism and hypermetabolism vary laparotomy. If the patient undergoes an abbreviated
with stress intensity and are responsible for a decreased laparotomy, the needle catheter jejunostomy (NCJ) can
response to nutritional support. The prolongation of be placed during a subsequent operation while for those
such metabolic state results in severe protein depletion. who do not undergo immediate laparotomy, the enteral
Enteral nutrition, using polymeric nutritive mixtures, nutrition can be delivered through a nasojejunal (NJ)
is usually given through a nasogastric tube or by perendo- tube for the first 24 hours after injury. A few patients
scopic gastrostomy when long-term refeeding is may have contraindication to upper gastrointestinal
expected. The association of enteral and parenteral endoscopy. In such patients a jejunostomy tube can be
nutrition is often necessary to achieve nutritional goals easily placed laparoscopically.
in the early postoperative period. Immune-enhancing diets (IEDs) are indicated for
In malnourished patients preoperative nutrition patients with major torso trauma and who are at known
should be given for 7 to 10 days. Longer preoperative risk for septic complications and MOF. Usage is limited
nutrition support would increase the risk of nosocomial up to 10 days, after which polymeric, high-protein for-
infection. Postoperative nutritional support should not mulas are used. Polymeric high-protein formulas are for
be less than 7 days. In order to avoid overfeeding, it is patients who do not meet the criteria for IEDs, who have
recommended to ensure energy support equivalent to normal gut digestive and absorptive capacity, and are
energy expenditure. Daily needs vary from 20 kcal/kg/day believed to have increased nitrogen requirements.
in non-malnourished patients to 35 kcal/kg/day in Elemental formulas are given to those who are intolerant
malnourished or severely stressed patients. Fat should to polymeric formulas or who have not received enteral
not exceed 30% of nonprotein energy supply. Standard nutrition for the first week postinjury. Renal failure
fat emulsions are usually given. Medium-chain triglyc- formulas (concentrated, reduced electrolyte) are for
erides are well tolerated and may be useful in selected those who need intermittent hemodialysis.
circumstances. According to the severity of the stress, Intolerance indicators of TEN are vomiting, abdominal
nitrogen support should vary from 0.25 g/kg/day to distention or cramping/tenderness, diarrhea, high naso-
0.35 g/kg/day. No benefit is demonstrated for nutri- gastric tube output, and contraindications of specific
tional support higher than 0.35 g/kg/day. In severely ill medications. If enteral access is delayed or hemodynamic
patients glutamine-enriched parenteral nutrition can be status prevents early enteral nutrition, early TPN is not
proposed. indicated unless the patient is severely malnourished.
Routine TPN may be associated with worse outcomes
than no nutrition in patients with normal to moderate
NUTRITION IN TRAUMA malnutrition.
For various reasons, trauma patients are at high risk
Trauma patients are prone to develop acute protein for acute renal failure (ARF). This can be treated with
malnutrition because of persistent hypermetabolism, CVVH/CVVHD, which allow TPN with high fluid vol-
which compromises the immune response and increases umes and high protein loads to be used. Alternatively
the risk of late MOF-associated nosocomial infection. standard isotonic, normal electrolyte solutions are used
Early administration of exogenous substrates to meet the in enteral nutrition support initially (Box 9-1).
increased metabolic demands would prevent or slow the
development of acute protein malnutrition and improve
patient outcome. NUTRITION IN ACUTE
Although difficult for centers without experience, RESPIRATORY FAILURE
total enteral nutrition (TEN) is preferred over total par-
enteral nutrition (TPN) because it is safer, less expen- Patients with trauma, burns, sepsis, acute respiratory
sive, and more convenient. Substrates delivered enterally distress syndrome (ARDS), and multiple organ dysfunction
Nutrition in the Intensive Care Unit 111
in the increased load on respiratory muscles and there- function of neutrophils and monocytes. Finally, and
fore may worsen the weaning difficulties. Central respi- probably most importantly, hyperglycemia can induce
ratory drive is often elevated in patients during weaning oxidative stress. The general belief is that glucose levels
trials. Therefore, the combination of increased load and should not exceed 220 mg%. However, a recent ran-
central drive leads to a rise in the work of breathing domized study in a surgical ICU which also included sep-
when ventilatory support is withdrawn. The increased tic patients showed a greater clinical benefit if the blood
work of breathing can lead to fatigue of the respiratory glucose could be maintained between 80 and 110 mg%
muscles weakened by the prolonged catabolic phase. with continuous drip of insulin.
Since the risk of nosocomial pneumonia increases by Fat is efficiently used when it provides 25–30% of the
approximately 1–3% per day of mechanical ventilation, total calorie requirement and 30–40% of nonprotein
prolonged ventilator dependency can cause further mus- calories. A mixed fuel source reduces carbohydrate needs,
cle loss through hypermetabolic septic episodes and the improves glucose control, and reduces insulin needs.
ultimate chances of successful weaning become slimmer Excessive fat (ω - 6) administration, however, results in
with each new episode. neutrophil and lymphocyte dysfunction, blockades the
Weaning difficulties are also often encountered in mononuclear phagocytic system, induces hypoxemia due
COPD patients with acute exacerbation. Pre-existing to ventilation-perfusion disorders and alveolocapillary
under-nutrition with the loss of diaphragmatic mass and membrane injury, induces hepatic steatosis, and increases
strength adds to the problems described above. In these PGE2 synthesis.
patients, inspiratory muscle workload is increased while Fat composition in nutrition is important, since it is an
the diaphragm is placed in adverse working conditions. essential compound of cellular membrane phospholipids.
The result is an increased work of breathing and muscle The proportion of polyunsaturated fatty acids (PUFA) of
fatigue. This situation is worsened during weaning from omega- 6 and omega-3 series is responsible for membrane
the ventilator, due to the fact that the workload of the fluidity, ionic channel flow, activity of membrane recep-
respiratory muscles increases. tors, and the mechanisms in cellular signal response.
Both omega-3 and omega- 6 compete for the same meta-
bolic pathways. The omega- 6 is a precursor of arachi-
NUTRITION IN SEPTIC PATIENTS donic acid from which eicosanoids -2 and leukotrienes-4
are synthesized. These products have intense inflamma-
In septic patients the judicious use of substrate admin- tory and immunosuppressive activity. The omega-3 is a
istration minimizes metabolic complications and over- precursor of docosahexaenoic (DHA) and eicosapenta-
feeding must be avoided. enoic (EPA), which are synthesized to prostaglandins,
The total energy expenditure (TEE) over the first thromboxanes -3, and leukotrienes -5. These cause
week is approximately 25 kcal/kg/day but during the inflammatory reaction and are less immunosuppressive.
second week TEE can increase significantly. The exact proportion of essential fatty acids has not
Indirect calorimetry may currently be the best way to been defined. Usage of physiologic mixtures of long- and
determine calorie needs and can provide improved medium-chain triglycerides as well as omega-3 is currently
knowledge on the proportion and quantity of substrates under investigation.
that should be used in septic patients. During the catabolic state, muscular and visceral pro-
Endogenous glucose production in sepsis is approxi- teins are used as energy substrates in the muscle and for
mately 2.5 mg/kg/minute while exogenous glucose hepatic gluconeogenesis (alanine and glutamine) in the
administration of 4–8 mg/kg/minute does not inhibit this synthesis of acute-phase protein reactants. Protein needs
process. It does, however, affect the respiratory quotient. exceed the normal requirement of 1 g/kg/protein/day and
Because of this, glucose should not be administered faster should be administered at 1.2 g/kg/day. Greater amounts
than 4 mg/kg/minute and should represent 50–60% of protein do not improve nitrogen balance but they
of total calorie requirements or 60–70% of nonprotein increase blood urea. The quantity of protein should con-
calories. Overfeeding produces hypertriglyceridemia, stitute 15–20% of total calories and be provided in a non-
hyperglycemia with potential hyperosmolar syndrome, protein calorie/nitrogen ratio of 80:1 to 110:1.
osmotic diuresis, dehydration, increased CO2 produc- Branched-chain amino acids (BCAAs) are precursors
tion (which can aggravate respiratory insufficiency and of glutamine in skeletal muscle. In a study of septic
prolong ventilator dependency), hepatic steatosis, and patients given parenteral nutrition with 45% BCAAs,
cholestasis. some positive benefits in mortality were noted with a
Hyperglycemia can glycosylate immunoglobulins and highly branched-chain formula. Additional benefits have
complement factors, and alter the respiratory burst of been noted through some nutritional parameters. The
neutrophils and alveolar macrophage. It can also inhibit use of branched-chain amino acids in septic patients,
adhesions, chemotaxis, phagocytosis, and antimicrobial however, still remains controversial.
Nutrition in the Intensive Care Unit 113
increase leading to higher energy consumption. If acute of nonsurgical patients with MOF. The goal of 1.2–1.5 g/
pancreatitis is complicated by sepsis, many patients are kg/day of protein intake is optimal for most patients
in a hypermetabolic state with an increase of resting with acute pancreatitis. If an MOF syndrome compli-
energy expenditure (REE). cates the course of the disease, the calorie and protein
Gastric and duodenal perfusion of enteral diets is a requirements have to be adapted; lower protein loads of
powerful stimulant of exocrine pancreatic secretion, ~1.2 g/kg/day should be given to patients with renal or
whereas jejunal administration induces minimal pancre- hepatic failure.
atic secretion. Lipid, protein, and carbohydrate metabolism It is important to deliver the caloric need by the
seems to be altered in acute pancreatitis. There is no enteral route. Enteral feeding is possible but prescribed
evidence that infusion of exogenous fat could develop intakes of nutrients are frequently not achieved.
pancreatitis. Nasojejunal tubes are feasible and desirable in the man-
In severe acute pancreatitis, protein catabolism is agement of patients with acute pancreatitis but their
increased. Parenteral administration of amino acids does placement is sometimes difficult without endoscopic
not stimulate the exocrine pancreas directly, but through help. There is some evidence that enteral feeding may
the stimulation of gastric acid. On the other hand, the improve disease severity and clinical outcome in
anatomic site of protein and amino acid administration patients with severe disease. The presence of complica-
determines the degree and extent of pancreatic stimu- tions (pancreatic ascites, fistula formation, or fluid col-
lation during enteral nutrition. Elemental diets are lection) is not a contraindication to enteral feeding.
regarded as the most beneficial diets for patients with Oral refeeding can be started when pain is controlled
pancreatitis. and the pancreatic enzymes return to normal. Patients
Glucose metabolism in acute pancreatitis is deter- are re-fed with small amounts of carbohydrate–protein
mined by an increase in energy demand. There is an diet; the number of calories is gradually increased with
increase of endogenous gluconeogenesis in patients careful supplementation of fat over a period of 3–6 days.
with acute pancreatitis as the metabolic response to If the enteral supply is inadequate, then the rest
severe inflammation. Intravenous administration of high should be given by the parenteral route. When enteral
doses of glucose carries the risk of hyperglycemia, as the nutrition is impossible, TPN should be started.
insulin response is often impaired. The insulin resistance
can be corrected only in part by exogenous insulin
administration. IMMUNONUTRITION IN THE
Parenteral nutrition in acute pancreatitis is useful as INTENSIVE CARE UNIT
an adjunct in patients’ nutritional maintenance. A reduc-
tion in mortality has been claimed with improved nutri- Immune system changes/depression is a complicated
tional status, especially in patients with moderate or factor in ICU patients. Recently, data from various experi-
severe acute pancreatitis. Patients with acute pancreati- ments demonstrated the beneficial effects of immuno-
tis who receive parenteral nutrition have shown an nutrition supplementation to enhance or modulate the
increased rate of catheter-related sepsis and metabolic immune status in various group of specific patients, i.e.,
disturbances such as hyperglycemia. However, both surgical, burn, and ARDS patients. Such nutrients include
catheter-related sepsis and hyperglycemia are often the n-3 fatty acid, glutamine, arginine, and nucleotides. Many
consequence of overfeeding rather than of the mode of clinical trials have shown risk of infection, length of
nutritional support. hospital stay, and medical cost are reduced by enriched
The reduction in the ingestion of food together with nutritional support with immunonutrition. Nevertheless,
an increased demand in patients with severe pancreatitis this administration is not appropriate for every ICU
often results in negative energy balance with the potential patient; patients with severe sepsis, shock, and organ
development of malnutrition. Patients with severe acute failure may actually be harmed.
pancreatitis are hypermetabolic, have a nonsuppressible
gluconeogenesis despite sufficient calorie intake, an
increased ureagenesis, and an accentuated net protein N-3 Fatty Acid
catabolism which can go up to 40 g of nitrogen/day. Fatty acids are components of cell membranes, and
In severely ill patients neither hypercaloric nor influence cell functions and biological responses.
isocaloric nutritional support can prevent protein catab- Following stress, injury, or sepsis the demands of fatty
olism. In contrast, both enhance the metabolic burden acids are increased. N-3 fatty acid is an essential fatty
as measured by energy expenditure, thermogenesis, acid, which is often found to be deficient in hospitalized
urea production rate, and glucose and lactate levels. patients. Although n-3 fatty acid is much needed, the
Therefore, a hypocaloric energy supply of ~15–20 kcal/ ratio of n-3/n-6 fatty acid still has not been clarified,
kg/day is more suitable during the early catabolic stage especially in the critically ill. Mechanisms by which
Nutrition in the Intensive Care Unit 115
n-3 and n-6 fatty acid may exert effects on the immune many of the effects of septic shock including vascular,
system are regulation of gene expression, signal trans- myocardial, and hemodynamic instability.
duction pathways, action of antioxidant enzymes, and
production of eicosanoids and cytokines.
Nucleotides
Nucleotides (purines and pyrimidines) are synthe-
Glutamine
sized either de novo or salvaged from RNA turnover. If
In the human body glutamine plays an important phys- protein intake is adequate, the main source of nucleotide
iologic role in energy production, interorgan nitrogen production is from de novo synthesis. Sufficient
and carbon transport, nucleotide synthesis, renal ammo- nucleotides promote restoration of intestinal function
niagenesis, glycogen synthesis, regulation of protein and immune status. The absence of nucleotides can
synthesis, and replication of cells. Glutamine is a NEAA in cause loss of T-helper lymphocytes and suppression of
healthy people, but in catabolic patients, such as those IL-2 production.
suffering stress, injury, and sepsis, it becomes essential.
Several studies proved that plasma glutamine declines in
catabolic patients. Studies using stable isotopes in the SELECTED READING
critically ill demonstrate systemic demand of glutamine
with large fluxes of glutamine from skeletal muscle. ASPEN Board of Directors and The Clinical Guidelines Task
Force: Guidelines for the use of parenteral and enteral
They show that the nutrient flow of glutamine is from
nutrition in adult and pediatric patients. J Parenteral
muscle, where it is synthesized, and released to the tissues Enteral Nutrition 26(1; Suppl), 1–35, 2001.
and not from the gut to the tissues. The human gut
Bertolini G, Iapichino G, Radrizzani D et al: Early enteral
extracts 50–85% of enteral glutamine.
immunonutrition in patients with severe sepsis. Results of
There is controversy as to the question of giving glut- an interim analysis of a randomized multicentre clinical
amine parenterally or enterally. Studies in experimental trial. Intensive Care Med 29:834–840, 2003.
animals proved that gut villous height and thickness
Cano N: Perioperative nutrition. From nutrition support to
increased after appropriate doses of enteral glutamine. pharmacologic nutrition in the ICU. Update in Intensive
In other studies, enteral diets containing glutamine Care and Emergency Medicine. 34:220–231, 2000.
decreased bacterial translocation across the intestine.
Cano N, Barnoud D, Leverne X: Nutritional management of
On the other hand, a randomized study with parenteral acute renal failure and acute liver failure. Crit Care Shock
glutamine improved several clinical outcomes up to 2:143–157, 1999.
6 months after administration.
Chioléro R, Tappy L, Berger MM: Timing of nutritional support.
The recommended dose of glutamine for less stressed Clinical nutrition: early intervention. In Labadarios D,
patients is 12–15 g/day and for critically ill patients is Pichard C, editors: Nestlé Nutrition Workshop Series.
>20 g/day up to 30 g/day. Recently, glutamine has Clinical & Performance Program, vol 7, Nestle: Karger,
become available as a dipeptide and enriched in certain 2002, p 151.
solutions. Consensus recommendations from the US summit on immune-
enhancing enteral therapy. J Parenteral Enteral Nutrition
26(2; Suppl):S61–S62, 2001.
Arginine
Griffiths RD: Specialized nutrition support in the critically ill:
Arginine is a semi-essential amino acid. In the body for whom and when? Clinical nutrition: early intervention.
arginine participates in the urea cycle and the citric acid In Labadarios D, Pichard C, editors: Nestlé Nutrition
cycle, and stimulates the secretion of anabolic hormone. Workshop Series. Clinical & Performance Program, vol 7,
Arginine is also a precursor for polyamine synthesis and Nestle: Karger, 2002, p 199.
a nitrogen source for nitric oxide synthesis. This latter Jolliet P, Pichard C: A practical approach to feeding intensive
function is important; nitric oxide plays a role in hyper- care patients. From nutrition support to pharmacologic
tension, myocardial dysfunction, inflammation, cell nutrition in the ICU. Update in Intensive Care and Emergency
death, and protection against oxidative damage. Enteral Medicine 34:1166–1178, 2000.
nutrition enriched with arginine leads to T-lymphocyte Kirby DF, Kudsk KA: Obtaining and maintaining access for
stimulation in critically ill patients. Doses of 15 g/day nutrition support. From nutrition support to pharmaco-
intravenous and 17–24 g/day of enteral arginine are ade- logic nutrition in the ICU. Update in Intensive Care and
quate for improving immune system and wound healing. Emergency Medicine 34:125–137, 2000.
In ICU studies an amount between 16 and 19 g/day had Kondrup J, Allison SP, Elia M et al: ESPEN guidelines for nutrition
a beneficial outcome. If the dose is too large it can screening 2002. Clinical Nutrition 22(4):415–421, 2003.
induce lysine deficiency and could be harmful. Very high Kudsk KA: Enteral versus parenteral feeding in critical illness.
nitric oxide levels, produced from arginine, may mediate From nutrition support to pharmacologic nutrition in the ICU.
116 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Update in Intensive Care and Emergency Medicine Sobotka L, editor: Substrate used in parenteral and enteral
34:115–124, 2000. nutrition. Basics in clinical nutrition. Galen 2:37–78, 2000.
Leverve X, Barnoud D, Pichard C: Nutritional support in acute Soeters PB, Dejong CHJ, von Meyenfeldt MF: Parenteral versus
respiratory failure. From nutrition support to pharmaco- enteral nutrition: can we get rid of the myths? Clinical
logic nutrition in the ICU. Update in Intensive Care and nutrition: early intervention. In Labadarios D, Pichard C,
Emergency Medicine 34:303–315, 2000. editors: Nestlé Nutrition Workshop Series. Clinical &
Meier R, Beglinger C, Layer P et al: ESPEN Consensus Group: Performance Program, vol 7, Nestle: Karger, 2002, p 183.
Consensus statement. ESPEN guidelines on nutrition Stroud M, Duncan H, Nightingale J: Guidelines for enteral feeding
in acute pancreatitis. Critical Nutrition 21(2):173–183, in adult hospital patients. Gut 52(Suppl VII):vii1–vii12, 2003.
2002. Tappy L, Chioléro R: Carbohydrate and fat as energetic fuels in
Sack GS, Genton L, Kudsk KA: Controversy of immunonutri- intensive care unit patients. From nutrition support to
tion for surgical critical-illness patients. Curr Opin Crit pharmacologic nutrition in the ICU. Update in Intensive
Care 9:300–308, 2003. Care and Emergency Medicine 34:54–65, 2000.
10
CHAPTER Catheter-Related
Bloodstream Infections
in the Intensive
Care Unit
STEPHEN M. LUCZYCKI, M.D.
117
118 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
the insertion of arterial catheters did not prevent arterial vancomycin may lead to the development of sub-
catheter colonization or infection. populations of S. aureus with intermediate or reduced
vancomycin sensitivity.
pathogens along the subcutaneous portion of catheters. infection ultimately affect the sensitivity of the diagnos-
This strategy has failed to show a risk reduction in the tic method used. In general, semiquantitative and quan-
development of catheter-related BSIs. titative culture methods are thought to be the most
reliable in the identification of catheter-related infection.
Semiquantitative cultures are obtained by cutting open
CATHETER CARE the desired portion of the catheter and rolling the device
onto a culture medium. Quantitative cultures are obtained
Catheter access and use can be modified to help by either sonicating or vortexing the catheter sample in
reduce the incidence of catheter infections. Excessive a broth and subsequently culturing the sample. A semi-
manipulation of catheters increases the risk of infection. quantitative catheter culture with a yield of ≥15 cfu
Catheter ports and hubs require disinfection prior to use. (colony forming units) or a quantitative yield of ≥100 cfu
In addition, the tubing and access hubs should be changed is considered indicative of a device-related infection.
every 48–72 hours. Well-trained staff that adheres to There is no definitive evidence to favor the culture of
strict aseptic principles can reduce the incidence of the catheter tip or the subcutaneous segment in the diag-
catheter infection. Institutions that utilize specialized IV nosis of catheter-related infection. The increasing use of
teams can also reduce the infection rate. In addition, the antiseptic- and antibiotic-coated catheters may affect the
reduction of nurse-to-patient ratios increases the risk of usefulness of these culture methods. Rapid diagnostic tech-
catheter infection. Routine replacement of central niques such as the acridine orange stain may be useful
venous catheters does not reduce the infection rate. The diagnostic modalities in the future.
use of guidewires to exchange catheters remains con-
troversial. Several studies have shown trends toward
increased colonization and infection, but these trends MANAGEMENT
do not appear to be statistically significant. Therefore,
guidewire exchange can probably safely be used, espe- Determining the etiology of fevers in the critically ill
cially where access is difficult and the risks of insertion can be challenging. Once the central venous device is
at a new site are thought to be high. Catheters should be suspected, paired blood cultures (one peripheral and
removed as soon as they are no longer needed to elimi- one central) should be obtained. Blood cultures from an
nate a potential source of infection. arterial line could be used if peripheral blood cannot be
obtained. However, a positive culture from the arterial
line may indicate an infected arterial line. In the seri-
DIAGNOSIS ously ill or septic patient empiric antibiotic therapy
should be instituted utilizing ICU-specific antibiograms.
The diagnosis of catheter-related BSI cannot be made on If no other source of fever is identified and the central
clinical findings alone. Fever, leukocytosis, insertion site line remains suspect, the line should be removed and
inflammation, and BSI alone are all unreliable in ultimately cultured. A central line can then be inserted at a new site
diagnosing catheter-related BSIs. Paired blood cultures or exchanged over a wire provided that the insertion site
(one from the catheter and one from a peripheral source) does not appear to be infected. If both blood and device
should be obtained when a catheter-related BSI is cultures are negative one must search elsewhere for the
suspected. Negative cultures have been shown to have a source of fever. If the blood cultures are negative and
high negative predictive value. When catheter removal is the catheter culture is positive, the clinician should con-
not desired, paired quantitative cultures can be obtained. sider a short course of antimicrobial therapy, follow
If the colony count of a culture obtained from the catheter closely for signs of ongoing infection, and repeat the blood
is 5–10 times greater than the colony count obtained from cultures when necessary. If both blood and catheter cul-
a peripheral sample, a catheter-related BSI is likely. One tures are positive, the catheter should be removed and
can also exploit the differential time to positive culture for the antimicrobial treatment is guided by the etiologic
blood sampled from the catheter and from the periphery organism. Infusates such as total parenteral nutrition
to aid in the diagnosis of catheter-related infections. When should also be cultured if contamination is expected.
blood cultured from the device has a positive result two Unfortunately there are few good data on the dura-
hours before peripheral cultures, a diagnosis of device tion of antimicrobial therapy. In general S. aureus,
infection can be made with a sensitivity and specificity Candida spp., and Gram-negative bacilli are treated for
similar to that of quantitative blood cultures. 10–14 days. Coagulase-negative Staphylococcus spp. can be
Samples of intravascular devices can also be cultured treated for a shorter course of 3–7 days. Some clinicians
to aid in the diagnosis of catheter-related infection. approach coagulase-negative staphylococcus line infec-
Differences in the culture methods, the portion of tions with catheter removal only and no antimicrobial
the catheter cultured, and the source of the catheter therapy. Persistent fevers and bacteremia despite
122 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
catheter removal and appropriate antimicrobial therapy Gowardman JR et al: Central venous catheter related blood-
should raise the suspicion of entities such as bacterial stream infections: an analysis of incidence and risk factors
endocarditis, septic thrombophlebitis, or other distant in a cohort of 400 patients. Intensive Care Med 24:
microbial metastasis. In these cases prolonged antimi- 1034–1039, 1998.
crobial therapy for 4–8 weeks is indicated. Lane RK et al: Central line infections. Curr Opin Crit Care
8:441–448, 2002.
Maki DG et al: Prevention of central venous catheter related
THE FUTURE blood stream infection by use of an antiseptic-impregnated
catheter: a randomized, controlled trial. Ann Intern Med
Future strategies aimed at preventing catheter-related 127(4):257–266, 1997.
BSIs will most certainly exploit both properties of the Mermel LA et al: Guidelines for the management of intravascu-
host and pathogen. The catheter design itself is con- lar catheter-related infections. Clin Infect Diseases
stantly evolving to minimize bacterial adherence and 32:1249–1272, 2001.
colonization as well as thrombus formation with the National Nosocomial Infections Surveillance System report,
ultimate goal of reducing associated BSI. Increasing abil- data summary from January 1992–June 2003. Am J Infect
ities to affect the immunomodulation of the critically ill Control 31:481–498, 2003.
may one day allow the clinician to minimize the devel- O’Grady NP et al: Guidelines for the prevention of intravascular
opment of nosocomial infections. However, the impor- catheter related infections. Clin Infect Diseases 35:
tance of hand hygiene, maintenance of strict aseptic 1281–1307, 2002.
techniques, and continuing education and training of Polderman KH et al: Central venous catheter use: 2. Infectious
staff remain the cornerstones in preventing catheter- complications. Intensive Care Med 28:18–28, 2002.
related infections in the critically ill. Raad II et al: The relationship between the thrombotic and
infectious complications of central venous catheters. JAMA
271(13):1014–1016, 1994.
SELECTED READING
Safdar N et al: A review of risk factors for catheter-related
Cook D et al: Central venous catheter replacement strategies: bloodstream infection caused by percutaneously inserted,
a systemic review of the literature. Critical Care Med noncuffed central venous catheters. Medicine 81(6):466–479,
25(8):1417–1424, 1997. 2002.
11
CHAPTER Current Practices
in Intensive Care
Unit Sedation
TIMOTHY J. BARREIRO, D.O.
PETER J. PAPADAKOS M.D., F.C.C.P., F.C.C.M.
Agitation and Anxiety Evaluation administration of large quantities of sedation and the devel-
Evaluation and Titration of Sedative Agents opment of post-traumatic stress disorders and memory
Sedation Scale (s) problems while others have not found that association.
Establishing and Implementing Sedation Guidelines In the past 5 years ICUs throughout the world have
and Protocols adopted the goal of maintaining an optimal level of
Review of Common Agents used in Sedation comfort and safety for patients. The use and better under-
Opioids standing of newer sedatives and analgesics has given crit-
Morphine Sulfate ical care practitioners the ability to titrate specific agents
Fentanyl for different patient types allowing patients to be com-
Remifentanil fortable throughout their stay in the ICU.
Meperidine As the customized care of patients continues to evolve,
Opioid Adverse Effects a common language is mandated for the titration and use
Nonopioid Analgesics of sedative agents. With this language also comes the
Benzodiazepines development of protocols and guidelines to better use
Midazolam these drugs and to maximize each drug’s unique phar-
Propofol macodynamic profile for individual patients. No longer
Haloperidol is it necessary to be trapped by the all-or-none effect of
Ketamine very long-acting compounds that depress respiration and
Etomidate prolong ICU stays.
Dexmedetomidine
Introduction to Muscle Relaxants
Depolarizing Drugs AGITATION AND ANXIETY EVALUATION
Succinylcholine
Nondepolarizing Agents There is no consensus as to what level of sedation is
Pancuronium optimal for patients in the ICU; most likely the optimal
Vecuronium level of sedation will vary according to patients’ under-
Rocuronium lying mental and physical problems, along with the
Atracurium needed level sedation for patient safety. Agitation and
Cisatracurium anxiety are common in ICU patients of all ages, occur-
Complications of Neuromuscular Blocking Agents ring at least once in most patients admitted to any ICU.
Conclusion Agitation can be caused by multiple factors such as
extreme anxiety, delirium, adverse drug effects, and
In publications from the late 1980s approximately half pain. Failure to provide adequate pain control is a signif-
of the patients in intensive care units (ICUs) described icant factor in the development of agitation in critically
their period of mechanical ventilation as unpleasant and ill patients. In most practices inadequate pain manage-
stressful, and that their time requiring mechanical venti- ment is often a result of the dosing of opioids at sub-
lation was associated with fear, agony, and panic. Some optimal levels; this is because of concerns about respira-
publications have suggested an association between the tory depression and the development of dependence.
123
124 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Table 11-2 Ramsey Scale for Assessing Table 11-4 Motor Activity Assessment Scale
Sedation Levels
Score Description Definition
Level Response/Description
0 Unresponsive Does not move with noxious stimulus
1 Patient awake and anxious, agitated, and/or restless 1 Responsive only Opens eyes or raises eyebrows or
2 Patient awake and cooperative, accepting ventilation, to noxious turns head toward stimulus or
oriented, and tranquil stimuli moves limbs with noxious stimulus
3 Patient wake; responds to commands only 2 Responsive to Opens eyes or raises eyebrows or
4 Patient asleep; brisk response to light glabellar tap touch or name turns head toward stimulus or
or loud auditory stimuli moves limbs when touched or
5 Patient asleep; sluggish response to light glabellar name is loudly spoken
tap or loud auditory stimulus but does respond to 3 Calm and Does not require external stimulus to
painful stimulus cooperative elicit movement and adjusts sheets
6 Patient asleep; no response to light glabellar tap or loud or clothes purposefully and follows
auditory stimulus commands
4 Restless and Does not require external stimulus to
Hansen-Flaschen J, Cowen J, Polomano RC: Beyond the Ramsay scale: need cooperative elicit movement and picks at sheets
for a validated measure of sedating drug efficacy in the intensive care unit. or clothes or uncovers self and
Crit Care Med 22(5):732–733, 1994. follows commands
5 Agitated Does not require external stimulus to
elicit movement and attempts to
patients with complex problems. For example, a patient sit up or moves limbs out of bed
who appears to be asleep with a sluggish response to and does not consistently follow
glabellar tap (Ramsey 5) may also be restless and anxious commands
(Ramsey 1). The Ramsey scale is simple, however, and is 6 Dangerously Does not require external stimulus to
agitated; elicit movement and pulls at tubes
widely used in many ICUs. uncooperative or catheters or thrashes side to side
The Riker Sedation–Agitation Scale (SAS) was the or strikes at staff or tries to climb
first scale formally tested and developed for reliability in out of bed and does not calm down
the ICU (Table 11-3). The SAS identifies seven symmetri- when asked
cal levels ranging from dangerous agitation to deep seda-
Devlin JW, Boleski G, Mlynarek M et al: Motor Activity Assessment Scale: a valid
tion. This scale provides a detailed description of a
and reliable sedation scale for use with mechanically ventilated patients in an
patient’s behavior, allowing the bedside physician to adult surgical intensive care unit. Crit Care Med 27(7):1271–1275, 1999.
adjust properly medications between agitation levels.
adverse events. For opioids desirable attributes include Fentanyl has no active metabolites. Fentanyl is not asso-
rapid onset, ease of titration, lack of accumulation of ciated with histamine release and so it infrequently
metabolites, and low cost. causes hypotension. Fentanyl, however, can cause
bradycardia and decrease sympathic tone; these in turn
CLINICAL CAVEAT can cause hypotension. Because of its rare hemodynamic
side effects, it is an ideal drug for patients in the ICU.
Opioid and Pain Control Fentanyl should be administered by continuous infu-
● Historically pain control has been poorly managed.
sion for sustained effect because of its short duration of
● Most physicians overestimate the risk of narcotic
addiction in postoperative patients.
action. Because of these characteristics, fentanyl has
● Unrelieved pain evokes powerful stress responses. become one of the most widely used agents in the ICU.
● Unrelieved pain can result in pneumonia and Caution should be used when fentanyl is administered at
atelectasis resulting from respiratory splinting, which high doses for prolonged periods of time. Prolonged
decreases tidal volume, vital capacity, and functional effects can be seen, because large amounts of the drug
residual capacity. accumulate in the fatty tissues and then have to be
● Patient-controlled analgesia (PCA) produces adequate metabolized in the liver. In these situations the terminal
pain control and at the response of patients’ needs. half-life of the drug can be as long as 16 hours.
Remifentanil
Morphine Sulfate Remifentanil (Ultiva, Abbot), a newer agent, has not
Morphine sulfate, the prototypical opioid, is the pre- been widely studied in ICU patients. The drug has a very
ferred opioid analgesic in patients with stable hemo- short half-life and may be best used in patients needing
dynamics. Morphine has a rapid initial redistribution phase serial examinations or neurologic evaluation. Remifentanil
of 1–1.5 minutes and an initial half-life of 10–20 minutes; is an ultrashort-acting narcotic that penetrates the blood–
the terminal elimination half-life is between 2 and 4.5 hours. brain barrier within 1 minute, and its blood concentration
Morphine has a lower lipid solubility which results in a decreases 50% by 6 minutes after a one-minute infusion.
slower onset of action when compared to fentanyl. This Because of its shortened duration of action, it requires
is important in that morphine slowly penetrates the continuous infusion for pain management. The novel
blood–brain barrier. The liver primarily metabolizes mor- aspect of remifentanil is its rapid hydrolysis by circulat-
phine; however, the kidney eliminates approximately ing and tissue nonspecific esterases (the beta-adrenergic
40% of the drug. The major metabolite of morphine blocker esmolol is metabolized by similar enzymes).
(morphine-6-glucuronide) is excreted in the urine and There does not appear to be a cumulative effect seen with
may accumulate in patients with renal failure. The opiate long infusions and organ dysfunction does not appear to
activity of the metabolite is several times greater than alter the metabolism of the drug. Side effects of remifen-
that of morphine and its accumulation in patients with tanil include respiratory depression, hypotension, brady-
renal failure has been reported to prolong narcosis. cardia, and skeletal hypertonus; this can make bag mask
Morphine also induces the release of histamine, increasing ventilation difficult or impossible. The administration of
the likelihood of causing hypotension secondary to vaso- propofol or a paralytic agent prior to its administration
dilation. The faster the rate of administration, the more can attenuate the skeletal rigidity seen with the drug.
pronounced the hypotension seen. Finally morphine can
also slow the heart rate, by its stimulation of the vagus
nerve and its depressant effects on the sinoatrial node. CLINICAL CAVEAT
Despite its side effects, morphine is still very useful in Opioid Reversal
the management of ICU patients. ● Narcan (naloxone hydrochloride) is an opioid
antagonist.
● Narcan can prevent or reverse the effects of opioids.
Fentanyl ● Narcan challenge test: inject 0.2 mg Narcan and
Fentanyl has the most rapid onset and shortest dura- observe for 30 seconds.
● Onset of action is usually within 2 minutes.
tion of the opioids. Fentanyl citrate is a synthetic narcotic
● Opioid dependence patients can have acute
analgesic that is 50 to 100 times more potent than mor- withdrawal if given Narcan.
phine, it is highly lipid soluble, and has rapid onset of action ● Smaller doses of 400 μg (dilute 9 cm3 saline with
because it quickly crosses the blood–brain barrier. Fentanyl 1 mg of Narcan) can help reverse the effects of
onset of action is within 30 seconds, and its peak effect the opioid but prevent abrupt withdrawal.
is within 5–15 minutes. The liver metabolizes fentanyl.
128 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
CLINICAL CAVEAT
Lorazepam
● Sedative of choice. Propofol
● Prolonged use has been associated with acidosis Propofol, 2,6-diisopropylphenol, is formulated as a 1%
and renal failure caused by accumulation of aqueous emulsion, containing 10% soybean oil, 2.25%
propylene glycol. glycerol, and 1.2% egg phosphatide. Although the mech-
anism of action of propofol is still not completely under-
stood, the drug appears to activate the GABA receptors
within the CNS. Propofol has a rapid onset of action,
within 1 to 2 minutes after a single intravenous dose, and
Midazolam a short duration of action, only 10 to 15 minutes when
The other commonly used benzodiazepine is midazo- discontinued. This short duration of action is due to its
lam, used initially in the operating room and now widely rapid penetration into the CNS and subsequent redistri-
accepted in the ICU. Midazolam is a slow-acting water- bution. Therefore, in the ICU propofol is used by con-
soluble benzodiazepine that is transformed to lipophilic tinuous infusion. Propofol has no analgesic activity but
compounds in the blood. Midazolam exhibits dose- has some antiemetic properties. The clearance of propo-
related hypnotic, anxiolytic, amnestic, and anticonvul- fol cannot be explained by hepatic clearance alone;
sant actions. The drug produces dose-related respiratory there appear to be extrahepatic sites of elimination.
depression and larger doses may cause hypotension and The clearance of propofol is rapid even after prolonged
vasodilation. Midazolam is metabolized in the liver to infusions, but accumulation of the drug in lipid stores
an active compound that is less potent and more tran- can result in prolonged sedation.
sient than the parent compound. The new SCCM guide- Propofol alters the sensorium at an extremely rapid
lines recommend midazolam for short-term use and rate and in a dose-dependent manner, from light seda-
rapid sedation of actively agitated patients. Midazolam tion to general anesthesia, making it a highly useful drug.
produces unpredictable awakening and prolonged extu- Propofol is a respiratory depressant. Propofol also pro-
bation times when infusions continue for longer than phylactically attenuates induced bronchoconstriction
48 to 72 hours. but does not affect resting airway tone. The most com-
Paradoxical agitation has been observed when using monly seen side effect of propofol, especially when it
benzodiazepines: this may be the result of drug-induced is given as a bolus, is hypotension. Propofol causes
amnesia or disorientation. The effect of these drugs can hypotension by reducing systemic vascular resistance
be reversed with a benzodiazepine receptors antagonist, and causing myocardial depression. These effects are
flumazenil (Romazicon, Roche). However, the routine attenuated in hypovolemic patients. Propofol decreases
use of flumazenil is not recommended after prolonged cerebral metabolism resulting in a decline in cerebral per-
benzodiazepine therapy because there is a risk of induc- fusion pressure. It has interesting effects on neurophysi-
ing withdrawal symptoms and increasing myocardial ology, causing disinhibition, dystonic or choreiform
oxygen consumption, which can occur even with small movements. Other side effects include phlebitis, hyper-
doses. lipidemia, and pancreatitis.
130 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
One of the most important benefits associated with doses; however, it should be noted that these occurred
propofol is a decrease in weaning time from mechanical in highly complex patients with a high mortality index.
ventilation. A large Spanish study, using a cost-of-care The SCCM guidelines recommend propofol as the
approach, evaluated the impact of prolonged sedation agent of choice for rapid awakening and early extuba-
of critically ill patients with midazolam or propofol, and tion. Since propofol is formulated as a lipid emulsion,
weaning time from mechanical ventilation. Although triglyceride concentrations should be monitored after
both drugs provided equivalent sedation, the administra- two days of infusion. Also, the total caloric intake should
tion of propofol was associated with a shorter weaning be adjusted because the lipid emulsion adds calories to
time than midazolam resulting in a favorable economic the nutritional prescription.
profile. Due to its rapid wake-up time, propofol is con-
sidered the fundamental drug in many fast-track surgical
procedures. Haloperidol
Within one year of its introduction in the USA, clusters Haloperidol, a butyrophenone neuroleptic drug, is
of infections in surgical patients treated with propofol the agent of choice for treatment of delirium in critically
were reported. The majority of cases were due to con- ill patients. Patients treated with haloperidol generally
tamination of the drug from poor aseptic techniques. seem to be calmer and are better able to respond appro-
This contamination resulted in the inclusion of an additive, priately to commands. Haloperidol does not cause major
ethylenediaminetetraacetic acid (EDTA), to help retard respiratory depression.
growth of microorganisms. EDTA at low concentrations The adverse effects associated with haloperidol
has no effect on the physical or chemical stability of the include occasional hypotension resulting from the alpha
emulsion compound. In the years following the intro- blocking properties of the drug. Although rare with
duction of the EDTA-containing formulations the inci- intravenous use, haloperidol may cause extrapyramidal
dence of fevers and infections were reduced to zero. effects such as drowsiness, lethargy and fixed stare rigidity
EDTA is a chelator of various ions, including calcium. and akathisia. A highly dangerous side effect is neuroleptic
In a randomized multicenter trial, patients were treated malignant syndrome (NMS) which has a mortality rate of
with either the original propofol formulation or the for- up to 30%. NMS may develop slowly over 24 to 72 hours
mulation with EDTA. The EDTA-containing formulation and can last up to 10 days after discontinuation of the drug.
had no effect on calcium or magnesium hemostasis,
renal function, or sedative efficacy.
One of the interesting aspects of propofol with EDTA CLINICAL CAVEAT
is it ability to modulate the system inflammatory response. Side Effects of Haloperidol
In a study of surgical ICU patients, those receiving ● Neuroleptic malignant syndrome (NMS) can
propofol with EDTA had significantly lower mortality develop over 24 to 72 hours after administration
rates at 7 days and 28 days compared to patients receiv- of haloperidol.
ing the original formulation. This potential positive effect ● NMS is characterized by hyperthermia,
of propofol with EDTA may be related to the ability of hypertonicity, and tachycardia.
EDTA to bind and increase the excretion of zinc; this, in ● TX: discontinue the drug, fluid resuscitation,
turn, may diminish the inflammatory response to stress cooling techniques, and intravenous dantrolene
by decreasing the release of cytokines involved in sodium, 2 mg/kg every 5 minutes to maximum
dose of 10 mg/kg.
inflammation and the generation of free radicals and
● Cardiac arrhythmias can occur. Most worrisome
other oxidases.
is torsade de pointes (polymorphic ventricular
In the USA a generic formulation of propofol is avail- tachycardia).
able. The major difference with the generic product is ● Total daily doses should remain less than 50 mg.
the presence of sodium metabisulfite (0.025%) as a pre- ● Monitoring QT interval is recommended.
servative. As a result of this additive, it carries an FDA ● For corrected QT intervals exceeding
warning about its use in patients sensitive to sulfite com- 480 milliseconds the drug should be stopped.
pounds and therefore should not be used in this group
of patients. Thus it is highly important for clinical staff to
know which propofol formulation is being used in their
facility.
The use of propofol is not currently recommended Ketamine
for pediatric patients, due to reports of metabolic aci- Ketamine, a phencyclidine derivative, is unique
dosis with accompanying lipemic serum, bradyarrhyth- among the intravenous agents in that it causes analgesia
mias, and fatal myocardial failure with excessively high as well as amnesia. The drug does not necessarily cause
Current Practices in Intensive Care Unit Sedation 131
a loss of consciousness, but patients lose their aware- skeletal muscle side effects, which include myoclonus
ness; this unique anesthetic condition is described as a (33%) and transient skeletal movements including
“dissociative state.” This is caused by electrophysiologic uncontrolled eye movements; both effects are transient.
inhibition of the thalamocortical pathways and stimula-
tion of the limbic system.
Ketamine and a benzodiazepine are frequently used for CLINICAL CAVEAT
sedation in pediatric patients. In the ICU ketamine can be Warning for Etomidate
given before airway intubation in hypovolemic patients, ● Etomidate inhibits 11-β-hydroxylase, an enzyme
dressing changes, laceration repair, abscess incision and important in adrenal steroid production.
drainage, and orthopedic manipulations. Ketamine can be ● A single induction dose blocks the normal
given orally, rectally, intramuscularly, or intravenously. stress-induced increase in adrenal cortical production
This drug is a racemic mixture, which is marketed in three for 4–8 hours and up to 24 hours in the elderly.
concentrations so care is needed to avoid dosage error. The ● Continuous infusions of etomidate are not
dose of ketamine is 0.5–1 mg/kg. Ketamine has an elimina- recommended.
tion half-life of 3 hours. Ketamine has no adverse effects on ● Blunts the patient’s ability to respond to stress.
hepatic and renal function. The effects of a single injection
of ketamine generally last less than 30 minutes, although
coadministration of other drugs may prolong the effects.
There are well-described side effects of ketamine. Dexmedetomidine
General anesthesia with ketamine is characterized by Dexmedetomidine (Precedex, Abbot) is a newly
a hyperdynamic circulatory response (tachycardia and approved selective α-2-adrenergic receptor agonist.
increased blood pressure) caused by directly simulat- It exhibits sympatholytic sedative and analgesics effects
ing the autonomic nervous system to release cate- and is eight times more potent for the α-receptor than
cholamines and steroids. Despite this side effect, protec- clonidine. Dexmedetomidine has been approved for short-
tive airway reflexes (coughing) and minute ventilation are term (24 hours) sedation and analgesia in the intensive care
maintained. setting. Because of its short-term effects, dexmedetomidine
Although ketamine is a direct myocardial depressant, is a highly promising therapy for ICU patients.
this drug inhibits reuptake of catecholamines and pro- Dexmedetomidine works by presynaptic activation of
duces mild to moderate increases in blood pressure, the α-2-adrenoreceptor thereby inhibiting the release of
heart rate, and cardiac output. These cardiostimulatory norepinephrine and terminating the propagation of pain
effects could be detrimental in patients with underlying signals. It also affects postsynaptic activity resulting in a
cardiovascular disease. decrease in blood pressure and heart rate. Together
Ketamine is useful in patients with airway disease in these two effects can produce sedation, anxiolysis, and
that it attenuates neurally induced bronchoconstriction. analgesia. Dexmedetomidine has several advantages for
It also has a small direct effect on smooth muscle activa- use as a sedative in the ICU. Because the drug does not
tion; however, it is unclear whether it can be utilized to cause respiratory depression, a patient can be extubated
improve asthma attacks. without prior discontinuation. This property also makes it
During emergence from ketamine, patients may ideal for patients being weaned from mechanical ventila-
have vivid dreams (both pleasant and unpleasant) and tion. The drug provides great flexibility. Since dexmedeto-
hallucinations. midine also lowers the requirement for narcotics it can
decrease opioid effects. Because elimination is primarily
hepatic, dexmedetomidine dosing should be lowered in
Etomidate patients with hepatic dysfunction. Also, inappropriate use
Etomidate is a nonbarbiturate, carboxylated, imidazole- of dexmedetomidine may induce or aggravate cardiac
containing compound. Etomidate is a hypnotic agent, conduction defects. Dexmedetomidine should not be
commonly used to induce general anesthesia in the used in hypovolemic or bradycardic patients or in patients
operating suite. It can also be used to facilitate rapid- with low cardiac output or heart conduction blocks.
sequence endotracheal intubation in the ICU. It is gen- Dexmedetomidine is a promising agent with multiple
erally used in conjunction with neuromuscular blocking actions that reduce analgesic and other sedative require-
agents. For induction of anesthesia, the initial dose is ments and produce a cooperatively sedate patient.
0.2–0.6 mg/kg over 1 minute. This drug, however, should It may open a whole new arena in the sedation of
not be given as an infusion. It is a favored drug because extubated patients who have high levels of anxiety.
of its few cardiovascular side effects. Adverse effects are Dexmedetomidine needs to be further studied to deter-
rare. Of particular importance are its neuromuscular and mine its role in the ICU.
132 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Pancuronium 0.07–0.1 Long acting; 6–120 Inexpensive Tachycardia; accumulation in renal failure
Vecuronium 0.1 30–45 CVS stability Active metabolite; accumulation in renal
and hepatic insufficiency
Atracurium 0.5 30–45 Reliable recovery Slow onset; no active metabolite
Rocuronium 0.6–1.2 30–90 Rapid onset None
Cisatracurium 0.1–0.2 30–90 Reliable recovery Slow onset
Succinylcholine 0.6–1 Ultrashort; 5–10 Fast onset and Hyperkalemia dysrhythmia
fast recovery
The main indication for use in the critically ill is rapid air- an active metabolite, 3-desacetylvecuronium, which can
way management. However, it is also associated with accumulate in patients with hepatic dysfunction. Also,
many cardiovascular side effects. up to 35% is renally excreted and dose adjustment
and careful monitoring is needed in renal insufficient
patients. Vecuronium is associated with acute quadri-
CLINICAL CAVEAT paretic myopathy syndrome (AQMS).
Succinylcholine Rocuronium
● Reported cases of acute rhabdomyolysis with
Rocuronium is a newer nondepolarizing NMBA with a
hyperkalemia followed by dysrhythmias, cardiac
arrest, and death after the administration of
monoquaternary steroidal chemistry. It has intermediate
succinylcholine in children. These children were duration of action and very rapid onset. When rocuronium
subsequently found to have skeletal muscle myopathy, is given as a bolus of 0.1–0.6 mg/kg, blockade occurs
frequently Duchenne’s muscular dystrophy. within 2 minutes. Continuous infusions, if needed, are usu-
● Relatively contraindicated in children and patients ally started at 10 μg/kg/minute. Rocuronium is not affected
with burns, skeletal muscle injury, history of by patients with renal failure and has little prolonged
malignant hyperthermia, and renal failure because action in patients with liver dysfunction.
of the risk of hyperkalemia (the risk in these
patients may last as long as 7 to 10 days). Atracurium
Atracurium is an intermediate-acting NMBA with
minimal cardiovascular side effects but is associated
with histamine release at higher doses. It is inactivated in
plasma by ester hydrolysis and by Hoffmann elimination
Nondepolarizing Agents
so renal and hepatic dysfunction does not affect the
Pancuronium duration of blockade.
Pancuronium, one of the original NMBAs used in the
ICU, is a long-acting, nondepolarizing compound that is Cisatracurium
effective after a bolus dose of 0.06 to 0.08 mg/kg for up Cisatracurium, an isomer of atracurium, is an intermedi-
to 90 minutes. It can be given as a bolus or continuous ate-acting benzylisoquinolinium NMBA that is increasingly
infusion. Pancuronium is vagolytic, which limits its use used in lieu of atracurium. It produces few cardiovascular
in patients who cannot tolerate an increase in heart rate. effects and has fewer tendencies to release histamine and
In patients with renal failure or cirrhosis pancuronium’s mast cell degranulation. Bolus doses are with 0.1–0.2 mg/kg
neuromuscular blocking effects are prolonged by the with a duration of action of 25 minutes. Infusion rates
increased metabolite 3-hydroxypancuronium. should be started at 2.0–3.0 μg/kg/minute. Cisatracurium is
also eliminated by ester hydrolysis and by Hoffmann elimi-
Vecuronium nation so patients with renal or hepatic dysfunction do not
Vecuronium is an intermediate-acting NMBA that is have a prolonged duration of blockade.
a structural analog of pancuronium but is not vagolytic.
It also can be given via bolus or continuous infusion. The
bolus dose of 0.08 to 0.10 mg/kg produces effects within Complications of Neuromuscular
3 minutes. Its neuromuscular blocking effects last Blocking Agents
approximately 30 minutes. A continuous infusion can be Multiple complications have been associated with the
used at doses of 1–2 μg/kg/minute. Vecuronium also has use of NMBAs, and the ICU physician should be familiar
134 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
with their common side effects. There are many drug or propofol: impact on weaning and costs. Crit Care Med
interactions with NMBAs that can prolong the neuro- 25(1):33–40, 1997.
muscular blockade. Antibiotics such as neomycin, strepto- Brook AD, Ahrens TS, Schaiff R et al: Effect of a nursing-
mycin, lincomycin, and tetracycline all have prolonged implemented sedation protocol on the duration of mechan-
the effects of NMBAs. Electrolytes play an important role; ical ventilation. Crit Care Med 27(12):2609–2615, 1999.
hypermagnesemia, hypokalemia, hypocalcemia, and Devlin JW, Boleski G, Mlynarek M et al: Motor Activity
lithium all prolong neuromuscular blockade. Also, patients Assessment Scale: a valid and reliable sedation scale for
who are paralyzed are at risk for keratitis and corneal use with mechanically ventilated patients in an adult surgi-
abrasions. The routine administration of ophthalmic cal intensive care unit. Crit Care Med 27(7):1271–1275,
ointment or drops is recommended. There is an increased 1999.
risk for deep venous thrombosis and the most notable Devlin JW, Fraser GL, Kanji S, Riker RR: Sedation assessment in
side effect is AQMS. AQMS is a serious complication of critically ill adults. Ann Pharmacother 35(12):1624–1632,
NMBAs, which significantly prolongs ICU and hospital 2001.
stay. This is one of the reasons that NMBAs should be Devlin JW, Holbrook AM, Fuller HD: The effect of ICU sedation
used with caution and only in experienced hands. guidelines and pharmacist interventions on clinical outcomes
On examination, the paralyzed patient has significant and drug cost. Ann Pharmacother 31(6):689–695, 1997.
motor deficits in the upper and lower extremities, along Ely EW, Truman B, Shintani A et al: Monitoring sedation status
with depressed deep tendon reflexes. Sensory function over time in ICU patients: reliability and validity of the
and ocular muscle function are usually preserved. On elec- Richmond Agitation–Sedation Scale (RASS). JAMA
289(22):2983–2991, 2003.
tromyography (EMG), there are low-amplitude compound
motor action potential and muscle fibrillations. Modest CK Hammond JJ: Protocols and guidelines in critical care: devel-
and lactate dehydrogenase increases are observed. This opment and implementation. Curr Opin Crit Care
7(6):464–468, 2001.
syndrome can be seen in patients receiving prolonged
NMBAs for greater than 48 hours or with concomitant use Hansen-Flaschen J, Cowen J, Polomano RC: Beyond the
of corticosteroids. Muscle biopsy shows Type II muscle Ramsay scale: need for a validated measure of sedating
drug efficacy in the intensive care unit. Crit Care Med
fiber atrophy with vacuolization, disordered sarcomeric
22(5):732–733, 1994.
architecture, and extensive loss of myosin.
Jacobi J, Fraser GL, Coursin DB et al: Clinical practice
guidelines for the sustained use of sedatives and analgesics
in the critically ill adult. Crit Care Med 30(1):119–141, 2002.
CONCLUSION Kress JP, Pohlman AS, Hall JB: Sedation and analgesia in the
intensive care unit. Am J Respir Crit Care Med
Critically ill patients frequently experience anxiety 166(8):1024–1028, 2002.
and pain and occasionally experience severe agitation. Mondello E, Siliotti R, Noto G et al: Bispectral Index in ICU:
These factors have a significant effects on a patient’s correlation with Ramsay score on assessment of sedation
sense of well-being, and perhaps equally important, on level. J Clin Monit Comput 17(5):271–277, 2002.
patient outcomes. Health care providers are responsible Murray MJ, Cowen J, DeBlock H et al: Clinical practice guide-
for maintaining a stress-free and comfortable environment lines for sustained neuromuscular blockade in the adult
to minimize these perceptions. The most important critically ill patient. Crit Care Med 30(1):142–156, 2002.
aspect of ICU sedation is an understanding of the drugs Nasraway SA, Jr., Jacobi J, Murray MJ, Lumb PD: Sedation,
used and their specific advantages and disadvantages. analgesia, and neuromuscular blockade of the critically
Each drug is ideal for a specific use. It is crucial for the ill adult: revised clinical practice guidelines for 2002.
clinician to develop guidelines and pathways for the use Crit Care Med 30(1):117–118, 2002.
of these drugs within a specific environment. Newer Riker RR, Fraser GL: Sedation in the intensive care unit: refin-
drugs certainly will become available and more is being ing the models and defining the questions. Crit Care Med
learnt about some of the new drugs and specific protocols 30(7):1661–1663, 2002.
that grade effect are being developed. Riker RR, Picard JT, Fraser GL: Prospective evaluation of
the Sedation–Agitation Scale for adult critically ill patients.
Crit Care Med 27(7):1325–1329, 1999.
SELECTED READING
Szokol JW, Vender JS: Anxiety, delirium, and pain in the inten-
Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ: The efficacy of sive care unit. Crit Care Clin 17(4):821–842, 2001.
dexmedetomidine versus morphine for postoperative Wheeler DS, Vaux KK, Ponaman ML, Poss BW: The safe and
analgesia after major inpatient surgery. Anesth Analg effective use of propofol sedation in children undergoing
98(1):153–158, 2004. diagnostic and therapeutic procedures: experience in a
Barrientos-Vega R, Mar Sanchez-Soria M, Morales-Garcia C et al: pediatric ICU and a review of the literature. Pediatr Emerg
Prolonged sedation of critically ill patients with midazolam Care 19(6):385–392, 2003.
12
CHAPTER Hypertension
EWAN M. CAMERON, M.D.
HEIDI B. KUMMER, M.D., M.P.H.
Evaluation
Pathogenesis EVALUATION
Secondary Hypertension
Effects of Hypertension The Joint National Committee on Prevention,
Effects of Hypertension on the Brain Detection, Evaluation and Treatment of High Blood
Effects of Hypertension on the Kidney Pressure has classified hypertension as follows. High
Anesthesia and Hypertension normal: 130–139 systolic, 85–59 diastolic; stage 1:
Treatment 140–159 systolic or 90–99 diastolic; stage 2: 160–179
Nitrates systolic or 100–109 diastolic; stage 3: >180 systolic or >110
Alpha2-Adrenergic Agonists diastolic. Blood pressure measurements should be accu-
Beta1-Adrenergic Antagonists rate and should also be confirmed on at least three
Calcium Channel Blockers different occasions. So-called white coat hypertension
Angiotensin Converting Enzyme Inhibitors can be excluded by obtaining ambulatory or at-home blood
Diuretics pressure monitoring. The latter is present in up to 20%
Hypertensive Crisis of patients with elevated blood pressure but it may be
Summary a precursor of sustained hypertension and certainly
warrants continued surveillance.
In addition to a history and physical examination,
In the general population hypertension is present in
routine testing should include urinalysis, complete
one in four adults in the USA. Among certain subgroups
blood count, creatinine and urea, potassium, and 12-lead
of the population, such as blacks and the elderly, the
electrocardiography. Severe or resistant hypertension or
prevalence of hypertension is even higher. The impor-
clinical or laboratory findings indicative of underlying
tance of hypertension lies in its widespread effect on an
disease such as that originating in the kidney or adrenal
individual’s health including the potential for causing
gland should be further investigated. In 90% of patients
stroke, myocardial infarction, renal failure, congestive
the diagnosis is one of essential idiopathic hypertension.
heart failure, progressive atherosclerosis, and dementia.
More recently isolated systolic hypertension has been
identified as a significant risk factor among the elderly =
137
138 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
different abnormalities have been described in the hyper- hypertension are renal or endocrine. Renal disease may
tensive patient, none has clearly been identified as primary. cause hypertension either by an inability to excrete
With the growth of new knowledge about hypertension sodium and water, or by elaborating excess renin. In the
in the last 20 years there has been some blurring between former retention of sodium will result in an increased
primary and secondary forms of hypertension. circulating volume leading to an increase in blood
Animal and population studies suggest that there is a pressure. In the latter high levels of renin produce high
genetic component although its influence is likely to vary levels of the vasoconstrictors angiotensin II and aldos-
among different patients. The genetic factor interacts terone. Another separate entity, renovascular hyperten-
with a number of environmental factors including salt sion, is due to atherosclerosis or fibrous dysplasia of one
intake, obesity, occupation, and family size and crowding. or both of the main arteries supplying the kidney. The
Overall these result in abnormal activity of the sympa- resulting poor renal blood flow stimulates the secretion
thetic nervous system. In the normal person changes in of higher levels of renin by the affected kidney. Patients
blood pressure are compensated by adaptive changes in known or suspected to have renovascular hypertension
activation of beta-adrenergic receptors and by secretion of should not receive angiotensin converting enzyme
renin by the juxtaglomerular apparatus of the kidney. (ACE) inhibitors as these may precipitate acute renal
Thus falls in blood pressure are accompanied by compen- failure.
satory increases in heart rate, stroke volume, and systemic
vascular resistance to maintain normal blood pressure.
In patients with hypertension, by contrast, there are
maladaptive compensatory mechanisms and therefore CLINICAL CAVEAT
patients thus affected tend to exist in a chronic vasocon-
Angiotensin Converting Enzyme Inhibitors
strictive state. The kidney also contributes significantly to and Renal Stenosis
the development of hypertension. Normally the kidney Patients known or suspected to have renovascular
secretes renin in response to hypertension-induced beta- hypertension should not receive ACE inhibitors as they
adrenergic stimulation. In turn renin promotes the may precipitate acute renal failure.
conversion of angiotensinogen to angiotensin I and
angiotensin II. Angiotensin II increases blood pressure by
causing vasoconstriction and by stimulating the release of
aldosterone from the zona glomerulosa of the adrenal The major endocrine causes of hypertension are
cortex. Aldosterone causes retention of sodium. hyperaldosteronism, Cushing’s syndrome, and pheochro-
The course of hypertension is modified by a multi- mocytoma. Together these three causes account for 1%
tude of factors including race, gender, cholesterol, of all cases of hypertension. For example, patients with
smoking, diabetes, and weight. The younger a patient is hypertension with profound hypokalemia in the absence
when hypertension is first diagnosed the greater the of diuretics should be considered to have hyperaldo-
reduction in life expectancy. In the USA blacks have steronism. Cushing’s syndrome should be suspected in
more than four times the morbidity associated with those with a combination of truncal obesity, muscle
hypertension. At all ages and in both races females with weakness, and glucose intolerance.
hypertension fare better than males. Atherosclerosis is Pheochromocytoma is characterized by diaphoresis
contributed to by many factors and so it is not surprising and paroxysmal hypertension or orthostatic hypoten-
that the effect of hypertension on outcome may be sion. The diagnosis is confirmed by showing increased
enhanced by certain other conditions. Thus the proba- presence of epinephrine and norepinephrine or their
bility of developing a morbid cardiovascular event with metabolites in a 24-hour urine sample. Other secondary
a given blood pressure will vary by many times. causes include hypercalcemia, acromegaly, oral contra-
Hypertensive patients will develop further increases in ceptives, and coarctation of the aorta.
blood pressure with time. From actuarial data and from
the era prior to treatment it is clear that hypertension
will significantly shorten life due presumably to the pro- EFFECTS OF HYPERTENSION
gression of the atherosclerotic process.
The importance of hypertension lies in its deleterious
effects on end organ function. The adverse effects of
SECONDARY HYPERTENSION hypertension on the heart include changes in diastolic
relaxation, impairment of coronary blood flow, progression
Secondary hypertension accounts for 4–5% of all of coronary artery disease, left ventricular hypertrophy,
cases of hypertension. The major causes of secondary ventricular ectopy and sudden death, and congestive
Hypertension 139
heart failure. The earliest change in the heart associated day of surgery? When should surgery be canceled in the
with hypertension appears to be loss of diastolic relax- hypertensive patient? Extensive studies performed in the
ation and the first manifestation of this abnormality is the past have demonstrated that hemodynamic stability in
sudden appearance of apparent cardiac failure often in hypertensive patients is superior when antihypertensive
the setting of stress or exercise. therapy is continued into the operative period. Nowadays
Impairment of coronary blood flow reserve will mani- it is standard practice to continue antihypertensive therapy
fest as angina in the absence of coronary artery disease. throughout the perioperative period. There are convincing
Thallium perfusion defects can be shown in those affected data that the perioperative use of antihypertensive med-
with hypertension and ambulatory recording has shown ication in those with known hypertension and in those
ischemia even in the absence of left ventricular hyper- with newly discovered hypertension results in signifi-
trophy. Animal studies of hypertension have shown that cantly less ischemia in the postoperative period. This
below certain regulatory thresholds the myocardium is effect does not appear to be related primarily to better
at increased risk of subendocardial ischemia. In hyper- control of blood pressure so much as improved control
tensive patients blood pressure that would not be con- of heart rate.
sidered abnormally low in normotensive patients may lead Patients with hypertension on the day of surgery
to significant subendocardial ischemia and subsequent should not have their surgery cancelled. In general, unless
myocardial infarction. Treatment with antihypertensive patients have diastolic blood pressure of >110 mmHg
therapy may reverse left ventricular hypertrophy. Patients or hypertension is associated with evidence of compro-
with hypertensive cardiomyopathy are at increased risk of mised end organ function, elective surgery should
sudden death. proceed. In the case of emergency surgery blood pressure
should be brought under control as soon as is practically
possible and in any case blood pressure control can be
EFFECTS OF HYPERTENSION continued in the operating room while surgery is pro-
ON THE BRAIN ceeding. While it is well recognized that hypertension is
a risk factor for poorer outcome there are no clear guide-
There is little question about the role of hypertension lines on when it is appropriate to intervene. Hypertension
in the genesis of stroke. Conversely lowering blood pres- is just one of many factors that can determine outcome
sure protects against cerebrovascular events. Strokes may and so its presence and the amount of control that
be either hemorrhagic or ischemic in origin. The under- should be exercised cannot be considered in isolation.
lying pathological change is damage to the cerebral blood Interestingly, studies on hypertension have shown that
vessel wall. For example, high blood pressure induces the use of an antihypertensive such as atenolol when
damage to the vascular endothelium that in turn leads to compared with a diuretic results in less ischemia that is
thrombus formation and vessel narrowing. Hypertension clearly associated with tachycardia rather than changes
also predisposes to hemorrhage as weakening of the wall in blood pressure.
occurs over time. In those patients with hypertension and diabetes the
occurrence of hypotension or hypertension alternating
with hypotension may increase the risk of postoperative
EFFECTS OF HYPERTENSION renal failure. As was mentioned above, longstanding
ON THE KIDNEY hypertension results in progressive loss of nephrons
and therefore loss of functional reserve. In addition the
Chronic hypertension induces permanent damage in autoregulatory mechanism operates at a higher level.
the kidney characterized by atherosclerosis of afferent These patients therefore cannot tolerate low blood
and efferent arterioles and glomerular tufts. Over time pressure. These patients warrant close monitoring with
there is loss of glomeruli resulting in gradual deteriora- an invasive blood pressure line. Similarly they have less
tion in overall function as well as reserve. In addition, coronary reserve, even in the absence of left ventricular
the autoregulatory curve is set higher so that lower levels hypertrophy.
of blood pressure are not well tolerated and may even The two most stressful periods in anesthesia are
produce acute renal failure. induction and extubation. These are the times when
exaggerated responses are likely to be seen and precau-
tions should be taken appropriately. Many drugs have
ANESTHESIA AND HYPERTENSION been used. The preoperative use of atenolol will help as
will intravenous lidocaine to blunt normal reflexes to
The two questions that have dominated this subject laryngoscopy and intubation. The introduction of the
over the years are the following. Should antihypertensive ultra-short-acting intravenous beta1-blocker esmolol has
medications be continued right up to and including the proved useful for rapid control of blood pressure and
140 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
DRUG INTERACTION
TREATMENT The preoperative use of a beta-blocker such as
atenolol when combined with a spinal anesthetic can
Nitrates lead to profound bradycardia and possible cardiac
These are time-honored drugs for control of intra- asystole.
operative hypertension. These drugs work by increasing
nitric oxide and thus causing smooth muscle relaxation.
Thus they are direct-acting vasorelaxants. Nitroglycerin Alpha1-adrenergic antagonists such as phentolamine
mainly works on the venous side and therefore is not as and phenoxybenzamine are reserved for preoperative
useful for control of high blood pressure. Sodium nitro- treatment of those patients with pheochromoctyoma.
prusside (SNP) works on both the venous and arterial
sides of the circulation. One advantage of SNP is that it has
rapid onset and offset. There are numerous side effects Calcium Channel Blockers
including profound hypotension, metabolic acidosis, These drugs – nicardipine, nefedipine, diltiazem, and
tachyphylaxis, reflex tachycardia, cyanide toxicity, and verapamil – act by blocking the influx of calcium through
thiocyanate accumulation in the presence of renal failure. calcium channels in smooth muscle and myocytes. As with
Hydralazine is another direct-acting vasodilator. One beta1-blockers they cause a decrease in the force of con-
must be aware of the possibility of reflex tachycardia. traction of the heart and also peripheral vasorelaxation.
Hypertension 141
Nifedipine is the most potent vasodilator and it should first-line treatment; when blood pressure becomes resist-
probably not be used in the recovery room for control of ant to treatment these drugs are frequently combined
postoperative hypertension as it may produce profound with other agents such as beta1-blockers or calcium
falls in blood pressure that result in stroke or myocardial antagonists. Diuretics have many metabolic side effects
ischemia. and preoperative preparation should include testing for
changes in electrolytes and renal function.
143
144 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
While there seems to be general agreement on the Box 13-4 Factors Associated with
preparation of patients presenting for cardiac surgery – Perioperative Myocardial
most of their usual medications are continued through Ischemia
the day of surgery, including heparin and nitrate infu-
sions in urgent/emergent cases – variation exists in the ● Age > 65
perioperative care of the patient coming for noncardiac ● Male gender
surgery (Box 13-5). ● Type-A personality
Many institutions prescribe antihypertensives, antiangi- ● Family history of coronary artery disease
nals, and lipid-lowering agents right through the day of ● Low activity level
● Smoking
● Drug (cocaine) and alcohol abuse
● Uncontrolled hypertension
Box 13-2 Signs and Symptoms ● Hypercholesterolemia/hyperlipidemia
of Myocardial Ischemia ● Diabetes mellitus
● Renal insufficiency
● “Silent” – no pain ● Obesity
● Pain or pressure – substernal or radiating to arms ● Known coronary artery disease, prior myocardial
and neck ischemia, angina
● Nausea and vomiting ● Congestive heart failure
● Diaphoresis ● Abnormal ECG/arrhythmias
● Shortness of breath – pulmonary edema ● Significant valvular disease
● ECG changes – arrhythmias ● Emergency surgery
● Hypotension – cardiovascular collapse ● Pain/anxiety
Figure 13-1 Stepwise approach to preoperative cardiac assessment. The steps are discussed in the text. *Subsequent care may include
cancellation or delay of surgery, coronary revascularization followed by noncardiac surgery, or intensified care.
(Reprinted from Eagle KA, Berger PB, Calkins H et al: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac
surgery – executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
(Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Anesth Analg 94:1052–1064,
2002.)
Myocardial Ischemia and Infarction in the Perioperative Period 145
Step 3 Recent coronary Yes Recent coronary angiogram Favorable result and Operating
evaluation or stress test? no change in symptoms room
No Unfavorable result or
change in symptoms
Clinical
predictors
Step 5
Major clinical
Step 4 Intermediate clinical Minor or no
predictors**
predictors clinical predictors
Poor Moderate or
Functional capacity excellent
(<4 METs)
(>4 METs)
Poor Moderate or
Functional capacity excellent
(<4 METs)
(>4 METs)
● Troponins
soon as feasible (but within 48 hours) postoperatively.
On rare occasion a patient who is not a candidate for
148 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
cardiac revascularization or who requires an urgent non- Recent studies looking at the effects of postoperative
cardiac surgical procedure may warrant preoperative aspirin administration (in the cardiac surgical popula-
placement of an intra-aortic balloon pump in addition to tion) or use of beta-blockers for at least seven days post-
optimizing medical therapy. operatively have shown promising results in terms of
improved outcome.
Ideally any patient who suffers a perioperative event
Intraoperative Myocardial Ischemia should undergo cardiac evaluation and further risk strat-
Infusing nitroglycerin as prophylaxis intraoperatively ification prior to discharge.
has no evidence to support it; however, many practi-
tioners believe in its effect and administer it routinely in
high-risk patients. Others use it as a first-line agent when
myocardial ischemia is detected. Identifying the etiology CURRENT CONTROVERSY
for the ischemia is key to successful therapy. Any inter- ● Continuation of aspirin in the perioperative period
vention should only be employed after ensuring adequacy ● Pulmonary artery catheters do more harm than good
of anesthetic depth/management and hemodynamic pro- ● Optimal hematocrit for patients at risk of myocardial
file. Control of heart rate with a selective beta-adrenergic ischemia
blocking agent is imperative. If hypotension is due to ● Mild hypo- or normothermia for patients with
volume or blood loss, blood pressure should be aug- myocardial ischemia
mented with a vasoconstrictor such as phenylephrine
while fluid or blood is being replaced. The controversy
over the optimal hematocrit for a healthy patient in gen-
eral and for the cardiac patient in particular persists; at CLINICAL CAVEAT
this point clinical judgment about the risk/benefit ratio ● Continuation of aspirin in the perioperative period
of a transfusion for the individual patient must guide may increase bleeding
transfusion therapy. If possible, coronary perfusion ● Beta-adrenergic blockers may cause bronchospasm
should be enhanced with nitroglycerin; if despite all ● Beta-adrenergic blockers may cause significant
therapies ischemic changes persist, the surgical proce- bradycardia
● Alpha-2 agonists may cause bradycardia and
dure should be finished as quickly and safely as possible.
hypotension
Unless contraindicated, the administration of an anti- ● ACE inhibitors may contribute to or exacerbate
inflammatory/antiplatelet agent like aspirin or thrombin intraoperative hypotension
inhibitor like heparin is strongly encouraged. If ischemia ● Therapy with nitrates may contribute to intraoperative
persists despite all of these therapies, consultation with hypotension
an interventional cardiologist for possible transfer from
the operating room directly to the cardiac catheteriza-
tion laboratory should be considered.
DRUG INTERACTIONS
Postoperative Myocardial Ischemia ● Beta-adrenergic blockers may potentiate narcotic-
The focus of much anesthesia-based literature has induced bradycardia
been on preoperative and intraoperative myocardial ● Alpha-2 agonists may potentiate anesthetic-related
ischemia. The fact that nearly half of all patients who bradycardia and hypotension
experience perioperative myocardial ischemia do so in ● Angiotensin enzyme inhibitors may potentiate
anesthetic-related hypotension
the postoperative period reminds us that our responsi-
bility to protect a high-risk patient does not end in the
recovery room with the end of surgery. Thus the same
considerations mentioned above should be given to
patients who develop signs and symptoms of myocardial FUTURE PERSPECTIVES
ischemia postoperatively in the post anesthesia recovery
unit (PACU) or on the ward. Unfortunately, postoperative With the advent of the electronic age and enhanced
ischemia is frequently asymptomatic; therefore during opportunity to perform large multicenter randomized
the early postoperative period these patients continue to controlled trials, some of the current controversies
be at very high risk of myocardial ischemia, infarction, or about appropriate monitoring and therapies for peri-
even sudden death. When ischemia is detected and does operative myocardial ischemia and infarction may be
not readily respond to anti-ischemic therapies such as answered in the near future. Whether to transfuse or
oxygen, nitrates, morphine, and beta-blockers urgent hemodilute, whether to keep patients cool or normo-
cardiologic consultation for potential intervention using thermic are all questions still being debated and investi-
TPA or angioplasty/stenting is indicated. gated; until further evidence is available individual
Myocardial Ischemia and Infarction in the Perioperative Period 149
and institutional practice will vary. Dealing with the SELECTED READING
possibility of increased intraoperative bleeding as a
Bode RH, Lewis KP, Zarich SW et al: Cardiac outcome after
result of continuation of aspirin therapy may turn out to
peripheral vascular surgery: comparison of general and
be a small price to pay for the benefit of increased pro-
regional anesthesia. Anesthesiology 84:3–13, 1996.
tection: not only the myocardium, but as a recent study
Cahalan MK: Detection and Treatment of Intraoperative
of patients undergoing cardiac surgery suggested, also
Myocardial Ischemia, IARS 2002 Review Course Lectures,
a multitude of perioperative complications, including
pp 27–30.
stroke and renal failure. “Triple A” therapy with aspirin,
Eagle KA, Berger PB, Calkins H et al: ACC/AHA guideline update
atenolol, and alpha-adrenergic agonists may well
for perioperative cardiovascular evaluation for noncardiac
become the optimum of care in this category of high-risk surgery – executive summary: a report of the American
patients, and quantification of C-reactive protein levels College of Cardiology/American Heart Association Task
may become part of routine preoperative blood testing Force on Practice Guidelines (Committee to Update the
to further evaluate patients at risk. Unfortunately despite 1996 Guidelines on Perioperative Cardiovascular Evaluation
our best care and therapies, a certain percentage of for Noncardiac Surgery). Anesth Analg 94:1052–1064, 2002.
patients still go on to suffer perioperative events, for rea- Fleisher LA, Eagle KA: Lowering cardiac risk in noncardiac
sons still obscure. The goal remains to try to reduce mor- surgery. N Engl J Med 345:1677–1682, 2001.
bidity and mortality to the best of our ability given our Landesberg G, Mosseri M, Wolf Y, Vesselov Y, Weissman C:
current state of knowledge. Over time we will improve Perioperative myocardial ischemia and infarction – identifi-
the overall outcome of patients at risk and those who cation by continuous 12-lead electrocardiogram with online
sustain a perioperative myocardial infarction. ST-segment monitoring. Anesthesiology 96:264–270, 2002.
Mangano DT, Layug EL, Wallace A, Tateo I: Effect of atenolol
on mortality and cardiovascular morbidity after noncardiac
surgery. N Engl J Med 335:1713–1720, 1996. [Erratum,
CASE STUDY N Engl J Med 336:1039, 1997.]
A 63-year-old white male (77 kg, 70 in) presented Mangano DT for the Multicenter Study of Perioperative Ischemia
for posterior C4–5, C5–6 facetectomies. He had Research Group: Aspirin and mortality from coronary artery
experienced right arm weakness when trying to lift bypass surgery. N Engl J Med 347:1309–1317, 2002.
wood and now was unable to lift his right arm, but Matot I, Oppenheim-Eden A, Ratrot R et al: Preoperative car-
denied any pain. His blood pressure was 120/80, heart diac events in elderly patients with hip fracture random-
rate 62, sinus. Past medical history was significant for ized to epidural or conventional analgesia. Anesthesiology
hypertension, high cholesterol, a 30-pack yr smoking 98:156–163, 2003.
history and daily alcohol intake. He denied any Mosca L: C-reactive protein – to screen or not to screen? N Engl
symptoms of chest pain or shortness of breath. J Med 347:1615–1617, 2002.
His medications included Atenolol, HCTZ, Zocor, Elavil,
and Prilosec. He was allergic to codeine. Only past Nishina K, Mikawa K, Uesugi T et al: Efficacy of clonidine
surgical history was a tonsillectomy as a child. for prevention of perioperative myocardial ischemia – a
Preoperative studies showed a hematocrit of 46, a critical appraisal and meta-analysis of the literature.
BUN of 28, and creatinine of 1.5; ECG: NSR, LAD, IMI, Anesthesiology 96:323–329, 2002.
without significant change from 5 months prior. Poldermans D, Boersma E, Bax JJ et al: The effect of bisoprolol
He received midazolam 2 mg in the preoperative on perioperative mortality and myocardial infarction in
area, was brought to the operating room and induced high risk patients undergoing vascular surgery. N Engl J
on the stretcher using fentanyl 50 μg, propofol 150 mg, Med 341:1789–1794, 1999.
and rocuronium 50 mg. He was easily intubated and Pronovost PJ, Jenckes MW, Dorman T et al: Organizational char-
the first postinduction blood pressure of 84 systolic acteristics of intensive care units related to outcomes of
was treated with 5 mg of ephedrine with good effect. abdominal aortic surgery. JAMA 281:1310–1317, 1999.
He was then positioned prone in Mayfield tongs and Raby K, Brull S, Timimi F et al: The effect of heart rate control
shortly after incision his blood pressure dropped again. on myocardial ischemia among high-risk patients after
At this time significant ST elevations were noted in vascular surgery. Anesth Analg 88:477–482, 1999.
lead II on the ECG. The hypotension was treated with
Ross AF, Tinker JH: Evaluation of the adult patient with
phenylephrine and the ST segments normalized.
cardiac problems. In Rogers MC, Tinker JH, Covino BG,
QUESTIONS Longnecker DE, editors: Principles and Practice of
Anesthesiology, Mosby Year Book, 1993, vol 11, pp 168–194.
1. At what point would you consider aborting the
procedure? Only if it happened again? Sandham JD, Hull RD, Brant RF et al for the Canadian Critical
2. Should this patient receive aspirin in the PACU? Care Clinical Trials Group: A randomized, controlled trial
3. Should you check CK MBs/troponin levels? In the of the use of pulmonary-artery catheters in high-risk surgical
operating room or in the PACU? patients. N Engl J Med 348:5–14, 2003.
4. How should this patient’s risk be stratified Valentine RJ, Duke ML, Inman MH et al: Effectiveness of pul-
postoperatively? monary artery catheters in aortic surgery: a randomized
trial. J Vasc Surg 27:203–212, 1998.
14
CHAPTER Adults with Congenital
Heart Disease
JACEK A.WOJTCZAK, M.D., Ph.D.
150
Adults with Congenital Heart Disease 151
may include recurrent laryngeal or phrenic nerve damage resulting pulmonary hypertension and congestive heart
and thoracic duct damage. Residual ductal shunts may be failure.
encountered in patients who have had coil embolization The patient with a corrected TOF should be acyanotic
procedures. If a small residual shunt remains, SBE pro- and should not have any residual VSD. Pulmonary insuf-
phylaxis is recommended, but when a PDA is eliminated ficiency is often present postoperatively but is usually
SBE is not needed. well tolerated by patients. Only some patients develop
significant pulmonary and tricuspid insufficiency with
severe right ventricular dilatation and dysfunction.
Cyanotic Heart Defects The long-term prognosis for patients with repaired
Tetralogy of Fallot TOF is excellent, with nearly 90% survival at 30 years.
This is a most common cyanotic lesion encountered Late sudden death due to ventricular arrhythmias is a
in adults. Approximately 25% of unoperated patients recognized sequela of TOF repair with an overall preva-
will survive to adolescence but only 3% survive to the lence of 3–6%. A sustained monomorphic ventricular
age of 40. tachycardia could be induced by programmed stimula-
Tetralogy of Fallot (TOF) consists of the obstruction tion in 15–30% of patients and half had frequent and
of the right ventricular outflow tract, VSD, right ventric- complex ECG. Sinus node dysfunction and intra-atrial
ular hypertrophy, and an aorta that overrides the pul- re-entrant tachycardia occurred in 20–30% of patients with
monary outflow tract. The clinical manifestations of TOF repaired TOF. In patients who have developed sustained
depend on the degree of stenosis of the right ventricular ventricular tachycardia treatment options include anti-
outflow tract and are due to right-to-left intracardiac arrhythmic drug therapy, map-guided ablation, surgery,
shunts with reduced pulmonary outflow and arterial and an implantable defibrillator.
hypoxemia. About 35% of children with TOF develop
hypercyanotic attacks or “tetralogy (tet) spells.” They are Transposition of the Great Arteries
due to a spasm of the infundibular cardiac muscle caus- Transposition of the great arteries (TGA) results from
ing sudden reduction in pulmonary blood flow leading to failure of the truncus arteriosus to spiral. As a result, the
severe hypoxemia, hypercapnia, and acidosis. aorta arises from the right ventricle and the pulmonary
Surgical repair of TOF consists of closure of the VSD artery arises from the left ventricle. Complete TGA is a
and enlargement of the right ventricular outflow tract. common congenital heart lesion accounting for about
The majority of present-day adults who underwent a sur- 7% of all congenital cardiac defects. To survive a patient
gical TOF correction had the repair performed through with TGA must have communications between the left
a right ventriculotomy which may cause arrhythmias, and right heart to allow mixing of the blood. Early
decreased right ventricular function, and late right ven- survival at birth is possible when prostaglandin E1 is
tricular failure. Recently, the surgical technique has been used to maintain ductal patency or a Rashkind balloon
changed and surgeons are using a transatrial approach. septostomy is performed to allow mixing. Patients with
Before the era of modern cardiac surgery, palliative TGA never reach adulthood without having corrective
procedures designed to increase pulmonary blood flow surgery. The majority of patients who reach adulthood
had been developed. They include Blalock–Taussig, have undergone Mustard or Senning atrial switch proce-
Waterstone, and Potts shunts. dures that create discordant atrioventricular connections
The Blalock–Taussig shunt consists of an anastomosis in the presence of the preexisting discordant ventriculo-
between the subclavian artery and ipsilateral pulmonary arterial connections. In the Mustard procedure the atrial
artery. The incidence of pulmonary hypertension is min- septum is excised and a baffle made of native peri-
imized with this shunt; however, complications include cardium or synthetic material is used to redirect pul-
thrombosis of the shunt and the development of sub- monary and systemic venous blood. Systemic venous
clavian steal syndrome. A modified Blalock procedure blood is routed to the left ventricle, which is connected
employs a synthetic graft between the vessels and to the pulmonary artery. Pulmonary venous blood is
preserves the continuity of the subclavian artery. routed to the right ventricle, which is connected to the
The Waterstone shunt is a direct anastomosis aorta. Baffle obstruction is one of the late complications
between the ascending aorta and the right pulmonary after the Mustard procedure and may occur within
artery. As the proper sizing of the anastomosis is difficult, months or a few years after the original operation. It has
an excessive pulmonary flow may lead to pulmonary to be considered in any patient with otherwise unex-
hypertension. plained peripheral edema, ascites, hepatomegaly, or pul-
The Potts shunt is a direct anastomosis between the monary symptoms. However, late cardiac arrhythmias
descending thoracic aorta and the left pulmonary artery. are the major problem after atrial switch procedures.
This operation has been abandoned because of the Twenty percent of neonates have abnormal sinus node
Adults with Congenital Heart Disease 153
function or junctional rhythm when discharged from the ventricle driving the pulmonary flow and their survival
hospital after atrial switch procedures. An increasing depends on low pulmonary vascular resistance, low left
number of these patients gradually develop signs of sick ventricular filling pressure, and adequately high central
sinus syndrome over the years. About 20% of these venous pressure. Hypoxemia, hypercarbia, metabolic
patients have had a pacemaker inserted because of acidosis, high positive airway pressure, and hypovolemia
severe bradyarrhythmias. Rapid atrial flutter and ventric- may be detrimental in these patients.
ular tachyarrhythmias are responsible for late sudden
death in these patients. However, the majority of patient
deaths are due to right ventricular dysfunction when the Obstructive Heart Defects
right ventricle, which becomes a systemic chamber, fails Pulmonary Stenosis
when subjected to abnormal afterload or preload. Pulmonary stenosis accounts for as many as 8–10% of
Over the past ten years atrial switch operations have all congenital heart defects. It can be valvular (most com-
been replaced by the arterial switch operation (Jatene mon), supravalvular, or subpulmonary. Valvular pulmonary
procedure). The arterial switch operation results in stenosis is often associated with a probe-patent foramen
anatomic correction of the discordant ventriculoarterial ovale and atrial septal defect.
connections. In this procedure the great arteries are tran- Clinical manifestations will depend on the degree of
sected distal to their respective valves and reconnected obstruction to ejection of the right ventricle. Mild to
to their anatomically correct ventricles. A successful moderate degrees of stenosis are often asymptomatic.
primary arterial switch must be performed within the Severe stenosis (gradient greater than 80 mmHg) causes
first 10 days of life. The major issue in those patients right ventricular hypertrophy and failure. The surgical
who survive to adulthood is the status of the transferred management of severe pulmonary stenosis with intact
coronary arteries; however, the incidence of coronary intraventricular septum has changed over the years from
insufficiency is low. Supravalvular pulmonary stenosis is closed (no cardiopulmonary bypass) to open valvotomy
probably the most common complication of the arterial (on bypass), and in the past few years balloon pul-
switch procedure. In contrast to the atrial switch proce- monary valvulotomy became the preferred treatment
dures, electrophysiologic abnormalities are uncommon method. However, if balloon pulmonary valvulotomy is
after the arterial switch procedure. ineffective in reducing the gradient, open valvotomy
may be performed. Adult patients after these procedures
Tricuspid Atresia/Single Ventricle are usually asymptomatic. Occasionally, an adult may
Tricuspid atresia is characterized by a small right require pulmonary valve replacement as a result of sig-
ventricle, a large left ventricle, tricuspid valve agenesis, nificant valvular obstruction and calcifications.
and markedly reduced pulmonary blood flow. Therefore,
it is a unique form of single ventricle, a term used to Coarctation of the Aorta
describe a group of CHDs in which there is abnormal Coarctation is a discrete narrowing of the aorta either
development of both chambers, resulting in a single proximal to the ductus arteriosus (preductal, infantile)
functioning ventricular chamber. All the blood from the or distal to the left subclavian artery (postductal, adult).
right atrium is diverted across an atrial septal defect into Infants with preductal coarctation of the aorta often
the left atrium, mixes with oxygenated blood, and enters have associated defects including patent ductus arterio-
the left ventricle for ejection into the systemic circulation. sus, ventricular septal defect, and bicuspid aortic valve.
Survival is possible if there is pulmonary flow through a They usually develop severe congestive heart failure as a
ventricular septal defect or patent ductus arteriosus. To result of this defect. After infancy coarctation is rarely
correct tricuspid atresia, the original Fontan operation associated with significant symptoms and is often diag-
was performed. Pulmonary flow was achieved by a right nosed during routine physical examination when sys-
atrial to pulmonary artery connection. However, this tolic murmur is detected in the second space at the left
direct connection leads to marked right atrial enlarge- sternal border. Upper extremity hypertension and
ment and the development of arrhythmias. The operation reduced pressure in the lower extremities is present. In
has undergone several modifications aimed at reducing older patients coarctation usually presents as an isolated
the incidence of atrial arrhythmias. In one of the modifi- lesion. Complications of unoperated coarctation include
cations inferior and superior vena caval blood flow is left ventricular hypertrophy and heart failure, cerebral
directed to the pulmonary arteries. Some surgeons have hemorrhage or thrombosis, rupture of the aorta, and
further modified this procedure by using an extracardiac necrotizing arteritis. Surgical corrections include the
conduit to connect the inferior vena cava to the pul- removal of the coarcted region and end-to-end anasto-
monary arteries. Therefore, patients who underwent mosis, subclavian artery flap procedure, or patch angio-
Fontan procedures have circulation in series without the plasty. The prognosis after repair of isolated coarctation
154 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
is very good; however, complications include restenosis, Paradoxical emboli originating in the lower part of the
late hypertension, and aneurysmal dilatation of the aorta. body in poorly mobile or postoperative adult patients
might reach the brain in cyanotic patients with a right-
to-left shunt or during a reversal of the shunt in patients
NONCARDIAC COMPLICATIONS with left-to-right shunt. The emboli may also originate
OF CONGENITAL HEART DISEASE from the intravenous lines and especially during place-
ment and use of central venous and Swan-Ganz
Pulmonary Complications catheters. Air filters should be used in all venous lines in
Dynamic lung compliance is decreased in patients patients with CHD. Hyperviscosity and reduction in
with increased pulmonary blood flow (left-to-right cerebral blood flow in patients with very high hemato-
shunt) and is unchanged in patients with decreased pul- crits may also play a role in increasing the risk of cere-
monary blood flow. The mechanism for this change is brovascular accidents in patients with CHD.
not clear. However, it is possible that the increase in pul- Patients with atrial fibrillation after late closure of an
monary artery pressure may result in an increase in the ASD have a high risk of TIA or stroke and may be anti-
tension of the walls of the pulmonary vascular system. coagulated for the first six postoperative months.
This “stiffer” vasculature may then oppose pulmonary Anticoagulation may be later discontinued, if patients
expansion resulting in decreased lung compliance, which remain arrhythmia-free.
in turn increases the work of breathing. Enlarged pul- Adults with cyanotic CHD have a decreased risk of
monary vessels may compress bronchi or cause a con- thrombotic intracranial events but a higher risk of
gestion and swelling of the bronchial wall, an increase in intracranial bleeding. A cerebral hemorrhage can occur
small airway resistance, chronic atelectasis, pneumonia, in patients with a history of aortic coarctation repair
or focal emphysema. The likely site of compression by even if blood pressure is not elevated.
the enlarged left pulmonary artery is the left mainstem Patients who have already undergone successful cor-
and upper lobe bronchi and the right middle lobe rection or palliation of CHD may have residual neuro-
bronchus may be compressed by the right lower lobe logic deficits related to the preoperative pathology as
pulmonary artery. An enlarged pulmonary artery can well as to intraoperative (e.g., hypothermic circulatory
also compress the recurrent laryngeal nerve. arrest) or postoperative events. These significant symp-
Patients with high pulmonary blood flow secondary tomatic hyperviscosity neurologic sequelae may include
to a large VSD or ASD, if not treated, will develop a pul- seizures, dyskinesia, hypotonia, or choreoathetosis.
monary arteriolar injury secondary to sheer stress, leading Patients with CHD may have an injury of the recur-
to muscular hypertrophy, intimal proliferation, and oblit- rent laryngeal nerve from prior surgery or compression
eration of arterioles. As the vascular disease progresses by the pulmonary artery. They may also have diaphrag-
and the pulmonary vascular resistance approaches sys- matic paresis or paralysis secondary to phrenic nerve
temic resistance, a right-to-left shunt develops, and the injury.
patient becomes cyanotic and polycythemic. This patho-
physiologic sequence is described as Eisenmenger’s
Hematologic Complications
syndrome. The presence of this syndrome precludes sur-
gical correction of the defects, as pulmonary resistance Patients with cyanotic CHD are usually polycythemic
is irreversibly elevated. These patients may have upper or erythrocytotic (an increase only in red cell number).
lobe pulmonary artery thrombosis and hemoptysis in Polycythemia is an adaptive response to chronic hypox-
end-stage disease. emia. Hypoxia triggers the release of erythropoietin by
Patients with CHD have blunted responses to hypox- the kidneys. Erythropoietin stimulates bone marrow pro-
emia but normal ventilatory response to hypercarbia. The duction of red cells and causes an increase in the circu-
oxygen–hemoglobin dissociation curve is normal or slightly lating blood volume. As the hematocrit increases, there
right shifted. In cyanotic patients arterial pCO2 is underes- is a marked increase in viscosity. The increased viscosity
timated by capnometry (end-tidal pCO2). In these patients and erythrocytosis is associated with the risk thrombosis
even moderate hypercarbia and hypoxemia will increase in children under the age of 5 years, especially when
pulmonary vascular resistance and right-to-left shunting. they are febrile or dehydrated. Due to high hematocrits
Chronic pleural effusions are fairly common in adult and limited pulmonary and systemic blood flows some
patients who have had a Fontan procedure. patients will complain of fatigue, faintness, headache,
dizziness, blurred vision or diplopia, myalgias and mus-
cle weakness, paresthesias of fingers, toes and lips, and
Neurologic Complications depressed mentation. Isovolemic phlebotomies are indi-
Major neurologic complications of CHD include cated in these patients based more on the development
brain abscesses and paradoxical cerebral embolization. of significant symptoms of hyperviscosity rather than for
Adults with Congenital Heart Disease 155
a given hematocrit. Dehydration must be first ruled out anatomy of the defect and a description of all previous
before any decision to phlebotomize is made. surgical procedures and detection of possible residual
Patients with current or even corrected cyanotic heart defects, sequelae, or late complications. For example, a
disease have a higher incidence of bilirubin gallstones history of continued postoperative hypoxemia indicates
and billiary colic. inadequate palliation and the existence of residual
About 20% of patients with CHD, both cyanotic and abnormalities. However, distinguishing between cardiac
acyanotic, have a variety of hemostatic abnormalities. and pulmonary causes of hypoxemia may be extremely
They include platelet dysfunction, thrombocytopenia, difficult.
hypofibrinogenemia, fibrinolysis, and abnormalities of A minimal workup should include a thorough clinical
the intrinsic and extrinsic coagulation systems with defi- assessment, ECG, chest x-ray, and transthoracic (TTE) or
ciencies of specific clotting factors. Patients may be very transesophageal echocardiographic (TEE) examination.
symptomatic with complaints of easy bruising, epistaxis, TTE and TEE may help to prove the existence of the
or excessive menstrual bleeding. lesion or residual shunt, better define its location, and
Prothrombin and partial thromboplastin time may be rule out chamber enlargement, baffle obstruction, valvu-
prolonged. The risk of spontaneous bleeding is low but lar insufficiency, or ventricular outflow obstruction.
the risk of excessive perioperative bleeding is fairly high, Confirmed existence of an intracardiac shunt has
especially in patients who are maintained on platelet several implications in the acute management of the
inhibitors (aspirin) due to their vascular anastomoses critically ill or anesthetized patient.
from Goretex (e.g., modified Blalock–Taussig anastomosis). Left-to-right shunts will result in pulmonary vascular
Moreover, excessive bleeding may be caused by an overperfusion; however, initially ventilation and gas
increased tissue vascularity in cyanotic patients, increased exchange are usually unaffected. These patients may
venous pressure, and collateral vessels in obstructive have a history of pulmonary banding to control the pul-
defects (e.g., coarctation). monary flow. In unrepaired patients one may expect
marked pulmonary hypertension. The presence of pul-
monary hypertension can be inferred from the marked
Renal Complications right ventricular hypertrophy on the ECG and prominent
Patients with CHD have a variety of renal abnormali- main pulmonary artery on the chest x-ray. It can be
ties. They may be related to renal hypoperfusion confirmed either noninvasively by Doppler echocardio-
hypoxia and hyperviscosity. These patients usually have graphy or by Swan-Ganz catheterization. However,
high plasma uric levels, due to low fractional uric acid placement of a flow-directed catheter may be very diffi-
excretion rather than to urate overproduction. cult due to the flow through the intracardiac shunt. Left
Hyperuricemia in CHD patients may be a marker of atrial pressure may be elevated due to increased pul-
abnormal intrarenal hemodynamics, as the enhanced monary venous return. Increased volume workload may
uric acid reabsorption is a result of renal hypoperfusion cause reduced myocardial contractility. These patients
and high filtration fraction. might require treatment with intravenous pulmonary
Glomerular enlargement and alteration in the vasodilators (e.g., milrinone, prostaglandin E1) as well as
glomerular capillary basement membrane have been the use of inhaled nitric oxide (NO). Some patients are
described in patients with CHD and appear to be a result at risk of pulmonary hypertensive crisis, which is easier
of hypoxia at an early age. These changes are associated to prevent than to reverse. Therefore, not only are
with benign proteinuria and contribute to the higher vasodilators needed but patients should be hyperventi-
incidence of nephrotic syndrome in these patients. lated (PaCO2 = 25−30) and well sedated (fentanyl and
Renal plasma flow is reduced in patients with cyanotic propofol infusions).
and acyanotic lesions and is due to the changes in the As discussed above, enlargement of pulmonary ves-
outer cortical flow. Successful surgical correction of sels may result in extrinsic compression of the airways
CHD may not result in a return of the renal plasma flow or congestion of the bronchial wall and an increase in
to normal. small airway resistance as well as alveolar edema. An
increased resistance to airflow combined with non-
compliant lungs will increase the inspiratory pressure
MANAGEMENT OF ADULT PATIENTS needed for adequate positive-pressure ventilation.
WITH CONGENITAL HEART DEFECTS Anesthetics that may induce myocardial depression
REQUIRING CRITICAL CARE AND should be avoided. The uptake of inhaled anesthetic
ANESTHESIA agents and therefore their cardiodepressive effects may
be increased.
Evaluation of patients with known CHD should be Right-to-left shunts will result in low PaO2, only min-
directed toward obtaining a complete description of imally improved by increasing the FIO2. The ventilatory
156 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
support and gas exchange will be less efficient. are more prone to atrial fibrillation. Sinus rhythm is
Capnometry (end-tidal pCO2 measurements) will under- hemodynamically preferred in CHD; therefore, cardio-
estimate the arterial pCO2 due to the large physiologic version, antiarrhythmic drugs (e.g., amiodarone), and
dead space. As the pulmonary flow is decreased manage- atrial pacing should be used to treat or prevent estab-
ment should be centered on the prevention of further lishment of atrial fibrillation.
reduction in flow. Therefore, excessive positive inspira- Gradual loss of sinus rhythm occurs after the Mustard,
tory pressure should be avoided and PEEP maintained at Senning, and all varieties of Fontan procedures.
the lowest possible level. Adequate intravascular volume Interventricular conduction abnormalities, particularly
and ventricular function should be maintained. right bundle branch block, are very common after
Patients with right-to-left shunts are at high risk of surgery for CHD. Cardiac pacing in adults with CHD
systemic emboli from lower extremity thrombophlebitis presents a variety of challenges. Anatomical abnormali-
and venous air embolism. They are also at risk of overdose ties and shunting may not allow endocardial lead place-
with intravenous drugs. However, if inhalational anesthetics ment and require transthoracic pacing.
are used during anesthesia, one may expect a delayed uptake Ventricular arrhythmias are reported in about 2% of
of inhaled agents. patients with repaired TOF. Although patients with
Polycythemia may be present in cyanotic patients and Mustard, Senning, and Fontan experience atrial tachy-
should be carefully controlled either with phlebotomy cardias, they are not prone to ventricular tachycardias.
or hemodilution, but the hematocrit should not be taken Class 1C and class 3 antiarrhythmic drugs should be used
below 50. Despite the dangers of polycythemia, these to suppress symptomatic ventricular arrhythmias.
patients are very dependent on high hematocrit to ensure Automatic implantable cardioverter and defibrillator
adequate oxygen transport. therapy is feasible in many patients with CHD.
Obstructive defects will result in fixed stroke volume
and dependence on heart rate to compensate for changes
SELECTED READING
in metabolic demand and peripheral vascular resistance.
Left or right ventricular hypertrophy and congestive heart Bancalari E, Jesse M, Gelband H et al: Lung mechanics in
failure will develop without corrective surgery. Therefore, congenital heart disease with increased and decreased
optimal myocardial perfusion should be maintained in pulmonary flow. J Pediatr 90:192–195, 1977.
those patients by increasing the duration of diastole and the Baum V: The adult with congenital heart disease. J Cardiothor
diastolic pressure. Tachycardia, which shortens diastole, Vasc Anesthesia 10:261–282, 1996.
should be avoided. Blood pressure should be maintained Gersony W, Rosenbaum M: Congenital Heart Disease in the
with pressors and volume. Adult, New York: McGraw-Hill, 2002.
Management of arrhythmias secondary to repaired, Lake C: Pediatric Cardiac Anesthesia, Stamford, CA: Appleton
unrepaired, or palliated CHD may be extremely difficult. & Lange, 1997.
History of early postoperative arrhythmias is associated Nollert G, Fishlein T, Bouterwek S et al: Long-term survival in
with a greater risk for development arrhythmias late in patients with repair of tetralogy of Fallot: 36-year follow-up
life. The spectrum of clinical consequences of arrhyth- of 490 survivors of the first year after surgical repair. J Am
mia in adults with CHD ranges from clinically occult Coll Cardiol 30:1374–1383, 1997.
arrhythmia to sudden death. Atrial arrhythmias are most Perloff J, Rosove M, Child J et al: Adults with cyanotic congen-
common and are usually due to intra-atrial re-entrant ital heart disease: hematologic management. Ann Intern
tachycardia that may respond to class 1A and class 3 Med 109:406–413, 1988.
antiarrhythmic drugs. Automatic antitachycardia pacing Perloff J, Warnes C: Challenges posed by adults with repaired
has also been of value in some patients. Patients with congenital heart disease. Circulation 103:2637–2643,
unrepaired heart disease or residual obstructive lesions 2001.
15
CHAPTER Pneumonia in Adults
JAMES E. SZALADOS, M.D., J.D., M.B.A.
Risk Factors for and Mechanisms of Pneumonia include abscess formation, pleural effusion and empyema
Development formation, bacteremia and sepsis, septic shock, acute
Diagnosis of Pneumonia respiratory distress syndrome (ARDS), meningitis, endo-
Radiologic Diagnosis of Pneumonia carditis, and multiple organ dysfunction or failure.
Nonradiologic Diagnosis of Pneumonia The rapid initiation of broad-spectrum empirical
Classification and Treatment of Pneumonia antibiotic therapy correlates with long-term morbidity
Community-Acquired Pneumonia and mortality from pneumonia. The earlier the specific
Typical Community-Acquired Pneumonias infectious agent is appropriately treated the better the
Atypical Community-Acquired Pneumonias outcome is likely to be.
Viral Pneumonia
Fungal Pneumonia
Nosocomial Pneumonia CLINICAL CAVEAT
Hospital-Acquired Pneumonia
Treatment of Serious Infection
Ventilator-Associated Pneumonia
Serious infection should be treated as a medical
Pneumonia in Patients with Compromised Immune Status
emergency and antibiotics must be initiated as soon as
Adjunctive and Supportive Therapeutic Strategies possible; there should be no delay in obtaining cultures
Fluid Resuscitation or awaiting culture and sensitivity data.
Nutritional Support
Pharmacologic Treatment
Antibiotic Principles
The Centers for Disease Control (CDC) defines pneu-
Nonantibiotic Adjunctive Pharmacologic Therapy
monia to be present when the chest radiograph reveals
General Principles of Chest Radiograph Interpretation
a new or progressive infiltrate, pleural effusion, or cavi-
tation, and any one of the following: (1) a change in
The incidence of pneumonia is increasing. The exact the character, quantity, or consistency of the sputum,
annual incidence of pneumonia is difficult to determine (2) the pathogen is isolated from the lower respiratory
because it is not a notifiable disease. The incidence tract, by cultures, or by lung biopsy, (3) a virus or viral
varies with geography, population demographics, antigen is isolated in respiratory secretions, (4) a diag-
comorbid conditions, and the severity of the flu season. nostic serum IgM antibody titer or a fourfold rise in IgG
There are approximately 4 million cases of community- antibody titers can be demonstrated in paired serum
acquired pneumonia and at least 300,000 cases of hospi- samples, (5) histologic evidence of pneumonia can be
tal-acquired pneumonia reported annually. Pneumonia demonstrated in tissue biopsy. Note that these general
accounts for the largest mortality of any common infec- criteria do not include sputum Gram stain or culture.
tious disease. Pneumonia ranks in the top seven among Pneumonia treatment is simplified by numerous
the major leading causes of death in adults in the USA. guidelines which are described below. The standard of
It is the fourth leading cause of death in the US elderly medical care for the management of pneumonia has
population. A large variety of organisms cause pneumonia evolved considerably over the last decade based on large
(Table 15-1). The important complications of pneumonia multicenter outcome studies. The present evidence-based
157
158 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
MYCOSES
Cryptococcus
Histoplasmosis
Coccidiomycosis
Blastomycosis
Aspergillus spp.
Candida spp.
DIAGNOSIS OF PNEUMONIA
Figure 15-3 Bilateral bronchopneumonia. Radiograph reveals Figure 15-5 Right pleural effusion. There is a characteristic
bilateral confluent infiltrates in pulmonary lobules (lobular fluid meniscus on the right and there is evidence of some aeration
pneumonia). The inflammation involves the terminal respiratory within the right lower lobe. The underlying pneumonia is not
bronchioles. apparent in this view but could be defined in a lateral decubitus
view after the surrounding fluid layers away from the pulmonary
tissue.
Table 15-3 Point Scoring System Reflecting Risk in Table 15-4 Fine Prediction Rule for Risk and
Community-Acquired Pneumonia (after Treatment Site in Community-Acquired
Fine MJ et al, 1997) Pneumonia (after Fine MJ et al, 1997)
Table 15-5 IDSA and ATS Guidelines for Empiric Treatment of Community-Acquired Pneumonia
1. OUTPATIENTS (ORAL)
a. Nonsevere pneumonia; no underlying Macrolide or doxycycline or fluoroquinolone Advanced macrolide
cardiopulmonary disease
b. Nonsevere pneumonia; underlying Beta-lactam plus macrolide or
cardiopulmonary disease and/or risk doxycycline; or fluoroquinolone
factors for DRSP alone
Viral Pneumonia
Viral pneumonias typically occur in the setting of an
outbreak and occur predominantly in the winter and
early spring. Patients at risk for viral pneumonias include
those with underlying heart disease, chronic pulmonary
disease, and pregnancy. Pulmonary infiltrates can occur
in 20% of young adults with varicella but a frank pneu-
monia presentation is rare and is more suggestive of a
bacterial superinfection (Figure 15-6). Herpetic pneu-
monias occur with high frequency in postoperative
cardiac and transplant patients. The true incidence is Figure 15-6 Influenzal viral pneumonia. There is evidence of
probably under-recognized. The route of infection is consolidation in the right middle and lower lobes in the setting
probably the aspiration of saliva contaminated by the virus. of pneumonia with positive viral titers.
Pneumonia in Adults 165
The clinical picture is usually limited to hypoxia and dys- are likely very important but largely under-diagnosed
pnea. The virus may be isolated in culture. Treatment is pathogens in nosocomial and especially ventilator-
with antiviral agents such as acyclovir. associated pneumonias. Histoplasma is found in soil
Pulmonary Hantavirus syndrome with the Sin contaminated with bird and bat excreta. Histoplasmosis
Nombre virus was identified in 1993 in the American is the most common systemic mycosis in the USA and is
Southwest and is acquired through exposure to the deer characteristically found in the Ohio and Mississippi river
mouse, its excrement, or contaminated dust; however, valleys. Although an estimated 500,000 people develop
the disease has been reported throughout the USA. The histoplasmosis in the USA annually, less than 1% develop
syndrome is characterized by a nonspecific 3–6-day pro- a clinically symptomatic disease. In immunocompetent
drome followed by hypoxemia and a sepsis syndrome. individuals with intact T-cell function, infection is usu-
Although the clinical picture suggests a pneumonia, the ally subclinical and self-limited. In those patients who
microscopic picture is more consistent with pulmonary develop symptomatic histoplasmosis, the presentation is
capillary leak syndrome such as occurs in ARDS. The usually that of a flu-like syndrome with a nonproductive
case fatality rate for Hantavirus pulmonary syndrome is cough and pleuritic chest pain. Less than 5% of infected
50% or more. individuals develop rheumatologic syndromes such as
Over the last two years there has been a growing pericarditis and arthralgias or inflammatory granuloma-
concern over large-scale epidemics of viral pneumonias. tous mediastinitis. In patients with impaired immunologic
The one with the greatest impact, severe acute respira- function or patients who have received a high inoculum
tory syndrome (SARS), is a coronavirus infection that exposure, such as construction or agricultural workers,
causes pneumonia and severe ARDS. It was first recog- there may be an acute overwhelming pulmonary histo-
nized in Southeast Asia in November 2002 from where it plasmosis characterized by profound hypoxemia and dif-
spread to other countries. Repeat epidemic episodes are fuse bilateral pulmonary infiltrates. Rare complications
likely. The SARS mortality rate worldwide is approxi- of histoplasmosis include chronic upper lobe cavitary
mately 10.5%; the ICU admission rate ranged from 20% pneumonic disease, fibrosing mediastinitis, and progres-
to 38%; over 60% of ICU patients require mechanical sive disseminated histoplasmosis. Definitive diagnosis
ventilatory support. The mortality rate of SARS patients usually requires immunodiagnostic testing which is not
admitted to the ICU ranges from 5% to 67%. definitive, or periodic acid Schiff staining. Treatment is
either with itraconazole or amphotericin B; the con-
comitant systemic corticosteroid therapy should be con-
CLINICAL CAVEAT sidered (Figure 15-7).
SARS Blastomyces is also found in moist soil rich with
● The most common clinical symptoms and signs of decaying organic material. Blastomycosis is endemic
SARS are fever, cough, dyspnea, myalgias, and along the Mississippi and Ohio river basins as well as the
malaise. Great Lakes. Approximately 75% of infected patients
● Common laboratory abnormalities include mild have isolated lung involvement and the remaining 25%
leukopenia, lymphopenia, and increased aspartate develop a disseminated lymphohematogenous disease
transaminase, alanine transaminase, lactic
involving primarily the skin, bone, and genitourinary
dehydrogenase, and creatine kinase.
● The chest radiograph pattern ranges from focal
system. Pulmonary blastomycosis develops approximately
infiltrates to diffuse airspace disease. The risk of six weeks after exposure and presents as a flu-like syn-
mortality increases with advanced age, drome with a productive mucopurulent sputum. Chest
comorbidities, a high lactic dehydrogenase, or a radiographs reveal nonspecific diffuse reticulonodular
high neutrophil count at admission. infiltrates. Chronic common blastomycosis is similar to
tuberculosis and is accompanied by night sweats, weight
loss, and productive cough, and may progress to cavitary
Emerging diseases are likely to become more of a disease. Blastomycosis can be diagnosed by PAS or
global threat as viruses increasingly jump species and silver staining of sputum. Ketoconazole, itraconazole, or
mutate rapidly. fluconazole are the mainstay therapies (Figure 15-8).
Coccidioides is found in semiarid desert soil.
Coccidiomycosis is endemic in the southwestern USA
Fungal Pneumonia and approximately 100,000 new cases occur annually in
Fungal pneumonias represent a subset of CAPs caused the Sonoran Desert and the Central (San Joaquin) Valley
by endemic fungi such as Histoplasma capsulatum, of California. Approximately 40% of infected individuals
Blastomyces dermatitidis, and Coccidioides immitis. develop clinically evident disease in one to three weeks
However, fungal pneumonias also represent opportunis- following exposure. The disease is typically a self-limited
tic infections in immunocompromised populations and flu-like pneumonitis characterized by nonproductive
166 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Nosocomial Pneumonia
Figure 15-9 Coccidiomycosis. A patient from the San Joaquin
The definition of a nosocomial pneumonia is one that Valley of California. Chest radiograph shows hilar prominence
starts at least 48 hours after hospital admission. indicative of both adenopathy and a focal coin-lesion type of
Nosocomial pneumonia or hospital-acquired pneumonia reaction in the mid-upper lung fields (coccidiomas).
Pneumonia in Adults 167
faecium and E. faecalis are becoming serious threats. diagnosis of VAP, giving direct visualization of the
However, the former is vastly more common than the airways which can reveal inflammation, mucus, and mucus
latter at the present time. Linezolid and Synercid are plugging. A protected brush specimen can be obtained
important antibiotics against this class of organism. either blindly or with a bronchoscope. The protected
Vancomycin resistance in Enterococcus and brush is designed to reduce false positive cultures which
Staphylococcus is a reflection of its overuse. It is esti- are due to contamination from upper airway secretions
mated that 60–65% of vancomycin use is inappropriate. and may represent only tracheobronchitis rather than
Pseudomonas aeruginosa is an extremely common true pneumonia. The protected brush is housed within a
pathogen for HAP and VAP with a higher mortality rate closed cannula. When the cannula is passed into the distal
than most other Gram-negative bacilli. Plasmid-mediated airways, the brush is advanced through the occluding
resistance is rapid. Pseudomonas pneumonia increases plug of the cannula and is exposed directly to distal res-
ICU mortality by a factor of 2.6–6.4. In patients who have piratory secretions. Structures are retracted into the can-
P. aeruginosa or acinetobacter infections, crude ICU nula and removed for plating and culture. Quantitative
mortality exceeds 70%. cultures revealing colony growth ≥103 colony forming
Fungal pneumonias are both under-diagnosed and units (cfu)/ml are considered positive and correspond to
under-treated in critically ill patients. Mycotic infection a bacterial density of 105–106 cfu/ml in undiluted respi-
is known to occur in the presence of adjunctive anti- ratory secretions.
biotic therapy, immunosuppression, and severe illness. Bronchoalveolar lavage is performed through a bron-
Unfortunately, fungal infection is more likely be a post- choscope by washing a specific lung segment with iso-
mortem diagnosis than a clinical one. A key limitation is tonic saline and collecting the effluent directly through
the inability to culture rapidly specimens containing fun- the bronchoscope suction for culture. When the BAL is
gal pathogens and perform sensitivity testing on isolates. performed using a wedged catheter tip, which isolates
The development of antifungal agents with decreased the lung segment during lavage, the technique is known
systemic toxicity has facilitated the treatment of as a protected BAL. A minimum lavage volume of approx-
mycoses in critically ill patients. Specific criteria for imately 120 ml is recommended for adequate sampling;
initiation and discontinuation of systemic fungal agents when smaller volumes of saline (10–50 ml) are used, the
remain controversial. technique is called a mini-BAL. A threshold of 104 cfu/ml
is considered positive for pneumonia when the BAL is
used but this corresponds to the same bacterial titer in
CURRENT CONTROVERSY undiluted respiratory secretions as a protected brush.
Treatment of Ventilator-Associated Pneumonia The sensitivity and specificity of BAL is considered to
The risk of undertreatment is increased morbidity range from 70% to 100%. Open lung biopsy is the most
and mortality. The risk of overtreatment includes the definitive diagnostic procedure for histopathologic diag-
development of resistant strains of bacteria, the nosis of pneumonia in immunocompromised hosts.
significant cost of continued surveillance cultures,
medications, consultations, drug level monitoring, and
the increased potential for medication errors.
䉴
There is no gold standard method for the diagnosis of
VAP. Studies have repeatedly been unable to demon-
䉴 KEY POINTS
Ventilator-Associated Pneumonia
strate with statistical significance the clear value of any ● The single best predictor of mortality in patients
technique over any other. However, a number of diag- with VAP is the resolution of pulmonary shunting as
nostic modalities are used in practice: endotracheal tube measured by the pAO2/ FIO2 ratio.
aspirates (ETA); bronchoscope-directed protected brush- ● Successful prevention of VAP is a clearly more cost-
ings (BDPB); protected brush specimen (PBS); broncho- effective strategy then surveillance and treatment.
scopic bronchoalveolar lavage (BBAL); and blind BAL or ● The avoidance of patient cross-contamination by
vigorous handwashing is probably the most
QTL which are quantitative tracheal lavage techniques.
important precaution that health care workers can
Endotracheal tube aspirates are the most commonly per- take to prevent spread of pneumonia and other
formed method of culturing respiratory secretions. Since infections in hospitals. Universal precautions should
endotracheal tube aspirates culture both contaminants be considered universally.
and colonization as well as infectious pneumonia, the ● The use of endotracheal tubes designed to permit
use of semiquantitative cultures and the determination continuous removal of pooled subglottic secretions
of sputum neutrophil count can greatly increase their has been proven to decrease the incidence of VAP.
sensitivity. Bronchoscopy is an important adjunct to the
170 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
䉴
䉴
bronchoscopic diagnosis of pneumonia. The key param-
KEY POINTS—Cont’d eters include temperature, quantity of secretions, leuko-
cyte count, chest radiographic findings, hypoxemia, and
● Patient positioning in semi-recumbent rather than BAL Gram stain and culture. A CPIS of >6 indicates infec-
supine position decreases the incidence of VAP. tious pneumonia with a sensitivity of 93% and specificity
The elevation of the head of the patient’s bed can of 100%. Therefore, a CPIS of >6 almost excludes
decrease the risk of aspiration. acute lung injury, pulmonary edema, or atelectasis as the
● More controversial strategies include stress ulcer etiology of a pulmonary infiltrate.
prophylaxis, selective digestive decontamination,
aggressive oral and dental care, and frequent
changes of ventilator circuits and filters.
● Potential future developments include the use of Pneumonia in Patients with Compromised
bioactive and drug-impregnated biomaterials for Immune Status
endotracheal tube construction. The causes of pneumonia in the immunocompro-
mised host include all pathogens listed above and extend
to opportunistic pathogens. Other causes of pulmonary
Pleural or parapneumonic effusions are associated infection in immunocompromised patients include
with up to 50% of bacterial pneumonias. These effusions Mycobacterium tuberculosis and M. avium-intracellulare,
can be free or loculated and may either resolve or develop Cryptococcus, Toxoplasma, and cytomegalovirus. Many
into empyema. These effusions should be drained of these infections also involve other organs such as the
immediately if there is radiologic evidence of an air–fluid brain and the eye (Figures 15-10 and 15-11). Pneumonia
level. Parapneumonic effusions should be evaluated by in immunocompromised patients presents atypically.
paracentesis for Gram stain and culture, pH, LDH, protein, Dyspnea, hypoxemia, nonproductive cough, and a gen-
and glucose in order to differentiate between trans- eralized radiographic infiltrate frequently constitute the
udative and exudative fluid. Grossly purulent fluid should presenting picture. Such patients may be hypothermic
be drained. rather than febrile, and may have a leukopenia rather
The clinical pulmonary infections score (CPIS) has than leukocytosis. The responsible pathogen may be
utility in both detecting the onset of VAP and also deter- isolated in only 40% of immunocompromised patients.
mining the sufficiency and adequacy of treatment. The The early evolution of systemic sepsis in this population
CPIS also correlates with 28-day mortality. The diagnosis of makes rapid diagnosis and intervention extremely
pneumonia is generally based upon variations of the CPIS important.
originally developed by Pugin et al. in 1990 (Table 15-7). Pneumocystis carinii (PCP) is a protozoan pneumonia
The CPIS has a specificity (85–95%) similar to that of which is common in HIV-infected patients. The pneumonia
Modified from Pugin J, Auckenthaler R, Mili N et al: Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic
“blind” bronchoalveolar lavage fluid. Am Rev Respir Dis 143:1121–1129, 1991.
Pneumonia in Adults 171
Fluid Resuscitation
In all patients with severe infective processes, sup-
Figure 15-11 Cryptococcus pneumonia. Bilateral infiltrates portive therapy is necessary to prevent secondary injury
with small thin-walled areas of cavitation. Radiographically, and the development of complications. Fluid resuscita-
cryptococcus mimics nonspecific pneumonitis and presentation
can vary from cavitations, miliary lesions, to larger infiltrates. tion is a basic tenet of managing infection. Many patients
Late-stage cryptococcus can be mistaken for pneumocystis, or are unable to “drink plenty of fluids” and therefore require
lymphoreticular malignancy, and it also resembles ARDS. intravenous hydration. Both systemic infection and
172 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Nutritional Support
Patients with severe infection are highly catabolic and
nutritional support should be instituted immediately, if
possible. Many patients with pneumonia are already
nutritionally depleted on initial presentation, and base-
line nutritional status (pre-albumin, transferrin) should
be documented. Daily calorie counts and serial nutri-
tional indices may be required to ensure adequacy of
Figure 15-13 Late-stage Pneumocystis carinii pneumonia. nutritional support. Unless there is a definite contraindi-
Upright anteroposterior (AP) view. Widespread bilateral interstitial cation to enteric feeding, it is the route of choice for
and alveolar infiltrates resembling ARDS. Interstitial markings nutritional support. Nutritional depletion has been shown
result in a “honeycomb” appearance. An endotracheal tube is to increase bacterial adherence to the airways, reduce
present.
alveolar macrophage function, impair neutrophil and
macrophage recruitment, decrease levels of circulating
systemic inflammatory response produce early periph- complement factors, and reduce levels of airway IgA.
eral vasodilatation and capillary leak which result in
diminished intravascular fluid volume. Since increased
stroke volume is usually not possible in such patients, Pharmacologic Treatment
the decreased intravascular volume is initially compen- Antibiotic Principles
sated for by tachycardia to maintain cardiac output and The ability of an antibiotic to exert its pharmacologic
oxygen delivery to tissues. In patients who are unable to effect is related to penetration into infected tissue and
mount a compensatory tachycardia (diabetes, myo- achievement of adequate tissue concentrations.
cardial pump dysfunction, beta-blocker therapy, etc.) Inappropriate treatment of pneumonia is most often due
there are early signs of diminished peripheral perfusion to either nonsusceptibility or resistance of the pathogen
and shock. In the setting of prolonged under-resuscitation, to the chosen antibiotic regimen. Inappropriate initial
the inflammatory cascade is activated, regional hypo- antibiotic selection can range from 27% to 73% and has
perfusion results, and acidosis and elevated serum lactate, a dramatic impact on outcome measured by length of
acute renal failure due to acute tubular necrosis from stay, multiple organ dysfunction syndrome, and mortality.
regional underperfusion results, and the patient becomes Antibiotics that have good penetration into respiratory
progressively more difficult to resuscitate later. secretions that is not dependent on localized inflam-
Vasopressors should not be used as the mainstay of mation include the quinolones, azithromycin, clari-
therapy for sepsis. Although vasopressors may be used thromycin, tetracycline, clindamycin, and TMP-SMX.
to temporize while fluid resuscitation is ongoing, the Antibiotics that have impaired penetration into respira-
substitution of vasopressors for fluid results in progres- tory secretions and/or are dependent on inflammation for
sive tissue ischemia and organ failure. The development concentration within lung tissue include aminoglycosides
of progressive hypoxemia with intravascular volume and the beta-lactams (penicillins, cephalosporins, and
therapy does not necessarily mean intravascular fluid carbapenems). Aminoglycosides have poor pulmonary
overload – it is also consistent with a worsening of the penetration, and especially do not penetrate well into
pneumonia or the interval development of ARDS. respiratory secretions. Therefore aminoglycosides should
Pneumonia in Adults 173
not be used as monotherapy for Gram-negative pneumo- develop a superimposed respiratory tract infection.
nias. Azithromycin has replaced erythromycin in clinical Since airway infection can predispose some patients to
practice because erythromycin has side effects of both QTc bronchospasm and thereby interfere with their ability to
prolongation as well as enteric prokinesis which causes cough and clear secretions, bronchodilator therapy is
cramping discomfort. Fluoroquinolones are also associated beneficial in this population. Patients who use bron-
with QTc prolongation, especially at higher doses. chodilator therapy regularly prior to admission may
Pathogen susceptibilities are often reported in terms require an increase in the dose or frequency. Nonsteroidal
of the minimum inhibitory concentration (MIC); the bronchodilators can be either beta-2 agonists such as
agent of choice will therefore depend on the MIC, guide- albuterol or anticholinergic such as Atrovent. The beta-2
lines and restrictions, and cost. Optimal pharmacologic sympathomimetics can still precipitate tachycardia.
action of antibiotics is that for which every concentration- Lev-albuterol is a selective isomer with significantly
dependent mechanism of action occurs when Cmax/MIC less cardiac activity and possibly also a longer effective
is greater than 10. half-life.
In any patient who has failed to respond clinically Steroids are important bronchodilators in patients
after 48–72 hours of antimicrobial therapy, the thera- with underlying chronic obstructive pulmonary disease
peutic strategy must be reevaluated. Generally, this will (COPD) or severe reactive airway disease. Methylpred-
require further workup including revaluation of culture nisolone is the intravenous steroid bronchodilator of
and sensitivity data, consideration of superinfection, choice; prednisone is administered enterally. Patients for
reconsideration of drug dosing or route of administration, whom steroids have been chronically prescribed prior to
and consideration of an alternative diagnosis. Evaluation admission require supplemental “stress doses” to avoid
of the patient’s immunologic status may also be necessary. adrenal insufficiency in the setting of infectious stress.
Other routes of antibiotic therapy may be important Mucolytic agents and expectorants may have a role
in the care of ICU patients. Inhaled antibiotic therapy when mucus clearance is difficult in the setting of
is probably underutilized. Inhaled antibiotics should be dehydration or inspissated mucus is difficult for the
considered for severe HAP and in the treatment of refrac- patient to clear. N-acetylcysteine, recombinant DNase,
tory pneumonia in populations such as patients with and guaifenesin are prototypic mucolytic agents. N-
cystic fibrosis. acetylcysteine can precipitate bronchospasm and should
Mechanisms of antimicrobial resistance include target- be administered concomitantly with bronchodilators.
mediated resistance, enzymatic inactivation, cell mem- Humidification of inspired gases is important when
brane permeability alterations, and active expulsion of the endotracheal tube bypasses the normal humidifi-
antibiotics from bacterial cells. Target-mediated resist- cation and filtering systems of the upper airways.
ance is a result of alterations in the number or affinity of Humidification is important to avoid dry mucosal sur-
antimicrobial binding sites within bacteria. Enzymatic faces in patients with inflamed upper airways and
inactivation results from the production of bacterial humidification can improve expectoration of lower air-
enzymes often carried by plasmids, which degrade way secretions. On the other hand, humidification sys-
antibiotic agents. Beta-lactamase production is the most tems must be carefully monitored for contamination
common form of enzymatic resistance. Cell membrane with hypophilic organisms such as Pseudomonas and
permeability changes cause decreased antimicrobial Legionella.
uptake into bacterial cells. The promotion of active Stress ulcer prophylaxis must be considered in any
reflux of antibiotic out of bacterial cells is an energy- hospitalized or critically ill patient exposed to metabolic
dependent mechanism which is carried on by plasmids stress; stress ulcer prophylaxis has been shown to
and the creation of molecules known as transposons. decrease the incidence of gastrointestinal bleeding as a
The rotation of first-line antibiotics of choice has been standard of care. The hypothesis that increasing gastric
demonstrated to decrease the rate of evolution of pH with stress ulcer prophylaxis increases incidence of
pathogen resistance. Therefore, the choice of antibiotic nosocomial pneumonia due to aspiration of colonized
should also be made in accordance with the preferred gastric contents is no longer favored. Commonly used
antibiotic in any particular cycle at any particular hospital. agents include proton pump inhibitors such as panto-
prazole or others; H2 blockers such as famotidine; or
Nonantibiotic Adjunctive Pharmacologic Therapy barrier agents such as sucralfate.
In rare cases the use of immunomodulatory agents The use of oral care agents such as topical Mycostatin
such as granulocyte colony-stimulating factor (GCSF) may liquid may be beneficial because it focuses attention
need to be considered to enhance host polymorpho- on oral care and the potential for bacterial and fungal
nuclear leukocyte (PMN) response. overgrowth in the oral pharynx of integrated patients
Bronchodilators are a very important adjunctive ther- who have decreased salivary production and clearance.
apy in those patients with reactive airway disease who Also, oral care agents may have an antiseptic effect
174 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
䉴
䉴 Radiologic Interpretations
KEY POINTS
(a) Technique:
(i) Anterior-posterior versus posterior-anterior versus lateral. Lateral decubitus films are sometimes obtained to
determine fluid layering.
(ii) Upright or supine. Upright films are necessary to better delineate pleural effusions and pneumothorax in and air
under the diaphragm.
(iii) Penetration: assessed objectively by comparison of lung fields and bony structures. Over penetration will
emphasize the denser bony structures and obliterate subtle findings within the lung parenchyma.
(iv) Rotation: relates to the patient’s position on the radiographic plate. Rotation is best assessed by looking at
clavicular symmetry.
(b) Hardware:
(i) Endotracheal tube: should be midway between the clavicles and the carina within the trachea. It is important to
note that the endotracheal tube will move approximately 2.5 cm in or out of the trachea with extension and
flexion of the neck, respectively.
(ii) Nasogastric and feeding tubes: must be followed within the esophagus into the stomach or small bowel. Tubes
that enter the trachea will often pass through one mainstem bronchus.
(iii) Tube thoracostomy: mention is usually made of the position of the tube, the intra- or extrathoracic placement of
a last collecting hole of the chest tube, and resolution of the liquid or air collection which the tube was intended
to treat.
(iv) Other hardware: tracheostomy tubes, pacemakers, implantable cardiac defibrillation wires, intra-aortic balloon
pump tips, prosthetic cardiac valves, evidence of vascular prostheses and stents, sternal wires, surgical clips,
orthopedic prostheses, and airway stents. The mention of other foreign bodies, especially in trauma cases, is
particularly important.
(c) Bony structures:
(i) Fractures and dislocations of the clavicles, sternum, scapula, ribs, and vertebrae.
(ii) Hyperostosis, osteopenia, or potential bony involvement of surrounding tumor or infection.
(d) Cardiovascular silhouette:
(i) The AP portable radiograph is an unreliable indicator of cardiomegaly.
(ii) The cardiac silhouette.
(iii) The thoracic aorta. Special mention should be made of calcifications within the thoracic aorta and dilatation of
the thoracic aorta.
(iv) The pulmonary vasculature. Hilar accentuation. Pulmonary arterioles seen end-on are usually apparent and
present as small opaque circles in the hilar regions and are normal findings. Evidence of vascular prominence,
interstitial prominence, or alveolar flooding consistent with stages of congestive heart failure and pulmonary
edema, respectively, must be noted.
Pneumonia in Adults 175
䉴
䉴 KEY POINTS—Cont’d
(v) The cardiovascular silhouette and trachea, taken together, are good indicators of mediastinal shift in the setting
of consolidation (mediastinal shift toward the side of consolidation) and abnormal collections of air or fluid
(mediastinal shift away from the side of the collection).
(vi) The hilum: reflects both adenopathy as well as pulmonary vasculature and peribronchial tissue.
(e) Lung fields:
(i) Expansion, hyperinflation, bullae, inspiratory effort, or atelectasis.
(ii) Infiltrates, consolidation, cavitation, masses.
(iii) Air bronchograms.
(iv) Pleural collections.
(f ) Diaphragm and surrounding abdominal tissue:
(i) Air under the diaphragm is indicative of either a recent abdominal intervention such as recent surgery,
paracentesis, or hysteroscopy; or it is a sign of a surgical emergency.
(ii) A large gastric air bubble may require a nasogastric tube.
(iii) Ileus may be apparent but is nonspecific and is an indirect incidental finding on a chest radiograph.
SELECTED READING Manocha S, Walley KR, Russell JA: Severe acute respiratory
distress syndrome (SARS): a critical care perspective. Crit
American Thoracic Society: Hospital-acquired pneumonia in Care Med 31:2684–2692, 2003.
adults: diagnosis, assessment of severity, initial antimicro-
Masur H, Kaplan JE, Holmes KK; US Public Health Service;
bial therapy, and preventative strategies. A consensus
Infectious Diseases Society of America: Guidelines for
statement. Am J Respir Crit Care Med 153:1711–1725,
preventing opportunistic infections among HIV-infected
1995.
persons – 2002. Recommendations of the US Public Health
Bartlett JG, Brieman RF, Mandell LA, File TM; Infectious Service and the Infectious Diseases Society of America.
Diseases Society of America: Community acquired pneu- Ann Intern Med 137:435–478, 2002.
monia in adults: guidelines for management. CID
Niederman MS, Mandell LA, Anzueto A et al; American
26:811–838, 1998.
Thoracic Society: Guidelines for the management of adults
Colice GL, Curtis A, Deslauriers J et al: Medical and surgical with community-acquired pneumonia. Diagnosis, assess-
treatment of parapneumonic effusions: an evidence-based ment of severity, antimicrobial therapy, and prevention.
guideline. Chest 118:1158–1171, 2000. Am J Respir Crit Care Med 163:1730–1754, 2001.
Fine MJ, Stone RA, Lave JR et al: Implementation of an Ost DE, Hall CS, Joseph G et al: Decision analysis and diagnostic
evidence-based guideline to reduce duration of intravenous strategies in ventilator-associated pneumonia. Am J Resp
antibiotic therapy and length of stay for patients hospital- Crit Care Med 168:1060–1067, 2003.
ized with community-acquired pneumonia: a randomized
Pugin J: Clinical signs and scores for the diagnosis of ventilator-
controlled trial. Am J Med 115:343–351, 2003.
associated pneumonia. Minerva Anesthesiol 68:261–265,
Katzan IL, Cebul RD, Husak SH et al: The effect of pneumonia 2002.
on mortality among patients hospitalized for acute stroke.
Pugin J, Auckenthaler R, Mili N et al: Diagnosis of ventilator-
Neurology 60:620–625, 2003.
associated pneumonia by bacteriologic analysis of bron-
Kirtland SH, Corley DE, Winterbauer RH et al: The diagnosis of choscopic and nonbronchoscopic “blind” bronchoalveolar
ventilator-associated pneumonia. a comparison of histo- lavage fluid. Am Rev Respir Dis 143:1121–1129, 1991.
logic, microbiologic, and clinical criteria. Chest 112:
Rex JH, Walsh TM, Sobel JD et al: Practice guidelines for the
445–457, 1997.
treatment of candidiasis. CID 30:662–78, 2000.
Luczycki S, Papadakos PJ, Szalados JE : Ventilator-associated
Wunderink RG, Waterer GW: Genetics of sepsis and pneumonia.
pneumonia: pathophysiology, diagnosis, and treatment.
Curr Opin Crit Care 9:384–389, 2003.
Crit Care Shock 2:72–87, 2002.
CHAPTER
16
Acute Respiratory
Distress Syndrome
PETER J. PAPADAKOS, M.D., F.C.C.P., F.C.C.M.
JACK J. HAITSMA, M.D., Ph.D.
Risk Factors ALI and ARDS, clinicians have used both local and
Clinical Manifestations systemic therapies to improve survival (Box 16-1).
Pathologic Manifestations
Pathophysiology
Management RISK FACTORS
Ventilator-Induced Lung Injury
Open Lung Strategy It has been recognized that ALI and ARDS may arise in
Open Lung Concept association with a number of different clinical conditions.
Experimental Therapies In reviewing the causes, sepsis continues to be the most
Conclusions commonly encountered factor: approximately 5–40% of
septic patients develop ARDS. Shock, pneumonia, and
Acute lung injury (ALI) and acute respiratory distress the systemic inflammatory response syndrome (SIRS) are
syndrome (ARDS) remain two of the most common the most common risk factors. Other frequently encoun-
conditions evaluated in the intensive care unit (ICU). tered risk factors include multiple transfusions, aspiration
ALI and ARDS are commonly encountered in the ICU injury, near drowning, pancreatitis, trauma, and many
and are associated with increased mortality, morbidity, others. These clinical risk factors are synergistic, and
and cost of care. ARDS is often seen in conjunction with when more than one of the clinical risk factors is present,
multiple organ failure. The overall hospital mortality rate the likelihood of ARDS is greater than the sum of the col-
is between 20% and 50%. This wide range of mortality lective risk factors. Another major risk factor that has only
illustrates that there is a lack of understanding of the exact recently come to light is the improper use of mechanical
etiology and management of these conditions and further ventilation. Certain ventilator settings may lead to the
improvements and investigations into these conditions development of ARDS. This so-called ventilator-induced
are needed. The exact incidence and prevalence of ALI lung injury (VILI) is highly important in that it may be
and ARDS are unknown at present. Current reports put preventable (Box 16-2).
the number somewhere in the range of 150,000 cases
in the USA or an estimated incidence of 75 cases per
100,000 population. CLINICAL MANIFESTATIONS
An American–European consensus conference has
recently defined ALI and ARDS in an attempt to remove The initial clinical presentation may vary, primarily
confusion related to terminology. This common language reflective of the underlying disease process and the
will allow investigators to evaluate and treat the same overall condition of the patient. However, when ARDS
disorders and will greatly decrease confusion in the becomes apparent the patient notes a significant distress
literature. Many investigators consider ALI and ARDS to associated with dyspnea and tachypnea and an increased
represent a manifestation of a systemic disorder that arises work of breathing. Hypoxia is noted on the pulse oximeter
from exaggerated proinflammatory pathways, culminat- or on the arterial blood gas (ABG).
ing in the production of diffuse damage to the capillary The hallmark of ARDS is the presence of hypoxemia
endothelial cell and/or the alveolar epithelial barriers. despite the administration of high concentrations of
In an attempt to improve outcomes in patients with inspired oxygen, evidence of increasing shunt fraction,
176
Acute Respiratory Distress Syndrome 177
SELECTED READING Dellinger RP, Zimmerman JL, Taylor RW et al: Effects of inhaled
nitric oxide in patients with acute respiratory distress
Acute Respiratory Distress Syndrome Network: Ventilation syndrome, results of phase 2 study. Crit Care Med 26:15–23,
with lower tidal volumes as compared with traditional 1998.
tidal volumes for acute lung injury and with acute respira-
Haitsma JJ, Papadakos PJ, Lachmann B: Surfactant therapy in
tory distress syndrome. N Engl J Med 342:1301–1308,
ALI/ARDS. Curr Opin Crit Care 10:18–22, 2004.
2000.
Papadakos PJ, Lachmann B: Lung recruitment in ARDS. Mt Sinai
Amato MBP, Barbas CSV, Medeiros DM et al: Effect of a
J Med 6 (1):73–77, 2000.
protective ventilation strategy on mortality in the acute res-
piratory distress syndrome. N Engl J Med 338:347–357, Pepe P: The clinical entity of adult respiratory distress syndrome.
1998. Crit Care Clin 2:377–385, 1986.
Artigas A, Bernard GR, Carlet J et al: American–European Slutsky AS, Tremblay LN: Multiple system organ failure: is
consensus conference on ARDS, Part 2. Am J Respir Crit mechanical ventilation a contributing factor? Am J Respir
Care Med 157–163, 1998. Crit Care Med 157:1721–1728, 1998.
17
CHAPTER Mechanical Ventilation
PETER J. PAPADAKOS, M.D., F.C.C.P., F.C.C.M.
BURKHARD LACHMANN, M.D., Ph.D.
181
182 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
A large group of patients in all ICU environments for conscious patients, whose respiratory efforts are not
needing a large amount of sedation that may cause res- sensed by the ventilator, which leads to patient discomfort
piratory depression are patients with complex histories and increased work of breathing. As a result, this mode has
of psychiatric disorders or patients that are withdrawing been largely abandoned outside of the operating theatre.
from drugs and alcohol. These patients may harm them-
selves and others if not acutely medicated.
ASSIST-CONTROL VENTILATION
BASIC MODES OF MECHANICAL This mode is similar to VC mode except that the ven-
VENTILATION tilator senses respiratory efforts by the patient. As in VC,
the physician sets a respiratory rate, TV, flow rate, I:E
As ventilator technology has progressed, the ways of ratio, FIO2, and PEEP. Breaths are delivered automatically,
delivering positive pressure ventilation have proliferated. regardless of the patient effort (“control”). In assist-
In daily practice, however, four basic modes of positive control (AC), however, the ventilator detects the
pressure ventilation are most commonly used. These patient’s effort and responds by delivering a breath iden-
modes can be classified on the basis of how they are trig- tical to the controlled one (“assist”). The patient can
gered to deliver a breath, whether these breaths are tar- therefore breathe faster than the back-up rate, but all
geted to a set volume or pressure, and how the ventilator breaths have the same tidal volume, flow rate, and inspi-
cycles from inspiration to expiration (Table 17-3). ratory time. Hence AC mode allows better synchrony
between patient and ventilator than VC mode, while still
providing baseline minute ventilation. A better descrip-
CONTROLLED MECHANICAL tive and accurate name for this mode is “volume-targeted
VENTILATION assist-control ventilation.”
Like all modes of mechanical ventilation, AC has sev-
Controlled mechanical ventilation (CMV) is the most eral disadvantages. If the back-up respiratory rate is set
common mode of ventilation in the patient under gen- too far below the patient’s spontaneous rate, exhalation
eral anesthesia in the operating theater. It is an excellent time progressively decreases, since the inspiratory time
starting block for the understanding of mechanical ven- is fixed by the back-up rate and flow rate. In the extreme
tilatory parameters. CMV or volume control (VC) was example, this may results in inadequate time for exhala-
the first volume-targeted mode. It is a pure “control” tion. As a result, lung volume remains above functional
mode; that is, the minute ventilation (VE) is completely residual capacity (FRC), and a process called dynamic
governed by the machine (VE = tidal volume (TV) × res- hyperventilation occurs. This increased lung volume is
piratory rate). The physician sets the respiratory rate, associated with elevation in the alveolar pressure at end-
TV, inspiratory flow rate, ratio of inspiratory to expira- exhalation, or “auto-PEEP.” Another problem occurs when
tory time (I:E), positive end-expiratory pressure (PEEP), patients with high minute ventilation requirements make
and the level of inspired oxygen (FIO2). In VC, the persistent efforts while a breath is being delivered. If this
patient is unable to trigger the ventilator to deliver addi- effort is strong enough, the patient may trigger the ven-
tional breaths. This works well with patients under gen- tilator again, a phenomenon known as “breath stacking.”
eral anesthesia, unresponsive, or heavily sedated, but not This can cause wide swings in airway pressure and
VOLUME PRESET
Controlled mechanical ventilation Time Volume Volume/time
Assist-control ventilation Pressure Volume Volume/time
Intermittent mandatory ventilation Time Volume Volume/time
Synchronized intermittent mandatory ventilation Time/pressure Volume Volume/time
PRESSURE PRESET
Pressure-support ventilation Pressure Pressure Flow
Pressure-control ventilation Time Pressure Time
184 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
V
Box 17-5 Key Indications for Positive
End-Expiratory Pressure IV
T2 T1
II Unstable
I
The use of an open-lung strategy will not only improve P
PI, III
oxygenation but also may also decrease the levels of
Figure 17-2 Physiologic behavior of the alveolus. The pressure
cytokines and prevent the loss of surfactant. There is (P)–volume (V) relation is displayed on X–Y axes. The status of the
evidence that this strategy also prevents the transmigra- bronchoalveolar unit is shown on the right-hand side. The arrows
tion of both cytokines and infectious agents across the show the direction from closed (bottom) to open (top). The ideal
lung. This lung recruitment should be applied to all alveolar status is IV or III.
patients no matter what mode of ventilation is applied
(Figure 17-2).
patient to be rapidly weaned from the ventilator. The
physician should work with the respiratory therapists in
CONCLUSIONS the ICU to manage the patient in an ongoing manner.
This is because a patient’s condition is ever changing and
The management of mechanical ventilation is no
may need adjustments throughout the day. The therapist
longer a hit-or-miss procedure but a therapy, which has
is also specially trained to manage the ever-advancing
physiological end points along with the basic goals of
technology of modern ICU ventilators.
oxygenation and removal of carbon dioxide. Which ven-
tilator settings are chosen from the outset will have a
great impact on patient management. Proper settings
will allow for improved oxygenation on the lowest FIO2 CASE STUDY
with the least atelectasis. Proper titration will decrease
Management of a Patient with Multiple Trauma
biotrauma and may affect cytokine levels thereby affect- A 25-year-old man involved in a high-speed head-on
ing other organs. The proper settings will allow for the collision presents to the emergency room with acute
respiratory distress and abdominal pain. The patient
was intubated with in-line traction. Trauma evaluation
showed a right femur deformity, chest deformity, and
Box 17-6 Treatment Strategies for abdominal rebound. An emergent x-ray showed multiple
rib fractures bilaterally, a right femur fracture, and no
Minimizing Auto-Positive
evidence of a spinal injury. A CT scan showed atelectasis
End-Expiratory Pressure in and a pulmonary contusion, and a grade II liver injury.
Volume-Targeted Ventilation The initial blood gas on a FIO2 of 100% was a PaO2 of
64 and PaCO2 of 38. The patient was placed on pressure
● Aggressive bronchodilator therapy. control after a lung-opening procedure (LOP) with an
● Pain control, sedation; consider selective use of opening pressure of 60 cmH2O for ten breaths. The
neuromuscular blockade. pressure control was titrated to generate a tidal volume
● Minimize I:E; e.g., increase expiratory time and of 6 ml/kg, a ventilatory rate of 14, and the initial PEEP
inspiratory flow rate, reduce tidal volume, reduce was set at 10 cmH2O. The repeat arterial blood gas was
respiratory rate. now a PaO2 of 475 and a PaCO2 of 34. The FIO2 was
● In selected cases, judicious application of (extrinsic) lowered to 50% and the rate decreased to 12. An epidural
PEEP will counter intrinsic PEEP and decrease the catheter was placed for pain management and the
work of breathing (asthma, chronic obstructive patient tolerated operative management of the fracture
pulmonary disease). on hospital day two without a problem. The patient
● In some selected patients with severe lung injury was weaned using pressure support over the course of
auto-PEEP can be used to advantage especially five days and was extubated without a problem. He
patients where the strategy of PCIRV is used. was transferred to general surgical ward on day six.
Mechanical Ventilation 189
SELECTED READING Lachmann B: Open up the lung and keep the lung open. Intens
Care Med 18:319–321, 1992.
Acute Respiratory Distress Syndrome Network: Ventilation with
Papadakos PJ, Lachmann B, Bohm S: Pressure control ventila-
lower tidal volumes as compared with traditional tidal vol-
tion: consensus and new horizons. Clin Pulmon Med
umes for acute lung injury and the acute respiratory distress
5(2):59–65, 1998.
syndrome. New Engl J Med 242:1301–1308, 2000.
Richard JC, Maggiore SM, Jonson B et al: Influence of tidal
Apostolakos MJ, Levy PC, Papadakos PJ: New Modes of mechan-
volume on alveolar recruitment. Respective role of PEEP
ical ventilation. Clin Pulmon Med 2(2):121–128, 1995.
and a recruitment maneuver. Am J Respir Crit Care Med
Botz GH, Sladen RN: Conventional modes of mechanical 158:1571–1577, 1998.
ventilation. Int Anesthesiol Clinics 38(1):19–27, 1997.
Dreyfuss D, Saumon G: Ventilator-induced lung injury: lessons
from experimental studies. Am J Resp Crit Care Med
157:294–323, 1998.
18
CHAPTER Weaning from
Mechanical Ventilation
MICHAEL J. APOSTOLAKOS, M.D.
Pathophysiology of Weaning Failure Respiratory failure may occur from any of these. For
Approach to Weaning from Mechanical Ventilation example, Guillain-Barré syndrome can lead to muscle
Predictive Criteria of Weaning Outcome weakness, acute bronchospasm to increased respiratory
Withdrawal of Mechanical Ventilation load, and a narcotic overdose to a decreased central
Modes of Mechanical Ventilation During Weaning drive. All of these may lead to respiratory failure. The
Summary factors of strength, load, and drive constantly interact.
Disorders may occur in isolation or in concert.
A significant proportion of patients admitted to inten- The relationship between respiratory load and muscle
sive care units (ICUs) undergo intubation with mechanical strength can be viewed as a balance. If muscle strength
ventilation. The majority of such patients are extubated is too weak or load is too heavy, muscular contraction
quite readily. However, as many as 20% of mechanically cannot be maintained and the muscles acutely fail.
ventilated patients will fail their first attempt at weaning. This is termed fatigue. The dominant feature of the
More than 40% of the time on mechanical ventilation is pathophysiology of weaning failure is high levels of load
spent trying to wean the patient from the ventilator. The relative to the strength of the respiratory muscles. For
causes of prolonged ventilator dependency are listed in those who fail, as the weaning progresses, load increases
Table 18-1. As mechanical ventilation is associated with as compared to those who succeed with the weaning
a host of complications, every effort should be made to dis- trial. Almost always the drive to breathe is high in such
continue mechanical ventilation as soon as the patient can cases.
resume and sustain spontaneous ventilation. However,
choosing the appropriate time for discontinuation of
mechanical ventilation may prove difficult. If chosen too APPROACH TO WEANING FROM
early, severe cardiopulmonary decompensation may fur- MECHANICAL VENTILATION
ther delay extubation. If chosen too late, the patient
remains at risk for ventilator-associated complications such The first step in weaning a patient from mechanical
as pneumonia. Various clinical and laboratory factors used ventilation is identifying and treating the process that
to evaluate respiratory capacity have been used as predic- caused the patient to go on the ventilator in the first
tive factors in weaning. These are utilized in an attempt to place (Table 18-2). Common causes of respiratory failure
optimize weaning. This chapter reviews the causes of leading to mechanical ventilation include pneumonia,
weaning failure and an approach to liberating patients sepsis, congestive heart failure, status epilepticus, and
from mechanical ventilation. major surgery. Major effort should be directed to reverse
this underlying process while ventilating the patient in a
nontoxic manner. It should be remembered that mechan-
PATHOPHYSIOLOGY OF ical ventilation is a supportive but not a therapeutic
WEANING FAILURE endeavor.
Common problems found in weaning patients
Weaning from mechanical ventilation depends on include fluid overload, altered mental status, acid–base
the strength of the respiratory muscles, the load applied changes, and electrolyte disturbances. These need to be
to the muscles, and the central drive to breathe. corrected if weaning is to be successful.
190
Weaning from Mechanical Ventilation 191
patient stress. The presence of a team member providing tidal volume (TV), minute ventilation (MV), maximum
assurance and explanation during a trial of spontaneous voluntary ventilation, respiratory frequency, and maxi-
breathing or a decrease in the level of mechanical venti- mal inspiratory pressure.
lator support may be valuable. If patients are alert, they VC is the greatest volume of gas that a patient is able
should be informed of progress. Environmental stimula- to exhale in taking a maximum inspiration from residual
tion such as the use of a television, radio, or books volume. TV is that volume of gas moved during a normal
should be provided. Sleep should be ensured because respiratory cycle. The threshold values for these two
deprivation causes impairment of the respiratory control parameters predictive of weaning remain controversial
system in addition to general discomfort. but are of the order of 5–8 ml/kg for TV and 10–15 ml/kg
Optimal patient posture during weaning from for VC. Measurement of VC is relatively difficult because
mechanical ventilation varies according to the underly- it depends on considerable cooperation from the
ing pathophysiology. Patients with intercostal muscle patient. Given the large degree variability in VC, it is not
weakness resulting from low cervical spinal cord lesions surprising that some studies have shown that VC often
show an increase in lung volumes on changing from the failed to predict weaning outcome with a high degree of
upright to the supine posture. Supine posture forces accuracy. Although slightly better, using a TV cutoff of
abdominal contents upward displacing the diaphragm 4 ml/kg, the positive predictive value was 0.67 and
cephalad. The diaphragm can then contract downward negative predictive value was 0.85, left significant room
across a longer distance increasing the volume of gas for improvement.
moved. Conversely, patients with diaphragmatic paraly- In a resting, healthy adult MV is about 6 l/minute.
sis do better in the upright position. Vital capacity falls Maximum voluntary ventilation (MVV) is the volume of
by 50% when these patients are supine. The displace- air that can be inhaled and exhaled with maximum effort
ment of the paralyzed diaphragm cephalad leads to a over one minute. Normal values for MVV range from
decreased functional residual capacity (FRC) and places 50 to 250 l/minute. The relationship between resting
the ancillary muscles of respiration at a mechanical MV and MVV indicates the proportion of the patient’s
disadvantage. ventilatory capacity required to maintain a certain level
Ventilator settings during periods of mechanical ven- of PaCO2 and also indicates the reserve available for fur-
tilation may affect progress with subsequent weaning ther respiratory demands. The combination of a MV of
trials. A major purpose of mechanical ventilation between <10 l/minute and the ability to double this value during an
weaning trials is to provide rest for the respiratory mus- MVV maneuver was associated with the ability to wean
cles. With most modes of ventilation (assist-control, successfully. However, both of these tests are associated
synchronized intermittent mandatory ventilation (SIMV), with significant false positive and false negative rates.
and pressure support ventilation (PSV)) inspiratory Furthermore, the MVV can be difficult to obtain in the
muscles do not stop contracting once the ventilator has critically ill patient, as they may be unable to cooperate.
been triggered. Thus, the inspiratory muscles are not One simple assessment of respiratory muscle function
simply “resting.” Adjustment of the ventilator settings is can be made by measuring muscle strength. Respiratory
necessary to minimize respiratory work. Even when muscle strength can be measured at the patient’s bedside
optimally adjusted, patients may still perform a consid- by recording the maximal inspiratory pressure (MIP) by
erable portion of the work of inflation during assisted means of an aneroid manometer. Maximum static inspi-
ventilation. ratory pressures for healthy young men and women are
approximately −120 cmH2O and −90 cmH2O, respectively.
Maximal inspiratory efforts may be performed easily in
PREDICTIVE CRITERIA OF uncooperative intubated patients by using a one-way valve
WEANING OUTCOME connected to the manometer, which allows the patient to
exhale freely but forces the patient to inhale against the
manometer. A MIP < −30 cmH2O is associated with suc-
CURRENT CONTROVERSY cessful extubation but a MIP > −20 cmH2O is associated
Criteria for Readiness to Wean with the inability to maintain spontaneous breathing.
The best criterion for readiness to wean from Studies have shown these values to have a better nega-
mechanical ventilation remains controversial. tive predictive value than positive predictive value.
Several more recent predictive criteria of weaning
outcome have been described. These include measure-
Conventional criteria for readiness to wean are rela- ments of transdiaphragmatic pressure, airway occlusion
tively easy to measure but their specificity and sensitiv- pressure, gastric intramural pH (pHi), and several inte-
ity are relatively poor. These include vital capacity (VC), grative indices. However, these techniques all share in
Weaning from Mechanical Ventilation 193
common the requirement for specialized equipment, ventilator inspiratory valve and circuit. Trial length varies
difficulty of measurement, or complicated equations, from 30 minutes to 2 hours. Intolerance is judged by
which make bedside utility poor. tachycardia or bradycardia (>20% increase or decrease
One exception to the above is the rapid shallow from baseline), tachypnea (>35 breaths/minute), hypox-
breathing index described by Tobin and Yang. They had emia (<90% saturated), hypertension (>180 mmHg sys-
found that MV is well maintained in patients who fail a tolic), hypotension (<90 mmHg systolic), and/or subjective
weaning trial, but its components TV and respiratory shortness of breath (anxiety, diaphoresis, agitation).
frequency are combined in a manner that results in inef- Despite selecting the patients able to undergo a trial
ficient gas exchange. In general, patients who fail wean- of spontaneous breathing according to weaning criteria
ing trials drop their TVs and increase their respiratory and monitoring them during the trial looking for intoler-
rates. Yang and Tobin have shown that the rapid shallow ance, it is common for marginal patients to require
breathing index as reflected by frequency (breaths/ reintubation within 48 hours of extubation. The frequency
minute)/tidal volume (liters) is the most accurate predictor of extubation failure as defined by reintubation within
of weaning outcome. Using a threshold of <105, the 48 hours of extubation varies from 4% to 19%. The spon-
frequency (f)/tidal volume (VT) ratio had a positive predic- taneous breathing trial evaluates respiratory mechanical
tive value of 0.78 and a negative predictive value of 0.95. function in the presence of an artificial airway. Patients
The advantages of the f/VT ratio as a weaning predic- with altered mental status, recurrent aspiration, or copious
tor are that it is easy to measure and not dependent on secretions may achieve ventilator independence but
patient cooperation or effort. The f/VT ratio was evalu- require continued airway protection. Thus, the decision to
ated while patients were spontaneously breathing extubate a patient requires, in addition to a successful spon-
through the endotracheal tube. A bedside spirometer taneous breathing trial, sufficient level of consciousness
was used to measure VT. The predictive value of this and adequate clearance of secretions.
index may be lower if measured while patients are on
the ventilator with either continuous positive airway
pressure (CPAP) or pressure support. MODES OF MECHANICAL
VENTILATION DURING WEANING
WITHDRAWAL OF MECHANICAL
VENTILATION CURRENT CONTROVERSY
Weaning Mode
Withdrawal of mechanical ventilation is considered The optimal mode of mechanical ventilation used
when the underlying process responsible for the acute during weaning is controversial but IMV weaning
respiratory failure is improving or resolved, the patient appears to slow the process.
is in good clinical condition, and gas exchange is ade-
quate (e.g., PaO2 ≥ 60 mmHg with FIO2 ≤ 0.50 and PEEP
≤ 7.5 cmH2O). Much has been written regarding the mode of
Several clinical parameters discussed above have mechanical ventilation to be used during weaning.
been used to predict weaning outcome so that the pres- There remain three methods in widespread use: pro-
ence of favorable weaning parameters supports the deci- gressive T-piece trials, intermittent mandatory ventila-
sion to undertake a weaning attempt. This is a trial of tion (IMV), and PSV. At this point no standardized
spontaneous ventilation prior to extubation. Usually, approach to wean patients from mechanical ventilation
such a trial is conducted by disconnecting the patient has been developed, and the choice of technique varies
from the ventilator and observing respiratory rate, pres- with the physician.
ence or absence of abdominal paradox, activity of acces- Recent studies suggest that IMV weaning prolongs
sory inspiratory muscles, level of consciousness, and time on the ventilator. This is likely due to the fact that the
monitoring oxygen saturation by pulse oximetry while physician slowly decreases the IMV rate over time. By the
the patient breathes spontaneously. time the IMV rate is slowed to the point where a sponta-
Spontaneous breathing trials have been described neous breathing trial is performed, valuable time is lost.
using a simple T-tube or low-level pressure support (PS) Results with the use of PS trials have been variable.
or CPAP at levels ≤7 cmH2O. The T-tube is simply the Those studies with well-defined protocols and rapid
endotracheal tube connected to flow by oxygen. PS or reduction of PS to lead to spontaneous breathing trials
CPAP are used to reduce the workload imposed on the show equivalence to daily T-piece trials.
respiratory muscles and compensates for the extra work Daily T-piece trials have consistently been superior to
of breathing imposed by the endotracheal tube and the IMV weaning and at least equivalent to PS weaning in
194 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
195
196 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
dose of 0.075 mg. Sedation and xerostomia are collateral Sedation and analgesia are useful to prevent sudden
effects of clonidine. increases in intracranial pressure because they reduce
the adrenergic discharge associated with pain and they
Nitrates control the psychomotor agitation.
Nitroglycerine induces vasodilatation mediated by Appropriate head position with a head-up tilt of
nitric oxide pathways. The short effect of this drug allows 20–30° without lateral deviations of the head improves
an intravenous continuous infusion at a dose of 5–10 μg/ venous return through jugular veins and it is considered
minute. Nitroprussate is a venous and arterial vasodilator a basic step in intracranial hypertension treatment.
used intravenously at a dose of 0.5–10 μg/kg/minute. Indeed an increase in venous return from the brain is
It is usually not used in brain-injured patients because it associated with a reduction in cerebral perfusion pres-
causes cerebral vasodilatation associated with a depressed sure when head tilt is applied. The reduction in cerebral
response to CO2. perfusion pressure may induce the vasodilatation of
cerebral vessels resulting in further intracranial hyper-
Calcium Antagonists tension. A head-up tilt of 30° has become a good practice
Nifedipine is a calcium antagonist that may be used of general intensive care also for the prevention of noso-
sublingually at a dose of 10 mg. comial pneumonia. It should be associated with a care-
ful management of systemic arterial blood pressure to
Alpha-1 Inhibitors prevent cerebral hypoperfusion.
Urapidil is an alpha-blocker that produces prevalently The most popular osmotic diuretic is mannitol,
arterial vasodilatation associated with a minor venous which inhibits water and sodium absorption in the
vasodilatation without significant changes in heart rate kidney resulting in osmotic diuresis. Mannitol induces an
and cardiac output. Urapidil can be used in boluses of osmotic gap between the intravascular compartment
12.5 mg or by continuous intravenous infusion. and the brain parenchyma resulting in a movement of
Even if hypotension decreases cerebral perfusion pres- water from the extravascular compartment into cerebral
sure and cerebral blood flow and may worsen ischemic capillaries with a reduction in intracranial hypertension.
injuries, severe hypertension when uncontrolled increases The blood–brain barrier must be intact for these effects
perilesional cerebral edema and poses at high risk for the to occur. Mannitol acts also as plasma expander reduc-
hemorrhagic progression of stroke especially in patients ing hematocrit and viscosity. These effects improve cere-
treated with anticoagulants that are contraindicated if bral blood flow and cerebral oxygen delivery. Moreover,
hypertension is uncontrolled. mannitol has also antioxidant properties that may result
in a neuroprotective effect. When used in continuous
intravenous infusion it may alter the blood–brain barrier.
Intracranial Pressure Management This alteration may allow mannitol to exit into the
Intracranial hypertension should be promptly identified extravascular compartment worsening cerebral edema.
and treated because it may result in dramatic consequences Plasmatic osmolarity should be below 320 mosm/l when
such as brain herniations. The treatment of intracranial mannitol is used because of the risk of tubular necrosis.
hypertension includes invasive monitoring of arterial Therefore mannitol can be used for the treatment of
blood pressure and intracranial pressure and should be per- an unequivocal intracranial hypertension at a dose of
formed in an intensive care unit (ICU) (Box 19-7). 0.25–1 g/kg. This regimen produces effects lasting
6–8 hours within 2 minutes. Euvolemia, serum osmolarity
below 320 mosm/l, diuresis, and renal function
Box 19-7 Methods for the Control of monitoring should always be ensured when mannitol is
Intracranial Hypertension used. Furosemide may exaggerate the collateral effects
of mannitol and should not be used in intracranial
● Sedation hypertension. Tris-hydroxymetil aminomethane (THAM)
● Analgesia increases pH resulting in a decrease in intracranial
● Appropriate head position hypertension. A dose of 60 mmol administered in 45 min-
● Osmotic diuretics utes decreases intracranial pressure within 15 minutes.
● Tris-hydroxymetil aminomethane (THAM)
Provided there is a careful monitoring of blood pH,
● Hyperventilation
● Muscle relaxation
THAM can be used with a continuous intravenous infu-
● Barbiturates sion of 3 mmol/hour.
● Hypothermia Hyperventilation increases pH, reducing PaCO2.
● Decompressive craniotomy A decreased PaCO2 causes cerebral vasoconstriction
with a reduction of both intracranial hypertension
200 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
and cerebral blood flow. Hyperventilation produces The mass effect associated with large ischemic lesions is
transient effects because a readjustment in brain pH promptly evident on CT scanning even when the direct
occurs after 24 hours. Moreover, the effects of hyper- signs of ischemia are not present. If the initial CT scanning
ventilation depend on the cerebral vessel response to is negative and in the case of neurologic deterioration
CO2 that may be altered in patients with stroke resulting CT scanning should be repeated after 24 hours until
in cerebral hypoperfusion of perilesional areas. Because 7 days after clinical presentation. The early finding of
the transient effect of hyperventilation on intracranial either hypodensity or mass effect has a negative prog-
hypertension sacrifices cerebral blood flow, the benefits nostic value. The diagnostic benefit resulting from
resulting from hyperventilation may be limited. In any contrast enhancement in the early phase of stroke is
case, PaCO2 should be maintained between 35 and controversial, while it is widely accepted for the later
40 mmHg because higher values exacerbate intracranial assessment of stabilized strokes. CT scanning is the first
hypertension. choice among neuroimaging techniques for the early
Barbiturates and propofol can induce a pharmaco- diagnostic workup of patients with stroke because it is
logic coma with the electroencephalographic features of widely diffused, easy to read, and not very expensive.
burst suppression. This produces a profound reduction NMR could give good diagnostic information especially
in cerebral metabolism and in cerebral blood flow because in anterior lesions but it may be difficult to perform in
of cerebral autoregulation resulting in a decreased the early phase of stroke because of the instability of the
intracranial pressure. Careful hemodynamic monitoring patient’s condition.
should be used when barbiturates or propofol are used Besides neuroimaging, the early diagnostic workup
at high doses because of the cardiovascular effect of for patients with stroke should include electro-
these drugs. cardiogram and eventually echocardiogram in order to
Hypothermia shows neuroprotective effects because identify an eventual cardiogenic cause of stroke.
it decreases cerebral metabolism. Hypothermia reduces Laboratory examinations should include complete blood
also the alterations of the blood–brain barrier after cere- count, glycemia, coagulation tests, electrolytes, blood
bral ischemia decreasing cerebral edema and intracranial gases, and indexes of renal and hepatic function.
hypertension. Unequivocal outcome benefits from Doppler examination of the anterior and vertebrobasilar
the use of hypothermia in patients with stroke are still circulations may be useful as well as transcranial Doppler.
lacking. Electroencephalogram may be useful to demonstrate
Decompressive craniotomy has shown experimental seizure activity. Lumbar puncture should be performed
effectiveness in large cerebral infarctions. It should be if subarachnoid hemorrhage is suspected with a negative
considered when every other treatment has failed but CT scanning. Radiographic examination of the chest
neurologic impairment is not already irreversible. should also be performed, while X-rays of the cervical
spine should be reserved for patients who are uncon-
scious or with cervical pain or lesions (Box 19-8).
Diagnostic Workup
The role of diagnostic workup in the management of
nontraumatic brain injury is very important to choose
the appropriate treatment. The use of specific therapy
such as thrombolytic therapy increases further the impor- Box 19-8 Diagnostic Workup for
tance of early diagnostic workup. Among neuroimaging Ischemic Stroke
techniques, computed tomography (CT) scanning is the
first choice in patients with stroke and it should be per- ● CT scan of the head
formed as soon as possible. Initially CT scanning should ● Electrocardiogram
identify or exclude the presence of intracranial hemor- ● Chest x-rays
rhages or nonvascular lesions (neoplastic tissue). CT ● X-rays of the cervical spine (in case of loss of
scanning is then important to identify the location and consciousness or neck pain)
extension of the neurologic lesion. Ischemic lesions will ● Complete blood count
not show direct signs on CT scanning until 12–24 hours ● Coagulation tests
after stroke; sometimes the occluded artery may result in ● Electrolytes
● Glycemia
a hyperdense image even if calcified vessels may cause
● Blood gas analysis
false positive findings. Even large ischemic strokes are ● Liver and kidney function tests
not evident on CT scanning in the first hours; 60% of ● Lumbar puncture (in case of suspected subarach-
cerebral infarctions will be evident on CT scanning noid hemorrhage with negative CT scan)
24 hours after symptom presentation, while 100% of ● Electroencephalography
cerebral infarctions are evident 7 days after presentation.
Nontraumatic Brain Injury 201
ischemic lesions in perilesional areas, given the alter- motor aphasia occur if the dominant hemisphere is
ations of cerebral autoregulation. Therefore systemic involved, neglect syndrome if the nondominant hemi-
arterial pressure should be maintained in the normal sphere is involved. Very large hemorrhages disconnect
range. Headache occurs at the onset in 30% of patients diencephalons from the reticular system and cause stupor
and later in 60% of cases. Vomiting is more common in or coma associated with mydriasis and positive Babinski’s
hemorrhagic strokes than in ischemic ones. Seizures are reflex.
common especially in hemispheric hemorrhages. They Hemorrhages involving the caudate are rare. Confusion,
are usually present at the onset or occur early; late vomiting, and headache are common in these cases. If the
seizures are rare. The clinical pattern is dependent on intraparenchymal hemorrhage involves the thalamus,
the site and the size of the hemorrhage. there is a contralateral alteration of the sensitivity of the
head, the face, the superior limb, and the chest. If the
injury extends to subthalamic areas, ocular signs (devia-
CLINICAL CAVEAT tion of the eyes, nystagmus) are common, while the
Clinical symptoms and signs of intraparenchymal involvement of the internal capsule results in alterations
hemorrhage: in motility. Thalamic lesions of the dominant hemisphere
● Alterations of consciousness cause aphasia, while those of the nondominant hemi-
● Coma sphere produce unilateral neglect syndrome.
● Systemic hypertension
● Headache
● Vomiting Infratentorial Hemorrhage
● Seizures Intraparenchymal hemorrhages of the mesencephalon
are rare. Sometimes they may cause an important mass
effect, but usually they are benign. The third and fourth
cranial nerves are typically involved. If intraparenchymal
hemorrhage involves the highest portion of the mesen-
Supratentorial Hemorrhage cephalon, Parinaud syndrome may occur with paralysis
Intraparenchymal hemorrhages occurring in the in looking up, mydriasis, intact convergence movements,
supratentorial area may involve the cerebral cortex, the and eyelid movements.
cerebral hemispheres, and basal nuclei. Cortical hemor- Intraparenchymal hemorrhages involving the pons
rhages are usually multiple and produce neurologic signs may have devastating consequences. Even small hemor-
dependent on the site of injury (alterations of mobility or rhages result in loss of consciousness and tetraplegia
sensitivity); seizures are common. Hemispheric hemor- with positive plantar reflex, miosis, and absence of
rhages are caused by hypertension in 31% of cases. horizontal eye movements after oculocephalic and
Changes of consciousness are rare, although coma may oculovestibular reflex elicitation. Ocular bobbing, a
occur if the hemorrhage is large. If the frontal lobe is sudden down-deviation of the eyes followed by a slow
involved, contralateral motility is altered (the superior return to the resting position, is pathognomonic. Severe
limb is more frequently involved than the inferior limb alterations in the respiratory pattern are always present
or the face) and headache, abulia, and disorientation in while an abnormal deglutition facilitates inhalation.
time and space may occur. Patients with hemorrhage Thermoregulation is often impaired with severe hyper-
of the parietal lobe present headache and deficit in the thermia and shivers so intense that they may be con-
contralateral sensitivity. If the dominant hemisphere fused with seizures. Survival is often limited to the first
is involved the patient may have difficulty in naming, 24 hours, but some patients progress to a vegetative
writing, reading, and calculating, while if the nondomi- state or, if injury is limited, to locked in syndrome.
nant hemisphere is involved neglect syndrome occurs. Bulbar hemorrhages are rare. They cause dizziness
Hemorrhages in the dominant temporal lobe cause sen- and headache followed by hemiparesis. They may be
sitive dysphasia with difficulties in the comprehension associated with nystagmus, abnormal deglutition, weak-
but not in the repetition of words. Ear pain may occur. ness of the limbs, and cerebellar ataxia.
Hemorrhage in the occipital lobe produces hemianopia
and pain in the homolateral eye, and sometimes halluci-
nations with bright colors may occur. Cerebellar Hemorrhage
Intraparenchymal hemorrhage involving putamen The clinical pattern associated with intraparenchymal
headache is rare, while alterations in motility are common. hemorrhages involving the cerebellum is variable: small
Large hemorrhages in this area cause contralateral flaccid hemorrhages may give mild neurologic signs, but if com-
hemiplegia and hemianesthesia, deviation of the eyes pression of the brain stem occurs consciousness and
toward the injured side, and hemianopia. Dysphasia or vegetative functions become impaired and obstructive
Nontraumatic Brain Injury 207
discontinuing anticoagulant or thrombolytic drugs, than in men (1.7:1). The incidence of subarachnoid hem-
administering plasma, coagulation factors, or protamine. orrhage shows a peak in the sixth decade. The mortality
Intracranial pressure monitoring is useful to guide medical from subarachnoid hemorrhage is high, even if during
treatment of patients with intraparenchymal hemorrhage recent years it has decreased. Mortalities after 30 days
and to identify early the cases requiring surgical treat- and after one year are equivalent, so subarachnoid
ment. When there is intracranial hypertension a head-up hemorrhage causes death mostly within the first month.
tilt of 20–30° improves venous return and mannitol One-half of patients with subarachnoid hemorrhage
administrations at a bolus dose of 1–1.5 g/kg followed by either die or have severe inability, while one-third sur-
doses of 0.5 g/kg every 4–6 hours should be considered. vive with a good functional recovery. Among strokes,
Mechanically ventilated patients may be treated with subarachnoid hemorrhage shows the best response to
temporary hyperventilation. Intraventricular catheters may surgical and medical intensive care.
be used to drain cerebrospinal fluid in the attempt to The cause of subarachnoid hemorrhage may be the
reduce intracranial hypertension. rupture of intracranial aneurysms (75–80%), the rupture
Antiepileptic drugs are administered to all patients of vascular malformations (4–5%), arteriopathies, infec-
with intraparenchymal hemorrhage even if conclusive tions (meningitides and meningoencephalitis), intoxica-
data for the doses and the duration of the antiepileptic tions (alcohol, carbon monoxide, cocaine, epinephrine,
therapy are lacking. amphetamines, monoamine oxidative inhibitors, opioids),
Corticosteroids are not recommended because they traumas (head trauma, electrocution, seizures, burns,
cause many complications and no demonstrable benefi- strangulations), cancer (ependimoma, glyoma, melanoma,
cial effect. metastasis), venous thrombosis and blood disorders (sickle
When medical treatment fails to control intracranial cell anemia, leukemia, lymphoma, anticoagulants, aspirin,
hypertension and to prevent neurologic deterioration, disseminated intravascular coagulation) (Box 19-19).
surgical treatment is indicated. Surgery is usually not nec- Intracranial aneurysms have an incidence of 2–5%
essary in conscious patients, while it is advisable when and, according to Carmichael’s hypothesis, degenerative
massive intraparenchymal hemorrhages are associated factors acting on a congenitally abnormal vessel con-
with severe neurologic impairments involving the func- tribute to their formation. Risk factors for intracranial
tion of the brainstem. Stereotaxic drainage is an alternative aneurysms are smoking, hypertension, alcohol, contra-
to open ceiling drainage. Recently, surgical evacuation of ceptives, and hormonal changes associated with the
the hematoma has been associated with fibrinolytic drugs menopause. Intracranial aneurysms may be saccular
that have been used to obtain dissolution of the clotting. (berry), fusiform, or dissecting (Box 19-20).
Saccular (berry) aneurysms are the most frequent and
represent the most common cause of subarachnoid hem-
Outcome
orrhage. They are often associated with type III collagen
The clinical pattern that characterizes the onset and deficiency related to congenital diseases including aortic
the early phase of the intraparenchymal hemorrhage is
the most important prognostic factor. Outcome is signif-
icantly worse in comatose patients. Other negative prog-
nostic factors include a volume of hemorrhage above Box 19-19 Causes of Subarachnoid
60 ml, the localization in deep structures, brain shift, and Hemorrhage
the age of the patient.
● Rupture of intracranial aneurysms
● Rupture of vascular malformations
SUBARACHNOID HEMORRHAGE ● Arteriopathies
● Infections (meningitides and meningoencephalitis)
Definition, Etiology, and Pathophysiology ● Intoxications (alcohol, carbon monoxide, cocaine,
Subarachnoid hemorrhage accounts for 6–8% of cere- epinephrine, amphetamines, monoamine oxidative
bral strokes. It is defined as a collection of blood in the inhibitors, opioids)
subarachnoid space between pia mater and arachnoid ● Traumas (head trauma, electrocution, seizures,
involving the base cisterns and the hemispheric and burns, strangulations)
● Neoplasias (ependimoma, glyoma, melanoma,
interhemispheric fissures. In the most severe cases blood
metastasis)
may reach cerebral ventricles, and in 30% of cases sub- ● Venous thrombosis
arachnoid hemorrhage is associated with intraparenchymal ● Blood disorders (sickle cell anemia, leukemia,
hemorrhage. lymphoma, anticoagulants, aspirin, disseminated
The annual incidence of subarachnoid hemorrhage is intravascular coagulation)
15–20 per 100,000 population, and it is higher in women
Nontraumatic Brain Injury 209
CLINICAL CAVEAT
coarctation, polycystic kidney disease, Marfan’s syndrome, Clinical symptoms and signs of subarachnoid
Ehlers–Danlos syndrome, and fibromuscular dysplasia of hemorrhage:
the renal arteries. Saccular aneurysms occur at the bifur- ● Acute and severe headache
cation of cerebral arteries, more frequently in the ante- ● Stiff neck
rior circulation (anterior communicant artery, posterior ● Photophobia
communicant artery, middle cerebral artery, carotid ● Nausea
artery). These aneurysms may rarely compress closed ● Vomiting
structures causing symptoms before their rupture. ● Loss of consciousness
Thrombosis may occur inside the aneurysm causing Before the rupture of the aneurysm minor bleedings
may cause:
acute headache, stiff neck, and inflammatory cells in the
● Headache
cerebrospinal fluid. The annual rupture risk for saccular ● Neck ache
aneurysms is 1.4–3% and it is not related to the aneurysm ● Chest pain
size or site. ● Back pain
Fusiform aneurysms are associated with atheroscle- ● Leg pain
rotic alterations involving the media and elastica of the ● Photophobia
arterial wall. The preferred sites are the basilar artery and ● Lethargy
the intracranial segment of the carotid artery. The rup-
ture of fusiform aneurysms is rare, while thrombosis may
occur inside the aneurysm causing embolism. Fusiform
aneurysms may compress the brainstem and structures
inside the sinus carvenosum such as the second, third, Classification
fourth, fifth, and sixth cranial nerves. Several clinical classifications of subarachnoid hemor-
Dissecting aneurysms are an infrequent cause of sub- rhage have been proposed to assess objectively the clin-
arachnoid hemorrhage. They can cause ischemic symp- ical progression of each patient and to achieve an early
toms derived from thromboembolism. outcome determination. The most common classifica-
tions are the Hunt and Hess grading system (Box 19-21)
and the World Federation of Neurologic Surgeons grad-
Clinical Symptoms and Signs ing system (Box 19-22). The latter uses the Glasgow
The typical clinical presentation of subarachnoid Coma Scale and is more objective, while the Hunt and
hemorrhage includes acute and severe headache with Hess grading system uses a more subjective evaluation of
stiff neck often associated with photophobia, nausea,
and vomiting. An initial loss of consciousness is very fre-
quent; sometimes it recedes, other times it persists.
Patients with perimesencephalic subarachnoid hemor- Box 19-21 Hunt and Hess Grading System
rhage usually present a subacute headache (progressing
over minutes) not associated with alterations of con- ● Grade I – normal neurologic examination, mild head
sciousness. Before the rupture of the aneurysm, clinical ache, and slightly stiff neck
symptoms like headache, nausea, neck ache, chest, back ● Grade II – moderate to severe headache and stiff
neck; no confusion or neurologic deficit except for
and leg pain, photophobia, and lethargy may be the con-
cranial nerve palsy
sequence of minor bleedings or warning leaks. Ischemic ● Grade III – persistent confusion and/or focal
symptoms like dizziness, focal sensory or motor changes, neurologic deficit
and speech and cognitive abnormalities may derive from ● Grade IV – persistent stupor; moderate to severe
thromboembolism. Aneurysmal enlargement may result in neurological deficit
the compression of surrounding structures such as cranial ● Grade V – coma with moribund appearance
nerves or brain parenchyma. In these cases symptoms
210 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
angiographically, and half of patients with vasospasm however, triple H therapy is largely accepted. An appro-
will present delayed ischemic deficits that may progress priate fluid management is fundamental in order to
to cause death. Acute vasospasm occurs a few hours obtain hypertension and hypervolemia. Conclusive data
after hemorrhage, while chronic vasospasm occurs 3–4 about the kind of fluid to be used are lacking. The long-
days after hemorrhage and recedes after 14 days. The lasting controversy between colloids and crystalloids has
term vasospasm is misleading because it is not a spasm still not produced an evidence-based endpoint. Usually
of the muscularis layer of the vessels but a proliferative colloids and crystalloids are used together in a dose ratio
arteriopathy resulting in the obstruction of the vessels of 1:3. Isotonic fluids with an adequate amount of sodium
and in the alteration of the cerebral autoregulation. This are necessary given the dangers of hyponatremia in these
arteriopathy seems to be induced by the presence of patients. Once provided a hypervolemic state, hyper-
hemoglobin in the subarachnoid space which results in tension may require inotrope or vasopressor drugs.
a peroxidative damage involving free radicals. The quan- Hypertension is associated with an important cardiovas-
tity of blood in the subarachnoid space seen on CT scan- cular risk and careful hemodynamic monitoring should
ning is predictive of vasospasm. Delayed ischemic deficit be used to obtain a pulmonary capillary wedge pressure
causes an alteration in consciousness progressing over (PCWP) equal to 15–18 mmHg. Transcranial Doppler may
minutes or hours; focal deficits are less frequent. Serial be useful in patients with subarachnoid hemorrhage to
transcranial Doppler is an effective monitor of cerebral identify when deliberate hypertension is necessary to
blood flow in these instances and should be associated ensure an appropriate cerebral blood flow. The use of
with clinical assessment. Vasospasm may be treated with transcranial Doppler to guide deliberate hypertension
calcium antagonists, triple H therapy, or angioplasty. may be especially beneficial in patients with cardiovas-
cular disease in whom long-lasting hypertension is detri-
mental. Transluminal angioplasty is able to limit ischemic
CLINICAL CAVEAT damage associated with vasospasm. When it is used
Treatments of vasospasm associated with within 6–12 hours after the onset of ischemic deficit,
subarachnoid hemorrhage: angioplasty is especially useful in patients not responsive
● Calcium antagonists to triple H therapy. Timing is important because when
● Triple H therapy the vasospasm-related morphological changes of the cere-
● Angioplasty bral vessels have occurred, angioplasty is less effective
(Box 19-26).
During neuroradiologic procedures it is possible to
administer intra-arterially papaverine, which in several
While other calcium antagonists are less useful, cases seems to be useful.
nimodipine is effective in the prevention of delayed Tirilazilad is a free radical scavenger that has been
ischemic deficits. Nimodipine prevents cytotoxicity used in the treatment of the vasospasm from subarach-
blocking calcium channels over neuronal membranes, noid hemorrhage. Results seem to be better in males than
and, although it does not reduce the incidence of symp- females, probably because of a shorter half-life in women.
tomatic vasospasm, nimodipine improves cerebral blood Phenitoine may also reduce the half-life of tirilazilad.
flow through collateral branches resulting in a better
functional outcome. Nimodipine may be used at a dose Rebleeding
of 60 mg through a nasogastric tube every 4 hours for 21 Rebleeding occurs in 20% of cases of subarachnoid
days or by a continuous intravenous infusion of 2 mg per hemorrhage and is associated with high mortality (70%).
hour for 14 days. Collateral effects are usually mild,
including: hypotension, flushing, edema, headache,
increases in pulmonary shunting, and decreases in gastro-
Box 19-26 Angioplasty
intestinal motility. Hypotension should be treated to
prevent negative effects on cerebral perfusion. Several
authors advocated triple H therapy to decrease ischemic This is indicated if:
● The neurologic deficit has no other possible cause
lesions from vasospasm. Triple H therapy is based on
than vasospasm
deliberate hypertension, hypervolemia, and hemodilu- ● The ischemic deficit is not responsive to
tion. The rationale for this therapy is that vasospasm triple H therapy
impairs cerebral autoregulation and makes cerebral ● The vasospasm is angiographically evident in an
blood flow dependent on systemic arterial pressure and accessible area
hematic viscosity. It is still a matter of controversy as to ● A recent infarction is absent
which is the most important among the three targets;
212 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
The risk for rebleeding is higher during the 24–48 hours subarachnoid space is high enough it may cause persist-
after the first hemorrhage. Clinically the level of con- ent intracranial hypertension resulting in cerebral death.
sciousness declines acutely and headache suddenly wors-
ens associating with confusion. If the patient is already Seizures
comatose, mydriasis and seizures occur, respiratory The incidence of seizures in the acute phase of sub-
pattern changes, and apnoea may result. The control of arachnoid hemorrhage is 10–15%. If seizures occur after
hypertension has an important role in the prevention of the acute phase, rebleeding should be excluded with
rebleeding after subarachnoid hemorrhage, although the appropriate examinations because seizures may be the
treatment of systemic hypertension is complex and con- sign of rebleeding. Seizures are usually associated with
troversial. Cerebral ischemia is more likely if patients severe acute hypertension that may be the cause of
receive antihypertensive treatment, but the incidence of rebleeding and should be prevented.
rebleeding is higher if systolic arterial pressure is higher
than 160 mmHg. Patients with a stable mean arterial
pressure higher than 130 mmHg that is not related to Medical Complications
pain, anxiety, or discomfort from mechanical ventilation Arrhythmias (QT tract alterations, atrial flutter and
should receive an antihypertensive treatment based on fibrillation, supraventricular tachycardia, and ectopic
labetalol or esmolol. Surgical repair of the aneurysm is beats) and electrocardiographic alterations like T wave
the best way to prevent rebleeding. inversion and ST-T tract changes are associated with 50%
of the cases of subarachnoid hemorrhage. Ischemic
Intracranial Hematoma myocardial lesions including necrosis have been
Among patients with subarachnoid hemorrhage, observed with an incidence around 1%. Acute pulmonary
around 15–20% also present with intracranial hematoma. edema occurs in 2% of cases. Probably cardiovascular
Immediate surgical drainage is necessary if signs of brain complications result from the high plasmatic levels of
compression occur, otherwise intracranial hematoma is catecholamines observed in patients with subarachnoid
drained when aneurysm is repaired. hemorrhage. Cardiac and pulmonary complications may
be precipitated by triple H therapy. Another common
Hydrocephalus medical complication associated with 4–30% of cases is
The incidence of hydrocephalus in patients with sub- hyponatremia. This has been considered the result of
arachnoid hemorrhage is 20%. It may be acute, subacute, inappropriate secretion of ADH, but it is usually caused
or late. Acute hydrocephalus is evident on the first CT by a cerebral salt wasting syndrome often associated
scanning and is usually associated with intraventricular with subarachnoid hemorrhage. Alterations in the pro-
hemorrhage. The treatment of acute hydrocephalus is duction of vasopressin, atrial, and cerebral natriuretic
based on immediate ventricular drainage avoiding a sud- hormone contribute to this salt wasting syndrome.
den decrease in cerebrospinal fluid that may precipitate Hyponatremia and hypovolemia are associated with
rebleeding, while lumbar puncture should be avoided. delayed ischemic deficit while hyponatremia and hyper-
Subacute hydrocephalus occurs during the first week after volemia are associated with cerebral edema and intra-
the onset of subarachnoid hemorrhage. Usually subacute cranial hypertension. Other medical complications often
hydrocephalus is communicant and is not associated with associated with subarachnoid hemorrhage are stress
neurologic impairment. While subacute hydrocephalus ulcers and deep venous thrombosis (Box 19-27).
should be monitored with serial examinations, its treat-
ment is reserved for the cases associated with neurologic
signs because it usually resolves spontaneously. Late
hydrocephalus occurs weeks to months after the first Box 19-27 Medical Complications of
bleeding and it is usually associated with a typical clinical Subarachnoid Hemorrhage
triad: ataxia, dementia, and incontinence. A permanent
ventricular shunting should be considered. ● Arrhythmias
● Electrocardiographic alterations
Persistent Intracranial Hypertension ● Ischemic myocardial lesions
● Acute pulmonary edema
Subarachnoid hemorrhage is usually associated with
● Hyponatremia
a sudden increase in intracranial pressure that may ● Hypovolemia
become higher than arterial pressure resulting in the ● Hypervolemia
transient loss of consciousness usually present in the ● Stress ulcers
acute phase. This may be a defensive mechanism that ● Thromboembolism
would limit bleeding. If the amount of blood in the
Nontraumatic Brain Injury 213
SELECTED READING Radiology: Trial design and reporting standards for intra-
arterial cerebral thrombolysis for acute ischemic stroke.
Adams HP: Treating ischemic stroke as an emergency. Arch Stroke 34:e109–e137, 2003.
Neurol 55:457–461, 1998.
Mayberg MR, Batjer HH, Dacey R et al: Guidelines for the man-
Adams HP, Brott TG, Crowell RM et al: Guidelines for the man- agement of aneurysmal subarachnoid hemorrhage. Stroke
agement of patients with acute ischemic stroke. Stroke 25:2315–2328, 1994.
25(9):1901–1914, 1994.
McGrath BJ, Guy J, Borel CO et al: Perioperative management
Archer DP, Shaw DA, Leblanc RL et al: Haemodynamic consid- of aneurysmal subarachnoid hemorrhage: 2. Postoperative
erations in the management of patients with subarachnoid management. Anesth Analg 81:1295–1302, 1995.
hemorrhage. Can J Anaesth 38(4): 454–470, 1991.
Muir KW: Medical management of stroke. J Neurol Neurosurg
Berger C, Schwab S: Stroke – a medical emergency. Eur Psychiatry 70:i12–i16, 2001.
J Emergency Med 6:61–69, 1999.
Obana WG, Andrews BT: The intensive care management of
Bleck TP: Medical management of subarachnoid hemorrhage. non traumatic intracerebral hemorrhage. In Andrews BT,
New Horizons 5(4):387–396, 1997. editor: Neurosurgical Intensive Care, New York: McGraw
Brisman MH, Bederson JB: Surgical management of subarach- Hill, 1993, pp 311–327.
noid hemorrhage. New Horizons 5(4):376–386, 1997. Practice advisory: Thrombolytic therapy for acute ischemic
Castillo V, Bogousslavsky J: Early classification of stroke. stroke – summary statement. Neurology 47:835–839, 1996.
Cerebrovasc Dis Suppl 3:5–11, 1997. Ropper AR, Shutz H: Spontaneous intracerebral hemorrhage.
Chaves CJ, Pessin MS, Caplan LR et al: Cerebellar hemorrhagic In Hacke W, editor: Neuro Critical Care, Berlin: Springer-
infarction. Neurology 46:346–349, 1996. Verlag, 1994, pp 621–631.
Davenport RJ, Dennis MS, Wellwood I et al: Complications Voelker JL, Kaufman HH: Intraparenchymal hemorrhage.
after acute stroke. Stroke 27:415–420, 1996. New Horizons 5(4):342–451, 1997.
Gebel JM, Broderick JP: Intracerebral hemorrhage. Neurologic Wahlgren NG: Pharmacological treatment of acute stroke.
Clin 18(2):419–438, 2000. Cerebrovasc Dis 7(Suppl 3):24–30, 1997.
Guy J, McGrath BJ, Borel CO et al: Perioperative management Weaver JP, Hanley D, Danchev D et al: Subarachnoid hemor-
of aneurysmal subarachnoid hemorrhage: 1. Operative rhage. In Ripple JM, Irwin RS, Fink MP et al, editors:
management. Anesth Analg 81:1060–1072, 1995. Intensive Care Medicine, Boston: Little Brown, 1996,
Higashida RT, Furlan AJ; Assessment Committees of the pp 2051–2058.
American Society of Interventional and Therapeutic Yamaguchi T, Minematsu K, Hasegawa Y: General care in acute
Neuroradiology and the Society of Interventional stroke. Cerebrovasc Dis 7(Suppl 3):12–17, 1997.
20
CHAPTER Traumatic Brain Injury
A. RAFFAELE DE GAUDIO, M.D.
SIMONE RINALDI, M.D.
214
Traumatic Brain Injury 215
Subdural Hematoma
Subdural hematoma is a blood mass between dura Box 20-6 Secondary Damage
mater and arachnoides. Usually it is associated with a hem-
orrhagic brain laceration; extradural or intraparenchymal Secondary damage includes:
hematomas may coexist. It is more frequent in the elderly. ● Cerebral edema
It is localized usually in the interhemispheric scissure, ● Ischemic brain damage
expanding to the frontal, parietal, and temporal lobes. ● Brain shift and herniation
● Hydrocephalus
Brain atrophy may allow the brain to move according to
the trauma-related accelerations and decelerations; this
movement would stretch the “bridge veins” between
dura mater and cerebral parenchyma making them bleed. encephalic lesions. Surgical treatment is impossible, and
The blood may also originate from cerebral cortex arter- medical treatment gives frustrating results and outcome
ies and veins. Subdural hematoma is rarely alone and is poor. Inhibition of proteolytic processes may be a
acute; usually it is associated with brain contusions and therapeutic strategy in the future.
lacerations that may take part in the hematoma devel-
opment. Disorders of consciousness are often early and
severe. A minor disorder of mentation is not unusual, Secondary Damage
although it often progresses to coma. Homolateral mydri- Secondary damage includes the insults that the brain
asis and contralateral hemiparesis may often be present receives in the postinjury phase of trauma. Every clinical
in association with signs of brainstem lesions like decer- complication that reduces cerebral nutrients and oxygen
ebration. Neurovegetative signs including hyperthermia, delivery (hypotension, hypoxia, anemia, hypoglycemia,
hypertension, and electrocardiographic abnormalities are hypocapnia, etc.) or increases cerebral oxygen consump-
also common. Surgical treatment is the therapy of choice tion (hyperthermia, seizures) contributes to secondary
for subdural hematoma. damage. Secondary brain damage includes cerebral edema,
ischemic brain damage, brain shift and herniation, and
Intracerebral Hematoma hydrocephalus (Box 20-6).
Intracerebral hematoma is a blood mass totally inside
the brain parenchyma, without extension to the brain Cerebral Edema
surface. At the moment of traumatic impact a breakage Brain swelling is a very dangerous secondary damage
of intracerebral vessels results in intracerebral hemor- because it may progress to brain ischemia and herniation
rhages. Intracerebral hematoma derives from these mul- given that the nervous parenchyma is embedded in the
tiple intracerebral traumatic hemorrhages. Frontal and noncompliant box of the skull. The brain is particularly
temporal lobes are the most frequent locations although susceptible to edema because it is not supplied with a
even deeper areas such as basal nuclei may be involved. lymphatic system to drain extraneous fluid in the inter-
Usually intracerebral hematomas are associated with stitial compartment. Ion and water movement between
brain lacerations and contusions as well as diffuse axonal the vessels and the brain occurs across the blood–brain
injury. The clinical picture usually includes disorders barrier which depends on the capillaries of the brain.
of consciousness, hemiplegy, anisocoria, and brain- Here endothelium has tight junctions and few endocytotic
stem involvement. A surgical approach to intracere- vesicles. This kind of endothelial differentiation derives
bral hematoma is not always possible and outcome is from the cross-talk with astrocytes. Cerebral edema may
usually poor. be vasogenic, cytotoxic, and interstitial (Box 20-7).
● Vasogenic edema is the result of fluid spilling across treatment of TBI and ischemia. Even nonneuronal cells
the vessels to the extracellular compartment. Usually (brain glia and lymphocytes) can release substances that
the vessels producing vasogenic edema show an bind to glutamate receptors. Excitotoxicity may be ongo-
abnormal barrier function. Brain contusions and lac- ing for several days, rather than just in the initial phase
erations usually are surrounded by injured vessels of TBI. Hence arresting excitotoxic processes may mod-
with poor barrier function. Moreover ischemia may ulate progressive brain injury in the initial days after TBI.
alter endothelial barrier function resulting in vaso- Ischemic brain injury associated with TBI causes neuronal
genic edema that increases intracranial pressure and apoptotic death. A calcium-binding peptide produced by
ischemia with a negative closed loop mechanism. astrocytes may be implicated in neuronal apoptosis.
Vasogenic edema affects preferentially white cere- Ischemic brain damage adversely affects outcome mor-
bral matter that appears swollen. bidity, and the difficulty in preventing ischemic damage
● Cytotoxic edema results from an increase in the intra- in cases with marked brain shift leads to poor outcome in
cellular water. Cerebral gray matter is usually more patients with TBI.
susceptible to cytotoxic edema as consequence of
either ischemia or hypo-osmolarity. Ischemia impairs Brain Shift and Herniation
neuronal metabolism and membrane ionic pump Intracranial hypertension is often associated with TBI
function. Hypo-osmolarity shifts water into neuronal because blood masses may evolve in brain shift and
cells that appear swollen. herniation. Cerebral masses move areas of cerebral
● Interstitial edema occurs in some kinds of hydro- parenchyma across dural folds resulting in brain shift
cephalus when fluids cross ependimal cells and accu- and herniation. If one hemisphere expands the cingulate
mulate in the periventricular areas. gyrus may herniate below the falx cerebri or the tempo-
ral lobe may herniate between the tentorium cerebelli
Ischemic Brain Damage and the brainstem. The latter herniation may injure the
Ischemic brain damage is one of the most important third cranial nerve with anisocoria and homolateral
factors precipitating TBI. Most ischemic brain damage is mydriasis. Moreover the contralateral cerebral pedicle
secondary to brain swelling, brain shift, and brain herni- may be compressed against tentorium cerebelli deter-
ation, rather than the direct effect of the primary damage mining paralysis homolateral to the cerebral lesion
upon the brain. (Kernoan Woltman syndrome). Even if initially the res-
TBI is strongly linked to ischemic brain damage. piratory pattern is not affected by this kind of herniation,
Ischemic brain damage results from pathogenetic mech- later pathologic respiratory patterns like Cheine–Stokes
anisms associated also with TBI, including excitotoxicity, breath may occur. Cerebellum may herniate into the
inflammation, free radicals, and apoptosis. Production of foramen magnum with a coning mechanism impairing
heat shock proteins and endogenous antioxidants are respiration and other brainstem functions. Brainstem
defensive mechanisms triggered by cerebral ischemia compression resulting from cerebellum herniation may
and TBI (Box 20-8). be fatal. Cerebral parenchyma may also herniate across
Phospholipase stimulation may cause alterations in skull defects. Brain shift compresses superficial cerebral
membrane phospholipids compromising the ability to arteries against dural folds determining occlusion and
accumulate excitotoxic amino acids. Inhibitors of both cerebral ischemia (Box 20-9).
cyclooxygenase and lipoxygenase pathways have been
shown to reduce cerebral deficits following ischemia and Hydrocephalus
trauma. Excitotoxicity is considered to be caused mainly Hydrocephalus is a dilatation of the cerebral ventricles
by the inappropriate release of glutamate. Multiple human with increased cerebrospinal fluid. TBI may obstruct
clinical trials focused on glutamate antagonists for the cerebrospinal fluid flow. When this obstruction occurs
MANAGEMENT OF TRAUMATIC
Hypotension and Fluid Resuscitation
BRAIN INJURY
In TBI hypotension may be a dangerous trigger of sec-
Prehospital and Emergency Room Care ondary damage. Concomitant multiple system trauma is
often associated with TBI resulting in significant blood
Prehospital and emergency room care of TBI should be
loss, hemodynamic instability, and shock. Prompt restora-
directed by the Advanced Trauma Life Support (ATLS)
tion of circulating blood volume to prevent secondary
guidelines for the early management of trauma. Prehospital
damage deriving from cerebral hypoperfusion is a
care of TBI includes airway management and treatment of
widely recognized priority. Fluid resuscitation in TBI has
hypoxia, hypotension, and fluid resuscitation and neuro-
been the focus of much discussion because of the possi-
logic assessment only after cardiorespiratory stability has
ble development of cerebral edema after administration
been guaranteed. Emergency room care includes car-
of large volumes of resuscitative fluids. The goal of fluid
diorespiratory stability optimization, considerations related
resuscitation in TBI should always be euvolemia to opti-
to the multiple trauma patient, neurologic assessment fol-
mize cerebral perfusion pressure without contributing
lowed by brain-specific therapies, and early diagnostic
to cerebral edema. The blood–brain barrier has peculiar
workup with indications for surgery (Box 20-15).
features being freely permeable to water, but nearly
impermeable to larger, colloid-sized molecules, and
minimally permeable to most ions. The osmotic gradient
Box 20-15 Prehospital Care of between blood and brain regulates water flux across the
Traumatic Brain Injury blood–brain barrier. The colloid osmotic pressure does
not influence greatly fluid flux across the blood–brain
Prehospital care of traumatic brain injury includes: barrier because plasma colloids account for a small
● Airway management fraction of the total number of particles in solution.
● Treatment of hypoxia Serum osmolality is the major determinant of fluid flux
● Treatment of hypotension across the normal blood–brain barrier. However, TBI
● Neurologic assessment after cardiorespiratory and hemorrhagic shock are associated with proinflam-
stability
matory mediator production that alters capillary perme-
Emergency room care includes:
ability in the brain. If the blood–brain barrier becomes
● Cardiorespiratory stability optimization
● Neurologic assessment permeable to ions but not to larger colloid particles,
● Eventual brain-specific therapies choice of fluid for resuscitation in TBI could be impor-
● Early diagnostic workup tant. If the blood–brain barrier is disrupted, however, per-
meability to both ions and colloidal particles may occur,
222 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
retrograde placement of a fiber optic catheter into the wavelengths in the range near to infrared and measures
jugular bulb that should be confirmed by radiologic the light reflected to the sensor. It measures arterial,
imaging. If cerebral metabolic rate remains stable, an venous, and capillary blood oxygen saturation. The
increase in cerebral blood flow results in an increased average oxygen saturation of all regional microvascular
jugular oxygen saturation. If jugular oxygen saturation hemoglobin is evaluated by near infrared spectroscopy
decreases below 55%, cerebral hypoperfusion is under and should be around 70%. Extracranial signals may
way because of intracranial hypertension, hypocapnia, interfere with near infrared spectroscopy. Although it is
or systemic hypoperfusion. Decreased jugular oxygen a noninvasive monitor of regional oxygen saturation,
saturation may occur independently of increases in jugular oxygen saturation is superior as an indirect
intracranial pressure. Cerebral hyperemia or depressed monitor of cerebral blood flow.
neuronal metabolism may cause a jugular oxygen satura-
tion higher than 85%. Both jugular oxygen saturations Electrophysiologic Monitoring
above 85% and below 55% are associated with poor Electrophysiologic monitoring includes passive moni-
outcome. Jugular oxygen saturation monitoring is useful toring methods such as electroencephalography and
if hemodynamic instability poses the patient at risk of active monitoring methods such as somatosensory
cerebral hypoperfusion. In this case vasopressor infu- evoked potentials. In ICUs monitors and ventilators may
sion may be titrated with a target jugular oxygen satura- interfere with electroencephalography. It has been used
tion above 55%. Jugular oxygen saturation monitoring to titrate barbiturate therapy and to assess seizures that
should be considered also to titrate other therapeutic may contribute to brain injury. Bispectral index cannot be
strategies such as hyperventilation, hypothermia, and recommended for barbiturate therapy titration, although
barbiturate coma, always aiming to a jugular oxygen its role in TBI is the object of studies. Somatosensory
saturation of between 55% and 85%. evoked potentials assess sensorial and motor pathways
and may provide diagnostic and prognostic information.
Tissue Oxygen Monitoring Initial bilaterally absent cortical somatosensory evoked
Tissue oxymetry probes allow one to monitor directly potentials indicate high probability of death, while
brain tissue oxygen content. The insertion technique normal evoked potentials predict good outcome.
for tissue oximetry probes is similar to that for intra- Electrophysiologic recovery often precedes clinical
parenchymal pressure monitoring. These probes mea- recovery.
sure brain tissue oxygen content in a small volume of
tissue. These results may be extrapolated to apply Temperature Monitoring
at least regionally. Tissue oximetry probes provide con- TBI may be associated with hyperthermia secondary
tinuous, real-time measurements of brain tissue oxygen to the damage of thermoregulatory centers. Lesions to
saturation. These data are very useful to titrate cerebral the brain are worsened by hyperthermia, which is a
perfusion pressure manipulation, hyperventilation, and cause of secondary damage in TBI. Core temperature
intracranial hypertension management. monitoring may underestimate brain temperature by
1–2°C, but it is a useful method for temperature moni-
Transcranial Doppler toring. Every effort should be made to maintain core
Blood flow through large cerebral vessels may be temperature below 37.5°C.
evaluated with transcranial Doppler ultrasonography.
This is a noninvasive method that provides an inter-
mittent evaluation. The transtemporal area is a natural TREATMENT OF INTRACRANIAL
acoustic window that allows the pulsed Doppler probe HYPERTENSION
to assess the anterior, middle, and posterior cerebral
arteries and anterior and posterior communicating TBI has been traditionally treated with early surgical
arteries. Systolic, mean, and diastolic flow velocities are treatment of intracranial mass lesions and careful critical
usually considered indices of flow. Hyperemic, normal, care treatment to avoid secondary damage and minimize
vasospastic, and absent flow may be differentiated using intracranial hypertension. When intracranial pressure is
derived indices such as the Gosling pulsatility index and monitored a stair-step approach is used to treat intracra-
the Lindegaard ratio. Transcranial Doppler should be nial hypertension. Methods to reduce intracranial pres-
used in association with other techniques because it sure are added considering the complications associated
provides intermittent measures. with each therapy. Usually the first step is sedation, anal-
gesia, and neuromuscular block; then cerebrospinal fluid
Near Infrared Spectroscopy drainage may be added if intracranial hypertension is
Near infrared spectroscopy monitors regional oxygen poorly controlled. If these treatments still fail to control
saturation in the brain. A scalp sensor emits light of intracranial hypertension, osmotic agents may be added,
228 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
while barbiturate coma should be reserved for intra- option in hemodynamically unstable patients, it requires
cranial hypertension refractory to all the previous treat- careful titration in these cases. Vasopressors or inotropes
ments in patients hemodynamically stable. Body position may be necessary to maintain an appropriate systemic
is also a determinant of intracranial pressure: a 30–45° arterial pressure, which is a primary target in TBI.
head elevation with the head kept in the neutral position
facilitates venous flow and intracranial pressure control.
Ventricular Drainage
Intracranial hypertension may be treated by draining
CLINICAL CAVEAT cerebrospinal fluid through a fluid-coupled intraventric-
Stair-step approach for the treatment of intracranial
ular catheter placed for intracranial pressure monitoring.
hypertension: The catheter may be placed 5–10 cm above the head and
● Appropriate body position with 30–45° head opened every 2–4 hours. Although ventricular drainage
elevation with the head in the neutral position may increase transcapillary filtration of fluid, this method
● Sedation and analgesia is effective in the treatment of intracranial pressure and
● Neuromuscular block in patients competing with should be used if appropriate sedation and analgesia,
mechanical ventilation eventually associated with muscle relaxation, fail to reduce
● Cerebrospinal fluid drainage intracranial hypertension.
● Osmotic agents
● Barbiturate coma
Osmotic Diuresis: Mannitol
If appropriate sedation and analgesia associated with
intermittent ventricular drainage fail to control intra-
Sedation, Analgesia, and cranial hypertension, osmotic diuresis using mannitol can
Neuromuscular Block be used. Mannitol (0.25–1 g/kg) is an osmotically active
In TBI sedation and analgesia should be titrated agent administered to increase plasma osmolality causing
according to hemodynamic stability, intracranial pres- an efflux of fluid from edematous areas of the brain that
sure, and the trauma-related disorder of consciousness. results in the reduction of intracranial pressure (if the
A general rule is to maintain a level of sedation deep blood–brain barrier is intact enough to be still impermeable
enough to facilitate mechanical ventilation and light to mannitol). Mannitol also causes a plasma expanding
enough to allow frequent clinical neurologic evalua- effect that increases cerebral blood flow. This may con-
tions. During the initial hypoperfusion phase sedation tribute to the reduction of intracranial pressure. Mannitol
should be carefully titrated in order to avoid systemic increases diuresis with an osmotic mechanism. Hypertonic
arterial hypotension. For this purpose short-acting saline (3%) increases plasma osmolality and expands
opioids are useful because they ensure cardiovascular plasma volume restoring systemic and cerebral perfusion.
stability and blunt sympathetic discharge. However Hypertonic saline has fewer side effects than mannitol,
pupillary examination should be performed before and it does not induce any osmolal gap so it allows an
opioids are administered. Prolonged administrations of easier titration. Hypertonic saline is particularly benefi-
benzodiazepines may delay the return of consciousness cial in the early hypoperfusion phase because it improves
because these drugs tend to accumulate. Benzodiazepines cerebral blood flow. However, mannitol and hypertonic
may also cause an emergence delirium state. Among opi- saline should be used in patients with unequivocal intra-
oids, sufentanyl and especially remifentanyl should prob- cranial hypertension unresponsive to appropriate sedation
ably be preferred for prolonged administrations because and ventricular drainage. Hemodynamic instability and
they have a good profile of the context-sensitive half-life hypovolemia contraindicate osmotic diuresis as does a
curve. Propofol has attractive properties for sedation in serum osmolality greater than 320 mosm/l.
TBI. Even used as the sole sedating agent, it ensures
deep levels of sedation resulting in the control of
intracranial hypertension and sympathetic discharges. Hyperventilation
Propofol has a short context-sensitive half-life. This prop- Hyperventilation decreases intracranial pressure
erty allows frequent clinical neurologic evaluations that because a reduction in PaCO2 determines cerebral alka-
are so important to monitor neurologic function in TBI. losis that results in cerebral vasoconstriction with a
Propofol has the advantage that it does not interfere decrease in cerebral blood flow and cerebral blood
with pupillary responses and the disadvantage that it has volume. The effect of hyperventilation on cerebral blood
a higher cardiovascular impact because of its negative flow is transient because readjustment of brain pH occurs
inotrope effect. Therefore, even if propofol remains an within 6–24 hours and thereafter the normalization of
Traumatic Brain Injury 229
PaCO2 can dramatically increase intracranial pressure. should be burst suppression. At the high doses used for
Thus it does not make sense to use prophylactic hyper- intracranial hypertension treatment barbiturates may
ventilation resulting in a PaCO2 below 35 mmHg, cause reductions in systemic arterial blood pressure and
especially in the first 24 hours after brain injury, when cerebral blood flow. This could be deleterious in the
cerebral blood flow is already reduced as much as 50% hypoperfusion phase of TBI when cerebral blood flow is
(hypoperfusion phase). Prolonged hyperventilation ther- already reduced. In this case the use of vasopressors
apy resulting in a PaCO2 below 25 mmHg should be should be considered. The use of barbiturates impairs
avoided in the absence of elevated intracranial pressure. a frequent clinical neurologic evaluation and delays
Although hyperventilation still has a role in the treat- awakening of patients.
ment of intracranial hypertension unresponsive to con-
ventional intracranial pressure-lowering therapies, its
use requires an appropriate cerebral oxygenation moni- Hypothermia
tor such as jugular oxygen saturation monitoring or In TBI the lesions to the brain are temperature
tissue oxygen monitoring because hyperventilation may dependent. Fever may worsen TBI, and an aggressive
precipitate cerebral ischemia. Ischemia related to hyper- treatment of fever is mandatory. Hypothermia reduces
ventilation may aggravate the pre-existing brain injury. cerebral metabolism and may have a beneficial effect
Cerebral vasoreactivity after TBI increases over time. In on intracranial hypertension. In several experiments
particular cerebral vessels show a decreased responsive- hypothermia resulted in a decreased intracranial hyper-
ness the first day after injury, and a progressive increase tension when used immediately after brain injury. Some
in PaCO2 reactivity between the second and the fifth day clinical trials failed to demonstrate an improvement in
after injury. Intracranial hypertension is often difficult to outcome with the use of hypothermia in TBI. Hypothermia
treat just three to five days after injury. Therefore hyper- to temperatures of 30–33°C prolongs ventilation and
ventilation therapy is likely to be performed just when increases the risk of nosocomial infections. These side
cerebral vessels are more sensitive to hypocapnia and effects could lead to increased morbidity and mortality
the brain is more susceptible to the hyperventilation- in TBI, even though hypothermia shows beneficial effects
related ischemia. When jugular oxygen saturation on cerebral metabolic rate and intracranial hypertension.
demonstrates that cerebral oxygen delivery significantly
outstrips cerebral oxygen demand, hyperventilation may
be beneficial in decreasing cerebral blood volume and Steroids
intracranial pressure without inducing ischemia. Glucocorticoids may reduce intracranial inflamma-
tion. Inflammatory mechanisms underlie blood–brain
barrier alterations resulting in vasogenic cerebral edema
Cerebral Perfusion Pressure and may be involved in excitotoxicity that may contribute
Manipulation (Vasoconstriction to cytotoxic edema. Although steroids at high doses for
and Vasodilatation Cascades) 24 hours are useful in the treatment of acute spinal cord
In the early hypoperfusion phase of TBI the mainte- injury if treatment is initiated within eight hours, they
nance of a high cerebral perfusion pressure could trigger have shown no beneficial effect in the outcome of TBI.
a vasoconstriction cascade leading to a reduction in Moreover, steroids increase the risk of infection.
intracranial hypertension. The target for cerebral per-
fusion pressure should be 60 mmHg, although some-
times cerebral perfusion pressure should be higher than Cranial Decompression
70–80 mmHg to remain in the autoregulatory range. If When intracranial hypertension is unresponsive to
cerebral perfusion pressure management may be useful all therapies wide bilateral frontoparietal craniectomies
to treat intracranial hypertension in the early hypoperfu- may result in a dramatic reduction of intracranial hyper-
sion phase, it could be less effective or even deleterious tension. Preemptive decompressive craniectomy may
in the late hyperaemic phase. have a role in high-risk patients.
CLINICAL CAVEAT associated with seizures that usually are present at the
time of injury. When seizures occur, benzodiazepines
What Fluid in Traumatic Brain Injury? and other anticonvulsants are used. Prophylaxis with
● Normal saline has an osmolarity slightly higher than phenytoin may be useful only in patients with significant
plasma and is the preferred fluid in TBI parenchymal lesions evident on CT scan and should be
● Other ions such as potassium, magnesium, and
prolonged for ten days after injury.
calcium should be administered to maintain normal
electrolyte homeostasis
● 5% dextrose in water is discouraged and may be
required only if patients become hyperosmolar Prevention and Treatment of Infectious
(>320 mosm/l) Complications
TBI patients who receive prolonged mechanical ven-
tilation show an increased risk of nosocomial pneumo-
Fluid management may be particularly challenging in nia that is associated with an increased mortality. Stress
head-injured patients because TBI is often associated ulcer prophylaxis, hypothermia, and barbiturates
with the syndrome of inappropriate antidiuretic hormone increase the risk further. Penetrating injuries and intra-
secretion and with diabetes insipidus. Sometimes even cranial pressure monitoring, especially using fluid-
when fluid management has achieved euvolemia, cerebral coupled devices, increase the risk of meningitides and
perfusion pressure is still inadequate. Particularly if these other neurologic infections. The risk is low if intracranial
cases occur in the early hypoperfusion phase of TBI, vaso- pressure monitoring lasts less than 5–7 days. The fre-
pressors and inotropes should be used because cerebral quent use of intravascular catheters for arterial pressure
perfusion pressure is the major determinant of cerebral monitoring, central venous pressure monitoring, jugular
blood flow and is the priority when cerebral hypoperfu- oxygen saturation monitoring, and fluid and drug infu-
sion is underway. sions increases the risk of bloodstream infections. The
frequent use of bladder catheters put the head-injured
CLINICAL CAVEAT patient at risk of urinary tract infection. The use of
antibiotics should follow the accepted microbiological
TBI is often associated with: principles. Cultures of cerebrospinal fluid, blood, fluid
● Syndrome of inappropriate antidiuretic hormone
from BAL, and urine should guide antibiotic therapy.
secretion (SIADH)
● Diabetes insipidus
233
234 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Eye opening. Spontaneous (4), response to verbal Etiologies of increased intravascular blood volume
stimuli (3), response to noxious stimuli (2), and include hypercarbia, hypoxia, and volatile anesthetics.
no eye opening (1). Studies looking at the relationship between intracra-
Motor response. Follows commands (6), localizes to nial volume and pressure have been performed by grad-
noxious stimuli (5), withdraws to noxious ually increasing the volume of an intracranial balloon in
stimuli/normal flexion (4), abnormal animals. The ICP increases at a relatively slow rate with
flexion/decorticate posturing (3), abnormal increased balloon volume. At a certain point (at an ICP
extension/decerebrate posturing (2), and no of approximately 20 torr) the ICP increases dramatically
movement to noxious stimuli (1). with small increases in balloon volume. At this point the
The GCS is a useful, rapid screen of head injury system changes from a relatively compliant system to a
severity. Mild head injury usually produces a score of relatively noncompliant system. Because small changes
13 to 15, moderate head injury produces a score of 9 to 12, in volume can lead to large increases of ICP and then
and severe head injury generally carries a score of 8 or cerebral herniation at this pressure, an ICP of 20 torr and
less. If the patient is intubated, the score is qualified with above is considered to be intracranial hypertension.
an “I.” Another important physiologic parameter is cerebral
The GCS is a useful screening tool for the initial assess- perfusion pressure (CPP). This can be calculated by sub-
ment but is less reliable for assessing subtle changes in a tracting the ICP from the mean arterial pressure (CPP =
patient’s status while in the ICU. A detailed neurologic MAP – ICP). Most authorities advocate maintaining a CPP
examination should be done for the initial presentation of 50 torr or greater. This ensures adequate cerebral
followed by more focused examinations concentrating blood flow (CBF). Insufficient CBF results in brain
on known deficits for subsequent evaluations. ischemia and cerebral injury. Therefore, it is important
to know the CPP and ICP in critically ill patients with
neurologic injury. The MAP is best measured using an
INTRACRANIAL PRESSURE intra-arterial catheter. This allows continuous assess-
ment of the MAP, which is not possible with noninvasive
Intracranial pressure (ICP) monitors are used prima- blood pressure monitoring. If the patient is felt to have
rily for patients with known or suspected intracranial elevated ICP (usually predicted by evaluation of the head
hypertension, and those with head injuries where a neu- computed tomography (CT) scan), an ICP monitor should
rologic examination is not possible. Patients who cannot be placed.
be followed with a neurologic examination include those
under general anesthesia, or those who are chemically CLINICAL CAVEAT
paralyzed or heavily sedated in the ICU. The use of an
ICP monitor alerts the clinician to an elevation of ICP, CPP = MAP − ICP
which can then be treated. Maintain ICP < 20 torr, CPP > 50 torr
Intraventricular catheters:
An understanding of ICP is important when making
● Most reliable means of measuring ICP
decisions about treatment. The intracranial vault can be ● Allows drainage of CSF in order to lower ICP
considered a fixed volume, which is about 1500 ml in ● More prone to complications
the adult. The intracranial vault contains three broad Intraparenchymal, subdural, and epidural monitors:
categories of substances. These are the brain and its ● More easily placed
support structures, cerebrospinal fluid (CSF), and blood. ● Less associated complications
The brain and its supporting structures account for ● Less reliable ICP measurement
about 85% of the volume. CSF and blood account for
10% and 5%, respectively, of the remainder. If any one of
these components is increased, intracranial hyperten-
sion can result. Processes that increase the volume of the ICP monitors include ventricular catheters connected
brain and its support structures include brain edema to an external strain gauge transducer or catheter-tip
(cytotoxic edema due to ischemic strokes and vasogenic pressure transducer devices, parenchymal catheter-tip
edema around tumors and abscesses) and the mass of pressure transducer devices, subarachnoid or subdural
tumors. Elevated volumes of CSF occur in various clini- fluid-coupled devices, and epidural devices. External
cal scenarios and is known as hydrocephalus. Elevated strain gauge transducers are located at the bedside and
volumes of intracranial blood can occur either extravas- are coupled to the patient’s intracranial space through
cularly or intravascularly. Intracranial hemorrhages (such fluid-filled lines. The catheter-tip transducers are either
as epidural hematomas, subdural hematomas, and intra- strain gauges or fiberoptic technologies and are placed
cerebral hematomas) can lead to critical elevations of ICP. intracranially.
Neurologic Monitoring 235
The fluid-filled lines connected to the external strain Fatal hemorrhage occurred in 1% of the patients with
gauges can become obstructed or have an air bubble epidural catheters.
in the line, which can lead to inaccurate pressures. The Occasionally, lumbar subarachnoid catheters (lumbar
external devices can be recalibrated after insertion. drains) are used in the ICU. These drains are used for
The transducer has to be positioned at the level of the some neurosurgical procedures (primarily cerebrovascu-
patient’s head and therefore has to be moved if the lar procedures) in order to “decompress” the brain and
height of the patient’s bed is moved. Intracranial trans- facilitate the surgical dissection. They are also used for
ducers are calibrated prior to insertion and cannot be some vascular surgery procedures (such as thoraco-
recalibrated once in place. Therefore, there is the poten- abdominal aneurysm resections). In these cases, there is
tial for measurement drift. The intracranial transducer a significant risk of spinal cord ischemia due to resection
devices give ICP measurements that are independent of of anterior spinal arteries (most significantly the artery of
head elevation. Adamkeiwicz). The catheters are used to drain CSF and
The ICP monitors can be placed in the epidural space, thus lower the ICP. This optimizes spinal cord perfusion
subdural space, subarachnoid space, brain parenchyma, and, theoretically, minimizes the risk of cord ischemia.
or intraventricular space. Intraventricular catheters have Postoperatively, ICP is not measured directly, but the
been used as the reference standard for ICP measure- catheters are drained at a predetermined level (highest
ment. Intraventricular catheters can be used to treat point of catheter) above the supine patient. Generally,
intracranial hypertension by draining CSF. The intra- the catheter height is placed at approximately 10 cm
ventricular catheters are usually connected to an external (10 cmH2O/CSF) above the patient. This will be the ICP
strain gauge transducer, but some incorporate intra- as long as the catheter drains freely. It is important not
cranial, fiberoptic transducers. This allows simultaneous to “overdrain” the catheter by placing it at or below the
drainage and ICP measurement. When using the external level of the patient. This could lead to complications. The
transducer, ICP measurements cannot be obtained while most severe complication is a subdural hematoma.
CSF is drained. There is potential for significant compli- Typically, the time patients are most at risk for overdrain-
cations when using intraventricular catheters. These ing is during transport. It is suggested that the catheter
devices are usually placed through the nondominant be clamped during these periods. The ICP will rise only
hemisphere away from the motor strip and the sagittal minimally if the catheter is clamped for a short period
sinus. The catheter has to travel through a significant (i.e., less than 30 minutes).
amount of brain parenchyma to reach the lateral ventricle. ICP can be measured using a variety of devices. The
There is the potential for bleeding, CNS injury, infection, intraventricular catheters are probably the most accurate
catheter misplacement, and obstruction. and can be used therapeutically. Unfortunately, these
The other devices (parenchymal, subarachnoid, sub- catheters have the highest risk for complications. The
dural, and epidural catheters) are less likely to cause a decision about which device to use should be made in
complication. The parenchymal catheters are placed a conjunction with the neurosurgical team and should be
short distance into the parenchyma. These devices can- based on the patient’s comorbidities.
not be used therapeutically to drain CSF. Many studies
support the accuracy of these devices for measuring
ICP. However, other studies have shown significant dis- ELECTROENCEPHALOGRAM
crepancies when compared to ventricular ICP. The deci- AND BISPECTRAL ANALYSIS
sion as to which device to use is multifactorial. Clearly,
if the head CT shows significant fluid in the ventricles, The EEG is another neurologic monitor of some use in
drainage via an intraventricular catheter would be bene- the ICU. A complex discussion of the EEG is well beyond
ficial. Patients who are coagulopathic are at increased the scope of this chapter. Briefly, neurons generate electric
risk for developing intracerebral hemorrhage as a fields when ions move between the intra- and extracellular
complication of intraventricular catheter placement. spaces. Neurotransmitter interactions with postsynaptic
Patients with fulminant hepatic failure and high-grade receptors affect ion channel permeability of the neuron,
encephalopathy have a high mortality often as a result of which allows movement of the ions. This results in
uncal and tonsillar herniation. A retrospective study by changes in its transmembrane voltage. This is known as
Blei and colleagues showed fewer complications with the postsynaptic potential (PSP). If the membrane poten-
epidural catheters (3.8%) compared to subdural (20%) tial of a neuron is depolarized beyond its threshold value,
and intraparenchymal (22%) catheters. The intra- an action potential (AP) is generated which then propa-
parenchymal catheters included intraventricular catheters. gates rapidly along the neuron’s membrane. The electric
In fact, fatal hemorrhage occurred with 5% of the subdural fields generated by the neurons result in electrical poten-
catheters and 4% of the intraparenchymal catheters. tial differences at the skin’s surface. Electrodes at the
236 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
skin’s surface act as transducers, which convert the to sedation (movement to noxious stimuli, hemody-
physiologic current at the skin to an electrical current namic response to stimuli, level of consciousness, etc.).
which is then processed by the EEG monitor. This prin- The BIS has been through multiple versions with
ciple applies to the electrocardiogram where the syn- improved clinical correlation in each. In the operating
chronous depolarization of all cells of the atria followed room the BIS indicates the potential for awareness and
by depolarization and repolarization of all cells of the hypnotic overdose. It cannot determine exactly when
ventricles produce the classic normal EKG with its P waves, consciousness returns. It does not predict unconscious-
QRS complex, and T waves. ness when ketamine or nitrous oxide is used.
Under normal circumstances the PSPs and APs gener- It would be desirable to use the BIS to monitor the
ated by neurons are not synchronous. The normal EEG level of sedation in the ICU. This could ensure patient
signal has no obvious repetitive pattern or any morphol- comfort and prevent oversedation. It is not clear that
ogy that correlates with underlying neurologic function. conclusions about BIS values obtained from healthy
Indeed, “spikes” or “sharp waves” due to synchronous patients undergoing anesthesia/sedation would be appli-
neuronal activity is diagnostic of seizure activity. Due to cable to critically ill patients in the ICU. Studies to
its complexity, interpreting raw EEG data is extremely address this issue are problematic, since it is difficult to
difficult. Methods to compress and simplify the raw EEG determine awareness and recall in ICU patients. In addi-
data require complex and intensive mathematical compu- tion, the electrical environment of the ICU can interfere
tations. These processed EEGs are used in the operating with the monitor. Studies in the ICU are ongoing. More
room to detect cerebral ischemia (e.g., during carotid studies are needed.
surgery) and to determine if drug therapy causes burst
suppression (e.g., during aneurysm surgery). Examples
of processed EEGs include the compressed spectral
CONCLUSION
array (CSA) and the density spectral array (DSA). The pri-
mary use of the EEG in the ICU is to make the diagnosis
Neurologic monitoring is an important part of the
of status epilepticus in the patient suspected of this dis-
care of patients in the ICU. While patients with known
order. Sometimes, the diagnosis is not obvious on obser-
CNS pathology clearly require this monitoring, a large
vation of the patient. The EEG is also used in the ICU
number of ICU patients are at risk to develop neurologic
as a confirmatory test when brain death is suspected.
injury. The neurologic examination, performed by physi-
Beyond these indications, there is not much use for the cians and nurses, is the main component of this moni-
EEG in the ICU. Certainly, it is not a very useful monitor toring. When indicated, monitoring ICP directly with
for following the patient’s neurologic status and correct- either a ventriculostomy or other intracranial device can
ing abnormalities. In the operating room there has been be very useful in diagnosing and treating intracranial
much work to use the EEG to determine depth of anes- hypertension. The EEG is an important tool in diagnos-
thesia. Similarly, in the ICU it would be desirable to have ing seizures and brain death. The role of the BIS monitor
a measure of sedation. Often this is difficult to determine. to measure the level of sedation of critically ill patients is
For example, it is very difficult to assess the adequacy of yet to be determined.
sedation of patients who are chemically paralyzed or
extremely edematous. Often, the patient’s eyes are
swollen shut. They are weak and unable to move their SELECTED READING
extremities well. The desire to obtain useful information
about anesthetic and sedation depth has led to the devel- Chestnut RM: Medical management of severe head injury:
opment of the bispectral index. present and future. New Horizons 3(3):581–593, 1995.
Bispectral analysis represents a different type of mathe- Ghajar J: Intracranial pressure monitoring techniques.
matical analysis of the raw EEG data from the analysis New Horizons 3(3):395–399, 1995.
performed by the processed EEG. The analysis is Johansen JW, Sebel PS: Development and clinical application
extremely complex and only became possible with the of electroencephalographic bispectrum monitoring.
advent of fast microprocessors. The bispectral index Anesthesiology 93(5):1336–1344, 2000.
monitor is a device manufactured by Aspect Medical Lang EW, Chestnut RM: Intracranial pressure and cerebral
Systems. It uses one- or two-channel EEG signal acquisi- perfusion pressure in severe head injury. New Horizons
tion. The analysis creates a dimensionless number 3(3):400–409, 1995.
known as the Bispectral Index Scale (BIS). The number Rampil IJ: A primer for EEG signal processing in anesthesia.
is scaled from 100 to 0 with 100 indicating an awake Anesthesiology 89(4):980–1002, 1998.
EEG and 0 representing complete electrical silence. Todd MM: EEGs, EEG processing, and the bispectral index
BIS values are then correlated against clinical endpoints (Editorial View). Anesthesiology 89(4):815–817, 1998.
22
CHAPTER Endocrine Dysfunction
CARLOS J. LOPEZ III, M.D.
237
238 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Box 22-2 Diagnosing Myxedema Supportive care during this time may include correct-
ing the core temperature by warming the patient; con-
sidering mechanical ventilation if mental status,
● Severe lethargy, loss of eyebrow hair, nonpitting
hypoventilation, or acidosis are at a critical stage; and
edema, macroglossia, hypothermia, bradycardia,
and hypercapnia
searching for precipitating causes. Myxedema can be
● Typically TSH > 60 μU/ml fatal and hypercapnia and hypothermia are poor prog-
● But lower with high-dose steroids or dopamine nosticators. However, early recognition, hormone
● May need free T4 level replacement, evaluation of pituitary–adrenal axis, and
supportive care will improve outcome.
Endocrine Dysfunction 239
Deficiency of cortisol has various clinical manifestations The diagnosis can be made by demonstrating a decreased
which depend on the extent and acuteness of onset. clearance of cortisol.
Acute adrenal insufficiency results from either addi-
sonian crisis due to acute hemorrhage into the adrenal
Acute Adrenal Insufficiency cortex or during periods of stress in patients with
Adrenal insufficiency can result from primary, sec- secondary and tertiary adrenal insufficiency. This is
ondary, or tertiary causes. Primary adrenal insufficiency, usually associated with a concurrent illness such as sepsis,
or Addison’s disease, is due to the destruction of the trauma, or surgery. Along with the signs of glucocorti-
adrenal cortex. Autoimmune diseases account for a large coid and mineralocorticoid deficiency, signs of cardio-
percentage of cases. Other causes include chronic infec- vascular collapse are pronounced. Hypotension, relatively
tions besides tuberculosis like AIDS-related infections such unresponsive to volume resuscitation, will predominate.
as cytomegalovirus (CMV), or fungal infections; Gram- It can progress to cardiovascular collapse and death.
negative bacterial infections; invasion of the adrenal by Hyperpigmentation seen in primary adrenal insuffi-
cancer cells that have spread from another part of the ciency is not seen in secondary adrenal insufficiency.
body, especially the breast; rarely, hemorrhage into the Diagnosis (Box 22-5) requires a high index of suspi-
adrenals during shock; abdominal trauma; and the surgical cion. While an insulin tolerance test would be the most
removal of both adrenals. Drugs such as ketoconazole sensitive diagnostic test it is not practical in the critically
and etomidate have also been implicated. It can be ill patient. A random cortisol level is obtained instead.
chronic, but can develop into acute addisonian crisis Normal patients with an intact hypothalamic–pituitary–
during periods of stress. The signs and symptoms are of adrenal (HPA) axis during periods of stress will have
both mineralocorticoid deficiency – hyperpigmentation, a random cortisol >18 μg/dl and generally >25 μg/dl.
vitiligo, hyperkalemia, hyponatremia, and hypovolemia – However, a low random cortisol level does not make the
and glucocorticoid deficiency – weakness, fatigue, hypo- diagnosis of adrenal insufficiency. The HPA axis needs
glycemia, and hypotension. to be checked. Traditional diagnosis requires a 250 μg
Secondary adrenal insufficiency is most commonly bolus of cosyntropin (ACTH). By convention this dose is
due to previous glucocorticoid use which suppresses thought to exclude adrenal insufficiency if the post-
the pituitary–adrenal axis. The subsequent ability of the stimulation level at 60 minutes increases the cortisol
adrenal gland to increase cortisol production in periods level by >8 μg/dl or if the level is >18 μg/dl. However,
of stress is decreased. In fact adrenal recovery may take the precise diagnostic criteria for adrenal suppression
9 to 12 months following the discontinuation of steroid are unclear. We know that levels of up to 25 μg/dl may
use. These patients should be considered to be at risk for represent an inadequate response. Moreover, the standard
secondary adrenal insufficiency. Other causes are post- test dose of 250 μg of ACTH is in fact several hundred-fold
partum pituitary necrosis, pituitary tumors, pituitary greater than the stress ACTH response. This supraphysio-
surgery, brain tumors, head trauma, radiation therapy, logic dose may in fact cause the adrenal to respond
and anoxic encephalopathy. Some clinicians believe that when it would not otherwise. One may therefore fail to
sepsis itself may suppress adrenal function, which returns diagnose patients with partial or relative adrenal insuffi-
once sepsis resolves. Patients typically manifest signs and ciency. Many clinicians are concerned that the standard
symptoms of glucocorticoid deficiency. testing is not sensitive enough. Therefore a lower dose
Tertiary adrenal insufficiency refers to tissue gluco- cosyntropin test of 1 μg is advocated by some. Under a
corticoid deficiency typically from sepsis or multiple protocol advocated by Marik and Zaloga, a hypotensive
organ dysfunction. These patients in effect have relative
tissue resistance to cortisol. These patients may have
high levels of circulating cortisol, which may make
the diagnosis of adrenal insufficiency difficult to make.
Box 22-5 Diagnosing Acute Adrenal
Insufficiency
patient with a random cortisol of <25 μg/dl undergoes a steroid dose. Generally those patients who are on a low-
1 μg ACTH stimulation test. An appropriate response is dose prednisone ≤5 mg/day or are getting minor or periph-
considered to be a subsequent cortisol level >25 μg/dl at eral surgery receive that dose. This is tailored upwards with
30 minutes. They follow this up with a 250 μg dose to full replacement reserved for patients on a high preopera-
differentiate between primary adrenal failure, HPA axis tive regimen or those scheduled to receive major surgery.
failure, and ACTH resistance. More experience, how-
ever, is needed before conclusions can be made. We are
currently assessing the use of a 1 μg dose of ACTH fol- DIABETES INSIPIDUS
lowed by a 250 μg dose which is injected at the time the
60 minute sample is obtained. When in doubt we treat Diabetes insipidus (DI) is a disorder of water imbal-
with a short course of steroids and observe. ance due to a lack of production of or response to anti-
diuretic hormone (ADH). ADH is secreted by the pituitary
and is responsible for the absorption of water in the col-
CURRENT CONTROVERSY lecting tubules. There are neurogenic and nephrogenic
ACTH Stimulation Test causes. Neurogenic (central) DI may be idiopathic in one-
● Precise diagnostic criteria for acute adrenal third of cases or caused by the destruction of hypophysis
insufficiency using cortisol assays are unavailable due to trauma, surgery, granulomatous disease, vascular
● Standard ACTH stimulation test with 250 μg is accidents, neoplasms, or infections. Nephrogenic DI
supraphysiologic can be caused by drugs, amphotericin B, democycline,
● May mask partial or relative adrenal insufficiency and lithium; renal failure including correction of post-
● Low dose with 1 μg is advocated by some
obstructive uropathy, systemic diseases such as amyloid-
● What cortisol level to use is still unclear
osis, multiple myeloma, and sarcoidosis; and pregnancy.
Central DI tends to be more severe. These patients
present with polyuria, polydipsia if alert, hypernatremia
Treatment is with stress doses of hydrocortisone IV with high serum osmolarity and low urine osmolarity
at 100 mg q 8 hours in patients with an established diag- <300 mOsm/kg. In the ICU these patients can have very
nosis. In patients with a possible diagnosis, emergent large urine outputs of ~1 l/hour up to 20 l/day. They will be
treatment can be started with dexamethasone IV 4 mg q hypovolemic and may even be in shock. While a water dep-
6 hours. Dexamethasone does not interfere with the rivation test and desmopressin challenge test may be useful
cortisol assay. Treatment can therefore be started while in differentiating a central from nephrogenic cause of DI,
testing is in progress. However, it has no mineralocorti- the most useful test in the critically ill patient is urine spe-
coid activity so it should be changed to hydrocortisone cific gravity. A urine specific gravity of <1.004, or a urine
once the cosyntropin test is complete or diagnosis is osmolarity <300 mOsm/kg, in the face of hypernatremia
made. Emergent treatment should also include D5NS to and large urine output is diagnostic for DI (Box 22-6).
treat the associated hypoglycemia and volume depletion. Treatment for central DI is with the use of desmopressin
(DDAVP) IV or SC at 1–4 μg q 6 to 24 hours depending on
severity or intranasally at 5–20 μg q 12 hours if mild. Free
DRUG INTERACTIONS water deficits must be calculated and replaced (Box 22-7).
Dexamethasone Initial fluids may include normal saline (NS) for volume
● Dexamethasone does not interfere with cortisol assay expansion but is soon switched to D5W and PO replace-
● Little mineralocorticoid activity ments. Potassium, magnesium, and phosphorus losses
● Switch to hydrocortisone once diagnosis is made are replaced simultaneously. In severe nephrogenic DI,
● If must continue dexamethasone add flucortisone thiazide diuretics are administered. DI may be masked
in patients with adrenal insufficiency, so care must be
taken when initiating steroid treatment.
Perioperative stress dose steroid replacement has tradi-
tionally required full replacement of hydrocortisone IV at
100 mg q 8 initiated at the time of surgery and subsequent Box 22-6 Diagnosing Central Diabetes
tapering over the next several days. This was regardless of Insipidus
the planned surgery in any patient who has received
steroids over the last 9 to 12 months. The normal basal pro- ● Polyuria, polydipsia if alert; hypernatremia
duction of cortisol, however, is 30 mg/day. A more tem- ● Urine specific gravity < 1.004
pered approach appears to be gradually developing ● Urine osmolarity <300 mOsm/kg
assessing the type of surgery planned and the preoperative
Endocrine Dysfunction 243
occurs in children and young adults due to new-onset and to increase glucose utilization and ketone clearance.
diabetes, noncompliance of insulin therapy, or concur- A bolus of insulin is given at 0.1 units/kg and a drip is
rent conditions such as infections, trauma, myocardial started at 0.1–0.2 units/kg/hour. Blood glucose should
ischemia, and emotional stress. On rare occasions it be monitored q 1 hour at first and a reasonable goal
occurs in severely stressed older patients with type II DM. should be a decrease of 100–150 mg/dl/hour initially.
Its pathogenesis is due to a complete or relative defi- Fluid deficits, typically of the order of 5–8 liters, are
ciency of insulin during periods of stress. This, coupled replaced aggressively with NS. Although patients may
with a secondary counter regulatory hormone excess actually be hypernatremic, the correction of volume sta-
of glucagon and catecholamines, results in the over- tus initially with NS is more important than the risk of
production and underutilization of glucose and lipolysis. increasing sodium content. Infusion of 500 to 1000
The clinical picture is due to these metabolic disturbances. cm3/hour for the first 1 to 2 hours is followed by 250 to
In DKA hyperglycemia results typically with a blood 500 cm3/hour for the next 2 to 4 hours depending on
glucose of 400–800 mg/dl. This is accompanied by an the extent of dehydration. Although care should be
osmotic diuresis, an anion gap metabolic acidosis due taken in patients with cardiac dysfunction, volume resus-
to the increased production of acetoacetic acid and citation should be started early and continued until after
β-hydroxybutyric acid, and the accumulation of ketones the resolution of ketoacidosis. When blood glucose
due to acetone and acetoacetic acid. Patients may pres- approaches 250 mg/dl the fluid is changed to D5W or
ent with polyuria, mild dyspnea, nausea, vomiting, vague D5W1/2NS in order to prevent hypoglycemia while con-
abdominal discomfort, lethargy, and occasionally an tinuing to give insulin. Insulin is maintained until the
altered mental status. Findings on physical examination ketoacidosis resolves. Potassium replacement must be
may include tachypnea, tachycardia, and a weak thready initiated early. In fact patients with normal and espe-
pulse consistent with hypotension. The diagnosis is cially with low potassium should have their potassium
established in a hyperglycemic patient by a serum sample replacement begun prior to insulin administration.
revealing an anion gap metabolic acidosis and positive Magnesium and phosphate replacement will also need to
for ketones. Urine for ketones which can be analyzed be addressed. Although a pH < 7.2 or even < 7.1 with a
rapidly at the bedside may also be useful. Hyperkalemia serum HCO3 < 10 is not uncommon, the use of NaHCO3
due to lack of insulin and acidosis is typically present should be avoided. We reserve its use for a persistent
in spite of large potassium deficits due to the osmotic pH < 7.0 after several hours of treatment. Underlying
diuresis. The diuresis may also cause hypomagnesemia precipitants are searched for and treated.
and hypophosphatemia. Free water loss at the expense of
sodium occurs readily. However, a low or normal sodium
is often seen on laboratory tests. This is due to the dilu-
tional effect of hyperglycemia and hypertriglyceridemia CLINICAL CAVEAT
on serum sodium concentrations. This “psuedohypona- Treatment of Diabetic Ketoacidosis
tremia” underestimates the true total body sodium level. ● Volume – NS at 500 to 1000 cm3/hour then D5W
A correction formula adding 1.6 mg/dl Na+ to the mea- or D5W1/2NS
sured Na+ concentration for every 100 mg/dl of glucose ● Insulin drip – continue <250 mg/dl until ketoacidosis
over 100 mg/dl is generally used (Box 22-8). True total resolves
● Potassium, magnesium, and phosphorus
sodium levels may actually be normal or high. The
replacements early
osmotic diuresis causes volume depletion and dehydra- ● Treat precipitating illness
tion as evidenced by the increased urea nitrogen, creati-
nine, and osmolarity. Increased plasma amylase without
evidence of pancreatits and hypertriglyceridemia can
also be seen.
Insulin, volume resuscitation, and electrolyte replace- Nonketotic Hyperosmolar
ment are crucial in the treatment of DKA. Insulin is needed
Syndrome
to decrease hepatic production of glucose and ketones
Nonketotic hyperosmolar syndrome (NKHS) is a con-
dition that occurs in older, type II diabetics and rarely in
type I diabetics. These patients typically secrete enough
Box 22-8 Correction of Serum Sodium insulin to prevent lipolysis and ketogenesis and the sub-
Concentration sequent DKA from occurring, but not enough to prevent
hyperglycemia. An altered mental status along with renal
Corrected [Na+] = 1.6 × [([Glucose]−100)/ insufficiency or prerenal azotemia appear to be impor-
100] mg/dl + [Na+] tant in the development of the hyperglycemia. Typical
precipitating factors are infections, stroke, myocardial
Endocrine Dysfunction 245
Alpha-adrenergic blockade is the cornerstone of hyper- careful consideration. Recent data for instance support-
tension control in these patients, and in fact needs to ing the concept of partial or incomplete adrenal insuffi-
occur before beta-blockade is introduced. Beta-blockade ciency and that tight blood glucose control improves
without adequate alpha-blockade can result in unop- mortality in mechanically ventilated patients forces us
posed alpha-mediated vasoconstriction and severe to view these “subtle or trivial” effects in a new light.
hypertension. Labetolol because of its combined alpha- So while we must manage life-threatening situations
and beta-blockade has been promoted as a first-line without delay, we cannot forget that other abnormalities
agent. However, there are reports of worsening hyper- which are thought to be minor may have a detrimental
tension in some patients presumably due to inadequate impact on our patients.
alpha-blockade.
Larsen PR et al, editors: Williams Textbook of Endocrinology, Marik PE, Zaloga GP: Adrenal insufficiency in the critically ill: a
ed 10, Philadelphia: WB Saunders, 2002. new look at an old problem. Chest 122(5):1784–1796,
Longnecker D et al, editors: Principles and Practice of 2002.
Anesthesiology, ed 2, Philadelphia: Mosby, 1998. Murray M et al; ASCCA, editors: Critical Care Medicine:
Marik PE, Kiminyo K, Zaloga GP: Adrenal insufficiency in critically Perioperative Management, ed 2, Philadelphia: Lippincott
ill HIV infected patients. Crit Care Med 30:1267–1273, 2002. Williams and Wilkins, 2002.
Marik PE, Zaloga GP: Adrenal insufficiency during septic Van den Berghe GW et al: Intensive insulin therapy in the crit-
shock. Crit Care Med 31:141–145, 2003. ically ill patients. N Engl J Med 345(19):1359–1367, 2001.
23
CHAPTER Critical Care
in Pregnancy
SUSAN E. DANTONI, M.D., F.A.C.O.G.
248
Critical Care in Pregnancy 249
Nonspecific Host Defenses conduit for pathogens to the lungs. Obstruction or injury
Specific Host Defenses to the genitourinary mucosa due to instrumentation,
Polymorphonuclear Leukocytes calculi, and cytotoxic agents may result in infections.
Cell-mediated Immunity Breakdown of the gastrointestinal mucosal barrier
Humoral Immunity commonly results from cytotoxic agents during treatment
Complement System for malignancies. The neutropenic patient may have a
Immunosuppression and Transplant Patients subtle, not easily apparent gastrointestinal source, or
Solid Organ Transplant Patients may present with an acutely ill fulminant picture. These
Bone Marrow Transplant Patients patients often have polymicrobial infections. A high
Human Immunodeficiency Virus Patients index of suspicion is necessary.
Summary The normal flora should be considered as a host defense
mechanism. It competes with nonindigenous pathogens
Host defense mechanisms are either nonspecific, that are introduced, and generally inhibits their growth.
nonimmune-mediated or specific, immune-mediated. Disruption of normal flora may allow the propagation of
Intact physical barriers are in part responsible for the nonindigenous pathogens. Patients who have been insti-
nonimmune-mediated defense mechanism. Conversely, tutionalized, have received broad-spectrum antibiotics,
the various immune components with their complex or who are neutropenic have altered flora.
interrelationships provide the immune-mediated response. Other nonspecific defense mechanisms include the
The immune-compromised host can be defective in any normal flow of secretions from either drainage, as in the
part of the host defense system, while the immune- biliary tract, or the ciliary action of the respiratory mucosa;
suppressed host refers only to the immune defective and the gastric acidity of the stomach, which kills bacteria.
group. Adequate nutritional status is crucial in providing sub-
strates for metabolic needs and protein synthesis.
252
The Immune-Compromised Host and the HIV Patient 253
Empiric broad-spectrum therapy should be chosen malignant cells. Acquired defects are the most common
with an understanding of the local microbiological flora. while congenital ones are rare. Human immunodefi-
Local sensitivity patterns of likely infections may alter ciency virus (HIV) infections, lymphoreticular malignan-
the specific choices. Treatment will include coverage cies, and cytotoxic and immunosuppressive chemotherapy
against Gram-negative bacteria including P. aeruginosa with azathioprine, vincristine, bleomycin, cyclosporine,
and Gram-positive organisms. In noncritically ill patients tacrolimus, OKT3, and high-dose corticosteroids result
monotherapy with imipenem-cilastatin, or an anti- in the majority of acquired cell-mediated deficiencies in
pseudomonal third-generation cephalosporin may be the developed world. HIV and severe protein malnutri-
sufficient. In critically ill patients combination therapy tion are the most common cause in developing nations.
is used. Coverage against nosocomial antibiotic-resistant Defects in cell-mediated immunity are associated with
organisms and Serratia, Citrobacter, and Enterobacter infections due to bacteria, fungi, viruses, and protozoa.
spp., which become rapidly resistant to β-lactams, is essen- These infections can be indigenous, community
tial. Possible combinations include an antipseudomonal acquired, or nosocomial in origin. Unusual infections
third-generation cephalosporin or an antipseudomonal due to cell-mediated infections may occur in various
penicillin plus an aminoglycoside or a fluoroquinolone organs. Lungs can develop pneumonias due to
(especially ciprofloxacin). Vancomycin can be added if Pneumocystis carinii, Legionella pneumophilia,
a Gram-positive infection due to methicillin-resistant cytomegalovirus (CMV), herpes simplex virus (HSV), vari-
S. aureus (MRSA) is suspected, or if patients become cella zoster virus (VZV), adenovirus, coccidiomycosis,
hemodynamically unstable. If fever persists after 4 to and Cryptococcus neoformans. The CNS can be infected
7 days, or there is rapid clinical deterioration, empiric cov- with C. neoformans, Toxoplasma gondii, and Listeria
erage for fungal infections with amphotericin B should monocytogenes. Mucocutaneous infections can occur due
be started. The broad-spectrum antibiotics should be to Candida spp., HSV, VZV, and CMV. Unusual dissemi-
continued for a minimum of 10 to 14 days or longer until nated infections with Mycobacterium avium intracellulare
the ANC is >500 cells/mm3. (MAI), CMV, and VZV can occur (Box 24-2).
Factors determining the pathogen and site of infec-
tion include the CD4 count, which reflects the progres-
CLINICAL CAVEAT sive decline of cell-mediated immune function; the
Empiric Neutropenic Therapy duration of immune suppression; and, if an organ was
● Noncritically ill – monotherapy may be sufficient transplanted, the time since the transplant and the organ
● Imipenem-cilastatin, or an antipseudomonal third- transplanted. As the CD4 site decreases opportunistic
generation cephalosporin infections particularly Pneumocystis carinii and CMV
● Critically ill – combination therapy is needed become more prevalent. As time progresses from 0 to
● Antipseudomonal third-generation cephalosporin 6 months from organ transplantation, typical postsurgical
or an antipseudomonal penicillin plus an or nosocomial infections are replaced by opportunistic
aminoglycoside or a fluoroquinolone infections. After 6 months the infections depend on level
● Add vancomycin if MRSA or hemodynamically of immune suppression and environmental factors. They
unstable
are similar to those in immune-competent individuals.
● Add amphotericin B if fever > 4 to 7 days or
decompensates
The treatment which is individualized on the basis of the
● Know local microbiological sensitivities
● Continue for 10 to 14 days or until
ANC > 500 cells/mm3 Box 24-2 Characteristics of Cellular-
Mediated Dysfunction
nature of the immune defect and the above factors, is antibody-producing B-lymphocytes, and is involved in
discussed elsewhere in this chapter. T-cell independent immune responses. Specific comple-
ment deficiencies also result if asplenia occurs. The spleen
is therefore important in the clearance of nonopsonized
Humoral Immunity and opsonized bacteria. Overwhelming septicemia may
Humoral immunity is mediated through antibodies occur in asplenic patients. Streptococcus pneumoniae
(immunoglobulins) produced by B lymphocytes. and Haemophilus influenzae infections predominate,
Immunoglobulins generally assume one of two roles. although Neisseria meningitidis has been described.
They may act as plasma membrane-bound antigen recep- Mortality approaches 80%; and multiple amputations are
tors on the surface of a B-cell or as antibodies free in frequent in survivors. Due to the rapid progression of ill-
cellular fluids functioning to intercept and eliminate anti- ness, febrile, splenectomized patients require treatment
genic determinants. These antibodies activate comple- with high-dose antipneumococcal antibiotics. The
ment and go on to destroy microorganisms by promoting incidence of penicillin-resistant S. pneumoniae has been
phagocytosis via opsonization, toxin neutralization, and increasing, and so initial therapy with ceftriaxone and
lysis of susceptible organisms. Similar to complement vancomycin is wise. All splenectomized patients require
immunity, humoral immunity is responsible for the clear- immunization with pneumococcal, meningococcal A and
ance of extracellular bacteria. For practical purposes C, and haemophilus influenza B vaccines. Uncommon
humoral and complement deficiencies can be considered infections with intraerythrocyte protozoa such as
together. Multiple myeloma (MM), chronic lymphatic Plasmodium malariae and Babesia can also occur in
leukemia (CLL), and Waldenström’s macroglobulinemia splenectomized patients.
are common causes of disease states associated with
impaired humoral defects. Several cytotoxic chemo-
therapeutic agents, including azathioprine, cyclophos- CLINICAL CAVEAT
phamide, and methotrexate, suppress humoral function Asplenia
along with other effects on the immune system (Box 24-3). ● Has both humoral and complement deficiencies
Pathogens frequently found include encapsulated ● Loss of both antibody-producing B-lymphocytes and
pyogenic bacteria such as Streptococcus pneumoniae, complement proteins
Haemophilus influenzae, and rarely Neisseria menin- ● Overwhelming sepsis can occur, mortality
gitidis. Pneumonias tend to predominate with S. pneu- approaches 80%
moniae, Haemophilus influenzae, and occasionally ● Encapsulated organisms: S. pneumoniae,
K. pneumoniae. CNS infections include S. pneumoniae, H. influenzae, and N. meningitidis
H. influenzae, and N. meningitidis. Overwhelming sepsis ● Immunization crucial, acutely treat with
can occur with S. pneumoniae, H. influenzae, and antipneumococcal antibiotics
N. meningitidis. CNS infections are predominantly
caused by these organisms.
Asplenia, either anatomic or functional, results in
immune defects which have properties of both humoral
Complement System
and complement deficiencies. The spleen contains many The complement cascade is involved in regulating the
immune response. Complement are proteins, C3 and C5
being the most crucial, which form complexes that
interact with specific cell receptors or directly with
Box 24-3 Characteristics of Humoral cell membranes. They facilitate phagocytosis, may
Dysfunction independently kill extracellular organisms, and mediate
acute inflammatory reactions. Acquired deficiencies in
● MM, CLL, Waldenström’s macroglobulinemia, and complement are the most common and occur in systemic
cytotoxic agents are causes lupus erythematosus (SLE) and MM, while congenital
● Immunoglobulin function and activation of
deficiencies are rare.
complement is decreased
● Poor phagocytosis by opsonization, toxin
The pathogens are similar to those present during
neutralization, and lysis of organisms humoral defects, and can present with overwhelming
● Failure to clear extracellular organisms and infections due to encapsulated organisms. Infections
encapsulated pyogenic bacteria with Neisseria meningitidis, Streptococcus pneumoniae,
● Humoral and complement deficiencies are and less commonly N. gonorrheae occur. Infections of
considered together the CNS and joints may occur along life-threatening
disseminated infections (Box 24-4).
256 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
● First 30 days – infections typical of the immuno- Bone Marrow Transplant Patients
competent patient Bone marrow transplants are performed for acute and
● Nosocomial, and reflect local sensitivity patterns chronic leukemias, lymphomas, solid tumors, multiple
● 30 to 180 days – infections from cell-mediated myeloma, and severe aplastic anemia. These patients
deficiency play a larger role
have a combined alteration in immune function due to
● Viral and opportunistic infections are most
common
both early ablative chemotherapy with its severe neu-
● After 180 days – reflect immunosuppressant state tropenia, and the depression in cell-mediated and
● If on high-dose immunosuppressants then humoral immunity mostly from immunosuppressive
opportunistic infections therapy. After a preparative regimen with ablative
chemotherapy and possibly radiation therapy, a pro-
found pancytopenia, ANC < 100 cells/mm3, for 7–10 days
occurs in all patients. The granulocytopenia generally
Treatment strategies consider possible site of infec-
resolves within 30 days, although some phagocytic
tion, pathogen if identified, local sensitivity patterns, and
dysfunction remains. At this point, cell-mediated and
time since transplant. Signs and symptoms of infections
humoral dysfunction becomes important. The pattern of
should be pursued aggressively. Prevention of viral infec-
infectious complications reflects the sequence and is
tions through the use of pretransplant immunization
characterized by three broad time periods (Box 24-6).
with pneumococcal and hepatitis, and yearly influenza A
The preengraftment period lasts from bone marrow
vaccines should be done. Prophylaxis against oppor-
ablation until 30 days post-transplant. It is characterized
tunistic infections with trimethoprim-sulfamethoxazole
by ongoing neutropenia and mucositis. Bacterial, fungal,
(TMP/SMX) for P. carinii and nocardia, acyclovir for
and viral infections similar to other neutropenic patients
HSV, ganciclovir for CMV, and flucanazole or ketocana-
are common. Treatment is aggressive, with empiric
zole for fungal infections is also performed.
broad-spectrum antibiotic regiments similar to those
CMV infections pose a very common problem in
used for other febrile neutropenic patients. Nearly all
transplant patients. It typically occurs from reactivation
patients experience fever during this period, and require
of CMV in a seropositive patient, but can be due to a new
empiric antibiotic coverage. Prophylaxis with acyclovir,
infection from a CMV-positive organ. It is the most com-
for HSV and VZV, along with TMP/SMX, for P. carinii, is
mon cause of fever in the post-transplant patient. CMV
given during this time.
infections can cause isolated fever, hypotension, hepatitis,
The postengraftment period lasts from 30 to 100 days
pneumonitis, encephalitis, enterocolitis, and glomerulo-
post-transplant. Neutropenia has recovered, and infec-
nephritis. Involvement of the transplanted organ occurs
tions are due mostly to cell-mediated and, to a lesser
frequently. The diagnosis is difficult. Shell vial culture of
the buffy coat is useful when prepared less than 24 hours
after obtaining a sample. Intranuclear inclusion bodies in
cells from biopsied tissue are useful if seen. New tech- Box 24-6 Pattern of Infectious
niques using polymerase chain reaction (PCR) are Complications in Bone
becoming more common. Treatment is with ganciclovir. Marrow Transplant Patients
When organ involvement occurs hyperimmune globulin
● Preengraftment period – 0 to 30 days: neutropenia
and mucositis
CLINICAL CAVEAT ● Bacterial, fungal, and viral – similar to other
Cytomegalovirus Infection neutropenic patients
● Most common cause of fever in the post-transplant ● Postengraftment period – 30 to 100 days: cellular
patient and humoral dysfunction
● Also may have hypotension, hepatitis, pneumonitis, ● Become susceptible to viral, especially CMV,
encephalitis, enterocolitis, and glomerulonephritis opportunistic infections
● Involvement of transplanted organ frequent ● Late post-transplant period – more than 100 days:
● Diagnose with buffy coat, intranuclear inclusion persistent cellular and waning humoral dysfunction
bodies on biopsy or PCR ● VZV reactivation and viral respiratory tract
● Treat with ganciclovir, occasionally hyperimmune infections
globulin and foscarnet ● Susceptibility to encapsulated pathogens remains
258 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
degree, humoral defects resulting from the antirejection (ELISA). A positive test is then confirmed by a repeat
immunosuppressive therapy. Patients become susceptible positive ELISA and a Western blot test. Once a patient
to viral infections, especially CMV, other opportunistic is infected with the virus, through either parenteral or
infections such as P. carinii, T. gondii, and aspergillosis, sexual transmission, viral replication soon begins. If viral
along with other bacterial infections. Treatment requires replication is not suppressed, it progressively results in
an aggressive search for a pathogen while broad empiric lymphopenia and CD4 T-cell reduction with impaired
coverage, including opportunistic coverage, is instituted. cell-mediated immunity. The cell-mediated defects
The late post-transplant period occurs after 100 days. result in the classic picture of opportunistic infections
Cellular-mediated immune dysfunction is present and and malignancies. HIV infections, however, may also
late infections due to VZV reactivation and viral respira- cause a reduction in immunoglobulin production by
tory tract infections such as respiratory syncytial virus B-lymphocytes and cause humoral immune defects.
(RSV), and parainfluenza virus may occur. A humoral These humoral defects lead to an increased susceptibility
defect characterized by a decrease in opsonizing anti- to encapsulated organisms such as S. pneumoniae and
bodies also persists for years, and predisposes patients to H. influenzae. AIDS can subsequently result if the HIV
infections with encapsulated pathogens. infection advances. AIDS is defined as the presence of an
Graft versus host disease (GVHD) is an immunologic opportunistic infection, malignancy, HIV-related syn-
response by the donor to recipient antigens, and is the drome, or depletion of CD4 counts (<200 cells/mm3 or
major complication of allogenic bone marrow transplants. <14% total) in a patient with evidence of HIV infection.
Acute GVHD occurs within the first 100 days and results The CD4 count correlates well with type and site of
in a skin rash that appears first in the hands, feet, and face; infections and malignancies found in patients with HIV.
large amounts of watery or bloody diarrhea; and liver dys- PCR assays for HIV type I RNA viral load are also useful
function. Chronic GVHD occurs more than 100 days after to assess clinically the degree of immunosuppression,
transplantation and resembles an autoimmune disorder. A but are less frequently used. Normal CD4 count has
dry, itchy rash of the skin with involvement of the face a wide range, typically considered to be from 500 to 1500
with the mouth and eyes is common. Chronic GVHD sub- cells/mm3. In general, the CD4 count goes down as
stantially increases susceptibility to infections. HIV disease progresses. However, any single CD4 count
value may differ from the last one even though the
health status has not changed. Patients with a CD4 count
Human Immunodeficiency Virus Patients > 500 cells/mm3 will have infections from community-
It is estimated that as of 2002 about 42 million people acquired organisms. On close examination these patients
worldwide and over 1 million people in the USA are may have a generalized lymphadenopathy. An increase
infected with HIV. Although the median incubation period in the incidence of tuberculosis has also been reported.
appears to be around 10 years, the progression from HIV As the CD4 count decreases below 500 cells/mm3 oppor-
infection to acquired immunodeficiency syndrome tunistic infections with esophageal candidiasis, reactivation
(AIDS) can vary from months to years. Fortunately since of HSV and VZV, and bacterial pneumonias such as
the implementation of highly active antiretroviral ther- S. pneumoniae appear along with a wasting syndrome
apy (HAART) in the USA in 1996, the number of persons comprising of low-grade fever associated with unexplained
diagnosed with AIDS and the number of deaths among weight loss. When the count goes below 200 cells/mm3
persons with AIDS have declined substantially. Not only the likelihood of P. carinii pneumonia (PCP) increases
has the progression of disease been altered, but the mor- significantly, along with the reactivation of coccidioido-
tality of AIDS patients admitted to the intensive care unit mycosis and histoplasmosis leading to disseminated
(ICU) has also improved. During the early phases of the infections. At 50–100 cells/mm3 CNS infections from
AIDS epidemic, admission to the ICU for patients with C. neoformans and T. gondii and disseminated M. tuber-
AIDS was associated with very high mortality approach- culosis occur. Lymphomas, primarily non-Hodgkin’s
ing 90%. Over the years this has improved significantly, lymphomas (NHL), can be anticipated as the CD4 counts
with recent survival rates of better than 50%. This decrease and primary CNS lymphomas are increasingly
improvement in ICU mortality appears to be due to the more common as the count decreases to less then
improved and aggressive use of antiretroviral therapy, 100 cells/mm3. With CD4 counts below 50 cells/mm3,
prophylaxis, and treatment of opportunistic infections disseminated infections with M. avium intracellulare,
and malignancies and supportive care. CMV, cryptosporidia, microsporidia, isospora, and pro-
HIV infections and AIDS are caused by the human gressive multifocal leukoencephalopathy (PML) from the
retrovirus HIV type I. HIV type I infects lymphocytes and Jakob Creutzfeldt virus (JCV) can occur.
other cells carrying the CD4 surface protein. Screening is Pulmonary and CNS infections comprise two of the
performed with an enzyme-linked immunosorbent assay most common causes of ICU admissions. Pneumonias with
The Immune-Compromised Host and the HIV Patient 259
and diuretics and digitalis can be added for symptomatic CASE STUDY
left ventricular disease. Nephropathy can occur and is
commonly characterized on biopsy as a focal segmental A 51-year-old patient is referred to you for
glomerulosclerosis. Patients present with nephrosis and management and admission to the ICU because of
can have a rapid course to end-stage renal disease in 1 to hypotension unresponsive to volume resuscitation.
The patient is now 11 days post a stem cell transplant
4 months. Response to antiretroviral therapy HAART has
for acute myeloid leukemia. The patient previously
been reported by clinical and biopsy data. ACE inhibitors had undergone induction chemotherapy with ara-c
are useful and the response to steroids is variable. Adrenal and daunorubicin and was in remission prior
gland involvement appears to occur commonly. It has to the transplant. On examination the patient is
been documented in up to two-thirds of HIV patients on anxious, diaphoretic, febrile to 39.9°C, tachycardic
postmortem studies with CMV infection found in up to with a heart rate of 130 regular, and a hypotensive
80% of cases. The frequent incidence of adrenal gland at 83/49. Physical examination aside from disclosing
involvement is reinforced by studies examining the mild cachexia and mucositis with mouth ulcers is
hypothalamus–pituitary–adrenal (HPA) axis in HIV/AIDS otherwise unremarkable.
patients. Although many of these patients are typically QUESTIONS
asymptomatic, unexplained hypotension or hypotension
1. What laboratory workup would you
out of proportion to the clinical picture should warrant
request?
an examination of the HPA axis. Treatment with supple- 2. What would you expect to find?
mental or replacement steroids during periods of stress 3. What are the possible causes of hypotension in this
may be warranted. Some of the other organs involved patient?
include the gastrointestinal tract with mouth ulcers, 4. How likely are you to find the organism and
gingivitis, esophagitis, anorexia, nausea/vomiting, and definitive site of infection?
profuse diarrhea; hepatobiliary tract with papillary 5. What antibiotic coverage would you chose?
strictures, papillary stenosis, pancreatitis, and hepatitis B
and C; hematologic system with anemia, neutropenia,
idiopathic thrombocytopenic purpura (ITP), and throm-
botic thrombocytopenic purpura (TTP); and the nervous SELECTED READING
system with peripheral neuropathy, myopathy, and
Barbaro G et al: Incidence of dilated cardiomyopathy and detec-
HIV-associated dementia.
tion of HIV in myocardial cells of HIV-positive patients.
N Eng J Med 339:1093–1099, 1998.
Braunwald E et al, editors: Harrison’s Principles of Internal
SUMMARY
Medicine, ed 15, New York: McGraw-Hill, 2001.
An understanding of the pathophysiology involved in CDC: HIV Infection and AIDS in the United States. Semi Annual
HIV/AIDS Surveillance Report. Vol 15, 2003.
the immune-compromised patient is crucial in not only
anticipating the clinical course of the disease process CDC: Update: The AIDS epidemic in the United States. MMWR.
but also in diagnosing infections and noninfectious 51:592–595, 2002.
complications and choosing appropriate therapy. These Goldman L et al, editors: Cecil Textbook of Medicine, ed 21,
patients may present with subtle, atypical signs and Philadelphia: WB Saunders, 2000.
symptoms which may progress rapidly to life-threaten- Humphreys MH et al: Human immunodeficiency virus-associated
ing situations. Yet there are patterns related to the glomerulosclerosis. Kidney Int 48:311–320, 1995.
specific deficiency, the time since onset, the time since Mayo J et al: Adrenal function in the human immunodeficiency
transplant, and even specific “markers” such as ANC and virus-infected patient. Arch Intern Med 162:1095–1098,
CD4 count which gives the clinician information to better 2002.
choose treatment. By understanding these diseases with Murray M et al; ASCCA, editors: Critical Care Medicine:
their particular patterns we may thus be able to choose Perioperative Management, ed 2, Philadelphia: Lippincott
timely, aggressive treatment and improve outcome. Williams and Wilkins, 2002.
25
CHAPTER Coagulation and
Disseminated
Intravascular
Coagulation
PER A. J. THORBORG, M.D., Ph.D.
LYNN K. BOSHKOV, M.D.
Physiology and Development of the Coagulation failure (MSOF), the most common cause of death in the
Pathophysiology of Disseminated intensive care unit (ICU).
Intravascular Coagulation Endothelial cells are normally antiadhesive (by release
Congenital Hypocoagulable States of nitric oxide (NO), prostacycline (PGI2), adenosine,
Acquired Hypocoagulable States and interleukin-10 (IL-10)), antithrombotic (due to
Increased Risk for Thrombosis expression of TM, heparans, and TFPI), and fibrinolytic
Clinical Findings in Coagulopathy (by secretion of tissue plasminogen activator (tPA)). The
Laboratory Findings in Coagulopathy underlying smooth muscle tone is predominantly relaxed
Key Laboratory Findings in Disseminated due to release of vasodilators such as NO and PGI2 oppos-
Intravascular Coagulation ing endothelin (ET-1), a polypeptide that is predominantly
Diagnosis of Disseminated Intravascular vasoconstrictive. The damaged endothelium exhibits the
Coagulation opposite characteristics. Vasoconstriction by serotonin
Treatment of Coagulopathy and Disseminated (5-HT) and thromboxane (TxA2) from activated platelets
Intravascular Coagulation serves to limit local blood loss after trauma. Primary
hemostasis is primed due to release of von Willebrand
factor (vWF), activation of platelet-activating factor (PAF),
and release of IL-8 and P-selectins. Secondary hemostasis
PHYSIOLOGY AND DEVELOPMENT is promoted by release of tissue factor (TF) and by expo-
OF THE COAGULATION sure of phosphatidylserine (from lipids in cell membranes),
which can mimic the activated platelet surface (platelet
Hemostasis is achieved through a three-phase process: factor 3, PF3). Endothelium released plasminogen acti-
primary hemostasis (minutes) where activated platelets vator inhibitor (PAI-1) will inhibit tPA, which promotes
form a platelet plug, secondary hemostasis (hours) deposits of fibrin. The activated endothelium allows
reinforces the frail platelet plug with fibrin strands, and adhesion molecules to bind and activated white blood cells
fibrinolysis (days) dissolves the clot after vascular wall (WBCs), attracted by inflammatory mediators, migrate
repair. This system is volume controlled by several mod- out into the tissues and eventually set the stage for tissue
ulators such as antithrombin (AT), the thrombomodulin repair. It has become clear that the endothelium itself is
(TM)/protein C (PC) and protein S (PS) system, and tissue a crucial regulator of the different stages of hemostasis,
factor pathway inhibitor (TFPI). and also that inflammation is a necessary component of
In the last ten years a revised coagulation concept, tissue repair.
based on new understanding of secondary hemostasis The primary hemostasis is initiated by activation of
and its modulation, has replaced the in vitro-based “coag- platelets that undergo a conformational change from dis-
ulation cascade” concept presented in 1964 by Davie, coid shape to irregular shape with multiple pseudopods,
Ratnoff, and MacFarlane. These new insights include the release of secretions (containing vWF, FV, FVIII, Ca2+, 5-HT,
regulatory role of the vascular endothelium as well as fibrinogen, ADP, TxA2) from granules, and extrusion of
the links between inflammation and coagulation. Loss of several types of domains with glycoprotein receptors, as
the normal modulation of the coagulation in, for example, the Ib (GPIb) and IIb/IIIa (GPIIb/IIIa) receptors. ADP as
sepsis, is now believed to contribute to multisystem organ well as TxA2 promote platelet activation. Other strong
261
262 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
activators are thrombin, PAF, and immune complexes. speed of inactivation. The third modulating system is the
Exposed collagen permits the platelet to attach to the PC system, activated by the large cell surface-bound
site of injury using its GPIb receptor and an intermediary molecule TM after TM is activated by thrombin. PC then
vWF molecule that allows binding to the site of injury. together with its cofactor PS inactivate FVa and FVIIIa.
Activated platelets form a three-dimensional plug using Deficiencies in any of these three modulating systems, as
their GPIIb/IIIa receptors and intermediary fibrinogen by consumption in DIC, or as a genetic predisposition,
molecules. The activated platelets expose a phospholipid can contribute to prothrombotic states of varying severity.
surface, PF3, which will become the catalytic center for Fibrinolysis occurs normally several hours to days
the secondary hemostasis. later by activation of plasminogen to plasmin by tPA.
The secondary hemostasis is most commonly triggered Plasmin then degrades fibrin (and fibrinogen) to fibrin
by appearance of TF in the blood, normally a membrane- split products (FSP), also known as FDP. Plasmin’s phys-
bound small protein not in direct contact with blood, iologic modulator is alpha2-antiplasmin with high affinity
that when combined with circulating FVIIa can activate for its catalytic site (when not occupied by fibrin). PAI-1
FIX and FX in the extrinsic tenase complex, enough to inactivates tPA and thereby controls the degree of acti-
form a small amount of thrombin. This initial thrombin vation of fibrinolysis. A distinction is sometimes made
formation serves to activate the platelet, but is too small between normal (secondary) plasma-activated fibrinolysis
for substantial fibrin formation. On the activated platelets, (by tPA) and abnormal (primary) clot-activated fibri-
the prothrombinase complex is the catalytic center nolysis that may appear after burns and prostate and
where FXa and FVa generate the first thrombin. Further neurosurgery, and after streptokinase or urokinase therapy.
thrombin feedback by activation of FVIII, FIX, and FXI When plasmin lyses a clot with cross-linked fibrin, small
in the intrinsic tenase complex serves to produce larger segments that can be analyzed with the D-dimer test
amounts of thrombin required for fibrin production. are formed. Of historical interest is that activation of the
It appears that a substantial “thrombin burst” is required contact system with FXII will also induce fibrinolysis
to form enough fibrin to stabilize the platelet clot, the through activation of pre-kallikrein to kallikrein and even-
more thrombin the more stable the clot. Formed fibrin tually plasminogen to plasmin.
is then cross-linked by FXIII, increasing clot strength. The development of the coagulation system in verte-
In this process the activated FVIII sheds its carrier protein brates has occurred over the last 1.5 billion years. In pre-
vWF that is used in the initial platelet adhesion. vertebrates there was only an antibacterial system where
The major new understanding is the role of thrombin, intruders were marked for phagocytosis by coagulation
which, once formed, maintains its own production for of an early version of fibrinogen on their surface. With
the prothrombinase complex, and the extrinsic tenase the development of a closed vascular system in the first
complex is no longer needed. Note that calcium is needed vertebrates, separate immune and coagulant systems
as a bridge to anchor the activated prothrombinase com- eventually developed, initially the contact system with
plex and intrinsic tenase complex to the PF3 surface in FXII. Studies have revealed that genes coding for coagu-
order to reach critical concentration of activated factors lation factors are derived from cytokine genes. With the
for reactions to occur. In patients treated with Coumadine, development of vertebrates, three main families of serine
the calcium-binding site is no longer exposed on factors II, proteases have undergone 10–12 generations of change,
VII, IX, and X, so calcium cannot anchor these factors to the last 8 generations in vertebrates. The first family was
the catalytic site. Secondly, phospholipid membranes are the ancestors to FXII, TPA, PC, thrombin, TF, and the
necessary for these catalytic reactions to take place, either complement system. The second family was factors VII,
normally on activated platelets (PF3) or after endothelial IX, X, XI, and kallikrein. The third family stems from the
injury as phosphatidylserine sites appear on cell development of an ancestor to ceruloplasmin that led
membranes of damaged endothelial cells. to FVIII and FV. The clinical interest this has today is
Several important modulating systems control sec- that it explains the commonly observed problem of
ondary hemostasis. First, TFPI rapidly inactivates the cross-activation of systems such that many mediators of
extrinsic tenase complex after it activates FX. In dissem- inflammation cause activation of the coagulation and
inated intravascular coagulation (DIC), however, this vice versa.
does not appear to be an effective pathway to neutralize
large amounts of TF. New data indicate that heparin stim-
ulates the release of TFPI and that a significant part (1/3) PATHOPHYSIOLOGY OF DISSEMINATED
of the heparin effect is mediated through this pathway. INTRAVASCULAR COAGULATION
The second important modulator is AT, formerly called
ATIII, which inactivates thrombin as well as FXa, FIXa, and In DIC increased TF exposure will induce a prothrom-
FXIa. Heparan, a naturally occurring glucosaminoglycan, botic state with initially normal fibrinogen and platelet
is the physiologic stimulant of this system, increasing the levels, sometimes referred to as compensated DIC.
Coagulation and Disseminated Intravascular Coagulation 263
thrombocytopenia (HIT)/1% HIT with thrombosis (HITT); improve platelet function by release of vWF. Conjugated
quinidine, cimetidine, ranitidine, sulfa, vancomycin). estrogens (dose 0.6 mg/kg for 5 days) have a longer dura-
Nonimmune-related mechanisms occur in DIC, cardio- tion of action (weeks) but the response comes slower than
pulmonary bypass, and hypersplenism. after DDAVP. Erythropoietin is frequently used to raise
Massive transfusion (>10 U/24 hours) can lead to hemoglobin in this type of patient.
thrombocytopenia from blood loss and failure to replace Massive transfusion is defined as transfusion of
platelets as well as from dilution (platelets and coagula- >10 U blood/24 hours. Coagulation problems are usually
tion factors) associated with massive fluid resuscitation. rare with loss of less than one blood volume unless the
Thrombocytopenia in acquired thrombocytopenia patient has a preexisting coagulation problem. After loss
can be treated with platelet infusions if there is a bleed- of more than one blood volume thrombocytopenia and
ing problem except in the contraindicated states of TTP- coagulation factor deficiencies are common. Risks
HUS, HIT/HITT, and the presence of platelet antibodies. include hypothermia, under-resuscitation leads to hypo-
Drugs known to induce thrombocytopenia should be volemia, while over-resuscitation may lead to dilution of
discontinued. coagulation factors and platelets. Hypocalcemia results
Dysfunctional platelets (thrombocytopathy) are less from chelation by ACD (citrate) in blood bags. Blood
common than low platelet count but may be present products replacement must be based on frequent labo-
with normal platelet count or with thrombocytopenia. ratory findings, possibly thromboelastograph (TEG). All
Acquired forms are uremia, postcardiopulmonary bypass, fluids except platelets should go through high-capacity
malignant paraproteinemia (Waldenstrom, multiple fluid warmers. The blood bank should be contacted
myeloma), hypothermia, after antiplatelet therapy (ticlo- early. Damage control is an alternative procedure for the
pidine, clopidogrel, abciximab, tirofiban, eptifibatide), patient where surgical hemostasis is difficult or impossible.
or after other drugs (COX and TxA2 inhibitors, CCB, In hypothermia a reversible platelet dysfunction occurs
H2-receptor antagonists, PCN, cephalosporin, dextran, due to decreased TxA2 and other platelet enzymatic
starch, gelatins, NTP, NTG). Treatment is to identify and activities. Hypothermia is also associated with enhanced
deal with the underlying condition or drug. DDAVP may fibrinolytic activity. Acidosis depresses platelet aggrega-
be helpful. Platelet transfusion into a toxic environment tion, fibrinogen levels fall, and FDP increases. The triad
may make the platelets rapidly dysfunctional. of hypothermia, coagulopathy, and acidosis has been
Drug-induced hypocoagulable states can be found in called “the triangle of death.” All these changes are
patients on various types of anticoagulants, after rat reversible with correction of hypothermia. The patient
poison intoxication, and in patients on fibrinolytic drugs. should be warmed actively with a warmed air convec-
See also under acquired thrombocytopenia and thrombo- tion blanket, in addition to fluid warmers.
cytopathy for drug-induced problems. The drug should be In cardiopulmonary bypass platelet dysfunction from
stopped, and correction carried out with blood products degranulation, loss of GP receptors, hypothermia, and
and high doses of vitamin K in the case of rat poison heparin- and protamin-induced malfunction add to con-
intoxication. sumptive dysfunction of primary and secondary hemo-
In liver failure variable impairment of the production stasis. Additionally, cytokine-activated TF expression and
of coagulation factors is often associated with hyper- increased primary fibrinolysis and decreased alpha2-
splenism, low platelet counts, and decreased clearing antiplasmin add to the scenario to create a complex state.
of FDPs and PAI leading to platelet dysfunction and Basically, all three steps of the hemostatic response are
impaired fibrinolysis. Fibrinogen production is usually affected. This may explain why 29% of patients on car-
well maintained until end-stage liver disease. FFP may be diopulmonary bypass bleed excessively, part of which is
required, and vitamin K should always be given. Anemia due to platelet dysfunction. In addition to perioperative
may be present when bleeding varices. When exposed to heparinization there is sometimes need for inhibition of
trauma or extensive surgery, massive transfusion scenarios a primary fibrinolysis as well as for fresh platelets. This is
often ensue. Release of thromboplastin can cause DIC. particularly indicated when risk for bleeding is higher as
One should plan for good venous access and frequent in repeat cardiac surgery, underlying coagulation abnor-
laboratory findings to guide replacement therapy. mality, or after aspirin ingestion the last week.
The patient with renal failure may have associated bone Antifibrinolytic therapy may be required in a variety of
marrow failure leading to thrombocytopenia, and this type situations including cardiopulmonary bypass, and after
of patient often additionally has a chronic anemia. Uremia tonsillectomy and gynecological and prostate surgery.
confers a platelet dysfunction that is reversible with dialy- Both FDP and D-dimers will be high, while other labora-
sis. Acute renal failure frequently has a component of asso- tory findings depend on the extent of the bleeding. Two
ciated low-grade DIC. Heparin overdosing is common for groups of fibrinolytics are available. The lysine derivates
dialysis patients, and heparin may need to be neutralized (aminocaproic acid 5 g bolus followed by a 1 g/hour
with protamine or with FFP. DDAVP can temporarily (day) infusion; tranexamic acid 10–15 mg/kg every 8 hours)
266 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
to keep APTT 1.5–2.5 times normal), and warfarin Trousseau described the association between cancer
(prophylaxis: 1–5 mg po qd; therapeutically 5–10 and DVT, but half of his patients also had tuberculosis.
mg/day: international normalized ratio (INR) 2–3 use Chronic DIC patients usually present with DVT, PE, or
heparin initially), as well as inferior vena cava (IVC) fil- arterial embolism, sometimes recurring and in multiple
ter for those patients where anticoagulation is perceived locations.
as too high of a risk. IVC filter may actually increase the
risk for DVT (if no anticoagulation) but should decrease
the risk for PE from lower parts of the body. LABORATORY FINDINGS
Thrombolytic therapy may be indicated in patients IN COAGULOPATHY
experiencing DVT, hemodynamically unstable PE, acute
myocardial infarction (MI), peripheral arterial occlusion, A particular laboratory may have established refer-
and ischemic stroke. The alternatives include tPA (bolus ence values that may be slightly different from the values
plus infusion: dose by indication), streptokinase (250,000 U cited below. The reference values of a local laboratory
for 24–72 hours by indication), and urokinase (4400 U/kg should be used when in doubt. In general a laboratory
loading plus 4400 U/kg/hour for 12 hours) all followed should be able to provide a complete blood count
by heparin. Contraindications for their use are recent (including a platelet count), PT INR, partial thrombo-
surgery, head trauma, hemorrhagic stroke, and active plastin time (PTT), and fibrinogen within 20–30 minutes.
bleeding. A major complication is bleeding, particularly Table 25-1 lists some common causes of abnormal coag-
intracranial bleeding. ulation parameters and typical patterns of associated
coagulation abnormalities.
Low platelet count (normal 150,000–400,000) is
CLINICAL FINDINGS IN COAGULOPATHY more common than platelet dysfunction. Bleeding is rare
when the count is >50,000, unless the platelets are dys-
Petechia on skin and mucous membranes or sponta- functional. High platelet counts in polycythemia vera or
neous gingival or epistaxial bleeding suggest an abnor- essential thrombocythemia are associated with throm-
mal primary hemostasis, most commonly due to low bosis or bleeding. A number of commonly used drugs
platelet number or abnormal platelet function. It can are associated with thrombocytopenia, including amio-
also be associated with hypofibrinogenemia due to slow darone, diltiazem, heparin, quinidine, cimetidine, raniti-
platelet plug formation. Patients with Type I vWD typi- dine, sulfa, gentamycin, and vancomycin. Three percent
cally present with these symptoms, or with a large post- of all heparin-treated patients develop HIT and a third
operative hematoma. Type II and III may present with a of them go on to develop HITT, also known as white
hemophiliac-type bleeding. clot syndrome. This immune type of thrombocytopenia
Overt bleeding as in hematochezia, melena, develops typically after 5–7 days of heparin therapy and is
hematemesis, blood in NGT, bleeding from previously dry different from the nonimmune transient drop in platelet
surgical incisions or wounds, hematuria, hemoptysis, counts commonly seen after heparin initiation. Platelet
bleeding from vascular catheter sites, hemarthrosis, and count should therefore always be checked twice a week
muscle, brain, or subcutaneous bleeding suggest a defect for all heparinized patients.
in the secondary hemostasis. Hemophiliacs typically Bleeding time (BT): a function test (Ivy 3–6 minutes).
present with hemarthrosis and muscle or brain bleeding. In GPIb receptor failure (postcardiopulmonary bypass,
Acute DIC patients bleed from multiple sites, display old bank platelets), blockage by dextran, and congenital
skin and mucous membrane ecchymoses, and signs of absence (Bernard–Soulier syndrome) platelets cannot
tissue ischemia. Petechia are commonly seen in throm- bind to vWF. BT is also prolonged in vWD and certain
bocytopenia accompanying decompensated DIC, the connective tissue diseases (scurvy, Ehler–Danlos) where
first usually found under the blood pressure cuff. The collagen has abnormal structure and vWF cannot bind
dead fetus situation in chronic DIC may show the signs normally. Inhibition of cyclooxygenase (COX) by ASA
of acute DIC. (irreversibly) prevents normal activation of the GPIIb/IIIa
Commonly, occult bleeding manifests with hemody- receptor by TxA2. Other drugs like nonsteroidal anti-
namic instability and falling hematocrit, such as in inflammatory drugs (NSAIDs), carbenicillin, ampicillin,
retroperitoneal bleeding, postoperative bleeding with piperacillin, heparin, nitroprusside, and dextran can also
clotted drains, hemothorax, intra-abdominal bleeding, affect platelet metabolic function but usually less pro-
and pelvic or femoral hemorrhage. nounced than ASA. Patients with severe anemia, myeloma,
Fibrinolysis-associated bleeding occurs mostly in spe- and uremia also may have prolonged BT.
cific settings (see above), but also in liver failure. See also PFA-100 (Platelet Function Analyser-100): an
under DIC. “in vitro bleeding time” that has replaced the BT at
268 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Vitamin K Normal Prolonged (major Prolonged Normal PTT normally not prolonged at
deficiency/ prolongation in (severe therapeutic doses of OACs
OACs severe deficiency) deficiency)
SH Normal Mildly prolonged Prolonged Normal PT INR usually not prolonged at
(massive doses) therapeutic SH doses
LMWH Normal Normal Normal Normal PTT cannot be used to monitor
(or slightly anticoagulation on LMWHs.
prolonged) Routine monitoring is usually
unnecessary. If assessment of
coagulation is necessary do a
heparin level
Acute DIC Decreased Prolonged Prolonged Decreased
Chronic DIC Decreased Prolonged Prolonged (rarely Decreased
or normal (rarely normal) normal) or normal
Liver disease Mildly to More prolonged Prolonged Normal In early liver disease the PT INR
moderately (decreased will be prolonged and the
decreased in end-stage PTT normal, reflecting the
liver disease) short half-life of FVII
Circulating Normal Normal or Prolonged Normal 1:1 mix that does not correct is
anticoagulant prolonged supportive of diagnosis.
“acquired Clinical problem is excess
factor bleeding. Lupus inhibitor
inhibitor” should be excluded
LAC Normal Normal or Often prolonged Normal 1:1 mix that does not correct is
(sometimes prolonged (depends on supportive of diagnosis.
decreased reagent Clinical problem is excess
if antiphospho- sensitivity) thrombosis. Specific LAC
lipid syndrome) testing indicated
DIC, disseminated intravascular coagulation; INR, international normalized ratio; LAC, “lupus anticoagulent/lupus inhibitor”; LMWH, low molecular weight heparin;
OAC, oral anticoagulant; PT, prothrombin time; PTT, partial thromboplastin time; SH, standard heparin.
many institutions. Citrated whole blood is forced under International Sensitivity Index (ISI). The local ISI value
high shear over a grid impregnated with the platelet permits calculation of the INR: INR = PT(ISI), a logarithmic
agonist pairs collagen/epinephrine or collagen/EDTA, relationship. INR is the recommended way to monitor
with the readout being time to occlusion of flow warfarin anticoagulation therapy with recommended
through tubing on the other side of the grid. Prolonged range 2–3 for all conditions except bileaflet prosthetic
closure times (range for each agonist pair is institution valves and recent MI (2.5–3.5).
specific) indicate platelet dysfunction. Prolongation to APTT (normal 21–35 seconds): kaolin is used to surface
collagen/epinephrine alone is highly characteristic of activate FXII as well as FXI in the intrinsic tenase complex.
drug effects (ASA, NSAIDs). Like the BT, the PFA-100 will As it is sensitive even to lower factor levels, a normal
also become abnormal if the platelet count is <80,000 or APTT does not rule out mild factor deficiency. In sys-
if the hematocrit is low (< 28). Because platelet adhesion temic heparin therapy (DVT, PE) the target APTT is
to collagen under high shear conditions is dependent on 60–85 seconds.
vWF, the PFA-100 is often abnormal (closure times pro- 1:1 mixing studies. These may be done for the PT or
longed) in patients with vWD, although normal values the PTT and can be helpful in distinguishing whether a
do not absolutely exclude this diagnosis. prolonged PT or PTT is due to factor deficiency or due
PT (normal 11–13 seconds) has largely been replaced to the presence of a circulating inhibitor (either to a
by INR due to quality variability in the tissue phospho- factor called an “acquired inhibitor” or to phospholipids
lipid used to activate the extrinsic tenase complex in the in the test system called the “lupus anticoagulant” or “lupus
PT test. The INR test uses human brain thromboplastin inhibitor”). In the 1:1 mix patient plasma is mixed in
as a reference substance that permits calculation of an equal proportion with normal plasma (assuring at least
Coagulation and Disseminated Intravascular Coagulation 269
50% of any given factor is present) and the test is PT/INR and PTT is hypofibrinogenemia. Required level
repeated. Full correction is seen in factor deficiencies, as is 50–100% for effective hemostasis. It is common prac-
even with sensitive reagents, the PT and PTT do not tice to give cryoprecipitate to the bleeding patient if the
begin to “pull out” unless factor levels are <40%. Lack of fibrinogen level is below normal range, while this is not
correction suggests the presence of either an acquired true for a stable nonbleeding patient. Iatrogenic hyper-
inhibitor (most commonly anti-FVIII or anti-vWF – these fibrinogenemia should be avoided, which can trigger
patients have a bleeding diathesis) or a lupus anti- thrombotic events.
coagulant (these patients have a thrombotic propensity). Factor assays are sometimes measured in hemophilia
Distinction between these two is often suggested by patients to guide replacement therapy before or after
the clinical presentation but can be clarified by a lupus surgery. In hemophilia A a FVIII level > 50% is recom-
inhibitor panel (see below). It is important, especially in mended, and since the half-life is 6–12 hours replenish-
the case of acquired factor inhibitors, to look not only for ment twice daily is required. In massive transfusions, FV
immediate correction of the test in question, but also for and FVIII drop off quickly (“labile factors”) since their
correction at 60 minutes after mixing, as many antifactor activity is lost rapidly in stored blood. DDAVP will induce
antibodies show complex kinetics and the mix may only transient release of vWF and also of FVIII, since vWF is
be abnormal at 60 minutes. the carrying molecule for FVIII. LMWH in higher dosage is
Lupus inhibitor panel and anticardiolipin antibodies. sometimes monitored by anti-Xa activity assays according
There is no single “gold standard” test for the lupus to patient weight.
anticoagulant/lupus inhibitor. In accordance with inter- AT (also known as ATIII; normal 70–130%) is usually
national standards most laboratories do three different low in DIC by consumption in the thrombin inactivation
tests (such as a sensitive PTT, dilute Russell’s viper venom as well as breakdown by elastase (from polymorpho-
time, hexagonal PTT, dilute PT, or other tests). Presence nuclear leukocytes). Congenital AT deficiency is more
of a lupus inhibitor is suggested by prolongation of a clot- uncommon. AT inhibits thrombin, FIXa, FXa, and FXIa
based assay and its correction with the addition of phos- but its activity is enhanced 100 times by heparin, or
pholipids. Making this diagnosis implies the patient has physiologically heparan. Low AT levels are responsible
a thrombotic propensity. Anticardiolipin antibodies are for “heparin resistance.” Since it is produced by the liver,
another part of the “antiphospholipid” spectrum. These advanced liver disease may lead to deficiency. Children
antibodies do not prolong clot-based assays but are with nephritic syndrome may also exhibit low AT levels
detected by separate enzyme-linked immunosorbent assay and heparin resistance. Rapid consumption of AT in DIC
(ELISA) testing. Their presence also implies a thrombotic and sepsis may lead to low AT levels. Low AT levels in
propensity. DIC make patients heparin resistant.
Reptilase is a thrombin-like enzyme that is not sensitive Calcium (normal 8.9–10.1 mg/100 ml) is required
to heparin (unlike APTT), and is used to diagnose heparin to hold coagulation factors down to catalytic centers
effect. on platelets via a calcium bridge. Calcium activity is
TT (normal 7–12 seconds) monitors fibrinogen trans- better monitored with ionized (or free) calcium (normal
formation to fibrin after addition of thrombin, a qualitative 1–1.25 mmol/l) since it is protein bound in the normal
test (as opposed to fibrinogen level, a quantitative test). state. Excess ACD in massive transfusion can rapidly
TT is prolonged in fibrinolysis and at low fibrinogen levels produce hypocalcemia, which needs to be corrected in
(<90 mg/100 cm3). It is sometimes used in DIC diagnosis, massive transfusion scenarios.
as well as to monitor heparin or thrombolytic therapy. Magnesium level can affect coagulation in that sub-
Activated clotting time (ACT; normal 94–120 seconds, stituting subnormal magnesium levels will improve the
therapeutic level 400–600 seconds) is used for monitoring clotting ability of FIX.
of intraoperative heparinization. Activation of the intrinsic D-dimers (normal < 250 μg/ml) and FSPs (or FDPs)
tenase complex is achieved by using celite (diatomaceous (normal < 10 μg/ml) are both indicative of plasmin activity
earth) to activate FXII. Platelet quantity, quality, hemo- on fibrin, but the presence of D-dimers is specific for cross-
dilution, as well as hypothermia all affect the ACT. When linked fibrin. FSPs are elevated in both primary and sec-
there is discrepancy between the clinical status and the ondary fibrinolysis, whereas elevated D-dimer implies that
ACT result, it usually means the patient is hypothermic, there has been clot formation with secondary fibrinolysis.
since the test cuvette is heated to 37°C. It is insensitive to Moderately to strongly positive D-dimers are present in
coagulation abnormalities. It does not correlate well with DIC. Elevated D-dimers are also seen in DVT and PE as well
microvascular bleeding after cardiopulmonary bypass. as in any clinical setting where there is widespread sec-
Fibrinogen level (normal 175–350 mg/100 ml) is usu- ondary fibrinolysis (postoperative major surgery, trauma).
ally low in consumptive processes such as DIC, in severe Weakly positive D-dimers are frequent in line draws and in
liver disease, or in massive transfusion by consumption sick hospitalized patients. FSPs are normally cleared by the
and/or dilution. The most common reason for elevated reticuloendothelial system (normal half-life 9 hours), as
270 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Preparation and Composition of Blood and Blood blood units are separated into two or three components:
Components and Derivatives into 1 U of red blood cells (RBCs), 1 U of plasma, and
Special Transfusion Needs: Leukodepletion, “CMV Safe,” sometimes into 1 U of “random donor” platelets. The
Irradiation, Washing plasma may be further separated into 1 U of cryoprecip-
Compatibility Issues itate (a small-volume product rich in fibrinogen) and 1 U
ABO Compatibility of cryosupernatant plasma. Platelets are most commonly
Replacement of the Total Blood Volume of an Adult not made from whole blood but are collected by aphere-
Red Blood Cells and Anemia sis harvest of donor platelet-rich plasma. One apheresis
Physiologic Response to Acute and Chronic Anemia platelet unit is equivalent to 5–6 “random donor” platelet
Serologic Safety of Uncrossmatched Red Blood Cells units. Apheresis can also be used to harvest RBCs and
Choice of the Perioperative Red Blood Cell “Transfusion Trigger” plasma, although these products are not yet available in
Choice of “Transfusion Trigger” in the Critical Care Setting most areas of North America. Plasma derivatives (albumin,
Plasma, Cryoprecipitate, and Coagulopathy plasma-derived clotting factor concentrates, intravenous
Plasma gammaglobulin, etc.) are made by subfractionation of
Cryoprecipitate pooled plasma or cryopsupernatant plasma from large
Plasma Derivatives numbers of donors (up to 20,000). Also, specialized hyper-
Albumin immune gammaglobulins (rhesus (Rh)-immune globulin,
Rhesus Immune Globulin cytomegalovirus (CMV)-immune globulin, etc.) can be
Other Plasma Derivatives made from plasma of special donors with high titers of
Platelets and Thrombocytopenia the desired antibody. The composition, shelf life, and
Triggers for Transfusion: Consensus Statements postissue storage conditions for red cells, plasma, cryo-
Massive Transfusion precipitate, and platelets are given in Table 26-1. Note
Transfusion Reactions and Complications that most RBC units currently have an additive solution
Alternatives to Blood Component Therapy added to them, which improves viability and increases
their shelf life. All blood components should be admin-
istered through a standard blood filter (“170–260 micron”)
to remove any aggregates that may have formed during
PREPARATION AND COMPOSITION storage.
OF BLOOD AND BLOOD COMPONENTS
AND DERIVATIVES
SPECIAL TRANSFUSION NEEDS:
Blood products in North America are normally LEUKOREDUCTION, “CMV SAFE,”
donated by volunteers, either as whole blood or by IRRADIATION, WASHING
apheresis. Over 11 million units of whole blood are col-
lected annually in the USA. In whole blood donation a Contaminating leukocytes in whole blood preparations
450 ml unit (U) is collected into citrate-based anticoagu- in North America partition about 80% into the red cell
lant. Autologous units (donated by a person for their component. Leukoreduction of red cells and platelets can
own later use) are stored as whole blood. Other whole remove 3–4 log of these leukocytes. This is usually done
273
274 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Blood Approx.
Component Contents Volume Shelf Life Comments
Whole blood RBCs and plasma. 450 ml blood 520 ml 35 days at 4°C. WBCs and platelets not viable
(autologous and 63 ml CPDA-1 anticoagulant. Transfuse within 4 hours after 24 hours. Factors V
predonation) Hct ~ 35 at room temperature and VIII significantly
decreased after 2 days
Red cell concentrate RBCs with about 25 ml plasma and 340 ml 42 days at 4°C. “Packed cells” (Hct 70) lack
(additive solution 100 ml of additive solution (saline, Transfuse within 4 hours the additive solution and
red cells – AS-1, adenine, dextrose). Hct 55–60 at room temperature are not usually provided
AS-3, AS-5)
Platelet Platelets (5.5 × 1010); some WBCs; 50 ml 5 days at 20°C with Refrigeration results in
“random donor” 50 ml plasma; few RBCs agitation echinocytic transformation
(Hct < 0.005) and dysfunction
Platelet “apheresis” Platelets (3.5 × 1011); fewer 300 ml 5 days at 20°C with 1 apheresis U = 5−6 “random
WBCs and RBCs than agitation donors.” Do not refrigerate
“randoms”; 300 ml plasma
FFP; FP Normal levels all coagulation factors, 250 ml 1 year frozen at −18°C; ~30 minutes to thaw.
natural inhibitors (AT, protein C, post-thaw: 4°C × 24 hours Post-thaw: major decreases
protein S) and plasma proteins. in factors V and VIII
No significant difference after 24 hours
between FFP and FP
Solvent detergent All coagulation factors. Plasma 200 ml 1 year frozen at −18°C; ~30 minutes to thaw. Storage at
plasma proteins. Significant decreases post-thaw: room 4°C may activate factor VII.
in proteins C and S vs. FFP and FP temperature × 24 hours Possibly prothrombotic vs.
FFP and FP
Cryoprecipitate ~150 mg fibrinogen, at least 80 U 15 ml/U. 1 year frozen at −18°C; ~15 minutes to thaw.
factor VIII, von Willebrand Note: also post-thaw: room Refrigeration may
factor, factor XIII comes in temperature × 4 hours re-precipitate proteins – warm
5 U pools to room temperature
AS-1, AS-3, AS-5, RBC additive solutions; AT, antithrombin III; CPDA-1, citrate phosphate dextrose-1 anticoagulant; FFP, fresh frozen plasma; FP, frozen plasma;
Hct, hematocrit; RBC, red blood cell; WBC, white blood cell.
COMPATIBILITY ISSUES
Replacement of the Total Blood Volume
ABO Compatibility of an Adult
ABO compatibility of donor and recipient is critically The total blood volume (TBV) of an adult is about
important for RBCs and plasma. There are four basic 70 cm3/kg, or for a 70 kg individual about 5 liters. If the
blood groups: O, A, B, and AB. The A and B genes code hematocrit is 0.40, about 2 liters of this TBV is red cells,
for glycosyltransferases that add A or B substance onto a and about 3 liters is plasma. Using the product volumes
base H substance on all red cells. Anyone who lacks A or and composition in Table 26-1 one can calculate that,
B on their red cells always has the corresponding natu- roughly, to replace the TBV of a 70 kg person would
rally occurring antibody in their plasma. Anti-A and anti-B require about 10 U of red cells, 10–12 U of plasma, and
are complement-fixing antibodies that are active at body 10–12 U “random donor” platelets = 2 U apheresis
temperature and cause nasty or fatal acute intravascular platelets. Keeping this in mind one can roughly estimate
hemolytic reactions (Box 26-1). the number of units of a particular product needed to
Basic donor/recipient ABO compatibility of RBCs and correct a given level of deficiency (Box 26-2).
plasma can be found in Table 26-2. When in doubt one
should use O red cells and AB plasma (O red cells can be
used for all blood groups because there is very little RED BLOOD CELLS AND ANEMIA
O plasma in red cells).
More than 11 million red cell units are transfused
annually in the USA to more than 3 million recipients.
CLINICAL CAVEAT
Physiologic Response to Acute
Blood Component Compatibility with Solutions and Chronic Anemia
and Drugs
Normal physiologic response to anemia consists of
● Compatible with isotonic crystalloid and with 5%
albumin
cardiac and peripheral tissue adaptations as well as
● Do not mix with drugs (acidic pH, protein binding), changes in RBC 2,3-diphosphoglycerate (2,3-DPG).
calcium-containing solutions (may clot), or Cardiac output is increased by increasing heart rate or
hypotonic solutions (lysis of RBCs and platelets) stroke volume. As the heart normally extracts ~80% of
O2 delivered, increased cardiac O2 extraction is largely
Table 26-2 Recipient and Donor ABO Groups and RBC and Plasma Compatibilities
achieved by increasing coronary artery flow by coronary can be by giving group O RBCs) serologic safety rises to
artery vasodilatation. As demand escalates in excess of 99.4%; for ABO and Rh compatibility to 99.8%; and for ABO
compensatory increases in heart rate and vasodilatation, and Rh compatibility with a negative antibody screen to
the heart shifts from aerobic to anaerobic metabolism 99.94%. Also even if irregular antibodies are present titers
and blood flow is shifted from the subendocardium to are often low, and the clinical sequelae are usually not
the epicardium, placing the subendocardium at ischemic immediate but delayed in the form of a delayed hemolytic
risk. Clearly patients with impaired ability to increase their transfusion reaction. Therefore, when faced with an exsan-
heart rate (intrinsic disease, pharmacologic blockade) or to guinating patient the clinical risk/benefit is usually over-
increase coronary flow through vasodilatation (stenotic whelmingly in favor of using uncrossmatched blood.
lesions) are at increased risk for ischemia. Animal studies
suggest the lower limit of cardiac tolerance for anemia in
the presence of a normal cardiovascular system is a hemo- Choice of the Perioperative Red Blood
globin (Hb) of ~3–5 g/dl, and in the presence of coronary Cell “Transfusion Trigger”
stenosis is in the range 7–10 g/dl. There is little to justify a specific Hb or hematocrit,
Peripheral tissue compensation for anemia is to such as the former “10/30” Hb/hematocrit rule, in making
increase O2 delivery by increasing blood flow through decisions regarding perioperative RBC transfusion, and
vascular beds, to recruit more capillaries, or in the case of withholding transfusion unless a patient is symptomatic
supply-dependent tissues to increase oxygen extraction. has been advocated by some expert groups. Adults with
However, these compensatory mechanisms may be Hb of <7 g/dl are more likely to manifest hemodynamic
limited and dependent on circulating intravascular volume symptoms than are children, who more often become
as well as on red cell mass in the case of the splanchnic dyspneic or show impaired levels of consciousness.
bed, muscles, and skin. With chronic anemia, RBC intra- However, multiple studies indicate that signs and symp-
cellular 2,3-DPG concentrations also increase, shifting the toms of anemia are unreliable especially in the surgical
oxyhemoglobin dissociation curve to the right, thereby setting, and that myocardial ischemia is often silent, par-
facilitating tissue off-loading of O2 (Box 26-3). ticularly postoperatively. Complicating this is the fact that
estimates of intraoperative blood loss are often difficult,
and estimates of intraoperative blood volume indirect
Serologic Safety of Uncrossmatched (inferred from arterial, central venous, and pulmonary
Red Blood Cells capillary wedge pressures). Even when invasive moni-
Once a blood sample reaches the hospital transfusion toring is used to measure whole-body O2 consumption,
service it takes about 10 minutes to do an ABO and or O2 extraction ratios, such measurements are global and
Rh type, about 30 minutes to do an antibody screen, and have not been verified as predictive of ischemia. The real
about 45 minutes to issue crossmatched RBCs if no irreg- issue of interest is the adequacy of O2 delivery to specific
ular antibodies are identified (in most hospitals 2–5% of organs and regions within these organs, and unfortunately
patients will have such antibodies). If RBC transfusion is it is not possible to measure this directly in the routine clin-
needed more urgently than this, uncrossmatched O or ical setting. The dynamic nature of surgical hemorrhage
group-specific uncrossmatched RBCs may be issued on and the anticipation of major blood loss are also frequent
request of appropriate personnel. Statistically, if a unit of factors in the decision to transfuse intraoperatively.
RBCs is randomly selected with no effort to ensure sero- It should also be noted that a Hb/hematocrit that is
logic compatibility with the recipient (ABO, Rh, or other adequate in the stable intraoperative setting (where the
clinically significant anti-RBC antibodies) it will serendip- patient is paralyzed and the ventilation and FIO2 con-
itously be compatible ~64% of the time. This is fortunate trolled) may no longer be adequate in the same patient
as available data show ~1 in 30,000 to 1 in 40,000 patients in the postoperative setting, breathing room air and with
get the wrong blood! If ABO compatibility is assured (as it exertional demands for increased O2 delivery. A recent
study in Jehovah’s Witnesses indicates that postopera-
tive morbidity and mortality begin to rise when the Hb
Box 26-3 Increment Expected per is <5 g/dl in patients without cardiovascular compromise
RBC Unit Transfused in and when it is <6 g/dl in patients with cardiovascular
Nonbleeding Patients compromise (Box 26-4).
● In an adult 1 U RBCs will increase the hematocrit Choice of “Transfusion Trigger” in the
by ~3 % and the hemoglobin by ~1 g/dl Critical Care Setting
● In the pediatric patient the roughly equivalent dose
is 10–15 ml RBCs/kg One recent randomized trial in which adult patients
were randomized to a hemoglobin (Hb) of 7–9 g/dl vs. a Hb
Blood and Blood Component Therapy 277
Box 26-6 Plasma Dosing Table 26-4 Major Plasma Proteins in a Single
10–15 ml Bag (U) of Cryo
● ~20/ml/kg will achieve coagulation factor
concentrations of ~30% of normal in nonbleeding, Constituent Amount per Bag Half-life (hours)
otherwise stable adults and children
● A minimum of 2–4 U (500–1000 ml) is generally Fibrinogen 150–250 mg 100–150
required to have an impact on a clinically significant Von Willebrand factor 100–150 U 12
coagulopathy in an adult (normal multimeric (40–70% of
pattern) original plasma)
Factor VIII 80–150 U 12
Factor XIII 50–75 U 150–300
Plasma should not be used as a volume expander, as
a nutritional supplement, or for nonurgent correction
of vitamin K deficiency (pharmaceutic preparations
of vitamin K will usually reverse this in 6–12 hours). The major plasma proteins contained in cryoprecipitate are
Hypofibrinoginemia (massive transfusion, disseminated given in Table 26-4 and dosing guidelines in Table 26-5.
intravascular coagulation (DIC)) is best corrected with Cryo is used in congenital and acquired hypofibrino-
cryoprecipitate (see below). genemia (fibrinogen < 100 mg/dl – DIC, obstetrical catas-
Although plasma is frequently used to correct mild pro- trophe, fulminant hepatic failure). It is also used in
longations of the PT INR (1.2–1.5) and the PTT (<1.5 times dysfibrinogenemias with microvascular bleeding. Although
normal) prior to invasive procedures (line placements, used in the past for treatment of both hemophilia A
biopsies, paracentesis), there is little evidence to support and von Willebrand’s disease (vWD), cryo is no longer
this, practice and the skill of the operator doing the proce- the first-line treatment for either as factor concentrates
dure is more predictive of bleeding. It should also be noted (now treated to inactivate viruses or made by recombi-
that increasing coagulation factor levels by 10% will have a nant technology) and DDAVP (which carries no risk of
significant effect on the PT and PTT when they are pro- transfusion-transmitted disease) carry less risk. Cryo is
longed more than twice mid-range normal but will have suitable for treatment of vWD unresponsive to DDAVP
only a minimal effect on more modest prolongations. It is if von Willebrand concentrates are unavailable, as well
difficult or impossible to correct the coagulopathy of severe as for treatment of moderate to severe factor VIII defi-
liver disease with plasma because the short half-life of ciency where DDAVP is ineffective and factor concen-
factor VII (4–6 hours) makes it difficult to infuse the prod- trates are unavailable. Factor XIII deficiency is usually
uct fast enough. In this setting 1-deamino-8-D-arginine vaso- treated with plasma, although cryo can also be used.
pressin (DDAVP) (for the platelet function defect), plasma Other uses for cryo, although not confirmed by random-
exchange (to correct the factor defect), and more recently ized clinical trials, include treatment of platelet dysfunc-
recombinant factor VIIa (if available) may be helpful. tion unresponsive to DDAVP (uremia, drug-induced).
Cryo is ineffective and contraindicated for treatment of
multiple organ failure.
Cryoprecipitate Cryo can also be used as a source of fibrinogen in
Cryoprecipitate (cryo) is supplied as individual “bags” making “homemade” fibrin glue, where it is mixed with
or units (each made from 1 U of plasma) or as 5 U pools. a source of thrombin (usually bovine) at the time of use.
Fibrinogen replacement Adult: 10 U (two 5-pools); child: 1 U/10 kg Fibrinogen of 75–100 mg/dl (measure postinfusion – dosing
(will increase fibrinogen by 60–100 mg/dl) frequency can vary from hours in active DIC to days)
Von Willebrand’s Adult: 10–12 U q 12 hours; This dose will usually ensure hemostasis
disease (second-line child:1 U/6 kg q 12 hours
therapy – see text)
Hemophilia A (factor VIII Assume 1 U contains 100 U factor VIII; Factor VIII levels of 35–100% depending on clinical setting
deficiency) (second-line 1 U/6 kg will usually give a factor VIII
therapy – see text) level of ~35%
Factor XIII deficiency 1 U/10 kg q 7–14 days 2–3% levels of factor XIII are hemostatic
Blood and Blood Component Therapy 279
Fibrin glue is used most commonly in cardiothoracic and this chapter. In dealing with the perioperative manage-
vascular surgery, neurosurgery, and maxillofacial surgery ment of patients with hemophilia (particularly those with
to provide local control of slow venous bleeding, diffuse inhibitors), vWD, and complex coagulopathies including
ooze, and lymphatic leaks. Commercial fibrin sealant congenital and acquired prothrombotic disorders such
preparations, which use human thrombin, may be pre- as antithrombin (AT, formerly antithrombin III) defi-
ferred as bovine thrombin may rarely be associated with ciency hematological consultation should be sought. If
formation of antifactor V antibodies. at all possible patients with hemophilia should not be
taken to surgery without being tested for the presence of
inhibitors and without a trial infusion of factor to assess
PLASMA DERIVATIVES adequacy of factor recovery. Likewise patients with
vWD should have the subtype of their vWD defined
Albumin prior to surgery and a DDAVP trial, if appropriate.
Patients with mild to moderate Type I vWD (where the
Albumin, unlike other blood products, comes in glass
defect is in endothelial cell release of normal von
bottles and must be vented for IV administration. The 5%
Willebrand factor (vWF)) will often respond to DDAVP.
solution is isotonic and the 25% solution hypertonic.
In other types of vWD an abnormal vWF is made and
Albumin and other colloids are often used to restore
DDAVP should not normally be used. Table 26-6 provides
intravascular volume in patients with hypovolemia.
some basic guidelines and caveats regarding perioperative
treatment of hemophilia and vWD (and of patients with AT
deficiency). Antifibrinolytic therapy (epsilon aminocaproic
CURRENT CONTROVERSY acid, tranexamic acid) can be a useful adjunct for oral
Albumin (Colloid) vs. Crystalloid in Acute surgery in patients with underlying coagulation disorders.
Resuscitation
● Two controversial recent meta-analyses of
randomized trials comparing albumin and PLATELETS AND THROMBOCYTOPENIA
nonalbumin volume expanders with crystalloid
for resuscitation found a 4–6% excess of deaths The basic composition, volume, shelf life, and storage
in the colloid group conditions for “random donor” and apheresis platelets
● Caution may be warranted in the use of albumin
are given in Table 26-1. Platelets are given both prophyl-
and other colloids for acute resuscitation
actically, to prevent bleeding, and therapeutically, to
treat active bleeding or to ensure effective hemostasis
during surgery or other invasive procedures (biopsies,
thoracentesis, paracentesis). Spontaneous bleeding is rare
at platelet counts of >10 × 109/l providing platelet func-
Rhesus Immune Globulin
tion is normal and there is no coincident coagulation or
Rh immune globulin (RhIg) is used to prevent forma- hemostatic defect, and this is the usual prophylactic
tion of anti-D anti-RBC antibodies by Rh-negative women “transfusion trigger.” In the absence of accelerated con-
(about 15% of Caucasians) exposed to Rh-positive blood. sumption, splenic sequestration, etc., approximately 80%
If anti-D is formed, hemolytic disease of the newborn of the transfused platelets will still be circulating 24 hours
may result. The source of the sensitizing Rh-positive later. Perisurgically, as well as for invasive procedures,
blood is usually exposure to fetal red cells as the result platelet counts of 40−50 × 109/l functional platelets, in the
of abdominal trauma or invasive procedures, or during absence of other coagulation defects, are usually enough
delivery. Usual preventative dose is 300 μg, best given to ensure hemostasis. For central nervous system and
within three days of exposure. life- or limb-threatening bleeding higher target platelet
counts (75−100 × 109/l) are often used. Platelets may also
be used to treat thrombocytopathy (postcardiopulmonary
Other Plasma Derivatives bypass, drug-induced, etc.). The normal dose in this sit-
A detailed discussion of the use of plasma derivatives, uation is sufficient to raise the platelet count by 40−50 ×
including the use of specialized plasma-derived and 109/l, as normal platelets will recruit dysfunctional
recombinant factors for treating hemophilia (factor VIII platelets into the hemostatic plug. Nontransfusion treat-
and IX concentrates, prothrombin complex concen- ments for platelet dysfunction may be useful as alterna-
trates, FEIBA, recombinant factor VIIa), as well as the use tives or adjuncts to platelet transfusion. These include
of specialized plasma derivatives (intravenous gamma- intravenous or intranasal DDAVP, keeping the hematocrit
globulin, hyperimmune globulins, antithrombin concen- around 30, and use of conjugated estrogens (in uremia)
trates, C1 esterase inhibitor, etc.), is beyond the scope of or antifibrinolytic agents (oral bleeding).
280 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Hemophilia A Surgery or trauma Factor VIII concentrate: • Severe hemophiliacs (<1% factor VIII) and
(factor VIII • Usual goal is FVIII level of 100% initially, moderate hemophiliacs (2–5%) require
deficiency): then 50% until wound healing begins, factor VIII concentrates. Mild hemophilia A
no inhibitor then 30% until healing complete may be responsive to ddAVP 0.3 mg/kg –
(usually 7–14 days) preoperative trial infusion recommended
• 1 unit/kg usually ↑s FVIII level by 2% • Neurosurgery goal: 100% initial then
• Usual dose: 50 U/kg initially then 50–100% × 10–14 days or until complete healing
25 U/kg q 8–12 hours (or by • Factor levels should be monitored
continuous infusion) perioperatively
Hemophilia B Surgery or trauma Factor IX concentrate: • ddAVP is ineffective in Factor IX deficiency
(factor IX • Usual goal is FVIII level of 100% initially, • Neurosurgery goal: 100% initial then
deficiency): then 50% until wound healing begins, 50–100% × 10–14 days or until complete healing
no inhibitor then 30% until healing complete • Factor levels should be monitored
(usually 7–14 days) perioperatively
• 1 unit/kg usually ↑s FIX level by 1%
• Usual dose: 100 U/kg initially, then
50 U/kg q 8–12 hours
(or by continuous infusion)
Hemophilia A Surgery or trauma • Activated prothrombin complex • Perisurgical management of hemophiliacs
or B with concentrates (aPCCs): 75 U/kg or with inhibitors can be very challenging.
inhibitors • Porcine factor VIII (if available and no Elective surgery should not be done on
antibody cross reactivity; VIII inhibitor patients without consultation
inhibitors only): 100–150 U/kg or with a hematologist
• Recombinant factor VIIa (rVIIa): • aPCCs prothrombotic especially with repetitive
90 μg/kg – repeat at 2–3 hour intervals doses in older patients or patients with
(usually at least 2–3 doses needed) liver disease
• rVIIa: issues of cost, availability, and possible
thrombogenicity
Factor XI Surgery or trauma • Plasma infusion q 12–24 hours to • Poor correlation of hemostatic control with
deficiency maintain factor levels of 40–60% either PTT or measured factor levels – often
(t1/2 ≈ 45–60 hours) a management challenge. Hematologic
• Factor XI concentrate unavailable in consultation advised
North America and thrombogenic
• rVIIa (experimental): 90 μg/kg – repeat
at 2–3 hour intervals (usually at least
2–3 doses needed)
Von Willebrand’s Surgery or trauma • Mild–moderate Type I vWD may respond • ddAVP is first-line treatment only for
disease (vWD) to ddAVP IV 0.3 μg/kg – usual rise in mild–moderate Type I vWD. Other treatment
factor VIII and vWF is 3–5 fold modalities should normally be used in the
• Other forms of vWD should be treated different Type II subtypes and in Type III
with von Willebrand concentrates • Plasma factor levels of vWF required
(Humate-P®): 50–60 U/kg will usually perioperatively are similar to those required
↑ plasma level in severe (Type III) for FVIII hemophiliacs
vWD to 100% • Hematological consultation is advised in treating
vWD patients
Antithrombin Surgery or trauma Antithrombin concentrates (Thrombate®) • In sick or pregnant patients higher doses (50 U/kg)
(AT) deficiency • 1 U/kg will ↑ AT by ~2% (t1/2 ~ 60 hours) should be used and t1/2 may be significantly less,
• Dose in patients with heterozygous AT so daily dosing may be necessary
deficiency needing surgery (heparin: • Hematological consultation is advised in treating
↑ hemorrhagic risk): 25 U/kg AT deficient patients perioperatively and
(should ↑ baseline levels by 50%) during pregnancy
Dosages are rough guidelines for use in the perioperative setting. Hematologic consultation should normally be sought in managing patients with the above-mentioned
conditions preoperatively, intraoperatively, and perioperatively.
Blood and Blood Component Therapy 281
Coagulopathy Multifactorial (see text) • Obtain baseline complete blood count (hemoglobin, hematocrit, platelet count),
PT INR, PTT, and fibrinogen and continue to monitor these as clinically indicated
(in major bleeding every 45–60 minutes)
• Transfuse RBCs to maintain a Hct > 24, platelets to keep platelet count > 50–80, plasma
to keep PT INR < 1.5–2.0, and cryoprecipitate to keep fibrinogen > 100
Hypothermia Transfusion of cold Use of a validated blood warmer is helpful in massive transfusion settings and most
blood; clinical causes rapid infusion devices have blood warmers. Platelets should not be given through
(trauma, etc.) blood warmers
Hypocalcemia Infusion of citrate • Check Ca2+ after transfusion of about 10 U RBCs in an adult and give Ca2+ as necessary to
correct the Ca2+. Formula administration may be harmful and should be avoided
• In truly massive transfusion (>2 blood volumes) Mg2+ should also be checked
Hyperkalemia K+ load in RBCs • Depending on their age RBCs may contain from 10 to 60 mEq/l of K+. This is usually not
a problem in adults, but rarely may be in neonates and small children receiving large
volumes of RBCs rapidly, especially in the presence of renal failure and acidosis
• K+ should be monitored and if necessary RBCs < 5 days old or washed RBCs used
Blood and Blood Component Therapy 283
allogeneic blood due to nonutilization of collected units. blood loss in cardiac surgery (especially reoperative
In addition about 1 in 17,000 standard risk donors are surgery) and in oral surgery and perhaps in other set-
hospitalized as a direct result of complications of the tings. Dose optimization is unclear, cost can be an issue,
autologous donation. Autologous predonation of high-risk and there are questions regarding possible prothrom-
patients (stable cardiac disease, on pharmacologic agents botic risk. Fibrin glues have been discussed above.
that block compensatory response) should be done only Recombinant factor VIIa is a new pharmacologic hemo-
under conditions of close monitoring and isovolemic fluid static agent whose therapeutic role is evolving. It is
replacement. extremely costly and not readily available. It is probably
now the established first-line therapeutic agent in con-
genital hemophiliacs with inhibitors and in acquired
CURRENT CONTROVERSY
hemophilia. Its role and cost/benefit in correction of
Autologous Predonation other hemostatic abnormalities (urgent warfarin reversal,
Once considered the “standard of care” for some refractory coagulopathy of hepatic dysfunction, severe
surgeries (orthopedic) recent studies have suggested congenital platelet abnormalities, microvascular bleeding
that, with declining transmissible disease risks, the risks
in trauma, etc.) remains to be established.
of autologous predonation in many cases appear to
There are currently no “red cell substitutes” licensed
outweigh the benefits.
in North America, although a bovine hemoglobin-based
O2 carrier (HBOC), Hemopure, was recently licensed in
South Africa. Three HBOCs have now completed or are
Isovolemic hemodilution appears to be safe and effec- undergoing US FDA phase 3 trials in the USA: Hemopure
tive, and considerably more cost-effective than autologous (bovine hemoglobin glutamer, Biopure Corp.), PolyHeme
predonation in selected surgeries (radical prostatectomy). (human pyridoxilated polymerized hemoglobin, Northfield
However, the technique is poorly standardized, data are Laboratories), and Hemolink (human hemoglobin raf-
conflicting, operating room time may be necessary, and fimer, Hemosol Inc., although this trial was halted pre-
meticulous attention to volume is crucial in borderline maturely). The products are being investigated primarily
cases. Intraoperative blood salvage (cell saver, etc.) is in the perioperative setting, although acute resuscitation
suitable for high-volume “clean” losses (vascular surgery). studies are planned. An earlier human diasporin-linked
If large-volume (>500–1000 ml) salvage is done, the device HBOC (Hemassist, Baxter) has been discontinued. All
should “wash” the salvaged blood and return only the the HBOCs have short plasma half-lives (days), and it
RBCs to the patient. Postoperative blood salvage (medi- is not clear that they are equivalent in efficacy or side
astinal drainage, knee and hip drains) is more contro- effects. Their clinical roles remain to be established, and
versial. In general such salvage is costly and little blood rather than “red cell substitutes” discussion is now turn-
is salvaged; there may also be issues of sterility and of ing to their potential broader role in “oxygen therapeu-
inducing coagulopathy. In selected surgical settings and tics.” Their presence in the plasma may also interfere
patients, particularly in bloodless medicine and surgery with certain laboratory tests (including optically based
programs, hypotensive anesthesia may be used. tests of coagulation and O2 determination by pulse
A variety of pharmacologic agents can be useful as oximetry). Perfluorocarbon solutions are also capable of
adjuncts or alternatives to blood products. Erythropoietin carrying O2 dissolved in solution, although like HBOCs
can be useful to increase the hematocrit preopera- they have short plasma half-lives and a variety of side
tively (see above) and is approved for this purpose in effects reported. One of them, Perflubron (Alliance
noncardiovascular surgery. The dose is 600 U/kg/week Pharmaceuticals), was being used in a phase 3 trial in
for 3 weeks prior to surgery (days –21, –14, and –7) or perioperative hemodilution, but this was recently
300 U/kg given 10 consecutive days before surgery and halted. Potential platelet substitutes are being developed
4 days postoperatively. It usually takes a minimum of (infusible platelet membranes, fibrinogen-coated albumin
10–14 days to get any meaningful increase in hematocrit. microspheres).
Adequate iron repletion should be ensured. Postoperatively Jehovah’s Witnesses refuse whole blood and all of its
there is resistance to the action of erythropoietin and it primary components (RBCs, platelets, and plasma) and
is less effective. DDAVP is first-line therapy in treatment pose special challenges in the perioperative setting.
of mild to moderate hemophilia A and mild to moderate However, plasma derivatives (cryo, albumin, fibrin glues)
Type I vWD and may be given both IV and intranasally. are considered “matters of conscience” and are accepted
IV dose is 0.3 μg/kg. A preoperative trial is recommended by some Jehovah’s Witnesses but not others. Autologous
to ensure hemostatic levels. DDAVP may also be useful in predonation is unacceptable to Jehovah’s Witnesses but
correction of platelet dysfunction (uremia, drug-induced). perioperative hemodilution and intraoperative salvage
Fibrinolytic inhibitors (aprotinin, tranexamic acid, procedures where the blood is kept in a continuous
epsilon aminocaproic acid) can be useful in attenuating circuit with the body are “matters of conscience.”
Blood and Blood Component Therapy 285
Erythropoietin (stabilized with traces of albumin) is Dzik S: The use of blood components prior to invasive bedside
acceptable to most Jehovah’s Witnesses, as are all phar- procedures: a critical appraisal. In Mintz PD, editor:
macologic blood-sparing agents. HBOCs, when available, Transfusion Therapy: Clinical Principles and Practice,
will be “matters of conscience.” The Jehovah’s Witness Bethesda, MD: AABB Press, 1999, pp 151–169.
community has a hospital liaison network which can Goodnight SH Jr, Hathaway WE, editors: Disorders of Hemostasis
provide information and put practitioners in contact and Thrombosis: A Clinical Guide, ed 2, McGraw-Hill:
with physicians experienced in managing Jehovah’s New York, 2001.
Witness patients who can provide advice. Goodnough LT, Bach RG: Anemia, transfusion and mortality
[editorial]. New Engl J Med 345:1272–1274, 2001.
SELECTED READING Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP:
Transfusion medicine: I. Blood transfusion. New Engl J Med
Expert Group Recommendations 340:438–447, 1999.
American College of Physicians: Practice strategies for elective Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP:
red blood cell transfusion. Ann Int Med 116:403–406, 1992. Transfusion medicine: II. Blood conservation. New Engl J Med
Expert Working Group: Guidelines for red blood cell and 340:525–533, 1999.
plasma transfusions for adults and children. Can Med Assoc Hebert PC, Wells G, Blajchman MA, Marshall J et al; Transfusion
J 156(Suppl 11):S1–S25, 1997. Requirements in Critical Care Investigators for the Canadian
Practice guidelines for blood component therapy: a report by Critical Care Trials Group: A multicenter, randomized con-
the American Society of Anesthesiologists Task Force on trolled clinical trial of transfusion requirements in critical
Blood Component Therapy. Anesthesiology 84:732–747, care. New Engl J Med 340:409–417, 1999.
1996. Jahr JS, Nesargi SB, Lewis K, Johnson C: Blood substitutes
General and oxygen therapeutics: an overview and current status.
Carson JL, Noveck H, Berlin J, Gould SA: Mortality and mor- Am J Therapeut 9:437–443, 2002.
bidity in patients with very low postoperative Hb levels Spence RK, Jeter EK, Mintz PD: Transfusion in surgery and
who decline transfusion. Transfusion 42:812–818, 2002. trauma. In Mintz PD, editor: Transfusion Therapy: Clinical
DeLoughery TG: Hemostasis and Thrombosis, Austin, TX: Principles and Practice, Bethesda, MD: AABB Press, 1999,
Landes Bioscience, 1999. pp 171–197.
27
CHAPTER Cirrhosis, Fulminant
Hepatic Failure, and
Liver Transplantation
JASON DZIAK, M.D.
ASHWANI CHHIBBER, M.D.
286
Cirrhosis, Fulminant Hepatic Failure, and Liver Transplantation 287
Table 27-3 Mechanisms of Drug Toxicity* Table 27-4 Positive Clinical Criteria for
Drug-Induced Hepatotoxicity
Direct toxicity (dose related)
Drug metabolite toxicity Age > 50 years
Immunoallergic Polypharmacy
Idiosyncratic reactions (sporadic and not dose related) Use of known hepatotoxic drugs or toxins
Drug serum levels (e.g., acetaminophen)
* Idiosyncratic reactions are most common. Specific serum autoantibodies
Specific liver biopsy findings (e.g., drug deposits, eosinophilic
infiltration)
DRUG INTERACTION
● Isoniazid and rifampin: rifampin is a potent p450 The Model End Stage Liver Disease or MELD score has
induction agent and greatly increases the quantity of
currently been adopted by the United Network for
hepatotoxic metabolites generated by isoniazid.
● Barbiturates and tricyclic antidepressants (TCAs),
Organ Sharing (UNOS) as an alternative to the CPS sys-
e.g., Amitryptilline: barbiturates such as sodium tem. UNOS is the national organization that assigns list-
thiopental are potent inducers of cytochrome p450 ing status for organ allocation to recipients based on
and greatly increase the metabolism of TCAs with a disease severity. The MELD is calculated using a formula
subsequent increase in hepatotoxic TCA with three primary variables which include serum crea-
metabolites. tinine, total bilirubin, and international normalized ratio
(INR). The formula for the MELD score and its correla-
tion with the former CPS-based UNOS listing criteria are
shown in Table 27-6.
The list of drugs that can result in hepatotoxicity is an
exhaustive one that will not be covered here. There are,
however, certain clinical indicators that are helpful to Fulminant Hepatic Failure
consider when assessing whether or not drug toxicity is Table 27-7 shows prognostic indicators that are asso-
the etiology of hepatic failure. These include the presence ciated with adverse outcomes in patients with FHF.
of an acute process (drug toxicity is rarely chronic in These variables were obtained from King’s College
nature), ruling out other etiologies of liver disease and Hospital in London, UK, and since their introduction in
specific chronological parameters. The time interval 1989 they are the most widely utilized FHF criteria. In
between use of the drug and the onset of hepatic toxicity patients with acetaminophen toxicity the presence of a
is generally 1 week to 3 months. Resolution or improve- single indicator is associated with a mortality rate of
ment of liver disease after withdrawal of the suspected at least 55%. The presence of severe acidosis in aceta-
agent or worsening of disease after accidental use of the minophen patients carries a mortality rate of 95%. The
drug are also suggestive chronologic markers. Table 27-4 presence of a single indicator in nonacetaminophen
lists the remainder of commonly observed positive clini- patients is associated with an 80% mortality rate, and the
cal criteria associated with drug-induced hepatotoxicity. presence of three indicators carries a mortality rate of
greater than 95%. All of these respective mortality rates,
however, vastly exceed perioperative mortality rates
associated with liver transplantation.
CLASSIFICATION OF SEVERITY OF
CIRRHOSIS AND FULMINANT HEPATIC
FAILURE
Table 27-5 Child-Pugh Scoring System
Cirrhosis
The Child-Pugh score (CPS) is the most commonly 1 Point 2 Points 3 Points
used classification scale for cirrhotic patients. Survival
has been shown to be inversely related to the CPS. Serum albumin >3.5 2.8–3.5 <2.8
Patients with 10 points usually require frequent medical (g/dl)
INR <1.7 1.7–2.3 >2.3
checkups. Patients with 12 points regularly require
Ascites None Slight or diuretic Moderate or
hospitalization for management of decompensated liver controlled severe
disease. Patients with 13–14 points generally require Encephalopathy None Mild or moderate Severe
management in the intensive care unit (see Table 27-5).
Cirrhosis, Fulminant Hepatic Failure, and Liver Transplantation 289
Table 27-6 MELD Score and UNOS Status Table 27-7 King’s College Hospital Criteria
< 24 3 CPS > 7 and requires continuous medical pH < 7.30 Age <10 years or >40 years
surveillance INR > 6.50 INR > 3.5
24–29 2b CPS > 10 or CPS > 7 with at least one of the Serum creatinine > 3.4 mg/dl Etiology: non-A and non-B
following criteria: significant variceal in patients with stage 3 or hepatitis, halothane hepatitis,
hemorrhage, hepatorenal syndrome, SBP, or 4 encephalopathy drug/toxin mediated
refractory ascites Duration of jaundice > 1 week
> 30 2a End-stage chronic liver disease with CPS > 10 before the development of
and life expectancy < 7 days encephalopathy
1 FHF with life expectancy < 7 days, primary Serum bilirubin > 18 mg/dl
nonfunction of liver transplant within
7 days, hepatic artery thrombosis within
7 days of liver transplant
(PTT) generally result from decreased synthesis of clot-
* Maximum MELD score is 40. MELD score formula: 10[0.957(Cr) + 0.378(Tbili)
+ 1.12(INR) + 0.643].
ting factors by the liver. Poor absorption of fat-soluble
vitamin K due to altered bilirubin excretion and poor
nutritional intake of vitamin K are other factors to con-
CURRENT CONTROVERSY sider when evaluating for a coagulopathy. The degree of
PTT abnormalities tends to parallel PT/INR abnormalities
Some clinicians advocate the use of CT-guided
hepatic volumetry and liver histology, i.e., parenchymal
in patients with acute or chronic liver disease.
necrosis of greater than 50% as prognostic indicators
for FHF. The practicality of these measures has been
questioned due to bleeding risk with hepatic biopsy CLINICAL CAVEAT
and the difficulty of transporting critically ill patients
Chronically cirrhotic patients are unlikely to
for CT evaluation.
respond to vitamin K administration for the treatment
of coagulopathy secondary to nonfunctioning
hepatocytes with impaired synthetic ability.
DIAGNOSTIC STUDIES
Serologic testing for viral hepatitis is routine for
Laboratory Testing patients with evidence of chronic or acute hepatic dis-
Specific laboratory tests are ordered routinely for ease. Quantitative DNA and RNA tests for hepatitis B and
patients with suspected or documented cirrhosis and/or C, respectively, are now commonly obtained if antigen
FHF. Certain results can detect treatable chronic liver or antibody tests are positive. Hepatitis B quantitative
disease before significant decompensation occurs. These DNA testing has largely replaced the e antigen test. Serial
tests also facilitate care of FHF patients and help rule out measurements of serum electrolytes and glucose levels
specific FHF etiologies. A complete blood count can are also routinely obtained. Cirrhotic patients may pres-
reveal anemia secondary to splenic sequestration, GI ent with decreased serum potassium and magnesium lev-
hemorrhage, or decreased erythropoietin production in els secondary to chronic diuresis. Hypocalcemia may be
the setting of hepatorenal syndrome. Thrombocytopenia present with advanced renal dysfunction due to hepa-
may present secondary to splenic sequestration, bone torenal syndrome or in the setting of citrate toxicity sec-
marrow suppression, disseminated intravascular coagu- ondary to blood product administration. Hypoglycemia
lation, or massive hemorrhage. Elevated white blood cell can occur with malnourishment or with impaired gluco-
count (WBC) can present with infectious processes such neogenesis and glycogenolysis at the hepatocyte level.
as spontaneous bacterial peritonitis (SBP). A full liver Hyperglycemia can be seen in patients with cirrhosis
panel is routinely obtained with subsequent serial meas- secondary to NASH who often exhibit insulin resistance.
urements. It is important to note that serum AST and Hyponatremia is a common clinical entity in cirrhotic
ALT levels may not be elevated in cirrhotic patients due patients due to either chronic diuresis or an overall total
to extensive hepatocyte destruction and subsequent body hypervolemic state. Table 27-8 outlines the remain-
decrease of transaminase production. Prolonged pro- der of standard laboratory screening tests obtained in the
thrombin time (PT)/INR and partial thromboplastin time setting of acute or chronic liver disease.
290 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
CURRENT CONTROVERSY
CLINICAL CAVEAT The practice of performing colonoscopy in hepatic
transplant candidates is controversial and not
Some degree of hyponatremia should be tolerated in supported by some data. Polypectomy in the presence
cirrhotic patients. Aggressive replacement of sodium of ascites can lead to an increased risk of colonic
with excessive fluids can precipitate central pontine perforation.
myelinolysis or volume overload with pulmonary edema.
blood–brain barrier that allows passage of plasma con- and dietary protein restriction are also commonly initi-
tents into the brain parenchyma. ated in the treatment of PSE.
CURRENT CONTROVERSY
The primary therapy for PSE is lactulose. Some clinicians consider a CPP below 40 mmHg for
Approximately 90% of patients with PSE will respond to longer than 1 hour a contraindication for liver
lactulose in combination with the correction of a coex- transplantation. However, there have been multiple
isting precipitating factor. Patients who are refractory to case reports of patients making full neurologic
lactulose therapy can be treated with oral neomycin in recoveries following prolonged episodes (24–38 hours)
combination with lactulose. Serial serum ammonia levels of severely impaired CPP.
worsening renal insufficiency may be the only symptoms Although the pathophysiology of HRS is complex and
present. Diagnosis of SBP is confirmed by an ascitic fluid controversial, it is generally thought to be due to renal
cell count of greater than 250 PMN/mm3 or a pure vasoconstriction that occurs in response to splanchnic
growth positive bacterial culture. Cultures are positive vasodilation and increased intra-abdominal pressure from
in approximately 50–75% of patients. The most common ascites. Activation of the renin–angiotensin–aldosterone
organisms (70%) are aerobic Gram negatives with E. coli system with simultaneous decreases in renal prostaglandin
and klebsiella predominating. The remaining 30% are production results in the observed renal vasoconstric-
Gram-positive cocci with S. pneumonia predominating. tion. Some clinicians have hypothesized a hepatorenal
The recommended treatment is appropriate intravenous sympathetic reflex that occurs secondary to portal
antibiotic therapy. hypertension as the initiating factor. The mechanism of
systemic and splanchnic vasodilation has multiple
hypotheses that include increased levels of nitric oxide
CLINICAL CAVEAT (NO), endotoxins, and bilirubin, and elevated levels of
Although the Gram stain of ascitic fluid is positive cytokines such as tumor necrosis factor and interleukin
in 30% of cases, the result of the Gram stain does not (IL)-1 and IL-6. Others have proposed the hypothesis of
correlate with culture growth in about one-third of elevated NO levels in the splanchnic circulation with
those cases. concomitantly low levels of NO present in the portal
circulation.
CLINICAL CAVEAT
Renal Manifestations
Hepatorenal syndrome (HRS) is the most common Nonsteroidal anti-inflammatory drugs should be
strictly avoided in any patient with acute or chronic
manifestation of renal disease in cirrhotic patients and
liver disease due to concerns of impaired renal
can also be seen in the setting of FHF. Other etiologies function. These medications can decrease already
of renal dysfunction can also be seen in both chronic significantly reduced levels of vasodilating
and acute liver disease. Simultaneous hepatic and renal prostaglandins and promote additional renal
damage can occur due to systemic conditions such as vasoconstriction.
collagen vascular disease or amyloidosis. Acute tubular
necrosis can be seen with acetaminophen toxicity and in
the setting of FHF. Prerenal azotemia is common in cir-
rhotic patients secondary to chronic diuresis or multiple Treatment of HRS focuses initially on treatment of
large-volume peritoneal taps. Intrinsic renal disorders refractory ascites, especially in type 2. This can be done
can also be seen with certain liver diseases such as the by large-volume paracentesis, although smaller volumes
association between IgA nephropathy and alcohol- have been advocated due to potential intravascular vol-
induced cirrhosis and the link between glomerulo- ume depletion. The use of selective renal prostaglandins
nephritis and hepatitis B and C. has shown no direct benefit. The use of vasopressin ana-
HRS is a diagnosis of exclusion and other clinical enti- logues such as ornipressin for splanchnic vasoconstric-
ties including GI bleed, SBP, nephrotoxic agents, and tion with or without intravascular volume loading has
hypovolemia must be ruled out before assigning the shown some positive results when used over a period of
diagnosis. There are two distinct clinical patterns of HRS time greater than 1 week. A TIPS procedure is advocated
that are generally recognized. Type 1 HRS is usually seen by some clinicians, but, as noted previously, this inter-
in the FHF population or in cirrhotic patients who vention is controversial and has a significant compli-
acutely decompensate. It is characterized by a doubling cation rate. Hemodialysis or continuous veno-veno hemo-
of the initial serum creatinine to a level greater than filtration (CVVH) can be used as a bridge to transplant.
2.5 mg/dl or a 50% reduction in the 24-hour creatinine CVVH offers more hemodynamic stability in this setting
clearance to a level lower than 20 ml/minute in less than and also has been shown to reduce vasopressor require-
2 weeks. Type 2 HRS is recognized as the more chronic ments. Liver transplantation is the definitive therapy
form of the disease and occurs in relatively compensated for HRS. The diagnosis of HRS, however, carries with it
patients with refractory ascites. Renal function generally a significant increase in perioperative hepatic transplant
worsens over months. Urinary parameters of HRS mortality rates, especially in patients with a serum
include urine volume of less than 500 cm3/day and urine creatinine > 2 mg/dl. Renal function may not return to
sodium of less than 10 mEq/day. However, there are well- normal after transplantation in the setting of HRS, espe-
documented cases of nonoliguric forms of HRS and cases cially with the use of nephrotoxic immunosuppressive
with significantly increased urine sodium excretion. medications in the postoperative setting.
296 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
CURRENT CONTROVERSY
Coagulation Manifestations
The presence of severely elevated ICP with
There are multiple mechanisms of coagulopathy in
prolonged episodes of decreased CPP is a relative
the setting of acute and chronic liver disease. contraindication to orthotopic liver transplantation. In
Thrombocytopenia can occur due to blood loss, seques- the past, HIV positive status represented an absolute
tration in liver and spleen, disseminated intravascular contraindication to liver transplantation. However, with
coagulation (DIC), or autoimmune destruction. Platelet the increasing acceptance of HIV infection as a chronic
dysfunction is also common. Vitamin K-dependent disease state, some transplant centers will consider
factors are often depleted secondary to malnutrition, these patients as potential organ recipients.
decreased synthesis, impaired fat absorption, or blood
loss. Essentially all of the factors, both pro- and anti- Recognized factors have emerged that are associated
coagulant, involved in the clotting cascade are produced with increased graft failure rates and increased recipient
by the liver with the exception of factor VIII and tissue mortality rates in the setting of OLT. Increasing patient
plasminogen activator (TpA). Because the liver is also age, elevated serum creatinine, worsening UNOS status,
the primary site of TpA metabolism, some degree of fib- and female gender of the donor have all been shown to
rinolysis is always present in this patient population and be associated with lower recipient survival rates.
does contribute to coagulopathy. Prolonged warm ischemic times, poor clinical status of
the recipient, and female gender of the donor have been
shown to be independent risk factors for graft failure
Immunologic Manifestations following transplantation.
Infectious processes other than SBP are common in OLT is commonly divided into three intraoperative
patients with cirrhosis and FHF due to immunosuppres- phases, which include the preanhepatic phase, the
sion. The source of infections in both groups is most anhepatic phase, and the postreperfusion or neohepatic
commonly the respiratory or urinary tract. These infec- phase. The preanhepatic phase involves induction and
tions predominate in FHF patients with one study find- maintenance of anesthesia, endotracheal intubation with
ing an 80% incidence. Bacteremia is also more common mechanical ventilation, line placement, and ultimately
in the FHF population and has been cited as high as 20%. surgical dissection of the liver with removal of the organ.
Defects in both humoral and cell-mediated immunity Anesthetic induction generally involves a rapid-sequence
have been seen in both populations. There is often induction and intubation. Barbiturates or propofol can
decreased complement production by liver in advanced be used as induction agents unless gross hemodynamic
disease which results in impaired opsonization of bacte- instability is evident, and succinylcholine is also used
ria. These patients demonstrate decreased IgM activity regularly. Despite the potential for significant decreases
against Gram-negative organisms, and also develop in pseudocholinesterase synthesis in the setting of
reticuloendothelial dysfunction. The macrophages in the advanced liver disease, metabolism of succinylcholine
reticuloendothelial system represent a critical filtering has not been shown to be affected clinically with a sin-
mechanism for blood-borne pathogens that becomes gle intubating dose. Inhaled agents such as isoflurane or
compromised. Bacterial translocation of viable bacteria desflurane, narcotics, and intermediate- to long-acting
and endotoxins into mesenteric lymph nodes also muscle relaxants are the standard maintenance anes-
occurs in the setting of splanchnic hypoperfusion. This thetic agents of choice. Muscle relaxants that require
is thought to initiate the release of multiple inflammatory renal excretion are generally avoided in the setting of HRS.
mediators.
Nitrous oxide is avoided due to associated bowel expan- the liver without the use of VVB. A perfusion team,
sion and the risk of potentiating air embolic events that however, is always immediately available throughout the
can occur in the setting of veno-veno bypass or vena preanhepatic and anhepatic phases whether or not VVB
cava manipulation. Line placement generally consists of is utilized.
at least one arterial line, pulmonary artery catheter, and The anhepatic phase consists of surgical vascular anas-
multiple large-bore access sites including a central tamoses of the hepatic veins to the vena cava and the
venous access port. portal vein anastomosis. The primary anesthetic goals of
Adequate venous access is critical for all portions of the this period in preparation for reperfusion of the graft are
case due to the potential for large fluid shifts, large shifts the optimization of serum potassium levels, ensuring
in SVR, acute blood loss, and augmentation of preload adequate intravascular volume, administering immuno-
with surgical caval manipulation. Immediate availability of suppressives, and correction of acid–base disturbances.
blood products is standard throughout the procedure. Serum potassium should preferably be below 4.0 mEq/l
Serial arterial blood gases are monitored throughout at reperfusion because of the significant rise in serum K+
the case to assess acid–base and pulmonary status. that occurs at this point in the procedure. Sodium bicar-
Serial complete blood counts, PT/INR, PTT, fibrinogen bonate, insulin, hyperventilation, calcium chloride, and
levels, glucose levels, and electrolyte levels, including potassium wasting diuretics are all commonly used to
calcium and magnesium, are also routinely obtained. decrease serum K+ to favorable levels. Patients with
Thromboelastography (TEG) is variably utilized in renal compromise are at particularly high risk of devel-
transplant centers and is advocated by some clinicians. oping hyperkalemic complications. CVVH or dialysis can
Continuous cardiac output pulmonary artery catheters be utilized for potassium clearance prior to graft reper-
with SvO2 capability are also commonly used for man- fusion if necessary. “Venting” through the graft prior to
agement in this patient population. reperfusion has shown to decrease the degree of potas-
sium elevation in some studies, and is practiced in some
centers. This involves allowing approximately 500 cm3
CURRENT CONTROVERSY of portal blood to reperfuse the liver. This blood is then
There have been some data to suggest that
discarded.
desflurane is associated with a lesser decrease in The neohepatic phase begins with reperfusion of the
splanchnic and hepatic blood flow compared to portal circulation through the liver, hepatic veins, and
isoflurane. Certain clinicians who advocate extubation vena cava. Management is focused on treatment of
in the operating room at the conclusion of the case postreperfusion syndrome (PRS) and any significant
also note that emergence time from anesthesia is hyperkalemic response. PRS is generally defined as a
shortened with desflurane use. mean arterial pressure that decreases greater than 30%
from baseline or that is less than 60 mmHg. This lasts
greater than 1 minute and occurs within the first 5 min-
The use of transesophageal echocardiography (TEE) utes of reperfusion. The pathophysiology of PRS is due
is used variably in transplant centers. Many practitioners to multiple factors including a significant decrease in
avoid this monitor due to the potential presence and SVR, relative hypovolemia, potential dysrhythmias, and
rupture of esophageal varices. acute metabolic acidosis with subsequent pulmonary
Removal of the organ in the preanhepatic phase can hypertension and right and left ventricular depression.
be facilitated by veno-veno bypass (VVB) or by partial Treatment consists of hyperventilation with 100%
caval clamping near the hepatic vein(s) insertions also inspired oxygen, volume resuscitation, and vasopressor
known as “piggy backing.” There have been no data to support. Anastamoses of the hepatic artery and the biliary
support the use of either technique, and this is an area drainage procedure (Roux-en-y choledochojejunostomy
of controversy. VVB is generally performed initially from versus choledochocholedochostomy) are the remaining
the femoral vein to the axillary vein with subsequent surgical goals of the neohepatic phase. Anesthetic man-
addition of the portal vein circulation. The liver is then agement at this point focuses on treatment of coagulo-
completely removed. VVB is not routinely performed by pathy and monitoring for signs of function of the new
some clinicians because of a higher risk of vascular graft. There are multiple mechanisms for impaired hemo-
injury, hemorrhage, thrombotic complications, and air stasis at this juncture. These include hypothermia,
embolus. If the partial caval clamping technique is cho- hypocalcemia, metabolic acidosis, platelet consumption,
sen, a test clamp is generally performed first to assess if hepatic dysfunction following graft reperfusion, release
hemodynamics can be corrected with volume loading of heparin and heparin-like substances from the new
and vasopressor support. If this test is successful, many graft, and enhanced fibrinolysis secondary to increased
surgeons will proceed with “piggy backing” and remove TpA activity with additional factor consumption.
298 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Treatment is focused on product administration (fresh liver transplantation has increased significantly over the
frozen plasma, packed red blood cells, platelets, cryo- past decade. The number of adult cadaveric livers, how-
precipitate), calcium replacement, correction of ever, has not increased proportionately, and, as a result,
hypothermia, treatment of acidosis, and surgical hemo- waiting list times and mortality rates in this adult popula-
stasis. Serial measurements of platelet counts, PT/INR, tion of recipients have risen dramatically. This procedure
PTT fibrinogen levels, TEG (if utilized), and clinical is being offered in response to this relative organ shortage.
reports of clot or subjective coagulopathy by the surgi- The use of live donor organ donation (right hepatic
cal team are followed. Appropriate cardiopulmonary lobectomy) is controversial. aLDLT does offer the advan-
support is provided throughout the postreperfusion phase. tage of decreased warm and cold ischemic times for the
Continued vasopressor administration may be necessary donated graft, and it also ensures an optimally screened,
due to delayed graft function or due to hypovolemia healthy donor. However, the complex nature of the
seen with continued blood loss. Some degree of pul- surgery and the potential risk to an otherwise healthy
monary edema may also be present secondary to volume patient bring up many clinical and ethical concerns
overload or secondary to lung injury that can occur with regarding live donation.
graft reperfusion and/or blood product administration. The size of the graft is crucial when performing
This pulmonary injury, when it occurs, is usually tran- aLDLT. This is calculated by either the graft-to-recipient
sient in nature, is often associated with an exudative weight ratio (GRWR) or the graft-to-recipient standard
edema, and generally presents within 1–2 hours after liver volume ratio (GSLV). It is now generally accepted
reperfusion. that a GRWR of at least 1% and a GSLV of at least 50% are
safe concerning the development of a “small for size” syn-
drome. However, graft congestion in the postreperfusion
CURRENT CONTROVERSY period can precipitate this syndrome despite adequate
size, especially since the right hepatic lobe has been
The use of antifibrinolytics such as aprotinin or
aminocaproic acid in the setting of postreperfusion shown to be very susceptible to venous congestion.
coagulopathy is controversial. Many clinicians avoid the There have been a significant number of biliary tract
use of these agents due to concerns of initiating a complications in the recipient population with the
hypercoagulable state with thrombotic complications. aLDLT procedure. These have been reported as high as
There are, however, no data to support this concern. 28–34% in some studies. Hepatic arterial thrombosis may
Multiple studies have shown a decrease in overall blood also be higher in this population due to the fact that
product requirements with the use of antifibrinolytics smaller vessels are used in the anastamosis. Postoperative
without an increased incidence of thrombotic care of these patients should involve frequent monitor-
complications. ing for signs of potential bile leaks or graft dysfunction
and frequent Doppler examinations of the hepatic artery
to ensure patency.
Clinical functioning of the new graft is assessed by
multiple parameters including improvement of coagu-
lopathy, decreasing vasopressor requirements, bile pro- Artificial Liver
duction, resolution of acidosis, improved calcium and The use of bioartificial hybrid devices for the treat-
magnesium homeostasis secondary to improved citrate ment of liver disease as a bridge to transplant has shown
metabolism by the new graft, and decreasing levels of limited usefulness in randomized trials. Some studies
serum lactate. Lactate is primarily metabolized in the using plasma exchange as the primary modality have
liver, and lactate levels are used as a marker of graft func- shown increased survival times and this intervention
tion in some facilities. Delayed graft function may be may have some utility as a bridge to transplantation in
seen in the setting of reperfusion injury with hepatic critically ill patients.
congestion. Diuresis and/or nitroglycerin have been
used routinely in some centers to reduce central venous
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28
CHAPTER Gastrointestinal
Bleeding
CHARLES R. PHILLIPS, M.D.
PER A. J. THORBORG, M.D., Ph.D.
300
Gastrointestinal Bleeding 301
clinical parameters of blood pressure, urine output, and (NSAIDs), and alcohol are associated with PUD and gas-
heart rate. Shock requiring aggressive hydration and blood tritis. NSAIDs are associated with a two-fold increase in
replacement corresponds to levels II and III depending the risk of bleeding and are felt to contribute to the devel-
on the patient and presentation. Reversal of shock should opment of 5–25% of all gastric ulcers. Cigarette smoking
be accomplished with rapid infusion of IV fluids. This has been associated with a higher recurrence rate of PUD.
may include blood and blood products but resuscitation A recent history of retching or vomiting prior to bleeding
should not be delayed for their arrival and crystalloid may be indicative of a Mallory–Weiss tear. Stigmata of liver
infusion should commence immediately, through a disease and portal hypertension such as spider nevi,
large-bore IV, ideally before hospital admission. Once palmer erythema, hepatomegaly, jaundice, asterixis, or
admitted, consideration for placement of an introducer ascites should be looked for on examination with concern
catheter into a central vein should be made in the event for a variceal source of bleeding if found. Drug-induced
rapid large-volume fluid infusion becomes necessary. coagulopathies with coumadin and low-molecular-weight
Monitoring of central venous pressure and mixed venous heparin should be evaluated for and a history of such med-
pO2 can also be helpful. Adequate urine output, resolution ications sought. Recent weight loss or a change in bowel
of orthostatic blood pressure changes, pulse rate < 100, habits may be indicative of colorectal cancer. A history of
supine blood pressure > 90, and level of consciousness can diverticular disease, prior malignancy, inflammatory
all be used to assess recovery from shock (Table 28-1). bowel disease, or significant vascular disease can aid in
When blood is to be replaced, transfusion with packed determining a diagnosis in lower GI bleeding. Crampy
red blood cells is preferred. Whole blood transfusion with abdominal pain out of proportion to examination findings
O negative blood is rarely used and should be reserved for occurring after meals followed by hematochezia may indi-
those patients with massive blood loss who cannot be cate mesenteric ischemia.
cross-matched rapidly. Patients requiring greater than 10
units of packed red blood cells should undergo a massive
transfusion protocol and should receive fresh-frozen UPPER GASTROINTESTINAL BLEEDING
plasma, platelets, and cryoprecipitate as needed. Timing
of transfusion and goal hemoglobin, platelet counts, fib- UGI bleeding is defined as bleeding from a GI source
rinogen, and international normalized ratio (INR) vary proximal to the ligament of Treitz. It is more common than
with the presentation but generally hemoglobin should be lower GI bleeding, accounting for 1–2% of all hospital
kept above 8 g/dl, except in heart disease where it should admissions in the USA per year. Despite improvements in
be kept above 10 g/d, fibrinogen above 100 mg/dl, and care and prevention, mortality and morbidity statistics have
INR less than 1.3–1.5. A blood warmer should be used if a not improved in the last 20 years. The increased use of
patient is to receive more than 3 liters of fluid. NSAIDs has probably contributed to an increase in the
number of patients presenting with UGI bleeds, though
their use has not been associated with worsening outcome.
HISTORY AND PHYSICAL UGI bleeding is often encountered in the critically ill
complicating other primary diseases. Clinically impor-
A thorough history and physical examination can aid tant stress-related UGI bleeding is seen in only 1–4% of
in determining the source of GI bleeding and its etiology. the critically ill; however, the death rate exceeds 50% in
Drugs, particularly nonsteroidal anti-inflammatory drugs this group. Within 24 hours of admission to the ICU,
75–100% of patients will demonstrate endoscopic evi-
dence of mucosal damage and most will have at least
Table 28-1 Classification of Hemorrhage Based occult bleeding making prophylactic acid suppression a
on Extent of Blood Loss
necessary part of ICU therapy. Studies have shown, how-
ever, that there is benefit with acid suppressive therapy
Parameter Class I Class II Class III Class IV only in patients who are mechanically ventilated for pro-
longed periods, have coagulopathies, recent prior bleed-
Loss of blood <15 15–30 30–40 >40
volume (%)
ing from PUD, major head trauma, or significant burns.
Pulse rate <100 >100 >120 >140 Thus acid suppressive therapy should be reserved for
Supine blood Normal Normal Decreased Decreased these subsets of patients only.
pressure
Urine output >30 20–30 5–15 <5
(ml/hour) Diagnoses and Management
Mental status Anxious Agitated Confused Lethargic
Presentation of Bleeding
Committee on Trauma: Advanced Trauma Life Support Student Manual, Patients with upper GI bleeding typically present
Chicago: American College of Surgeons, 1989, p 57. with hematemesis and melena. Nasogastric tube (NGT)
302 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Resuscitation
IVF - crystalloid, colloid, PRBC, FFP, Plts
Endoscopy
Scelrotherapy Evidence of major bleed Minimal Major Figure 28-1 Algorithm for the
or bleed bleed treatment of acute upper GI bleeding.
banding
+
octreotide Injection/cautery
Medical Angiography/
management embolize,
colonoscopy,
Bleeding enteroscopy,
Bleeding Continued controlled
controlled bleeding or tagged RBC
recurrence Bleeding scan
continues or recurs
TIPPS or surgery Massive bleeding
continues
1. Ciprofloxacin
2. Propranolol
3. Hepatology referral Re-scope 24-48 hours Surgery
Specific Causes
Blood No blood
Diverticulosis UGI workup Rectal inspection
Diverticulosis is responsible for 30–40% of all cases of anoscope
lower GI bleeding and is the leading cause in patients (-) (+)
over 50 years. Colonic diverticuli occur where major
branches of the vasa recta penetrate the colonic wall.
These points of penetration occur through connective Bowel prep
tissue between sections of muscle and represent rela-
Colonoscopy (+)
tively weak areas in the colon wall. With increased pres- Endoscopic therapy
sure colonic tissue may herniate through these areas and (-)
may then over time erode into the arteries resulting in Bleeding stops
bleeding. The bleeding can be large volume and is usually Bleeding scan
(+)
painless, presenting typically as hematochezia, but can (-) Observe
present as melena. This is due to the fact that whereas
diverticuli occur more frequently in the left colon, bleed- Angiography (-) Bleeding continues
ing from diverticuli occurs more often in the right colon. (+)
Frequent recurrent bleeding or massive life-threatening
Embolize Bleeding continues Surgery
bleeding from diverticuli is an indication for hemicolec-
tomy, which is curative. Figure 28-2 Algorithm for the treatment of hematochezia.
Gastrointestinal Bleeding 305
Ischemic Colitis
The second leading cause of lower GI bleeding in SUMMARY
patients over 50 years is ischemic colitis. It typically pres-
ents as crampy abdominal pain out of proportion to exam- GI bleeding remains a significant cause of morbidity
ination findings followed by bleeding for one to two days. and mortality, especially in those patients who develop
It can occur anytime but is often precipitated by meals. The bleeding while in hospital. Early recognition and prompt
bleeding is usually mild and self-limiting but occasionally resuscitation is essential in the management of these
can present as massive bleeding. Over 90% of patients with patients to minimize complications associated with
mesenteric ischemia have underlying atherosclerotic dis- shock and anemia. Prompt therapy guided by early diag-
ease. Ischemia is felt to be caused by a relatively low flow nostic evaluation aimed at determining the site and cause
state through diseased blood vessels supplying the bowel. of bleeding should follow a formulation of a differential
Abdominal angina is a term sometimes used to describe the diagnoses based on bleeding characteristics, patient age,
pain experienced after meals when demand for blood history and physical examination, and laboratory results.
exceeds available supply due to atherosclerotic lesions. Early referral to gastroenterology should be made.
Colorectal Cancer H2 blockers have no role in the acute management of
Malignancies in the lower GI tract rarely present with UGI bleeding, whereas proton pump inhibitors reduce
massive bleeding but when they do there is a very poor rebleeding in PUD and gastritis. Empiric use of octreotide
prognosis. Therapy is surgical resection to control bleeding. for suspected portal hypertension related bleeding
Angiodysplasias should be done.
Vascular malformations and anomalies in the lower GI Stress ulcer prophylaxis in the ICU is important in
tract are typically located in the cecum and right colon. select patients but indiscriminant use of such therapy
Their cause is unclear but it is felt that most of these are with either H2 blockers or proton pump inhibitors should
acquired with age. Bleeding is usually intermittent and be avoided.
small volume presenting with signs and symptoms of
blood loss anemia, but they can present with brisk CASE STUDY
bleeding. They are usually easily seen on endoscopy and
are amenable to cautery. If refractory to endoscopic A 63-year-old male is admitted to the ICU with
community-acquired pneumonia. Medical history is
and/or medical therapy, surgery is then indicated.
significant for type II diabetes and moderate
Inflammatory Bowel Disease emphysema with ongoing tobacco use. Chest x-ray
Inflammatory bowel disease to include Crohn’s disease reveals an area of dense consolidation in the left upper
and ulcerative colitis are the most common causes of lower lobe superimposed with changes consistent on chronic
GI bleeding in patients less than 50 years. It rarely presents obstructive pulmonary disease. Examination reveals
with life-threatening hemorrhage, instead usually present- mild distress on 4 liters nasal oxygen, a blood pressure
ing with moderate bleeding, with blood mixed with stool of 115/65, a respiratory rate of 24 with mild accessory
and associated with crampy abdominal pain and sometimes muscle use, febrile to 38.7°C, and decreased breath
fever. Occasionally an ulcer can erode into a major vessel sounds were appreciated on the left with rare
and these patients will present with massive bleeding. expiratory wheezes in all lung fields. Patient was only
Infectious Colitis taking minimal PO fluids, refusing to eat.
Invasive infectious pathogens can cause a hemorrhagic QUESTIONS
colitis and present as hematochezia. Salmonella, yersinia, 1. Should acid suppression therapy be initiated at
shigella, Campylobacter jejuni, Clostridium difficile, this time?
Escherichia coli, Vibrio parahaemolyticus, Entamoeba 2. What are the risks/benefits associated with acid
histolytica, and schistosomatidae are the most common suppression?
of the pathogens responsible. Fever, diarrhea, crampy Patient’s respiratory status deteriorated and he was
abdominal pain, recent travel, and recent contact or subsequently intubated. Shortly thereafter he became
family illness are important clues in a patient’s history septic requiring vasopressors despite aggressive
pointing to an infectious etiology. hydration with IV crystalloid and colloid.
Meckel’s Diverticulum QUESTIONS
Meckel’s diverticulum is a congenital abnormality in
1. Should acid suppression therapy be initiated if not
the terminal ileum. The diverticulum is lined with
already done?
ectopic gastric cells and acid secreted from these cells 2. If yes which agent/s would you use? And why?
can cause ulceration into the adjacent bowel wall and The next day the patient’s nurse notices a large
blood vessels supplying the bowel. It typically presents volume of bright red blood in his orogastric tube
in childhood or early adult as painless hematochezia or aspirate and a short time later he develops melena.
melena, and can cause massive bleeding.
306 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
SELECTED READING
CASE STUDY—cont’d
Aggressive resuscitation with IV crystalloid and 4 units Abraham J, Fennerty B, Piesegna J et al: Acid suppression in a
of packed red blood cells enacted cardiovascular stability. critical care environment: state of the art and beyond. Crit
Care Med 30(6 Suppl):S349–S350, 2002.
QUESTIONS Feldman M: Gastrointestinal bleeding. In Sleisenger & Fordtran’s
1. What are the next steps in evaluating and treating Gastrointestinal and Liver Disease, ed 7, 2002, Chap 13.
this patient’s bleeding? Navab F, Lindenauer P, Higgins T et al: Management of upper
2. What are the likely causes of his bleeding, and gastrointestinal bleeding. Baystate Health System Clinical
what therapies could be employed to control Practice Guideline, 2000.
bleeding caused by them?
Sharara A, Rockey D: Gastroesophageal variceal hemorrhage.
3. If not on acid suppression therapy would you now
N Engl J Med 345(9):669–681, 2001.
start? If on therapy would you change therapy given
this new bleeding? Which treatment would you use? Vernava A, Moore B, Longo W, Johnson F: Lower gastrointestinal
4. What is this patient’s estimated mortality based bleeding. Dis Colon Rectum 40(7):846–858, 1997.
solely on his bleeding episode in the ICU?
29
CHAPTER Renal Failure
and Support
RINALDO BELLOMO, M.D., F.R.A.C.P., F.C.C.P
CLAUDIO RONCO, M.D., Ph.D.
307
308 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
loop of Henle from ischemia by decreasing its transport- anti-DNA, antismooth muscle, etc.) are extremely useful
related workload. Animal data are encouraging, as are screening tests to help support the diagnosis of vasculi-
ex vivo experiments. There are no double-blind ran- tis or of certain types of collagen disease or glomerulo-
domized controlled studies of suitable size to prove that nephritis. If thrombotic thrombocytopenic purpura
these agents reduce the incidence of renal failure. (TTP) is suspected, the additional measurement of lactic
However, there are several studies that support the view dehydrogenase, haptoglobin, unconjugated bilirubin,
that loop diuretics may decrease the need for dialysis in and free hemoglobin is needed. In some patients specific
patients with developing ARF. They appear to achieve findings (cryoglobulins, Bence-Jones proteins) are almost
this by inducing polyuria, which results in the preven- diagnostic. In a few rare patients a renal biopsy becomes
tion or easier control of volume overload, acidosis, and necessary.
hyperkalemia, the three major triggers for renal replace-
ment therapy in the ICU. Because avoiding dialysis sim-
plifies treatment and reduces cost of care, loop diuretics MANAGING ACUTE RENAL FAILURE
may be useful in patients with renal dysfunction espe-
cially in the form of continuous infusion. Other agents The principles of management of established ARF are
such as theophylline, urodilatin, and anaritide (a syn- the treatment or removal of its cause and the mainte-
thetic atrial natriuretic factor) have also been proposed. nance of physiologic homeostasis while recovery takes
Studies so far, however, have been experimental, too place. Complications such as encephalopathy, pericarditis,
small, or have shown no beneficial effect. myopathy, neuropathy, electrolyte disturbances, or
other major electrolyte, fluid, or metabolic derangement
should never occur in a modern ICU. Their prevention
Radiocontrast Nephropathy may include several measures, which vary in complexity
In patients receiving radiocontrast a randomized con- from fluid restriction to the initiation of extracorporeal
trolled trial (RCT) suggested that half-isotonic saline infu- renal replacement therapy.
sion to maintain intravascular fluid expansion is superior Nutritional support must be started early and must
to the addition of mannitol or furosemide. A more recent contain adequate calories (30–35 kcal/kg/day) as a mix-
RCT of similar patients demonstrated a beneficial effect ture of carbohydrates and lipids. Adequate protein
of N-acetylcysteine treatment before and after radio- (about 1–2 g/kg/day) must be administered. There is no
contrast administration. A further study of 1620 patients evidence that specific renal nutritional solutions are
recently demonstrated that isotonic saline is superior to useful. Vitamins and trace elements should be adminis-
half-isotonic saline. Since these preventive interventions tered at least according to their recommended daily
have minimal toxicity they should be considered when- allowance. The role of newer immunonutritional solu-
ever a patient is scheduled for the administration of intra- tions remains controversial. The enteral route is pre-
venous radiocontrast either in or outside the operating ferred to the use of parenteral nutrition.
room. Hyperkalemia (> 6 mmol/l) must be promptly treated
with insulin and dextrose administration (exclude spuri-
ous hyperkalemia secondary to hemolysis, thrombocyto-
DIAGNOSTIC INVESTIGATIONS sis, and a very high white cell count), the infusion of
bicarbonate if acidosis is present, the administration of
An etiological diagnosis of ARF must always be estab- nebulized salbutamol, or all of these together. If the
lished. Such diagnosis may be obvious on clinical “true” serum potassium is > 7 mmol/l or electrocardio-
grounds. However, in many patients it is best to consider graphic signs of hyperkalemia appear, calcium gluconate
all possibilities and exclude common treatable causes by (10 ml of 10% solution IV) should also be administered.
simple investigations. Such investigations include the The above measures are temporizing actions, while renal
examination of urinary sediment and exclusion of a uri- replacement therapy is being set up. The presence of
nary tract infection (most if not all patients), the exclu- hyperkalemia is a major indication for the immediate
sion of obstruction when appropriate (some patients) institution of renal replacement therapy.
and the careful exclusion of nephrotoxins (all patients). Metabolic acidosis is almost always present but rarely
In specific situations, other investigations are neces- requires treatment per se. Anemia requires correction to
sary to establish the diagnosis, such as creatine kinase maintain a hemoglobin level > 70 g/l. More aggressive
and free myoglobin for possible rhabdomyolysis. A chest transfusion needs individual patient assessment. Drug
radiograph, a blood film, the measurement of non- therapy must be adjusted to take into account the effect
specific inflammatory markers, and the measurement of of the decreased clearances associated with loss of renal
specific antibodies (anti-GBM, antineutrophil cytoplasm, function. Stress ulcer prophylaxis is advisable and
312 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
(PD), each with its technical variations. All of these tech- ● Ability to control fluid status
offers several advantages, disadvantages, and limitations. ● Ability to allow full nutritional support
In the critically ill patient RRT should be initiated ● Ability to control acidosis
early, prior to the development of complications. Fear of ● Absence of specific side effects
tional IHD with cuprophane membranes, especially CRRT and slow low-efficiency extended dialysis
hemodynamic instability, and from the risks and limita- (SLED) offer many advantages over PD and conventional
tions of continuous or intermittent PD. However, con- IHD (3–4 hours/day, 3–4 times/week), and while CRRT is
tinuous renal replacement therapy (CRRT) or slow almost exclusively used in Europe, Japan, and Australia, a
extended IHD minimize these effects. The criteria for minority of American ICU patients receive CRRT. Some
the initiation of RRT in patients with chronic renal salient aspects of CRRT and IHD require discussion.
failure may be inappropriate in the critically ill. A set of
modern criteria for the initiation of RRT in the ICU is
presented in Box 29-3. Continuous Renal Replacement Therapy
With either IHD or CRRT there are limited data on CRRT was initially performed as an arteriovenous
what is “adequate” intensity of dialysis. However, this therapy (continuous arteriovenous hemofiltration,
should include maintenance of homeostasis at all levels, CAVH) where blood flow through the hemofilter was
and better uremic control may translate into better driven by the patient’s blood pressure. The need to can-
survival. An appropriate target urea is 15–25 mmol/l, with nulate an artery, however, is associated with 15–20%
a protein intake around 1.5 g/kg/day. This can be easily morbidity. Accordingly, double-lumen catheters and
achieved using CRRT at urea clearances of 30–40 l/day peristaltic blood pumps have come into use (continuous
depending on patient size and catabolic rate. If IHD is venovenous hemofiltration, CVVH) with or without con-
used, daily treatment and extended treatment become trol of ultrafiltration rate.
desirable. In a venovenous system dialysate can also be deliv-
There is a great deal of controversy as to which mode ered countercurrent to blood flow (continuous veno-
of RRT is “best” in the ICU, due to the lack of RCTs venous hemodialysis/hemodiafiltration) to achieve either
comparing different techniques. Trials of sufficient almost pure diffusive clearance or a mixture of diffusive
statistical power are difficult to conduct and may never and convective clearance.
Renal Failure and Support 313
No matter what technique is used, the following anticoagulation is very effective but requires a special
outcomes are predictable: dialysate or replacement fluid. Regional heparin/protamine
● Continuous control of fluid status anticoagulation is also somewhat complex but may be
● Hemodynamic stability useful if frequent filter clotting occurs and further anti-
● Control of acid–base status coagulation of the patient is considered dangerous.
● Ability to provide protein-rich nutrition while Low-molecular-weight heparin is also easy to give but
achieving uremic control more expensive. Its dose must be adjusted for the loss of
● Control of electrolyte balance, including phosphate renal function. This is difficult to monitor. Heparinoids
and calcium balance and prostacyclin may be useful if the patient has devel-
● Prevention of swings in intracerebral water oped heparin-induced thrombocytopenia and thrombosis.
● Minimal risk of infection Finally, in perhaps 10–20% of patients anticoagulation is
● High level of biocompatibility best avoided because of endogenous coagulopathy or
However, CRRT mandates the presence of specifi- recent surgery. In such patients mean filter lives of >24
cally trained nursing and medical staff 24 hours a day. hours can be achieved provided that blood flow is kept
Small ICUs often cannot provide such level of support. If at about 200 ml/minute and vascular access is reliable.
CRRT is only used 5–10 times a year, the cost of training
may be unjustified and expertise may be hard to main- CLINICAL CAVEAT
tain. Furthermore, depending on the organization of
patient care, CRRT may be more expensive that IHD. Anticoagulation During Continuous Renal
Finally, the issues of continuous circuit anticoagulation Replacement Therapy
● Anticoagulants should not be used during CRRT
and the potential risk of bleeding have been a major
within 24 hours of surgery. They are unnecessary
concern. and dangerous
● Adequate filter life can be achieved without any
anticoagulation if vascular access is adequate and
Anticoagulation During Continuous
blood flow is kept at 200 ml/minute or above
Renal Replacement Therapy
Anticoagulants are frequently used during CRRT.
However, circuit anticoagulation increases risk of Particular attention needs to be paid to the ade-
bleeding. Therefore, the risks and benefits of more or quacy/ease of flow through the double-lumen catheter.
less intense anticoagulation and alternative strategies Smaller (11.5 Fr) catheters in the subclavian position are
(Box 29-4) must be considered. a particular problem. Larger catheters (13.5 Fr) in the
In the vast majority of patients low-dose heparin femoral position appear to function more reliably.
(< 500 IU/hour) is sufficient to achieve adequate filter
life, is easy and cheap to administer, and has almost no
CASE STUDY
effect on the patient’s coagulation tests. In some patients
a higher dose is necessary. In others (pulmonary Continuous Renal Replacement Therapy after
embolism, myocardial ischemia) full heparinization may Cardiac Surgery
actually be concomitantly indicated. Regional citrate A 46-year-old man undergoes pericardectomy for
constrictive pericarditis. He has a renal transplant with
chronic rejection, and a BUN of 70 mg/dl. The
operation is complicated by severe intraoperative
Box 29-4 Strategies for Circuit bleeding from the pericardial bed. Such oozing
Anticoagulation During continues postoperatively at a rate of 300 ml/minute.
Continuous Renal Despite 5 units of fresh frozen plasma, 3 units of blood,
Replacement Therapy and 5 units of platelets intraoperatively, his INR is
2.5, APTT is 56 seconds, HB is 7 g/dl, and platelet
count is 56,000/mm3. The surgeon does not want to
● No anticoagulation take him back to the operating room because attempts
● Low-dose prefilter heparin (<500 IU/hour) at intraoperative hemostasis have already failed.
● Medium-dose prefilter heparin (500–1000 IU/hour) A normal clotting profile must be urgently restored.
● Full heparinization However, the patient has a pulmonary artery occlusion
● Regional heparin/protamine anticoagulation pressure of 20 mmHg, pulmonary congestion (revealed
● Regional citrate anticoagulation on chest x-ray), a urine output of 20 ml/hour on a
● Low-molecular-weight heparin frusemide infusion at 30 mg/hour, and a PaO2 of
● Prostacyclin 67 mmHg on 70% FIO2.
● Heparinoids
Continued
314 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
CASE STUDY— Cont’d cuprophane are known to trigger the activation of several
inflammatory pathways when compared to high-flux
CLINICAL NEED synthetic membranes (also used for continuous hemo-
Fluid must be removed and clotting factors and filtration). It is possible that such proinflammatory
blood must be given simultaneously while avoiding effect contributes to further renal damage and delays
further pulmonary edema. recovery or even affects mortality. The matter remains
RESPONSE
unresolved.
The limitations of applying “standard” IHD to the
Double-lumen catheter is inserted, and CVVH
treatment of ARF has led to the development of new
started without anticoagulation. Blood flow is 200 ml/
minute, net fluid removal at 1000 ml/hour. Fresh
approaches (so-called “hybrid techniques”) such as SLED
frozen plasma (10 units), cryoprecipitate (10 units), and intermittent extended hemofiltration. These tech-
platelets (20 units), and red cells (6 units) are given niques seek to adapt IHD to the clinical circumstance
over 4 hours. CVVH is continued at 1000 ml/hour for and there by increase its tolerance and its clearances.
4 hours. Net fluid removal was decreased to 300 ml/hour.
Filter clotted at 12 hours. Bleeding stopped at 4 hours.
Gas exchange was markedly better at 12 hours. CURRENT CONTROVERSY
Second filter started without anticoagulation for another
16 hours. Patient was extubated at 28 hours after ICU How Often Should Dialysis Be Done?
admission and discharged from ICU at 38 hours. ● A randomized controlled trial has shown that daily
dialysis increases survival and improves the rate of
CONCLUSION renal recovery in ICU patients
CRRT without anticoagulation is safe and effective ● Second daily conventional dialysis is inadequate
after surgery and can help save lives. therapy for critically ill patients
Aminoglycosides Normal dose q 36 hours 50% normal dose q 48 hours – 2/3 redose after IHD
Cefotaxime or ceftazidime 1 g q 8–12 hours 1 g q 12–24 hours after IHD
Imipenem 500 mg q 8 hours 250 mg q 8 hours and after IHD
Meropenem 500 mg q 8 hours 250 mg q 8 hours and after IHD
Metronidazole 500 mg q 8 hours 250 mg q 8 hours and after IHD
Co-trimoxazole Normal dose q 18 hours Normal dose q 24 hours after IHD
Amoxycillin 500 mg q 8 hours 500 mg daily and after IHD
Vancomycin 1 g q 24 hours 1 g q 96–120 hours
Piperacillin 3–4 g q 6 hours 3–4 g q 8 hours and after IHD
Ticarcillin 1–2 g q 8 hours 1–2 g q 12 hours and after IHD
Ciprofloxacin 200 mg q 12 hours 200 mg q 24 hours and after IHD
Fluconazole 200 mg q 24 hours 200 mg q 48 hours and after IHD
Acyclovir 3.5 mg/kg q 24 hours 2.5 mg/kg/day and after IHD
Gancyclovir 5 mg/kg/day 5 mg/kg/48 hours and after IHD
Amphotericin B Normal dose Normal dose
Liposomal amphotericin Normal dose Normal dose
Ceftriaxone Normal dose Normal dose
Erythomycin Normal dose Normal dose
The values represent approximations and should be used as a general guide only. Critically ill patients have markedly abnormal volumes of distribution for these agents
which will affect dosage. CRRT is conducted at variable levels of intensity in different units also requiring adjustment. The values reported here relate to CVVH at
2 l/hour of ultrafiltration. Vancomycin is poorly removed by CVVHD. IHD may also differ from unit to unit. The values reported relate to standard IHD with low-flux
membranes for 3–4 hours every second day.
316 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Bellomo R, Kellum JA, Wisniewski SR, Pinsky MR: Effects of Mehta R, Dobos GJ, Ward DM: Anticoagulation procedures
norepinephrine on the renal vasculature in normal and in continuous renal replacement. Semin Dial 5:61–68,
endotoxemic dogs. Am J Respir Crit Care Med 1992.
159:1186–1192, 1999. Ronco C, Bellomo R, Homel P et al: Effects of different doses in
Bellomo R, Ronco C: Adequacy of dialysis in the acute renal continuous veno-venous haemofiltration on outcomes of
failure of the critically ill: the case for continuous thera- acute renal failure: a prospective randomized trial. Lancet
pies. Int J Artif Organs 19:129–142, 1996. 355:26–30, 2000.
Bonventre JV: Mechanisms of ischemic acute renal failure. Ronco C, Brendolan A, Bellomo R: Current technology for
Kidney Int 43:1160–1178, 1993. continuous renal replacement therapies. In Ronco C,
Cole L, Bellomo R, Silvester W, Reeves JH: A prospective, mul- Bellomo R, editors: Critical Care Nephrology, Dordrecht,
ticenter study of the epidemiology, management and out- The Netherlands: Kluwer Academic, 1998, pp 1327–1334.
come of severe acute renal failure in a “closed” ICU system. Tan HK, Baldwin I, Bellomo R: Hemofiltration without anti-
Am J Respir Crit Care Med 162:191–196, 2000. coagulation in high-risk patients. Intensive Care Med
Davenport A: The management of renal failure in patients at 26:1652–1657, 2000.
risk of cerebral edema/hypoxia. New Horizons 3:717–724, Tepel M, van der Giet M, Schwarzfeld C et al: Prevention of
1995. radiographic contrast agent-induced reductions in renal
Gettings LG, Reynolds HN, Scalea T: Outcome in post- function by acetylcysteine. N Engl J Med 343:180–184,
traumatic acute renal failure when continuous renal 2000.
replacement therapy is applied early vs. late. Intensive Tetta C, Mariano F, Ronco C, Bellomo R: Removal and gener-
Care Med 25:805–881, 1999. ation of inflammatory mediators during continuous renal
Marshall MR, Golper TA, Shaver MJ, Chatoth DK: Hybrid renal replacement therapies. In Ronco C, Bellomo R, editors:
replacement modalities for the critically ill. Contrib Critical Care Nephrology, Dordrecht, The Netherlands:
Nephrol 132:252–257, 2001. Kluwer Academic, 1998, pp 1239–1248.
30
CHAPTER Urologic Concerns
in Critical Care
RALPH MADEB, M.D.
CRAIG NICHOLSON, M.D.
ALI BORHAN, M.D.
ERDAL ERTURK, M.D.
EDWARD M. MESSING, M.D.
317
318 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
CLINICAL CAVEAT
Urethral Catheterizations
● Catheter size is usually referred to using the French
scale (1 Fr = 0.33 mm in diameter). Therefore an
18 F catheter is approximately 6 mm in diameter.
● Usually an 18 F Foley is recommended for male
patients and a 16 F Foley is recommended for
female patients.
● A large 22 or 24 F three-way Foley should be placed
for patients who have gross hematuria and are at risk
from obstructing clots resulting in the need for manual
clot evacuation or continuous bladder irrigation.
● Coudé or curved tip catheters are specifically
designed to help bypass areas of the male urethra
that are difficult to negotiate such as the prostatic
urethra in a patient with prostatic enlargement.
● Difficulty in catheterizing the male patient can result
from various causes including BPH or prostatic
adenocarcinoma, urethral strictures (including urethra
meatal stenosis, and bladder neck contractures).
If the initial attempt for Foley placement has failed
in a patient who has a history of or is suspected of
having one of the above mentioned pathologies,
further attempts at catheterization should be avoided
and urology consulted for urethral evaluation and
placement.
Figure 30-3 Proper positioning of a female patient in the frog-leg position for urethral catheterization. (Used with permission from Han M:
Urological procedures. In Chen H, Sonnenday CJ, editors: Manual of Common Surgical Procedures, ed 2, Philadelphia: Lippincott Williams
and Wilkins, 2000, pp 205–236.)
cystoscope can be passed under direct vision into the created by a scissors or scalpel blade. Alternatively, a
bladder or to the level of the obstruction where a guide Council-tipped catheter, a Foley catheter manufactured
wire can be placed through the compromised urethral with a smooth edged hole at the tip, can be used if avail-
lumen into the bladder through the working port of the able. The lubricated catheter is then passed over the
cystoscope. After visualizing the wire in the bladder the guide wire into the bladder. When urine drains the bal-
flexible cystoscope is withdrawn making sure not to loon is inflated and the guide wire is withdrawn. Patient
remove the guide wire simultaneously from the bladder. preparation and equipment is identical to that of urethral
A specialized catheter hole puncher is then used to create catheterization in addition to the equipment needed for
a hole at the tip of a straight urethral catheter (Figure 30-5). cystoscopy, which usually includes a flexible cysto-
The hole punch creates a smooth hole at the tip of the scope, light source with fiber-optical light, 0.035 or
urethral Foley catheter which is much easier to pass 0.038 F flexible tip guide wire (so that the wire does not
through a narrowed urethra than the more jagged opening perforate through the bladder wall), 1 liter of normal saline
or sterile water irrigant, and transurethral resection
(“TUR”) tubing. If the obstruction is caused by a tight
urethral stricture or bladder neck contracture, urethral
dilation may be needed prior to insertion of the Foley
catheter of sufficient luminal size to drain a bladder par-
ticularly if bleeding and clots are anticipated. Dilation is
performed with Heyman serial dilators that are more
rigid than a rubber or latex catheter but still flexible
enough to negotiate urethral curves and bends. Serial
dilations in the bladder (so there is a return of urine) are
done starting at 8 F and increasing by 2 F sizes until a
dilator 2 F sizes larger than the catheter to be placed is
passed. This ensures smooth catheter passage.
If the patient is receiving anticoagulation (e.g., full-
dose heparin) urethral dilation can induce significant
bleeding and should be avoided and alternative access
should be sought. It is important to ensure that the
Figure 30-4 Flexible cystoscope with an attached light source patient does not have an active urinary tract infection as
and a deflectable tip. (From Carter HB: Basic instrumentation and
cystoscopy. In Walsh PC, Retik AB, Vaughan D, Wein AJ, editors: urethral instrumentation can worsen the infection and
Campbell’s Urology, ed 8, Philadelphia: WB Saunders, 2002, make the patient bacteremic and/or uroseptic. If cysto-
pp 111–121.) urethroscopy is needed, the patient should receive
Urologic Concerns in Critical Care 321
Indications Contraindications
Figure 30-6 Stamey percutaneous cystotomy set with obturator and catheter. (From Carter HB: Basic instrumentation and cystoscopy.
In Walsh PC, Retik AB, Vaughan D, Wein AJ, editors: Campbell’s Urology, ed 8, Philadelphia: WB Saunders, 2002, pp 111–121.)
● Start the procedure with positioning and prepping the patient. The patient is placed in the supine position and the
suprapubic area is percussed in order to confirm an adequately distended bladder. If the bladder is not distended the
patient’s bladder can be filled by injecting normal saline through the urethra until the bladder is filled. Using a catheter
tip syringe gently close the distal urethra around the tip to prevent escape of the solution through the urethral meatus.
Alternatively, if available an ultrasound can be used to localize the bladder. This is especially useful in patients who have
had previous abdominal surgery or pelvic irradiation.
● The suprapubic area is shaved, prepped with povidone-iodine solution, and draped in a sterile fashion.
● The percutaneous tract and the surrounding area (2–3 cm above the superior margin of the pubic symphysis in the
midline with a 2 cm radius) should be anesthetized with 1% lidocaine (Figure 30-7). Infiltration of local anesthetic
should reach to the anterior rectus abdominus fascia.
● The catheter of choice (Bonanno or Stamey) is assembled
● For the Bonanno catheter: the disposable catheter sleeve is advanced over the radiopaque catheter thereby straightening
the J of the distal catheter. After the catheter is straightened the 18-gauge needle is inserted into the catheter. Once the
bevel of the needle is seen extending from the end of the catheter, the disposable catheter sleeve is removed.
● For the Stamey catheter: the needle obturator is guided into the catheter tip to stretch and straighten the self-retaining
mechanism of the Malecot catheter. The catheter is then locked in place by turning the Luer lock thereby closing the
Malecot wings.
● An 18–24-guage 5-inch spinal needle with a 10 ml syringe is then inserted perpendicular to the anesthetized skin and
advanced while withdrawing on the syringe (see Figures 30-7 and 30-8). Correct placement is usually 4 cm above the
pubic symphysis in the midline. The needle is usually directed using a 45–60° angle (Figure 30-8). Correct placement of
the needle is confirmed by withdrawing urine into the syringe.
● Some people find it useful to leave the spinal needle in place as a guide.
● The catheter is then placed in the same tract or adjacent to the spinal needle if left in and is inserted into the bladder.
The suprapubic catheter is then advanced until the bladder is punctured and urine will be seen emerging from the
catheter. Once urine is brought forth, the catheter can be advanced another 1–2 cm.
● The next step involves the disengagement of the suprapubic catheter from the obturator and final advancement of the
catheter into the bladder.
● For the Bonanno catheter: the needle is stabilized while the catheter is advanced over it. The catheter should be
advanced until the suture disk lies flush with the skin.
● For the Stamey catheter: the catheter is stabilized and the white hub of the needle obturator is rotated counterclockwise
opening the Malecot wings. The catheter is then fully advanced as with the Bonanno tube. The catheter is then slowly
withdrawn until the Malecot wings meet resistance of the bladder wall.
● Aspirate as needed to confirm correct intraluminal placement (Figure 30-8). The catheter is then secured to the skin
with permanent suture (2-0 silk or nylon suture can be used). The tube is then attached to the urinary drainage bag
utilizing a gentle curve so that it is not kinked. Abdominal fixation in multiple sites may be necessary to avoid kinking.
Urologic Concerns in Critical Care 323
Figure 30-7 Localization of the bladder with a spinal needle placed percutaneously above the pubic bone (left). Placement of a percuta-
neous cystotomy catheter with obturator (right). (From Carter HB: Basic instrumentation and cystoscopy. In Walsh PC, Retik AB, Vaughan D,
Wein AJ, editors: Campbell’s Urology, ed 8, Philadelphia: WB Saunders, 2002, pp 111–121.)
transient hematuria, and leakage around the catheter distended with the patient placed in the Trendelenburg
site. Bowel injury is the most feared complication. If position thereby displacing any loops of bowel that
bowel is entered, one may exchange the needle and encroach on the dome of the bladder. Ultrasound guid-
continue with the procedure. In order to minimize ance is also helpful in preventing injury to the bowel.
bowel injury, the bladder should be adequately Transient hematuria is also common with suprapubic
catheter placement. If the bladder is filled with clots emergent percutaneous drainage. Under semi-urgent and
there is a possibility for the smaller catheters to become elective tube placement the following contraindications
obstructed. This can usually be relieved with gentle irri- for percutaneous nephrostomy tube placement exist:
gation of the catheter with normal saline. Leakage around uncorrected coagulopathy, hyperkalemia (>7 mEq/l),
the catheter may indicate catheter damage or plugging, urothelial neoplasms, and anatomical variations that may
obstruction, bladder spasms, or that the tube has become preclude the procedure. However, there are many times
partially dislodged where some holes are in the bladder when urgent tube placement is performed in light of
and others are intramucosally located, or even outside these relative contraindications as in the situation in
the wall of the bladder. Administration of antimuscarinic which drainage may be necessary to reverse intravascu-
agents such as oxybutynin or tolterodine can assist with lar coagulopathy arising from urosepsis.
reducing bladder spasms. In most centers, percutaneous nephrostomy tube
placement is performed in an interventional radiology
suite. Patients must be hemodynamically stable enough
Percutaneous Nephrostomy Catheter to lie prone for roughly one hour. In ICU patients this
A percutaneous nephrostomy tube is an alternative often requires nursing and respiratory staff to accompany
method of gaining access to and diverting urine away them for the procedure. Under conscious sedation, fluo-
from (or simply draining) the urinary system. Originally, roscopic or computed tomography (CT) guidance is used
percutaneous tube placement was considered to be a with the administration of intravenous contrast to visualize
substitute for surgical nephrostomy in critically ill the opacified collecting system. Alternatively, ultrasound
patients or as a temporizing measure prior to definitive guidance can also be used in patients with contrast allergy,
surgery. With advancement of percutaneous experience pregnant women, or patients with high-grade obstruction
and instruments and improved radiographic imaging, necessitating urgent decompression. Usually an 8 to 10 F
the clinical benefits of percutaneous access to the renal catheter is placed for urgent decompression with larger
collecting system have been expanded (Table 30-3). tubes reserved for drainage of thick, purulent, or bloody
Frequently in the ICU setting patients have postrenal fail- material. The technique is performed by placing a needle
ure and develop hydronephrosis secondary to supravesical or catheter-sheathed needle into the pelvicaliceal system
ureteral obstruction. Moreover, patients in the ICU who via a translumbar approach (Figure 30-9). The needle
have multiple medical comorbidities can develop should not go directly into the renal pelvis, but instead go
supravesical obstruction with primary or superimposed first through the renal cortex, because the decompressed
renal infection, leading to urosepsis, which requires renal pelvis is often too flimsy in its own right to permit
the somewhat firm tube in place. After radiographic
(fluoroscopic) confirmation of needle placement is
obtained, a J-shaped guide wire is then passed through
Table 30-3 Indications and Applications of the needle into the renal pelvis and the needle or sheath
Percutaneous Nephrostomy Tube is pulled out, leaving the guide wire in place. The tract
is then serially dilated with a 6 to 10 F Teflon fascial dila-
Obstruction
tor and a pigtailed 8 F catheter is passed through the dila-
Pyonephrosis
Acute and obstructive pyelonephritis tor into the renal pelvis. Because this provides direct
Renal or ureteral calculi access to the upper collecting system, urine for culture
Fungus ball or sloughed papillae and/or cytology can be obtained simultaneously. The
Renal abscess, urinoma, lymphocele tube is then locked in place causing the tube to curl or
Obstructing neoplasms
pigtail in the renal pelvis, and is then sutured to the skin
Diversion
Urinomas (Figure 30-10). Urinary drainage is ensured by the multi-
Fistula and fibrosis ple side holes in the pigtail portion of the nephrostomy
Infection and abscesses tube which resides within the renal pelvis.
Functional assessment Complications of nephrostomy tube placement include
Oliguria and azotemia
bleeding, worsening or development of urosepsis, pneu-
Renal salvage
Collecting system access mothorax or hemothorax, and bowel, vascular (e.g., infe-
Stricture dilation rior vena cava or major renal vessels), or visceral injury. If
Culture, biopsy, and cytology access to the necessary calyx is over the twelfth rib there
Stent placement is an increased chance of lung and splenic injury, pneu-
Calculus therapy
mothorax, and hemothorax. As with all other surgical
Drug instillation
Nephroscopy procedures any coagulopathy must be corrected and an
Intrarenal surgery adequate platelet count is needed prior to percutaneous
tube placement.
Figure 30-9 Typical patient position during percutaneous nephrotomy placement in an interventional radiology suite. (From McDougall EM,
Liatsikos E, Dinlenc CZ, Smith AD: Percutaneous approaches to the upper urinary tract. In Walsh PC, Retik AB, Vaughan D, Wein AJ, editors:
Campbell’s Urology, ed 8, Philadelphia: WB Saunders, 2002, pp 3320–3360.)
Figure 30-10 Self-retaining nephrostomy tube in place. A, Diagram of a standard self-retaining nephrostomy tube in place with the tip coiled
in the renal pelvis. This catheter has a string that forces it to maintain its pigtail configuration. B, Radiograph demonstrating the typical radio-
graphic appearance of a standard self-retaining percutaneous nephrostomy catheter. (From Zagoria RJ, Tung GA: Interventional genitourinary
radiology. In Zagoria RJ, Tung GA, editors: Genitourinary Radiology – The Requisites, ed 1, St. Louis: Mosby-Year Book, 1997, pp 371–399.)
326 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
than nephrostomy tube placement. Moreover, they cite the percutaneous nephrostomy group, which was half as
the decreased risk of major complications such as hemor- costly as stent placement. As expected, this was largely
rhage, pneumothorax, and visceral injury that exists with due to the higher costs of anesthesia, the operating
percutaneous nephrostomy tube placement. Table 30-5 room, and its staff. Patient satisfaction was also evaluated
reviews the advantages and disadvantages of ureteral stent using a visual analog pain scale. Flank pain was noted to
versus percutaneous nephrostomy for drainage of an be greater in the nephrostomy tube arm with the need for
obstructed upper urinary tract. a significantly increased amount of parenteral narcotics.
As seen from Table 30-5, the choice for drainage is This result was probably confounded by the general anes-
controversial since each procedure has significant thesia and pain medication received in the operating
advantages and disadvantages. Despite strong arguments room in the stent group. Finally, there was no significant
on both sides of the controversy, only two prospective, difference between the duration of pain medication
randomized studies have directly compared the efficacy needed after the procedure between the two groups.
of both drainage procedures for decompression of an The authors concluded that the choice of drainage can
obstructed, infected urinary system. The first trial was be individualized according to the patients and institu-
performed by Pearle and colleagues, who randomized tional characteristics.
42 patients presenting with acute urinary tract obstruc- The second study was performed by Mokhmalji and
tion with signs and symptoms of infection due to ureteral associates who randomized 40 patients with stone-
calculi to either percutaneous nephrostomy placement induced hydronephrosis to either percutaneous nephros-
or cystoscopic ureteral stent placement. There was one tomy tube or ureteral stent placement. Unlike the Pearle
treatment failure in the percutaneous nephrostomy arm, study, only 65% of the patients had signs and symptoms
which was salvaged by ureteral stent placement. Neither of infection. The rest of the patients had a procedure
treatment modality demonstrated superiority in promoting done for other reasons including persistent renal colic,
a more rapid recovery from acute obstruction after elevated creatinine, and the presence of large obstruct-
drainage. The two treatment arms were comparable with ing calculi. In this study all patients in the nephrostomy
regard to time to clinical improvement including nor- group had successful nephrostomy tube placement, while
malization of temperature, time to normal white blood only 80% of the stent patients randomized to stent place-
cell count, and length of hospital stay. Procedure and ment were able to be successfully stented. Percutaneous
fluoroscopic time were significantly shorter in the stent tube placement was associated with a significant
group, while cost analysis demonstrated an advantage to decrease in indwelling tube drainage time, with over
Table 30-5 Advantages and Disadvantages of Ureteral Stent versus Percutaneous Nephrostomy Tube
Placement for Upper Urinary Tract Decompression
half of the stented patients and only 20% of the nephros- up to 5% in patients with abdominal trauma. Renal injury
tomy patients requiring an indwelling tube for management has evolved over time as a result of the
4 weeks. In addition, the duration of antibiotic use was increased use of CT scans in the trauma setting. This has
longer in the stented group, although the difference did allowed for better radiologic staging of renal trauma
not reach statistical significance. Unlike the Pearle study, thereby permitting the vast majority of these injuries to
a trend for a reduction in the quality of life was seen in be managed nonoperatively. Nonetheless, certain injuries
the patients with stents compared to those who under- will require surgical management. Overall, the main objec-
went percutaneous nephrotomy tube placement. This tive in dealing with patients with renal trauma is to prevent
was most pronounced for male patients and patients significant hemorrhage while retaining as much kidney
younger than 40 years of age. Other trends seen were a function as possible in order to avoid end-stage renal
shorter x-ray exposure time and decreased analgesic use failure.
in the percutaneous nephrostomy tube arm. Based on The approach to any patient with renal trauma
the findings that the nephrostomy tube arm had a involves assessing whether the cause of the injury is due
shorter indwelling tube time and antibiotic usage as well to penetrating or blunt trauma. This is extremely impor-
as a marginally higher quality of life score, the authors tant, as the management of the injury will be quite
concluded that percutaneous nephrostomy tube place- different. Ninety percent of real injuries occur from blunt
ment was favored over cystoscopic stent placement for trauma including falling from heights, motor vehicle acci-
drainage of an obstructed upper tract. dents, and violent assaults. Most renal injuries occurring
In our opinion, the optimal choice for drainage of an from blunt trauma are minor and rarely, if ever, require
obstructed, infected upper urinary tract remains a matter surgical intervention. Alternatively, penetrating trauma,
of controversy, as the current prospective trials fail to which compromises 10% of patients with renal trauma,
show a clear-cut advantage of either procedure. Currently, requires surgical exploration unless there is definitive
the choice for which procedure we use depends on clinical and radiographic evidence establishing the
multiple factors including patient preference, availability extent of injury. In one study of a level III trauma center,
of a skilled endoscopist or interventional radiologist, only 2% of renal injuries resulting from blunt trauma
patient clinical parameters (which may preclude anes- required surgical intervention. Therefore, nonoperative
thesia), and availability of an operating room. Larger management of renal trauma has been espoused by
prospective, randomized trials with adequate patient multiple level III trauma centers that have significant
numbers and ability to perform subgroup analyses are experience managing kidney injuries.
awaited.
Physical Examination
Initial work-up of renal trauma follows the same
NONOPERATIVE MANAGEMENT assessment and resuscitation algorithms as established by
OF GENITOURINARY TRAUMA the American College of Surgeons Trauma Life Support
program (ATLS). After assessing for adequate airway,
Although recent developments of trauma systems and breathing, circulation, disability, and exposure, as out-
centers have contributed to the declining rates of mortal- lined by the well-known mnemonic “ABCs of trauma,” a
ity from major traumatic injuries, the best care provided more detailed physical examination to assess for renal
to a patient with polytrauma comes from the organized trauma can be performed. External evaluation of the
team of specialists including members of the trauma abdomen, back, and chest should be performed as
ICU. As trauma to the genitourinary tract occurs in 10% abdominal and flank tenderness, contusions and abdom-
of all serious traumatic injuries the urologist is a critical inal and flank ecchymosis, lower rib fractures, and pen-
member of this team. In the majority of cases traumatic etrating wounds of the upper abdomen, flank, and lower
injury to the genitourinary tract when encountered in an thorax have all been associated with renal trauma. A
ICU setting will be managed nonoperatively. The follow- palpable flank mass should cause the evaluating exam-
ing sections discuss the nonoperative management of iner to suspect retroperitoneal and renal injury.
renal, bladder, and urethral injury. Injuries to the ureter, Urinalysis should be quickly performed in patients
testicles, and penis are not included as in the majority of suspected of having renal injury. Hematuria (macro- and
cases they are operatively managed. microscopic) is the most common sign of penetrating
and blunt renal trauma. It has been estimated that dip-
stick urinalysis can detect the presence or absence of
Renal hematuria in over 97% of cases. A key point to remem-
Out of all injuries to the genitourinary tract, renal ber is that the presence and amount of hematuria does
injuries are the most common. It has been estimated that not correlate with the degree of renal trauma. Moreover,
renal trauma occurs in 1–3% of all trauma patients and the absence of hematuria does not preclude renal injury
Urologic Concerns in Critical Care 329
as its absence has been reported in 25–36% of patients the status of the renal vascular pedicle. Furthermore, they
with thrombosis of the renal artery and in 33% of provide information about the contralateral kidney and
patients with ureteropelvic junction injury. If urine is the extent of devitalized renal parenchyma, and the state
microscopically analyzed the presence of greater than of neighboring viscera which are important factors needed
5 red blood cells per high-powered field indicates the when a management plan is being formulated. Thus, CT
possibility for renal trauma. The presence of hematuria scans have replaced intravenous pyelography as the
in patients presenting to a trauma center usually signifies primary modality for the assessment of renal injuries.
a significant renal injury with estimated rates of grade IV Indications for radiographic imaging in patients with
and V injuries around 25%. abdominal trauma include:
● All patients with penetrating injuries to the flank,
Imaging and Radiographic Staging abdomen, and lower back
Patients that have hematuria and are stable enough to ● Blunt trauma associated with gross hematuria
undergo imaging can safely be staged with a radiographic ● Microscopic hematuria with and without shock or a
procedure. The different imaging modalities that have been positive diagnostic peritoneal lavage
used to assess the extent of renal injury include contrast- The advances of current CT scanners have con-
enhanced CT scan, intravenous pyelography, angiography, tributed to the highly accurate organ injury grading scale
retrograde pyelography, ultrasonography, radionuclide of renal injuries developed by the American Association
scintigraphy, and magnetic resonance imaging (MRI). With for Surgery of Trauma (AAST). The scale classifies renal
the advance of CT scanners, CT scan is the procedure of injuries into five grades which correlate with patient out-
choice to detect renal injury in the trauma setting. CT come and permit selective management to be undertaken
scans are noninvasive, readily available in most trauma (Figure 30-11). Moreover, the scale has been prospec-
centers, and can rapidly and accurately detect the sever- tively validated and found to correlate directly with the
ity and depth of renal injuries, the presence of urinary need for surgical intervention. Table 30-6 reviews the
extravasation and perirenal hemorrhage, and determine renal injury scale. Overall, grade I injuries are subcapsular
Figure 30-11 Classification of renal injuries by grade based on the organ injury scale of the American Association for the Surgery of
Trauma. (From McAninch JW, Santucci RA: Genitourinary trauma. In Walsh PC, Retik AB, Vaughan D, Wein AJ, editors: Campbell’s Urology,
ed 8, Philadelphia: WB Saunders, 2002, pp 3707–3744.)
330 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Table 30-6 Renal Injury Scale of the American Association for Surgery of Trauma
hematomas and renal contusions, while grade II injuries diligent follow-up with routine hematocrit or hemoglo-
are small parenchymal lacerations into the renal cortex. bin checks (e.g., hemoglobin checks every 6 hours for
Grade III injuries are parenchymal lacerations that extend 48 hours while vital signs are stable, which can then be
through the corticomedullary junction, and grade IV tapered to every 12 hours and then once a day) and a
injuries are those that involve the collecting system and/or repeat CT scan 3–7 days after the injury to evaluate for
vascular injuries with contained hemorrhage. Grade V size of the hematoma, urinary extravasation, and perfu-
injuries are completed shattered kidneys and pedicle sion of the kidney laceration or fragment. It is also criti-
avulsions of the great vessels. cal to obtain delayed images in order to ensure that the
contrast can be seen flowing through the renal pelvis
Nonoperative Management and down the ureter. Between 3 and 7 days after the
Fortunately, the vast majority of renal injuries are con- original insult, marginally perfused kidney lacerations
tusions or minor lacerations which are now adequately and fragments that can recover will appear as recovering
staged with the increased use of CT scanners in the while devitalized tissue will become more apparent.
trauma setting. Significant injuries (grades II–V) have Furthermore, minor urinary extravasation will disappear
been estimated to occur in only 5.4% of renal trauma by this time, while larger leaks will become more readily
cases. Most trauma surgeons and urologists would agree identified. These can be controlled either by percuta-
that grades I and II renal trauma are managed nonopera- neous nephrostomy tube placement or internal ureteral
tively and only require conservative management. stent placement. It is also important to realize that
Extensive perirenal and large subcapsular hematomas expectant management does not invariably lead to non-
rarely require surgery. These hematomas become organ- surgical management and active monitoring can indicate
ized and eventually reabsorb in a 2–3 month period. when conservative management has failed. Therefore
Periodic CT scan with frequent creatinine evaluations on the urologist should be actively involved with the ICU
an outpatient basis can ensure the hematoma is resolving team in the patient’s progress and the possibility for sur-
with no damage occurring to the affected kidney. With gical intervention. Indications for deferred open surgical
appropriate and radiologically confirmed staging of treatment are recurring or persisting related bleeding
grades III–V renal trauma there is controversy as to what particularly with hemodynamic instability despite ade-
is the most appropriate method of management. The only quate fluid resuscitation, and secondarily infected
absolute indication for surgical exploration is massive life- hematomas that have to be evacuated and surgically
threatening hemorrhage from a macerated and severely drained. A summary algorithm for initial nonoperative
injured kidney (grade V renal trauma). Consequently, management of renal trauma is shown in Figure 30-12.
there are multiple reports from many trauma centers that
show appropriately staged blunt and penetrating renal
injuries can undergo selective nonoperative manage- Bladder
ment, including major lacerations and some collecting Bladder injuries in trauma patients usually occur from
system injuries. a blow to the abdomen when the bladder is distended
The nonoperative course of a ruptured (grade III or IV) (mostly from motor vehicle accidents, crushing injuries,
kidney requires strict hemodynamic monitoring and falls, or violent blows to the lower abdomen) or in
Suspected renal
trauma
Observation
Observe with selective
renal exploration
Figure 30-12 Decision-making algorithm for adult patients with renal injuries.
332 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
combination with pelvic fractures. In these cases the and the bladder is well healed. If the bleeding does not
normal protective barrier of the pelvic ring is lost and clear during this three-week time period or if multiple
the shearing forces of the injury may tear the bladder clots are formed not allowing for adequate urinary
from its attachments. It has been estimated that in drainage, conservative management should be aborted
greater than 80% of patients with bladder injuries there and surgical correction undertaken. In general, all
is an associated pelvic fracture. Although rare, penetrat- intraperitoneal and penetrating wounds to the bladder
ing and blast injuries can injure the bladder during gun- need to undergo prompt surgical correction. A summary
shot wounds to the lower abdomen. algorithm for nonoperative management of bladder and
urethral trauma is shown in Figure 30-13.
Physical Examination and Radiologic Imaging
Gross hematuria (95%) is the hallmark finding in blad-
der injury. In addition the patient may also complain of Urethra
suprapubic tenderness. If there is a concomitant urethral Traumatic injuries to the urethra resulting from exter-
injury (see below) there may be blood at the urethral nal trauma are the most devastating and debilitating
meatus or a history of an inability to urinate. Definitive injuries of the lower urinary tract. The potential compli-
diagnosis of a bladder laceration can be obtained by con- cations of urethral trauma are associated with consider-
ventional cystography or CT cystography. Conventional able long-term morbidity including incontinence,
cystography uses conventional x-rays or fluoroscopy, impotence, strictures, and fistula formation. The reported
while CT cystography can be performed during the incidence of urethral injury with pelvic fracture in the
abdominal and pelvic CT scan performed for evaluation world literature ranges from 1.6 to 25% (mean 10%)
of other organ injuries. We routinely perform CT cysto-
graphy in our center as it is quick and does not need an
additional trip to the radiology suite after CT scans are
obtained for nonurologic reasons. It is important to
remember that the bladder needs to be distended ade-
quately in order to show bladder leakage; an inadequately
distended bladder can cause a false negative result. The
procedure is usually done by using retrograde filling of
the bladder with a minimum of 350 cm3 of diluted con-
trast (5%) and axial images are obtained through the
pelvis. If urethral injury is suspected a retrograde ure-
throgram should first be performed to rule out urethral
damage. It is crucial that even with CT scans, images also
be obtained after the bladder is completely drained to
make sure that no extravesical pooling of contrast is
identified. With conventional cystography, oblique and
lateral images during filling and after drainage are also
mandatory. The adequacy of cystography for the diagno-
sis of traumatic bladder injury has varied in different
studies from 85 to 100%. To achieve a high degree of
accuracy careful attention to proper technique must be
performed. Radiologically, bladder injuries can be classi-
fied as being extra- or intraperitoneal depending if the
rupture is in the peritoneum or not. Intraperitoneal rup-
tures account for one-third of major bladder injuries,
while two-thirds are extraperitoneal or combined.
Nonoperative Management
Extraperitoneal bladder ruptures are the most fre-
quent type of bladder injury and can usually be conserv-
atively managed by urinary catheter drainage. These
injuries are usually handled by placing a Foley catheter Figure 30-13 Decision-making algorithm for patients with
pelvic fracture and suspected bladder or urethral injury, or both.
(see Box 30-1 and Figures 30-1–30-3) for 10–21 days (From McAninch JW, Santucci RA: Genitourinary trauma. In
allowing the bladder to heal. Afterwards a cystogram is Walsh PC, Retik AB, Vaughan D, Wein AJ, editors: Campbell’s
performed in order to ensure that any leakage has ceased Urology, ed 8, Philadelphia: WB Saunders, 2002, pp 3707–3744.)
Urologic Concerns in Critical Care 333
with 66% of them being complete posterior urethral adequately staged with the increased use of CT
ruptures. The primary aim in the management of posterior scanners in the trauma setting.
urethral disruption is the re-establishment of a continuous ● Most renal injuries are conservatively managed with
urinary tract while minimizing the incidence of long-term serial hemoglobin or hematocrit checks and delayed
complications. Double vertical fractures, fractures and dis- reimaging.
locations involving the pubic symphysis, and Malgaigne’s ● Extraperitoneal bladder ruptures are the most
fractures (fracture through the ipsilateral ischiopubic frequent type of bladder injury and can be
rami or pubic symphysis and usually associated with mas- conservatively managed by urinary catheter drainage
sive posterior disruption through the sacrum or ilium) for 10–21 days. Afterwards a cystogram is
performed in order to ensure that any leakage has
are among the fractures associated with highest incidence
ceased and the bladder is well healed.
of urethral trauma.
● Traumatic injuries to the urethra resulting from
external trauma are the most devastating and
Physical Examination and Radiologic Imaging debilitating injuries of the lower urinary tract.
Clinically, urethral disruption is suspected by the ● Clinically, urethral disruption is suspected by the
triad of blood at the urethral meatus, inability to urinate triad of blood at the urethral meatus, inability to
with a palpable full bladder, and a high-riding prostate urinate with a palpable full bladder, and a high-
on digital rectal examination. When blood at the meatus riding prostate.
is discovered or these clinical symptoms suggest urethral ● Currently, the most widely accepted approach in
disruption it is mandatory to perform a retrograde ure- the management of posterior urethral disruption is
throgram to rule out urethral disruption. If the contrast initial immediate placement of suprapubic catheter
and delayed repair in order to re-establish urethral
does not leak and makes its way into the bladder in a
continuity under controlled circumstances.
retrograde manner without evidence of extravasation, a
urethral catheter can be placed. If urethral disruption is
suspected, a urethral catheter is not inserted to avoid
converting a partial rupture into a complete one and a
SELECTED READING
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operative management of blunt grade 5 renal injury. J Urol
Nonoperative Management 164(1):27–31, 2000.
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controversial and still remains unresolved, mainly due to microscopic hematuria in patients with blunt renal trauma.
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31
CHAPTER Trauma: The Golden
Hour, Principles of
Assessment, and
Resuscitation
MARC J. SHAPIRO, M.D., F.A.C.S., F.C.C.M.
The Golden Hour emergency room, lethality is uniform. The second group
Primary Survey (35%) are those that arrive in the emergency department
Secondary Survey (ED) and require aggressive evaluation and therapy.
Tertiary Survey These patients will be discussed as part of the term
Ancillary Studies “golden hour” below. The third mode of death (20%)
Resuscitation occurs days or weeks after admission in patients who
Monitoring usually reside in the ICU. These patients progress to
The Elderly Trauma Victim severe sepsis, hypotension, and even multiple organ fail-
ure before succumbing to death. In the following sec-
The field of trauma, or injury, is continuously evolv- tions on trauma assessment and resuscitation, methods
ing as knowledge is gained into therapeutic manage- of care are discussed so as to prevent the progression to
ment. Currently trauma is the leading cause of death in this most serious of clinical conditions.
the USA of individuals under 44 years of age and the
fourth leading cause of death overall. Of the approxi-
mately 60 million injuries annually occurring in the USA,
THE GOLDEN HOUR
half, or 30 million, require some form of medical care.
About 12% of these injured patients, or 3.6 million, require
CLINICAL CAVEAT
hospitalization, with many of these patients residing in
the intensive care unit (ICU). Approximately 9 million of The Golden Hour
these injuries lead to various types of disabilities, with ● Try to be thorough but expeditious
450,000 being serious and permanent, such as paraplegia. ● Do not spend too much time in the radiology
In the USA 150,000 victims die as a result of their injury; department
thus there is a 3:1 ratio of permanent disability to death. ● Hemodynamically labile patients need
Fifty one percent of all injury deaths are a result of motor expeditiously to have determined the etiology
vehicle crashes in the USA. The annual cost related to of hypotension and have it treated. This may
trauma is over $400 billion annually and is in part involve moving the patient to the operating
accounted for by medical expenses, lost wages, insurance- room, ICU, or interventional radiology
related costs, property damage, fire loss, employer costs,
and indirect loss from work-related injuries.
There is a trimodal distribution of death due to When the term “golden hour” was first utilized and
trauma. Early or immediate death (45%) occurs at the popularized by R. Adams Cowley, one of the founders of
scene of the incident and is related to a devastating and MIEMS, the Maryland Institute of Emergency Medical
catastrophic injury such as cerebral herniation, aortic Services, in Baltimore in 1963, the approach to the
transection, or cardiac rupture. Other than preventive trauma patient was relatively straightforward, with a
measures, there is little medically that can be done. limited number of diagnostic tests available as part of the
Although rapid transport from the scene has allowed initial evaluation. Most trauma centers try to adhere to
some of these patients to arrive in extremis in the this concept; however, frequently those seriously ill
337
338 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
blood sugar, type, and cross for 4–6 units of packed ● Massive hemothorax
cells, prothrombin time (international normalized ratio), The algorithm “ABCDE” has been used for the pri-
partial thromboplastin time, amylase for blunt trauma, mary survey. Coincident with the drawing of laboratory
and drug and alcohol screen when appropriate. studies, the airway of the patient needs to be assessed.
However, the role of clinical laboratory values in assist- If there is evidence of respiratory insufficiency or hypox-
ing in the management of patients early on in their resus- emia, an airway needs to be established. Acutely a
citation may be misleading. Even though the hematocrit nasopharyngeal or oral airway may not be enough to
may be normal early on after the injury, it may be ele- allow the patient to maintain a patent airway or to clear
vated due to dehydration from the environment or as a secretions and endotracheal intubation is necessary.
result of polyuria from an intoxicated patient. The hema- Although the prehospital support population is begin-
tocrit may also be low due to the effects of dilution from ning to get away from rapid sequence intubation (RSI),
the resuscitation. However, a low hematocrit in the it is still popular in the emergency room. Box 31-1 pres-
acute setting implies that there is blood loss and blood ents one formula used with preoxygenation on 100%
should be given. The white blood cell count is also ele- oxygen.
vated after injury due to the demargination of leukocytes
from the effects of cortisol, glucagon, and epinephrine.
The inability to normalize elevated lactate, correct a sig- CLINICAL CAVEAT
nificant base deficit, or correct a metabolic acidosis is a
poor prognostic sign. An arterial blood gas can be bene- Primary Survey and the ABCs
ficial, although this requires another puncture. Once the ● Airway with cervical spine control
● Breathing
laboratory values are obtained, fluids, as discussed
● Circulation with hemorrhage control and cardiac care
below, can be given. ● Disability with rapid neurologic evaluation
The role of gastric tonometry to guide resuscitation ● Exposure of the patient without inducing hypothermia
remains unfounded due to its limitations to distinguish ● Resuscitate, draw serum chemistries, place a gastric
between intramucosal carbon dioxide and that residing and bladder drainage tube if no contraindication
within the gastric lumen. There also remains debate as to
Trauma: The Golden Hour, Principles of Assessment, and Resuscitation 339
Neurologic Evidence-Based Recommendations box.) blood is present at the meatus or there is concern due
Other recommendations included: to a severe pelvic fracture a urethrogram should be per-
● Intracranial pressure (ICP) monitoring in severe head formed. If normal, a Foley catheter can be placed and a
injury with a GCS of 3–8 cystogram should be performed.
● Initiation of therapy at an ICP of 20–25
● Avoidance of hypotension
● Avoidance of hypoxia
Secondary Survey
● Maintenance of cerebral perfusion pressure By convention, the secondary survey, which is a more
> 70 mmHg in-depth evaluation of the entire patient from top to
● Providing 140% of resting-metabolism caloric support bottom and front to back, may then be accomplished,
in nonparalyzed, brain-injured patients (100% in while the patient is in the emergency room. If any life-
chemically paralyzed patients), using feedings that threatening injuries are identified, they should be
contain ≥15% of calories as protein, by the seventh treated. Limb-threatening injuries should also have an
day after injury action plan by this point.
● Consideration of high-dose barbiturate therapy in
CLINICAL CAVEAT
Tertiary Survey
Neurologic Evidence-Based Recommendations
● Recommendation against the use of prophylactic This process identifies and catalogues all injuries
antiseizure medications to prevent LATE post- within 24 hours. Some injuries are identified as a result
traumatic seizures of repeated examinations, clinical suspicions confirmed
● Avoid chronic, prolonged hyperventilation in the by radiography, or other diagnostic modalities. As patients
absence of increased ICP begin to normalize after resuscitation, they may have
● Avoid glucocorticoids in the treatment of severe head new complaints or distracting injuries become less dis-
injury tracting. Additional lacerations and possibly underlying
bony injuries may be discovered. The oral cavity may
reveal loose teeth, which could possibly be aspirated if
The National Acute Spinal Cord Injury Study found dislodged. A mandible fracture may be palpated. Seat
that in traumatic patients a 30 mg/kg bolus of methyl belt marks may become more obvious, raising suspicion
prednisolone followed by 5.4 mg/kg for 24 hours, and for of hollow viscous injury, blunt cervical carotid, or
another 24 hours in those having treatment initiated at brachial plexus injury. As many of these patients arrive
3–8 hours after injury, had an improved functional outcome in the ICU still with a cervical collar in place, laryngeal
although there was an increased incidence of pneumonia fracture as well as clearing of the cervical spine should
and severe sepsis with the 48-hour administration. be accomplished. Figure 31-1 shows one method to try
The “E” in the algorithm is for exposure, in that the to clear the cervical spine early. Occasionally fractures of
patient must be examined front to back and top to bottom the digits, ankles, or even fibula are found at this point.
and in order to do that the anatomy must be available. The hemodynamically labile patient may not be able
Hypothermia is a real concern, however, and patients to be transported safely out of the ICU. Thus high-quality
should remain covered to prevent a loss in temperature. radiographs, computed tomography (CT) scanning, and
Coincident with resuscitation should be gastric multiplanar angiography may have to be delayed or alter-
decompression and bladder decompression. Only after native studies, such as portable radiographs, fluoroscopic
the patient has had a rectal examination, and in the male on-table angiograms, ultrasound, or even diagnostic
there is no evidence of a scrotal hematoma, a high-riding peritoneal lavage, will have to be performed as bedside
prostate, or blood at the urethral meatus, should a Foley procedures.
catheter be inserted. If there are any of these findings, a Depending on the need for neuromuscular blocking
urethrogram should be performed and, if normal, a Foley agents, anxiolytics and analgesics will also alter the
can be placed, followed by a cystogram. Although ure- ability to perform a complete neurologic examination. The
thral injuries in females are rare due to the short length, a level of sedation or somnolence can also be assessed
pelvic examination should be performed and if abnormal through such methods as the Ramsay Scale, allowing for the
Trauma: The Golden Hour, Principles of Assessment, and Resuscitation 341
No neck pain Neck pain No neck pain Neck pain Needs head Does not need
or body CT head CT
No C-spine X-rays in dept No C-spine Keep
Lat, dens, A/P Keep collar on collar on
ED Lat C-spine ED Lat C-spine
swimmers if needed
May remove + swimmers
collar Suspicious Re-examine
CT C-spine or
Dept A/P, dens Dept A/P, dens,
CT C-spine Stable Lat C-spine
Suspicious No
suspicion swimmers
Suspicious No Suspicious
Follow stable Spine May remove
protocol suspicion
consult collar
Spine consult
(flexion-extension) May remove CT
Unstable collar C-spine
resuscitation should continue in the ICU and should artery can also be used. Arterial access allows for con-
include crystalloids and blood early on. The use of albu- tinuous blood pressure monitoring and access for blood
min and hydroxyethylstarch as colloid volume is usually gasses and serum chemistries. However, it has been
initiated in the ICU. These more expensive agents than shown that the presence of an arterial cannula leads to
crystalloids have not been shown to have an advantage increased phlebotomy, so serum chemistries should be
early on in the trauma patient. drawn judiciously with as little blood as possible.
Other agents that have been used with limited suc- Central venous pressure (CVP) may provide a crude
cess with nonsurgical coagulopathic bleeding is factor measure of central pressure. The pulmonary artery
VIIa, which is given in the dose of up to 90 units/kg. catheter is helpful when used early, although its popu-
It works temporarily for a couple of hours, which might larity, even in trauma patients, has diminished. The vol-
be enough to warm and further resuscitate the patient umetric pulmonary artery catheter calculates right
and allow assessment of whatever might be bleeding. ventricular end diastolic volume as a reflection of pre-
As a procoagulant factor VIIa may also cause vascular load. It correlates fairly well with cardiac index and our
thrombosis, but in combat situations has been found to practice is a goal of 120–150 ml/m2. In addition these
stop, albeit temporarily, bleeding. catheters can provide information used to calculate
A human and a bovine blood substitute are currently oxygen delivery and consumption index with goals
undergoing investigation in the trauma setting. One of 150 and 600 ml/minute/m2, respectively. These
thought is to give these compounds in the prehospital catheters are placed in the operating room or the ICU.
setting so as to begin resuscitation with a compound
providing oxygen-carrying capacity early and to cut
down on the number of allogeneic blood transfusions. CURRENT CONTROVERSY
Pulmonary Artery Catheter
Although there are studies showing that right
Monitoring ventricular end-diastolic pressure index correlates well
Once the patient has been placed in the ICU, moni- with cardiac index, others still use pulmonary artery
toring is crucial. There are advantages to getting trauma wedge pressure, oxygen delivery, or oxygen
victims quickly from the ED to the ICU for continued, consumption to guide goal-directed therapy.
aggressive resuscitation. Patients with labile blood pres-
sures may have to bypass departmental radiology studies
such as CT scans or plain films. The latter can be done in If there is no concern of esophageal injury, trans-
the ICU, but foremost is to try to return the patients’ vital esophageal cardiac monitoring can be utilized, providing
signs to their normal physiologic level. Warm fluids rap- information on filling pressures and cardiac perform-
idly given are continued. Pulse oximetry and EKG moni- ance. Transthoracic or transesophageal echocardiogra-
toring are routine as is frequent vital sign recordings. phy can assess preload by evaluating end-diastole cardiac
End tidal CO2 monitoring may also be useful if available. chamber size. However, in most institutions it requires
An arterial line should be placed after ascertaining the specialists to perform the test, and is operator depend-
best location. The radial artery is a common choice if the ent, is variable in reproducibility, must be repeated for
Allen’s test reveals a patent palmer arch. The femoral further evaluations, and is expensive. Esophageal
Doppler sonography, in which an ultrasound probe is
placed within the esophagus and positioned at the level
of the descending thoracic aorta, measures blood flow
CLINICAL CAVEAT velocity to calculate flow. This allows cardiac index
Monitoring determinations on a continuous basis and can help in
● EKG and pulse oximetry monitoring should be done goal-directed therapy.
in the ED Thoracic bioelectric impedance using surface electrodes
● An arterial line can be useful for blood pressure is still being investigated in the ICU setting.
monitoring; however, beware of over-
phlebotomization
● A CVP is a poor method to monitor preload in the The Elderly Trauma Victim
trauma setting
● Less invasive methods of cardiac monitoring such as
The elderly represent the fastest growing segment of
esophageal Doppler can be used successfully as the the population. As one ages there is a decrease in fixed
use of the pulmonary artery catheter is decreasing expiratory volumes over 1 second (FEV1), functional vital
● The utility of bioimpedance is still being evaluated capacity (FVC), FEV1/FVC, and peak expiratory flow rate
(PEFR). These changes all lead to a predictable decrease
344 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
345
346 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
PARTIAL THICKNESS
First degree Epidermis Hyperemic Painful/hypersensitive Scarless within 7 days
Second degree
Superficial Superficial dermis Moist, blistering, blanching Painful/hypersensitive Minimal scarring
hyperemia with rapid capillary refill within 2 weeks
Deep Deep dermis Pale pink or dark red, nonblanching Decreased pinprick Hypertrophic scarring
hyperemia or with delayed sensation, intact in many weeks
capillary refill pressure sensation
FULL THICKNESS
Third degree Entire dermis Dry, pearly-white or leathery Insensate By contracture
Fourth degree Deep tissues Necrotic, with thrombosed vessels Insensate Requires debridement
or amputation
in a reperfusion injury within the burn. This results in Patients with larger burns will have more significant
the formation of oxygen free radicals which can further shock due to the large loss of intravascular volume into
potentiate the tissue injury. the interstitium. This is the reason resuscitation formulas
have been developed to estimate the fluid needs of a burn
victim based on their weight and the %TBSA burned.
PATHOPHYSIOLOGY OF BURN Smoke inhalation injury is present in approximately
SHOCK AND SMOKE INHALATION 20% of burn admissions and increases the mortality asso-
ciated with burns of any size. Inhalation injury is due to
In addition to the local tissue injury, burns also have the inhalation of the chemical products of combustion.
systemic effects. Burns with a percent total body surface There are three main components contributing to the
area (%TBSA) greater than 20% can result in hypovolemic pathophysiology of smoke inhalation. The first of these is
shock or burn shock. There are two main losses of intra- carbon monoxide (CO) toxicity. Carbon monoxide causes
vascular volume in thermal injury victims. First, the a functional anemia, as hemoglobin will preferentially
direct thermal injury to the tissue causes changes in bind CO rather than oxygen (by a factor of 250-fold).
dermal collagen resulting in a hydrostratic vacuum in the The carboxyhemoglobin (COHb) that is formed will shift
burned skin. This effectively draws fluid into the inter- the oxyhemoglobin dissociation curve to the left, thus
stitial space at a significant rate. Obviously, the larger decreasing oxygen delivery to the tissues. Patients can
surface area burned results in a greater loss of fluid into therefore be severely hypoxemic, manifested by a low
the wound. oxygen saturation (SaO2), while maintaining a normal
The second etiology of burn shock is the increase in arterial oxygen tension (PaO2).
microvascular permeability to albumin. In burns with a Cyanide toxicity may also be present. Inhalation of
%TBSA > 20% this increase in permeability occurs through- hydrocyanide, produced when synthetic materials such
out the body in burned and nonburned tissue. An increase as plastics are burned, leads to rapid systemic absorption
in microvascular permeability is observed due to the and binding of the mitochondrial cytochrome a-a3 system,
direct effects of heat as well as the release of factors such thus impairing ATP production and forcing cellular anaer-
as histamine, thromboxane A2, leukotrienes, bradykinin, obic metabolism. Cyanide toxicity should be suspected in
serotonin, and cytokines such as interleukin (IL)-1, IL-6, a patient with a persistent metabolic acidosis despite ade-
and IL-8. These result in a net loss of fluid and protein from quate resuscitation and adequate urine output.
the intravascular to the extravascular space, thus causing Finally, acrolein and aldehyde gases dissolved within
the edema that occurs in the areas of thermal injury (as the smoke are directly toxic to the airway epithelium.
well as the edema that develops in unburned tissue as the When these compounds come into contact with the air-
resuscitation of large burns proceeds). way, the pseudostratified ciliated epithelial cells literally
It is the combination of both hydrostatic forces and fall off the trachea and bronchi, leaving a raw basement
increases in microvascular permeability that produces the membrane. This raw surface then secretes a proteina-
hypovolemic shock observed in thermal injury victims. ceous material which solidifies and forms obstructing
Treating Thermal Injury and Smoke Inhalation 347
airway casts if not removed. Unlike the immediate effects smoke inhalation. Smoke inhalation is highly unlikely in
of carbon monoxide and hydrogen cyanide, the airway patients injured outdoors since the smoke dissipates
damage from acrolein and aldehyde persists until the quickly. Findings that may be associated with inhalation
airway epithelium heals (which can take several weeks). include a history of hoarseness, wheezing, facial burns,
Also, acrolein and aldehyde set off an inflammatory singeing of facial hair, carbon deposits in the oropharynx,
cascade in the airway circulation which affects the lung or carbonaceous sputum. Patients with significant smoke
parenchyma. This results in the development of acute inhalation will have a COHb level of >10%. Chest radio-
respiratory dysfunction syndrome (ARDS). graphy is useless in diagnosing inhalation injury. It is typi-
cally obtained to exclude underlying pulmonary pathology
or evidence of thoracic trauma and therefore should
INITIAL MANAGEMENT PRIORITIES be obtained. A definitive diagnosis of inhalation injury is
made by bronchoscopy; if positive, carbonaceous deposits,
Stop the Burning Process hyperemia, edema, superficial sloughing, and/or ulcera-
tion of the mucosa will be seen below the level of the
The approach to the evaluation and treatment of a burn vocal cords.
patient is similar to that of a trauma patient and, in fact, If there is a suspected CO exposure, 100% oxygen
the patient should be assessed for concomitant trauma. should be administered. Patients with COHb levels <15%
The initial goal should be to stop the burning process. The are frequently asymptomatic and smokers can have
patient’s clothing should be removed and the burn COHb levels of 5–7%. The classic cherry-red skin color is
wounds should be irrigated with cool water. The use of ice rare and can be difficult to evaluate if the skin is burned.
or ice water can cause vasoconstriction and can poten- A baseline COHb level and arterial blood gas should be
tially cause ischemia to the burned skin, thus making the obtained if CO exposure is suspected. Table 32-2 gives
burn deeper. Acid burns cause a coagulation necrosis symptoms associated with varying levels of COHb.
and should be irrigated for at least 30 minutes. Alkali If, despite adequate resuscitation, the patient has a
burns cause liquefaction necrosis and are therefore more progressive metabolic acidosis, cyanide toxicity should
destructive. These types of burns should be irrigated for be expected. Blood cyanide levels of >0.1 mg/l should be
60 minutes. Powdered chemicals should be brushed off immediately treated. The antidote for cyanide poisoning
and not irrigated. If a powdered chemical goes into solu- requires two interventions. First, sodium thiosulfate
tion, the surface area of skin damaged will be signifi- (125–250 mg/kg) is administered to transfer sulfur to the
cantly increased. Eye burns require continuous irrigation cyanide ion. Next, hydroxycobalamin (4 g) is given to
with normal saline for up to 1 or 2 hours. chelate the cyanide to permit excretion.
Burn patients are at great risk for developing hypother- Large surface area burns also require intubation and
mia. The damaged skin has limited ability to regulate blood ventilatory support. Patients with large burns become
flow and therefore the convective loss of heat from a hypercatabolic and produce large amounts of carbon
thermal injury victim is great. Since the majority of the dioxide. If the patient is unable to increase and maintain
above-mentioned techniques require wetting the patient, an adequate minute ventilation, hypercapnia ensues.
every effort should be made to insulate the patient and to Patients with underlying pulmonary pathology associ-
increase the ambient temperature of the environment to ated with an increase in physiologic dead space are more
minimize the risk of hypothermia. prone to this complication.
Circumferential third-degree torso burns can restrict
respiratory excursion due to the constricting effects of
Airway/Breathing the burned skin. This restriction is not usually present
The airway should be initially assessed to ensure
patency. The presence of stridor is an immediate indica-
tion for endotracheal intubation. Burns to the face are
not at immediate risk for airway compromise; however, Table 32-2 Carbon Monoxide Effects
subsequent edema formation in addition to resuscitation
fluids can make securing an airway more difficult later. It COHb (%) Signs and Symptoms
is therefore recommended that patients with facial burns
be prophylactically intubated with a 7.5 mm internal 0–10 None
diameter (i.d.) endotracheal tube or larger. This caliber 10–30 Headache
30–50 Dizziness, weakness, presyncope
of endotracheal tube will permit flexible bronchoscopy
50–70 Syncope, coma, cardiovascular depression
for diagnosis and therapeutic lavage if needed. 70–80 Further cardiovascular depression
Patients burned in an enclosed space or found uncon- 80–100 Death
scious in a burning structure should be suspected of having
348 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Circulation
Since burned tissue swells, all constricting clothing
and jewelry should be removed to prevent circulatory
compromise. Finger rings should be removed as soon as
possible since swelling of the digits may make removal
later more difficult. Earrings should also be removed
since increasing edema of burned ears could lead to
pressure necrosis.
Burns with %TBSA greater than 20% will require
Figure 32-1 Correct placement of esharotomy incisions. resuscitation. It is necessary, in these patients, to secure
adequate intravenous (IV) access. Large-bore (at least
16-gauge) IV catheters should be placed, preferentially
initially, but becomes more problematic during fluid through unburned skin, although this is not always
resuscitation. Progressive tissue edema below the burned possible. Catheters can be placed through burned skin,
skin decreases total thoracic compliance and eventually but since adhesive tape will not adhere to the burn, they
impairs ventilation. This is manifest by a gradual increase should be secured with sutures. Central venous catheters
in peak airway pressures and worsening respiratory provide more definitive venous access. Due to the high
acidosis. The treatment is a chest wall escharotomy; a cut incidence of catheter colonization and infection, antibiotic-
into the burned chest skin along the right and left anterior impregnated central venous catheters should be used if
axillary lines and joined horizontally across the costal available. An indwelling urethral catheter should be placed
margin. This will improve respiratory excursion and to monitor urine output during resuscitation.
therefore improve compliance. Figure 32-1 illustrates the Resuscitation formulas have become the standard for
placement of escharotomy incisions along the anterior initiating and conducting the treatment for burn shock.
axillary lines connected by a subcostal incision. An escharo- The most commonly used formula is the Parkland (or
tomy should only be performed by a knowledgeable Baxter) formula. Correct application of this formula
surgeon. requires an estimation of the second- and third-degree
%TBSA involvement and the patient’s weight. The extent
of the burn can be approximated using the “Rule of
CLINICAL CAVEAT Nines” (Figure 32-2), a guide to estimating %TBSA burned
Acute increases in peak airway pressures in patients based upon dividing the adult body into 11 regions each
with circumferential torso burns should first be evaluated corresponding to 9%TBSA. The head and each upper
for airway obstruction, right main stem intubation, or extremity represent 9% of the TBSA; the anterior torso,
pneumothorax prior to considering chest wall posterior torso, and each lower extremity represent 18%
escharotomy. of the TBSA. Children under 30 kg require a slightly dif-
ferent approximation of %TBSA due a disproportionately
larger head; a child’s head represents 18% of the TBSA and
Anticipation and treatment of pulmonary complications each lower extremity represents 14% of the TBSA. A rough
is necessary in order to decrease the morbidity and mor- estimate for irregular burns is that the patient’s palm (not
tality associated with large burns (with or without smoke including the fingers) represents about 1% of the TBSA.
inhalation injury). Patients with smoke inhalation injury A computerized estimation of the %TBSA burned may be
are at risk for pneumonia, ARDS, bronchiectasis, tracheo- generated at the website www.sagediagram.com.
malacia, and subglottic stenosis. Humidified oxygen, Fluid resuscitation with lactated Ringer’s (LR) solution
encouraging the patient to cough, and chest physiotherapy should be guided by the Parkland formula which directs
Treating Thermal Injury and Smoke Inhalation 349
9%
CLINICAL CAVEAT
9%
Posterior
18% The rate of IV fluid administration should be
calculated from the time of injury. For example, if a
patient sustains a burn 3 hours prior to instituting IV
fluids, half of the calculated 24-hour fluid requirement
1% should be administered within the first 5 hours.
and the pedal vessels of the feet. One should not await Deep partial-thickness and full-thickness burn wounds
the presence of neurologic signs such as paresthesias, should be treated with a topical antimicrobial agent to
pain, or paralysis to make the diagnosis of impaired distal decrease the risk of developing an invasive burn wound
perfusion. Figure 32-1 illustrates placement of escharo- infection. Table 32-3 lists distinguishing characteristics
tomy incisions along the lateral and medial aspects of the of four commonly used topical antimicrobial agents.
extremities and over the dorsal aspect of the hand. A lat- One effective treatment strategy is to treat deep partial-
eral incision is made first; if no improvement in Doppler thickness or full-thickness wounds with silver sulfadiazine
flow is detected within 5–10 minutes, the medial incision (Silvadene) or Acticoat (an ionic silver-coated polyethylene
is then made. It is important that the escharotomy inci- fabric). Wounds treated with silver sulfadiazine should be
sion is made along the entire length of the full-thickness cleansed once or twice daily and the cream reapplied.
burn and that it crosses the joints. Wounds treated with Acticoat need to be moistened
with water (not saline, as this will cause the dressing to
dry out) several times a day and the dressing changed
BURN WOUND CARE every 3–4 days.
Infected full-thickness burns should be treated with
Basic principles of burn wound care involve keeping mafenide acetate, as this is the only agent that can
the wounds clean, moist, and protected. It is essential penetrate the eschar, and the dressings changed twice
that the patient be kept in a warm environment above daily. Note that mafenide acetate is a strong carbonic
30°C. Burns should be cleansed with a warm chlorhexi- anhydrase inhibitor and can cause a hyperchloremic
dine solution. First-degree burns may be treated with any metabolic acidosis.
moisturizing cream. Superficial or deep partial-thickness
burns to the face or neck should be treated with petro-
latum. This should be reapplied several times per day to OTHER CONSIDERATIONS
maintain moisture. Burns to the ears should be treated
with mafenide acetate (Sulfamylon) cream if cartilage Systemic Wound Management
is exposed. Large blisters, especially those located over Ibuprofen should be administered on a scheduled
the palms or the soles should be evacuated but left intact basis (1200 mg loading dose followed by 800 mg every
and dressed with a moisturizing ointment and gauze 8 hours) for the first 72 hours after a burn injury occurs
dressing. to decrease thromboxane A2 production and the result-
Superficial partial-thickness burns elsewhere on the ant dermal vasoconstriction.
body may be treated with petrolatum or temporary skin Tetatus toxoid should be administered if the patient’s
substitutes such as xenografts, cadaveric allografts, Apligraf last immunization was more than 5 years previously.
(collagen/fibroblast matrix with overlying keratinocytes), There is no role for the administration of prophylactic
Biobrane (collagen/nylon mesh with an outer silicone systemic antibiotics.
film), or Trancyte (human newborn fibroblasts cultured
on the nylon mesh of Biobrane). These temporary skin
substitutes promote reepithelialization and reduce wound Pain Control
pain, evaporative losses, and edema, and are left in place Partial-thickness burns are associated with a signifi-
to adhere to the wound bed until healing occurs. cant amount of pain due to the exposure of pain fibers
Table 32-3 Characteristics of Topical Antimicrobial Agents Used in the Treatment of Deep
Partial- and Full-Thickness Burns
Silver sulfadiazine, Gram positive, Poor Transient leukopenia in 5–15%; some Gram-negative
1% cream (Silvadene) Gram negative, yeast organisms, e.g., clostridia, are resistant
Ionic silver fabric Gram positive, Poor None
dressing (Acticoat) Gram negative, yeast
Mafenide acetate, Gram positive, Good Painful; carbonic anhydrase inhibitor causing acidosis
11.1% cream (Sulfamylon) Gram negative
Silver nitrate, 0.5% solution Gram positive, Poor Can cause hyponatremia, hypokalemia, hypochloremia,
Gram negative, yeast hypocalcemia, and met-hemoglobinemia; stains
environment, equipment, and personnel
Treating Thermal Injury and Smoke Inhalation 351
in the dermis; adequate analgesia is essential and can prophylactically treated with antacids, H2 receptor
usually be achieved by the intermittent administration of antagonists, or proton pump inhibitors.
small amounts of IV narcotics. Patients requiring mechan-
ical ventilation are commonly treated with a continuous
infusion of IV narcotics. Patients with full-thickness burns CONCLUSIONS
usually have decreased narcotic requirements as these
burns have destroyed the pain fibers in the dermis. The USA has one of the highest rates of fire-related
deaths. The successful management of a burn patient
requires an understanding of the pathophysiology asso-
Nutritional Support
ciated with thermal injury and a high index of suspicion
Patients with extensive thermal injury will experi- for smoke inhalation injury. Continued assessment of the
ence a hypermetabolic state with increased oxygen con- airway, adequate IV fluid resuscitation, pain control,
sumption and catabolism resulting in the wasting of lean nutritional support, and appropriate wound care are
body mass. Patients with burns of >20%TBSA will have a essential components of the care of patients with ther-
resting energy expenditure (REE) 1.5 to 2 times normal mal, chemical, or electrical burns. The anticipation and
and will require supplemental nutritional support. One treatment of complications associated with different
formula for calculating the REE (in kcal/m2/hour) in a burn injuries play an equally important role in the man-
burn patient, developed at the US Army Institute of agement of these complex patients.
Surgical Research, is:
REE = BEE × [0.89 + (0.014 × %TBSA burned)]
SELECTED READING
where BEE is the basal energy expenditure and can be
Demling RH: Burn care in the immediate resuscitation period.
calculated from the Harris–Benedict equation: In Wilmore D, editor: American College of Surgeons
for males, BEE = 66 + (13.7 × wt) + (5 × ht) − (6.8 × age) Surgery: Principles & Practice, New York: WebMD
Corporation, 2002, pp 49–61.
for females, BEE = 65 + (9.6 × wt) + (1.8 × ht) − (4.7 × age)
Demling RH: Burn care in the early postresuscitation period.
where wt is weight in kilograms and ht is height in In Wilmore D, editor: American College of Surgeons Surgery:
centimeters. Protein requirements may be in the range Principles & Practice, New York: WebMD Corporation,
2.5–3 g/kg/day. 2002, pp 479–489.
Enteral feeds represent the optimal route of caloric Demling RH: Burn care after the first postburn week.
support; however, patients with a >20%TBSA burn may In Wilmore D, editor: American College of Surgeons
have an ileus in the early postburn period and will not Surgery: Principles & Practice, New York: WebMD
tolerate enteral feeds. These patients often require naso- Corporation, 2002, pp 491–503.
gastric tube decompression until the ileus resolves; Demling RH: Miscellaneous thermal injuries. In Wilmore D, editor:
gastrointestinal motility usually returns by the third to American College of Surgeons Surgery: Principles &
fifth day postinjury. Serum glucose levels should be mon- Practice, New York: WebMD Corporation, 2002, pp 505–515.
itored every four hours once feeds begin as burn patients Herndon DN, editor: Total Burn Care, ed 2, Philadelphia: WB
will experience some degree of peripheral insulin resis- Saunders, 2001.
tance. Continuous insulin infusions may be necessary Lentz CW, Peterson HD: Smoke inhalation is a multi-level insult
to control hyperglycemia. These patients are also at risk to the pulmonary system. Curr Opin Crit Care 3:221–226,
for the development of stress gastritis and should be 1997.
33
CHAPTER Environmental Threat
and Disaster Response:
Natural Disasters and
Biological, Chemical,
and Nuclear Threat
JAMES E. SZALADOS, M.D., J.D., M.B.A.
352
Environmental Threat and Disaster Response 353
LD50 refers to the dose required to cause death in 50% defined by threat levels. Quarantine may be necessary to
of patients, or the dose that results in a 50% chance of prevent continued spread of offensive agents. Quarantine
survival or death in a person receiving it. LD50 is a measure refers to a compulsory physical separation of affected
of toxity and also defines the practical applicability of persons and the definition further extends to a restriction
agents as potential MCBWs. of movement and to segregation as an affected group.
The effects of agents must be considered. Lethality is Isolation is less restrictive and refers to separation and
only one index of effect; short-term and long-term inca- confinement of affected individuals known or suspected
pacitation and public panic and anxiety are also important. to be affected with an infectious agent. Disaster manage-
ment assistance teams (DMATs) are disaster relief per-
sonnel usually deployed within 24–48 hours.
GENERAL PRINCIPLES OF CONTAINMENT A variety of command posts may need to be established
for various services and teams or locations. Command
posts report to a command center which has operational
control over disaster management personnel. Individual
PEARLS
command centers report to a tactical command center
Principles of Response which coordinates the allocation of personnel and
Situational awareness: resources. A strategic command center, usually geo-
● Index of suspicion graphically removed from the immediate disaster area,
● Education and familiarity with potential problems usually coordinates government agency activities.
● Communication
Communications are critical and likely to be extremely
Response deployment:
vulnerable. Communications may be targeted. Landline
● Coordination and leadership
● Chain of command telephone communications may be physically compro-
Source control: mised or overwhelmed by excessive use. Efficient com-
● Perimeter establishment munication requires prioritization and organization.
● Quarantine and isolation Access overload control for cellular radio telephones
● Disinfection and decontamination (ACCOLC) assigns priority to cellular phones used by
● Antidotes and antibiotics emergency personnel during periods of circuit overload.
● Supportive critical care Cellular, radio (UHF and VHF), and internet communica-
tions provide redundancy. A system of couriers can be
locally effective in the setting of a total communications
The first priority of disaster medicine is the prevention breakdown. External communication is also necessary
of secondary casualties. Caregivers who are inexperienced with local, state, and federal agencies; with the media;
in disaster or military medicine are especially vulnerable. and with families.
The disaster plan is an operations blueprint that defines the Methods for cataloging the injured must be in place.
policies and procedures to be implemented in the event of Principles of disaster response form the basis for a dis-
an emergency. The plan must include every conceivable aster plan. Disaster plans exist at the institutional, com-
aspect of mass casualty care including a contact hierarchy munity, state, regional, and federal levels. Knowledge of
and contact information, personnel assignments, internal the plan and repetitive rehearsal are important to the
and external communication protocols, decontamination plan’s success. Preparation activities increase organiza-
procedures and equipment, quarantine and lockdown, tional capacity in the event of a disaster. Preparation
evacuation plans, and supply management. The effective- includes resources (material and personnel) inventories,
ness of any disaster plan will depend on the weakest link. prearranged agreements with suppliers and personnel,
The chain of command is the hierarchy for various staff orientation and training, and drills. Response activi-
professionals involved in the response. Responsibilities ties control the situation when it occurs. The first level is
are based on training and experience. Although health organizational and requires internal leadership and coor-
care providers are experienced in providing medical care dination with local and regional agencies. The second is
in general, they lack the specialized training required to a coordinated and dedicated staff response.
manage disasters. Inexperienced providers risk becoming
casualties.
Law enforcement, the fire department, emergency GENERAL PRINCIPLES OF MEDICAL
medical systems, environmental agencies, public health MANAGEMENT
organizations, and the military are included in the com-
mand structure. Natural Disasters
The first principle of management is containment with A “disaster” is defined as a “situation or event which
a perimeter. Multiple circumferential perimeters are overwhelms local capacity, necessitating a request to
354 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
national or international levels for external assistance” or ● A sudden or increased incidence of a stable
a sudden event which “causes great damage, destruction, endemic disease
and human suffering.” Natural disasters can include hur- ● A similar genetic type of organism isolated from
ricanes, tornadoes, volcanoes, earthquakes, flood, fire, different times or locations
or drought. Natural disasters can have both initial and ● A simultaneous cluster of outbreaks in
secondary impact. Initial impact is the result of trauma or noncontiguous geographic areasx
environmental exposure. Secondary injuries may occur as
a result of impact on technological infrastructure, damage
to nuclear, toxic chemical, or biologic facilities with leak- Overview
age of hazardous materials, the precipitation of dangerous Throughout history epidemics have killed countless
conditions, loss of power, and spread of disease. Initial millions, eliminated cultures, defeated empires and their
priorities will include evacuation, evaluation and resus- armies, and thereby irrevocably altered the course of civ-
citation, and containment of casualties. ilization. That the power of infectious agents could be
Public health issues include the availability of basic strategically and tactically directed for political and mili-
services (water supply, food supply, electricity, sanitation tary purposes is a logical extrapolation. Bacteria, viruses,
and waste disposal, housing and shelter, and disposition fungi, and their biological toxins, as well as newer chem-
of human and animal remains). Medical care ranges from ical toxins could be deployed to kill or disable combat-
trauma resuscitation to vaccination and treatment of ants or cripple the civilian or agricultural infrastructure
secondary illnesses. Psychological support may be nec- of enemies.
essary to minimize post-traumatic stress disorder (PTSD) The key advantages of such agents are that they are
or crisis incidence stress disorder (CISD) and long-term relatively inexpensive to produce, allow for the preserva-
psychological impact of the disaster. The purpose of tion of structural integrity following attack, and allow for
psychiatric intervention is twofold: to provide immediate selective immunization, barrier protective, or antidotal
relief and early return to normal activities, and to prevent defensive measures. In addition, such agents can be easily
the development of chronic syndromes. deployed, are difficult to detect, and it can be difficult to
Vector control may be necessary to prevent spread of trace temporal, spatial, and causal origins when used for
disease by mosquitoes, flies, and rodents. terrorist purposes. The key disadvantage remains epidemi-
ological unpredictability.
A key function of health care providers will be the
Conventional Weapons rapid diagnosis of index cases and communication with
Explosives remain the most likely mass casualty cause public health authorities. A key dilemma for public health
in the USA and elsewhere. Explosives directly cause blast, authorities will be the differentiation of the presenting
burn, and penetrating trauma. Additionally, explosive symptoms of the pathogens listed below from other dis-
devices will indirectly cause other injuries and fatalities eases with similar symptoms, especially in the flu season,
depending on the arena in which the explosives are and to differentiate isolated endemic cases from index cases
deployed: buildings, subways, airplanes, industrial com- of potential epidemics. Biologic agents can be categorized
plexes, for example. Since the US health care system is as either infectious agents per se or biological toxins.
currently functioning near or at capacity, special plans
must be in place for the care of large numbers of acute Infectious Agents
casualties. Infectious biologic agents used in biologic warfare or
bioterrorism can include bacterial, viral, and atypical
organisms. Almost any agent that incapacitates troops
Biologic Agents can be employed in the battlefield. The most effective
terrorism agents are those which incite panic. Bacterial
PEARLS
agents which have been successfully weaponized include
Clues Signaling a Biologic/Chemical/ anthrax (Bacillus anthracis), plague (Yersinia pestis), and
Toxicologic Event tularemia (Francisella tularensis) (Boxes 33-1 and 33-2).
● Large numbers of patients with a similar syndrome Anthrax is a spore-forming gram-positive bacillus that is
● Large numbers of patients with an unusual disease endemic worldwide. Occupationally, cutaneous anthrax is
or syndrome
contracted by individuals working with contaminated
● A higher morbidity or mortality than expected with
common disease
animal fibers such as goat hair. Gastrointestinal anthrax is
● A single case of a very uncommon disease enzootic in Third World countries with domestic ungulate
● An unusual clinical presentation of a known disease herds. The use of anthrax as a germ-warfare agent requires
● An unusual geographic or seasonal distribution that anthrax spores be concentrated, electrostatically
stabilized, and disseminated at a target. An outbreak of
Environmental Threat and Disaster Response 355
Because smallpox is considered to have been eradicated generally symptomatic unless the cause is otherwise iden-
worldwide since 1977, even a single case of smallpox tified to not be viral, in which case specific therapy is usu-
would likely indicate a terrorist attack. Smallpox has an ally available and should be instituted as soon as possible.
incubation period ranging from 7 to 17 days, with an aver- Q fever, caused by Coxiella burnetii, is an enzootic ill-
age of 12 days; the illness typically follows a brief prodromal ness in ungulates with worldwide distribution. Humans
period of 2–4 days during which the virus can be isolated are infected by inhalation of contaminated aerosols
from the blood. The prodromal symptoms are flu-like and or by insect vectors. C. burnetii is a pleomorphic cocco-
include fever, myalgias, nausea, and vomiting. The disease bacillus with a gram-negative cell wall which possibly
typically begins with a centrifugal rash which progresses in enters host cells. Person-to-person transmission is poss-
a uniform pattern from maculopapules to vesicles to pus- ible, especially in the pneumonic form of the disease.
tules and scabs over a 1–2 week period. It is important to The incubation period for Q fever is 14–40 days and
note that the centrifugal distribution and the homogeneity once again, the prodrome and clinical illness are non-
of the rash are key differential diagnostic points: in chick- specific. Clinical manifestations range from pneumonia,
enpox, lesions are distributed evenly over the body begin- to endocarditis, hepatitis, osteomyelitis, encephalitis,
ning on the trunk and in chickenpox, individual lesions and meningitis. The radiographic appearance of Q fever
form and scab over at different times. In its most prominent pneumonia is variable; however nonsegmental and seg-
form, death may occur before the rash becomes manifest, mental pleural-based opacities are common findings.
and in its most discreet form, the disease may follow its full A pleural effusion is found in approximately 35% of
course to recovery. The mortality in the past has ranged cases. The pneumonia is rarely fatal. The treatment of
from 25–50%; however, those statistics reflect mortality choice is doxycycline or tetracycline, which can also be
within a partially immunized population. Vaccination has used for postexposure prophylaxis. An investigational
been shown to be effective up to four days after exposure. vaccine is currently under development.
Treatment is supportive. Notably, monkeypox is another Community surveillance and centralized reporting
Orthopoxvirus disease caused by a variola virus. It is form the basis for a bioterrorism response. Potential indi-
endemic in African monkeys and can rarely be spread to cations for intentional release of a bioweapon include
humans. unusual temporal or geographic presentations, unusual
Viral hemorrhagic fevers include Marburg and Ebola, severity, and rapid epidemiologic spread.
which belong to the Filovirus class. The incubation Rapid diagnosis can be achieved using either immuno-
period for filovirus fevers ranges from 2 to 19 days and logic testing or electron micrography for many agents.
symptoms begin with the abrupt onset of fever, myalgia, Containment and prevention of secondary spread are
and headache. Progression of symptoms to gastroenteritis, vital. Access to the National Pharmaceutical Stockpile for
pneumonitis, pancreatitis, pharyngitis, and encephalitis is treatment will be managed by the Center for Disease
common. With further progression, petechiae, diffuse Control in the armed forces. Rapid immunization or dis-
hemorrhage, and a truncal maculopapular rash may pensation of prophylactic medication will help contain
become evident. Typically, in the second week, the centers of outbreak.
patient will either defervesce and improve rapidly, or
will die in shock from multiorgan failure. The mortality
of Marburg at the present time is approximately 25%. Toxins and Chemical Agents
Ebola has higher mortality depending on the subtype of A disaster that involves the release of toxic chemicals
virus: Sudan subtype has mortality of 50%, and Zaire and widespread toxic exposure of a population can
subtype has a much higher mortality of 90%. There occur in two different scenarios: first, the intentional
are no vaccines or similar preventive measures; antiviral release of a chemical warfare agent directed against the
chemotherapy such as Ribavirin may be effective as population; and second, the accidental or intentional
treatment. Management is supportive and extensive spillage of stored or transported toxic chemicals in a
quarantine precautions are indicated. These viruses can populated area. A third potential scenario is chemical
be weaponized for aerosolized dissemination. terrorism directed at the food supply chain, a scenario of
The viral encephalitides include a variety of agents which is discussed below.
such as the Togavirus subclass of alphaviruses (Eastern Broadly speaking, a chemical attack could occur
equine, Western equine, Venezuelan equine); the flavi- through the use of either toxins or synthetic chemical
viruses (West Nile, Dengue, St. Louis); the Bunyaviruses agents. The toxins represent a category of agents related
(Rift Valley); the Arenaviruses (Lassa, Junin, and Machupo). to biological agents and also chemical agents. The toxins
Patients with viral encephalitis tend to have signs and are products of biological processes or organisms which
symptoms of meningeal inflammation but, in addition to must be concentrated and weaponized prior to deploy-
headache, fever, and nuchal rigidity, the patients with ment. In general, toxins are proteins with high affinity
encephalitis also have alterations in consciousness. to cellular binding sites. The toxins represent chemicals
Infections may be acute, subacute or chronic. Treatment is that include some of the most potent and deadly
Environmental Threat and Disaster Response 357
compounds known. Similar to chemical agents, toxins causes localized pain, and muscle and regional lymph node
can be inhaled, ingested, or dermally absorbed. necrosis.
Staphylococcal enterotoxin B is a seven-component
Toxins pyrogenic protein toxin isolated from S. aureus. The toxin
Botulinum toxin is the most potent toxin known classes and subclasses stimulate T-cells and cause fever
(Box 33-3). It is a naturally occurring product of and myalgia, nonproductive cough and interstitial
Clostridium botulinum and is comprised of seven differ- edema, headache, and gastrointestinal complaints. The
ent molecular toxins. The LD50 is 0.001 μg/kg. The LD50 is 0.02 μg/kg.
mechanism of action of botulinum toxin is through bind-
ing to the neuronal cell membrane at the nerve termi- Chemical Agents
nus, followed by endocytosis, then the light chain of Chemical agents are classified as vesicants, nerve
botulinum toxin cleaves specific sites on SNARE proteins agents, toxic inhalants, cyanogens, or riot control agents.
preventing assembly of the symmetric fusion complex Vesicants
and blocking the release of acetylcholine. The intensive Vesicants include the mustards (HD, HT, HN),
care unit (ICU) at Unity Health System in Rochester, Lewisite (L), and phosgene (CX) and are defined to be
New York, recently cared for a patient exposed to agents that produce blisters or vesicles. These agents
botulinum toxin who was in the ICU for almost a year. have been available since World War I. The mustards
Botulinum toxin produces a flaccid paralysis. A pentava- enter the body through the mucous membranes or the
lent antidote available from the US Department of Defense skin and react with proteins and nucleic acids. DNA repli-
must be administered early. cation is inhibited. There are no immediate signs or
Clostridium tetanii produces tetanus toxin. The LD50 symptoms on contact, inhalation, or ingestion, unless
is 0.002 μg/kg. Tetanus produces a rigid, tetanic paralysis. direct exposure to concentrate occurs. Odor is variable.
Ricin is a protein byproduct of castor bean processing Symptoms occur 2–24 hours after exposure and include
in the production of castor oil. Ricin is a toxic byproduct destruction of the spleen and bone marrow. The eyes are
of castor oil fermentation and affects cellular protein syn- extremely sensitive to mustard gas. Mucosal sloughing of
thesis. Inhalation exposure produces symptoms within the lower respiratory tract followed by pneumonia and
4–8 hours manifested by pulmonary edema and respira- pulmonary edema result from heavy exposure. The
tory tract necrosis. Treatment is supportive. Processing mustards are also teratogenic.
yields 3–5% ricin by weight and there is thus a large Lewisite inhibits multiple enzymes by reacting with
amount of ricin available. The LD50 is 3.0 μg/kg. Inhalation either glutathione or sulfhydryl groups. Lewisite contains
causes acute respiratory distress with pulmonary lesions; arsenic and reacts with enzymes to cause pulmonary
ingestion causes gastrointestinal hemorrhage with necrosis edema, diarrhea, fever, and lethargy. Lewisite causes
of the liver, spleen and kidneys; intramuscular injection immediate pain and irritation on contact, with erythema
and blistering. Although Lewisite also inhibits DNA repli-
cation, it generally spares the bone marrow. It causes
more severe tissue destruction. Death is usually from
respiratory failure, bronchospasm, or pneumonia. The
Box 33-3 Botulism
clinical effects are similar to mustard gas exposure and
include profound shock from plasma leakage. Lewisite
● Botulism results from the ingestion of botulinum
has an odor similar to that of geraniums. The specific
toxin types A–G which are produced by C. botulinum
antidote is Dimercapterol (2,3-dimercaptopropanol),
and two other clostridial species. Botulinum toxin is
the most potent neurotoxin known and affects the otherwise known as British Anti-Lewisite (BAL), and
presynaptic releases of the acetylcholine, blocking aggressive intravenous fluid management. Iodophors
neuromuscular transmission. The onset of botulinum and topical antibiotics may limit skin damage. Lewisite,
toxin is generally slow and incapacitation is progres- like the mustards, is teratogenic.
sive ending in respiratory fatigue and generalized Phosgene is commonly grouped with the blister agents
paralysis in 24–72 hours. Specific antitoxin therapy and is a urticant causing extreme irritation of tissues.
is available. Phosgene has not been previously used in warfare. Like
● The onset of botulism ranges from 24 hours to the vesicants it also inhibits DNA replication. Epithelial
several days depending on the dose ingested. sloughing occurs from the skin and the respiratory, gas-
Person-to-person transmission is not generally an
trointestinal, and genitourinary tracts. It is a potent pul-
issue. Botulism can be treated using an equine
monary irritant. There is immediate pain on contact and
polyvalent antitoxin if administered early. In the
setting of established botulism, long-term mechani- ocular exposure results in conjunctivitis and keratitis.
cal ventilatory support and routine critical care The main lesion is pulmonary edema with necrotizing
management are necessary. bronchiolitis and thrombosis of pulmonary vessels.
There is no laboratory test or antidote. Rapid topical
358 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
decontamination is essential. An effective decontami- immediately on exposure and usually last 15–30 min-
nant is 0.5% sodium hypochlorate if immediately avail- utes. Treatment is supportive; however, asthmatics may
able; otherwise copious water irrigation should be used. require bronchodilator therapy and persistent ocular
Iodophors may limit toxicity. Treatment is decontamina- irritation may require ophthalmology consultation.
tion and supportive care. Agent 15 is a nonlethal psychotomimetic agent which
Nerve Agents causes incapacitation from delirium. It can be ingested,
Nerve agents include Tabun (GA), Sarin (GB), Soman inhaled, or absorbed. Symptoms are anticholinergic (delir-
(GD), and VX. The effects of nerve agents occur in seconds ium, temperature, dry mouth, and papillary dilatation).
to minutes depending on the concentration of vapor. Physostigmine is an antidote.
Biotoxicity is a function of acetylcholinesterase inhibition Other Chemicals
in the plasma, on red blood cells, and at the synapses. A large variety of hazardous materials are stored near
Accumulation of acetylcholine causes symptoms within populated areas and are transported on public roads
minutes. Symptoms are therefore both nicotinic and every day. These include hydrocarbons, corrosive
muscarinic, being due to both nicotinic and muscarinic agents, oxidizing agents, compressed gases, insecticides,
overactivity and include bronchorrhea, rhinorrhea, and and heavy metals. Examples include ammonia, pentabo-
bronchoconstriction; miosis; bradyarrhythmias; nausea, rane, potassium cyanide, sodium superoxide, and vana-
vomiting, and diarrhea; muscle fasciculations; and loss of dium tetrachloride.
consciousness and apnea. GB and VX are odorless, and GA
and GD smell fruity. Sarin has an LD50 that is 26 times less General Principles of Chemical/Toxic Response
than cyanide gas. Antidotes include atropine (6 mg IV/IM), The critical points regarding the medical response are
diazepam, and pralidoxime hydrochloride (2-PAM). (a) that medical personnel typically do not have the
MARK and nerve agent antidote kits (NAAKs) contain training or experience to become involved at “ground
these antidotes. zero” and that the best of intentions may have disastrous
Toxic Inhalants effects, (b) that in any chemical or biological disaster
Toxic inhalants include phosgene (CX, CG), diphos- there will be some patients who present without decon-
gene (DP), chloropicrin (PS), and chlorine (Cl). The toxic tamination or treatment, (c) that the medical response
inhalants/pulmonary agents specifically attack the lung must be prepared to triage, continue supportive care,
tissue and cause pulmonary edema; their specificity dif- specifically identify the threat, and institute antidotal
ferentiates these agents from the vesicants, which inciden- therapy, and (d) the leadership of the hospital-based care
tally involve the respiratory tract. CG and DP are colorless team (Box 33-4).
and have the odor of green corn or freshly mown hay. Protective containment actions are (a) the initial
These agents have a latent period of several hours. isolation zone: surrounds the incident and includes
Pulmonary edema occurs due to an acetylation reaction upwind and downwind areas; and (b) the protective
which precipitates acute leakage at the alveolar–capillary actions zone: areas downwind from the incident. These
membrane. Treatment is supportive and often requires areas are considered perimeters. The key purposes of
airway maintenance, fluids/vasopressors, theophylline, a perimeter are minimization of secondary injury and
and methylprednisolone. spread of the toxin. Protective actions also include the
Cyanogens use of protective gear including the battledress overgar-
Cyanogens are variants of cyanide and include hydro- ment (BDO) and the mission-oriented protective posture
gen cyanide (AC) and cyanogen chloride (CK). These com- (MOPP) suits. In some circumstances protective action
pounds combine with the iron molecule of cytochrome a3 can also include prophylactic administration of antidotes
and precipitate anaerobic glycolysis and lactic acidosis
due to cellular hypoxia. Cyanogens may have the odor of
bitter almonds. The onset of effect is within 15–30 seconds
and includes vomiting, convulsions, and respiratory fail- Box 33-4 Management
ure. Antidotes consist of thiosulfate and sodium nitrite
which form thiocyanate and methemoglobin, binding ● Continued medical education is fundamental to an
cyanide. effective and concerted disaster response and
national security.
Riot Control Agents
● Mass simultaneous casualties in a concentrated area
Riot control agents are used by police departments
with the same or similar presenting symptoms raise
and include lacrimants and irritants. Riot control agents immediate suspicion for chemical or toxin exposure.
include chloroacetophenone (CN), ortho-chlorobenzyl- ● General management principles include decontami-
idene-malononitrile (CS), dibenz(b,f)-1,4-oxazepine nation, ventilation, antidote administration, and
(CR), and Adamsite (DM). The riot control agents are lac- supportive therapies.
rimants, skin irritants, and vomiting agents. Effects occur
Environmental Threat and Disaster Response 359
Nuclear Threat
Although nuclear attack in the form of warfare remains Box 33-6 Dirty Bomb
an ever-present possibility, the indiscriminate global rami-
fications have made retaliation a sound mutually accepted The “dirty” bomb is a high-yield conventional explosive
deterrent strategy. Nuclear casualties are most likely to contaminated with radioactive material such as uranium,
arise from a reactor mishap, inadvertent spillage of con- cobalt-60, cesium-137, plutonium, or thorium.
tained nuclear waste, or a terrorist attack (Box 33-6).
360 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Resuscitation and Stabilization cases this would be accomplished with a rapid sequence
Diagnosis induction and oral intubation. Next, attention is turned
Treatment to the cardiovascular system. Many agents can cause
Specific Toxicities hypotension (usually by increases in venous capacitance).
Acetaminophen Therefore, hypotensive patients should have IV access
Salicylates established and be treated with isotonic crystalloid solu-
Carbon Monoxide tions to correct intravascular volume deficiencies. Certain
Cocaine and Amphetamines/Metamphetamines agents are associated with life-threatening tachycardia
Beta-blockers and Calcium Channel Blockers and hypertension, which would require pharmacologic
Other Agents intervention. When the patient is hemodynamically stable
Chemical Warfare Agents with adequate oxygenation and ventilation, attention
Conclusion should be turned toward identifying the toxic agent and
the extent of the exposure. In addition, a patient pre-
Patients suffering from either intentional or accidental senting with an unexplained depression of level of con-
poisoning frequently require an admission to the intensive sciousness should receive intravenous thiamine (100 mg),
care unit (ICU). Poisoning may also be associated with intravenous dextrose (ampule of D50), and intravenous
traumas, such as carbon monoxide with burns, and illegal naloxone (0.4–2 mg).
drugs with motor vehicle accidents. Resuscitation and
stabilization should be the first priority when treating the
poisoning victim. It is then important to limit absorption DIAGNOSIS
of the toxin, identify the toxin, and initiate specific ther-
apy. This chapter focuses on these points and examines After the initial resuscitation, attention should be turned
the identification and treatment of specific agents. A dis- toward determining the responsible toxin(s). When pos-
cussion of the treatment of patients exposed to chemical sible, the administered substance (ingestion, injection,
weapons completes the chapter. inhalation) and extent of exposure (quantity, timing, and
chronicity) should be determined. Sources for this infor-
mation include the patient, family members, and friends.
RESUSCITATION AND STABILIZATION Next, a physical examination should be performed, which
could supply useful information, since many toxins pro-
Identifying the toxic agent should never delay the duce predictable physiologic changes (see Tables 34-1
resuscitation of the patient. Using basic life support guide- and 34-2). In addition, there are constellations of symp-
lines, the patient’s airway, breathing, and circulation toms that characterize certain poisoning syndromes. These
should be assessed and problems treated. Many agents can are known as “toxidromes” (Table 34-3).
cause respiratory insufficiency and therefore supplemental Laboratory examinations may be of benefit in the eval-
oxygen should be administered. In some cases tracheal uation and treatment of patients suffering from poison-
intubation and mechanical ventilation are required. If a ing. These examinations include an arterial blood gas,
patient is at risk for aspiration, due to a depressed level of qualitative toxicology screens, quantitative analyses,
consciousness, the airway should be protected. In most and, perhaps, an EKG. An arterial blood gas is useful for
361
362 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
TREATMENT
several reasons. Determining hypoxia, hypercarbia, and
anion gaps may be useful in determining the offending
After the initial stabilization of the patient, efforts are
agent. In addition, the information gained may prompt
turned toward decreasing the exposure to the agent
emergent treatment such as securing the airway and
through gastrointestinal (GI) decontamination and/or
providing mechanical ventilation. Qualitative toxicology
enhanced elimination. During this time it is important to
screens are performed on urine samples and report only
continue efforts to support the airway and ventilation
the presence or absence of a substance. They are limited
and to maintain hemodynamic stability.
GI decontamination can be accomplished through
several modalities. This includes gastric emptying proce-
Table 34-2 Clues to Diagnosis in Poisoning: dures, adsorption of drugs, and increasing transit through
Neurologic Findings the GI tract. Gastric emptying procedures include ipecac-
induced emesis and gastric lavage. Ipecac-induced emesis
Pinpoint Pupils (Miotic) Dilated Pupils (Mydratic) has very limited utility. It is not used when managing
adult poisoning victims. It is contraindicated in patients
Cholinergics Alcohol
with depressed level of consciousness or when corrosive
Narcotics Anticholinergics
Organophosphates Antihistamines substances or hydrocarbons are ingested. Complications
Phenothiazine Phenytoin of induced emesis include aspiration pneumonitis,
Phencyclidine (PCP) Sympathomimetics esophageal rupture, and Mallory–Weiss tear (upper GI
hemorrhage). Gastric lavage with a large-bore (36–40 F)
Reproduced with permission of the Society of Critical Care Medicine from orogastric tube has been used. It is contraindicated in
Zimmerman JL: Poisoning/overdose. In Dries DJ, editor: 5th Critical Care
Refresher Course, ed 5, Des Plaines, IL: Society of Critical Care Medicine, 2001, caustic and hydrocarbon ingestions, in patients at risk of
pp 123–136. GI perforation, in combative patients, and in patients
Poisoning 363
with severe coagulopathies. The current recommenda- Renal replacement techniques used to enhance elimi-
tion is that gastric lavage only be used for life-threatening nation include intermittent hemodialysis, intermittent
quantities of poison when the therapy can be instituted hemoperfusion, continuous hemofiltration (CVVH), and
within 60 minutes of the ingestion. There is no good continuous hemodialysis (CVVHD). Hemodialysis should
evidence showing the benefit of gastric lavage (although be used early in the treatment of toxicities involving
the highest risk patients are often excluded from the methanol, ethylene glycol, salicylates, lithium, boric acid,
studies). The decision to perform gastric lavage must be and thallium. Hemoperfusion involves passing whole
made on a case-by-case basis. Its use is limited. blood through an adsorbent containing (charcoal) car-
Single-dose activated charcoal is the most common tridge. Charcoal hemoperfusion is the preferred method
technique used for GI decontamination. The activated for eliminating carbamazepine, phenobarbital, phenytoin,
charcoal adsorbs the toxin in the GI tract thus limiting and theophylline. Continuous renal replacement tech-
systemic absorption. The usual dose is 1 g/kg. Activated niques are of primary benefit for patients who are not
charcoal is not effective in adsorbing iron, lithium, hemodynamically stable enough to tolerate intermittent
cyanide, strong acids and bases, alcohols, and some techniques.
hydrocarbons. Activated charcoal is contraindicated in
patients with depressed levels of consciousness who do
not have airway protection, or if a GI perforation is SPECIFIC TOXICITIES
known or suspected. Studies suggest that the maximum
benefit of activated charcoal is obtained when it is Clearly there is a large variety of substances that can
administered within one hour of the ingestion. cause toxicities. An exhaustive discussion of many dif-
Cathartics and whole bowel irrigation have been used ferent agents is beyond the scope of this chapter. This
in poisonings. It is felt that limiting the contact time with chapter examines substances that are more likely to be
the GI tract may be of some benefit in limiting absorp- associated with critically ill patients in the ICU. Although
tion. There is no clinical evidence showing the benefit of not yet seen in the West, a terrorist attack using nerve
either technique. agents is a distinct possibility. These agents will be briefly
The other major treatment category for managing toxic discussed.
exposures is enhanced elimination. Enhanced elimination
can be achieved with multiple-dose activated charcoal
(MDAC), urinary alkalinization, and renal replacement Acetaminophen
therapies. Acetaminophen (N-acetyl-p-aminophenol (APAP))
MDAC is used to adsorb agents that are initially toxicity is commonly seen. The reason for this is multi-
absorbed but then reenter the GI tract. Toxins (or their factorial. Clearly, it is easily available to individuals wish-
metabolites) reenter the GI tract either through the ing to harm themselves. In addition, it is present in a large
enterohepatic circulation (present in bile) or through number of medications, which may not be known to
active secretion or passive diffusion distal to the stom- many patients. For example, patients taking percocet for
ach. There is no strong evidence demonstrating the effi- pain may supplement themselves with acetaminophen
cacy of MDAC. However, it has been recommended that and easily achieve toxic doses. Many lay people are
MDAC be used in the cases of life-threatening ingestion unaware of the potential toxicity of APAP. APAP can lead
of carbamazepine, dapsone, phenobarbital, quinine, or to hepatotoxicity and potential mortality that is prevent-
theophylline. MDAC is administered either as bolus able. APAP toxicity is the second leading cause of acute
doses (0.5–1.0 g/kg every 4 hours) or a continuous infu- liver failure in the USA and is the leading cause in the
sion (0.25–0.5 g/kg/hour, not less than 12.5 g/hour). UK. APAP is metabolized in the liver to the toxic metabo-
Urinary alkalinization has been of proven benefit in lite N-acetyl-p-benzoquinoneimine, which results in liver
poisoning involving weak acids such as salicylates, phe- cell injury and death. Maximal hepatic cell injury occurs
nobarbital, and primidone. The weak acids are ionized in at 72–96 hours postingestion. Initial symptoms include
the alkaline urine where they are trapped in the renal right upper quadrant pain and abnormal liver function
tubules, and then cleared. Urinary alkalinization is tests. The severity of symptoms is somewhat variable
achieved by administering a sodium bicarbonate drip. and depends on the quantity of ingestion. Toxicity may
The drip can be made in multiple ways including adding occur when 7.5–10 g are ingested over 8 hours. Fatalities
three ampules of sodium bicarbonate to 1 liter of sterile are rare for doses less than 15 g. Symptoms may progress
water or varying amounts of sodium bicarbonate (e.g., to encephalopathy, coagulopathy, jaundice, and renal
75 mEq) in D5W. The drip rate is then adjusted to failure. When patients develop encephalopathy (fulmi-
achieve a urinary pH of 7.5–8.5. Electrolytes should be nant hepatic failure), they have a mortality approaching
monitored and corrected as needed. 80%. At this point, liver transplant may be their only
364 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
option (60–80% survival). The treatment for APAP toxicity the long-term sequelae and mortality associated with CO
beyond the supportive measures described earlier is to poisoning.
administer N-acetylcysteine (NAC (mucomyst)). For acute,
single ingestions an APAP level is obtained at 4 hours after
ingestion (or immediately on admission if the time of the Cocaine and Amphetamines/
ingestion is unknown). The Rumack–Matthew nomo- Metamphetamines
gram is used to determine whether or not to institute These drugs are widely used and abused in the USA
NAC therapy. The initial dose of mucomyst is 140 mg/kg and may be seen in patients presenting to the ICU.
administered orally (PO or NG) followed by 70 mg/kg Clearly use of these agents may lead to severe trauma,
doses every 4 hours for 17 doses. The treatment duration which would then complicate the treatment of the
and dosing should be coordinated with the local poison patient’s injuries. Adverse sequelae of the use of these
control service. drugs have complicated the course of routine surgical
procedures. The most severe sequelae include cardio-
vascular complications (severe hypertension, arrhyth-
Salicylates mias, myocardial ischemia, and aortic dissection) and
Salicylate toxicity should be suspected if a metabolic neurovascular complications (seizures, cerebral infarction,
acidosis with an anion gap is present on blood gas analysis. and intracranial hemorrhage). The management of these
Initial symptoms include tinnitus and nausea/vomiting. complications is largely supportive (managing hyper-
Tachypnea, respiratory alkalosis, and hyperthermia are tension, cardiac ischemia, arrhythmias, seizures, etc.).
seen. Symptoms may progress to include depressed level of
consciousness, coma, seizures, coagulopathy, transient
hepatotoxicity, and hypoglycemia. Treatment includes Beta-blockers and Calcium
alkalization of the urine and administering activated char- Channel Blockers
coal. In severe cases hemodialysis may be required. Occasionally, overdoses of beta-blockers and calcium
channel blockers are seen. The most common manifes-
tations include bradycardia, hypotension, and atrio-
Carbon Monoxide ventricular conduction abnormalities. Central nervous
Carbon monoxide (CO) poisoning is common and system (CNS) abnormalities, such as lethargy, confusion,
could be the result of accidental exposure (car/structure and coma, are sometimes seen. The cardiovascular abnor-
fires, poorly ventilated heaters, poorly ventilated genera- malities are difficult to manage with traditional inotropes
tors, etc.) or intentional exposure. CO binds to hemoglo- and vasopressors. Initial management includes isotonic
bin with an affinity 200–250 times greater than oxygen. intravenous fluid, atropine, and glucagon. Glucagon stim-
This results in poor oxygen delivery to the tissues which ulates cyclic adenosine monophosphate (cAMP) thus
leads to cell hypoxia and possibly cell death. Clinical bypassing the adrenergic receptors. In some cases high-
manifestations are nonspecific and may be confused dose vasopressors/inotropes may be required.
with other illnesses unless the exposure is known or sus-
pected. Common symptoms include headache, nausea,
and vomiting. Other signs and symptoms include con- Other Agents
fusion, arrhythmias, angina, syncope, seizures, tachycar- Other agents that may be seen in toxic levels in the
dia, and tachypnea. Clearly, death can be the result of ICU include benzodiazepines, opioids, digoxin, etc.
severe exposures. Of those that recover from acute CO Benzodiazepines and opioids are commonly used in the
exposure, 10–30% have delayed neuropsychiatric seque- hospital for sedation and analgesia. Patients may receive
lae. Many may have a permanent neurologic injury. excessive dosages of these agents. Treatment primarily
Quantitative CO levels should be obtained on either arte- involves respiratory support until serum levels decrease.
rial or venous blood gases. Management includes admin- Occasionally, a benzodiazepine antagonist (flumazenil)
istering 100% oxygen until CO levels return to normal or narcotic antagonist (naloxone) may be used to treat
and treating clinical abnormalities (cardiac ischemia, overdoses. Caution should be used with both. Flumazenil
arrhythmias, acid–base disorders, etc.). In severe cases use has been associated with seizures. Complete block of
hyperbaric oxygen therapy may be instituted. This can narcotic receptors in the setting of severe injury or sur-
decrease the half-life of carboxyhemoglobin from 40 to gery will result in severe pain with possible hypertension,
80 minutes (with isobaric 100% oxygen) to 15 to 30 min- tachycardia, and pulmonary edema. If naloxone is used,
utes. Hyperbaric oxygen therapy is not widely available, small doses should be administered until the respiratory
which limits its use. Furthermore, outcome studies have status improves while maintaining adequate pain control.
not shown a benefit of hyperbaric oxygen therapy on Toxic digoxin levels are occasionally seen in the ICU
Poisoning 365
especially in patients on chronic doses who develop be administered early (i.e., in the field). If the patient sur-
renal insufficiency. Manifestations include a large variety vives to the ICU, continued treatment will probably be
of cardiac arrhythmias, anorexia, nausea/vomiting, and necessary. Atropine antagonizes the muscarinic and CNS
hyperkalemia. The standard of care for life-threatening effects. It is preferable to glycopyrrolate, which does not
digoxin toxicity is to administer digoxin-specific anti- cross the blood–brain barrier. The initial dose of atropine
body fragments (digibind). There are many other agents is 2 mg IV and should be repeated every 5–10 minutes
that can cause toxicity in the ICU. When unexpected until pupillary dilation occurs and heart rate rises above
symptoms are encountered, an investigation of agents 80 beats/minute. An atropine infusion (0.02–0.08 mg/
used/exposed to should be undertaken and treatment kg/hour, up to 1000 mg/day) may be required for per-
initiated. This often involves consultation with the local sistent bradycardia. The oximes (pralidoxime) reverse
poison control service. nicotinic receptor dysfunction and thus reduce or
reverse skeletal muscle weakness. They reactivate AChE
by cleavage of phosphorylated active sites, detoxify
CHEMICAL WARFARE AGENTS unbonded nerve agent molecules by direct action, and
have an endogenous anticholinergic effect. Irreversible
In the current world situation a major chemical attack bonds between the nerve agents and AChE form after
in a large populated area is a distinct possibility. There 2 minutes of exposure to soman, after 5 hours for sarin,
were 27,000 casualties due to the use of chemical weapons after 13 hours for tabun, and after 48 hours for VX gas.
(including mustard gas and tabun nerve agent) by the This gives time to administer the pralidoxime for most of
Iraqis during the Iran–Iraq war. Even more concerning, the agents. Other potential treatments include diazepam
there were several fatalities and hundreds of casualties (control seizures and limit long-term neurologic sequelae),
when the Aum Shinrikyo cult released sarin nerve gas in clonidine to control CNS cholinergic symptoms, and
a Tokyo subway. These agents could be used in a terrorist magnesium to reduce presynaptic ACh release.
attack in the future. It is therefore reasonable for physi- Mustard gas is the most likely used vesicant. It causes
cians managing ICUs to have knowledge of the identifi- NAD+ depletion, which disrupts glycolysis and causes
cation and treatment of these agents. the release of destructive proteases. There is a latency
There are several classes of chemical weapons that may period between exposure and the development of symp-
be employed. These include the nerve agents (sarin, tabun, toms. Therefore, close observation is required for all
soman, VX), blistering agents (mustard gas, Lewisite), suspected exposures. The clinical symptoms include
choking agents (chlorine, phosgene, chloropicrin), blood cutaneous manifestations, ocular symptoms, respiratory
agents (hydrogen cyanide and cyanogen chloride), and complications, and bone marrow suppression. The cuta-
toxins (saxitoxin, ricin, and botulinum toxin). It is beyond neous manifestations are universal and range from first-
the scope of this chapter to discuss all of the agents. This degree chemical burns to severe edema, vesication, and
chapter briefly discusses the more likely agents, namely necrosis. Management includes decontamination, burn
the nerve agents and blistering agents. care, fluid resuscitation following burn protocols, pain
Nerve agents are irreversible anticholinesterases of control, and perhaps antibiotic therapy. Ocular symptoms
high potency and are chemically related to organophos- (85% of victims) include pain, blurred vision, lacrimation,
phate insecticides. They inactivate acetylcholinesterase corneal edema, and vesication. Management includes
(AChE), which causes accumulation of acetylcholine at copious irrigation and standard corneal abrasion treat-
muscarinic, nicotinic, and CNS synapses. The muscarinic ment. Respiratory compromise occurs in over 70% of the
effects include miosis, glandular hypersecretion (sali- victims ranging from tracheobronchitis to pulmonary
vary, bronchial, and lacrimal), sweating, bradycardia, hemorrhage and pulmonary edema. Management is pri-
atrioventricular block, QT prolongation, bronchocon- marily supportive with endotracheal intubation and
striction, diarrhea, and incontinence of urine/stool. The mechanical ventilation. The lung injury may be perma-
effects on the nicotinic receptors progress from fascicu- nent. Bone marrow suppression occurs with severe
lations to skeletal muscle weakness to paralysis. AChE exposure and may result in immunosuppression and
inactivation in the CNS results in irritability, giddiness, increased bleeding risk. Bone marrow suppression is a
ataxia, fatigue, amnesia, hypothermia, lethargy, seizures, poor prognostic sign.
coma, and respiratory depression. Death can occur It is hoped that the ICU physician will not have to
through a variety of mechanisms. Treatment must be deal with mass casualties from a terrorist chemical
instituted rapidly if there is going to be any chance of attack. This is not an exhaustive discussion, but covers
survival. the more likely agents. For both nerve agents and mus-
Like other poisonings, attention to basic resuscitation tard gas it is important to be aware of potential provider
(intubation, controlled ventilation, etc.) must be made. exposure to these agents. Decontamination should be
Atropine and oximes are effective antidotes but need to accomplished prior to ICU admission.
366 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
SELECTED READING
CONCLUSION
Abraham RB, Rudick V, Weinbroum AA: Practical guidelines
Poisoning and toxicity problems are common prob- for acute care of victims of bioterrorism: conventional
injuries and concomitant nerve agent intoxication.
lems in the ICU. As in all cases, attention to the basics of
Anesthesiology 97:989–1004, 2002.
resuscitation (airway, breathing, and circulation) should
be the clinician’s first priority. After stabilization, atten- White SM: Chemical and biologic weapons. Implications for
anesthaesia and critical care. Br J Anaesthesia 89:306–324,
tion should be turned toward agent identification, limit-
2002.
ing absorption, and administering antidotes. Early and
aggressive treatment in the ICU can limit morbidity and Zimmerman JL, Rudis M: Poisoning. In Critical Care Medicine,
ed 2, Mosby, 2001, Chap 73.
mortality.
35
CHAPTER Ethics in Critical Care
DAVID KAUFMAN, M.D., F.C.C.M.
JEFFREY SPIKE, Ph.D.
Principles of Medical Ethics the mechanisms that led to the conflict or problem in
Autonomy the first place. A little preparation will allow one to be
Beneficence and Nonmaleficence more comfortable when confronting these situations,
Justice making responses more likely to be useful (and less
Arguments likely to make things worse).
Case Studies There are four basic principles of medical ethics that
The Jehovah’s Witness give us the tools to begin to resolve some of these con-
The Transplant flicts: autonomy, beneficence, nonmaleficence, and
Brain Death justice. The weight we give each of these four different
General Comments principles is often determined by our individual and
Capacity societal morals (Box 35-1).
Choice of a Health Care Agent
Futility
Informed Consent
Pharmaceutical Connection
PRINCIPLES OF MEDICAL ETHICS
367
368 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
approved for the treatment of septic shock and costs laceration. Given the fact that she would not accept a
between $6000 and $10,000 for a course of therapy. transfusion at a presenting hemoglobin of 6.0 g/dl a
Should the price play a role in our decision to use this splenectomy was performed with her consent rather
novel new drug? Do we give activated protein C to than observation. Postoperatively she had unexpected
someone who is 100 years old and suffering from severe bleeding and her hemoglobin dropped to 2.3 g/dl. At
septic shock and, we believe, is unlikely to survive more this point she developed a lactate level of 3.5 mmol/l and
than a couple of hours? Do we give it to someone who a delirium. Her husband, who is not a Jehovah’s Witness,
is young and who is suffering from very mild septic demands that a blood transfusion be given. She has not
shock and is very likely to survive with standard therapy? filled out a health care proxy.
Tackling justice at the bedside is a prickly path that, if This case, like many in the ICU, does not have an
taken, must be done consciously and cautiously. It can obvious answer. The principle of autonomy would dic-
be very tempting to use one’s authority to impose one’s tate that we follow her initial wishes but we cannot be
own value judgment, and it is important to remember sure that she would not choose a transfusion if she was
that not everyone has the same values. so morbidly anemic. We could even speculate that by
not appointing a proxy, she knew her husband would be
asked to decide, and she preferred it that way.
Arguments The principle of beneficence could also be inter-
These four principles serve a very practical function. preted in different ways. Should we say that it is in her
They allow the clinician to view an ethical dilemma from best interests to have a blood transfusion or is it in her
different perspectives. They are not meant to provide a best interests not to have a blood transfusion because it
simple solution to problems, so much as helping in goes against her religious beliefs? It is most important
understanding the source of the problem. The four prin- when facing this situation to realize that many Jehovah’s
ciples are independent, meaning there is no reason to Witnesses never change their mind, and accept death
expect them to lead to a single answer to a dilemma. over transfusion, but that some do change their mind
Once a problem is analyzed using this scheme the con- (and even make subtle provisions to enable that to hap-
flicting positions in a dilemma are better appreciated. pen). The tone of the family meeting should be a quiet
Even if the dispute continues after the analysis, at least enquiry into which of these scenarios is the more likely,
the problem can be understood from more than one per- without calling into doubt the scientific validity of the
spective. This appreciation for other perspectives may metaphysical beliefs of the faithful.
lead to softening of firmly held positions and make an
eventual compromise easier, even if it does not lead to The Transplant
an immediate resolution. A 23-year-old woman presents to the emergency
An argument in philosophy means a conclusion with department and is transferred to the ICU following an
premises that provide support, like evidence for a scien- overdose of acetaminophen. This is her third suicide
tific theory. A dilemma is when there are arguments for attempt. Despite appropriate therapy, she develops
two incompatible conclusions. The goal of analyzing ethi- fulminant hepatic failure. A liver is identified and she is
cal dilemmas is not to prove only one view is right, but to scheduled for a transplant. She has hepatic encephalopa-
show persons holding each position that the other position thy and does not presently have capacity. The anesthesia
is also reasonable. Which course to follow may be decided resident on rotation asks why a patient that has tried to
by which argument has better support, or by which person commit suicide is scheduled for a transplant when
has more at stake or more authority to make the decision or donated livers are such a limited resource.
will suffer the consequences of the decision. The issue of justice is woven into every transplant deci-
sion. Since organs are a limited resource, for each person
who receives a vital organ somebody else must be denied
Case Studies the organ who will die as a result. Ranking systems are
There are many unique ethical situations that arise in attempts to remove justice from bedside decision-making
the ICU that deserve mention. Three situations, however, and, appropriately, place them in the hands of society.
bring out special features of this environment and are Since this patient does not have capacity we would turn to
particularly illustrative. We will use them to investigate her health care agent or, more likely if she did not a have
the different view obtained from the vantage point of the a health care proxy, her next-of-kin to make a decision.
four basic principles of medical ethics discussed above. Since it was a suicide attempt the agent would be invoking
the principle of beneficence over autonomy since she may
The Jehovah’s Witness very likely refuse a transplant if she had capacity.
A 58-year-old woman who is a Jehovah’s Witness pres- A waiting list for livers may include many patients
ents to the ICU after a skiing accident that led to a splenic who have potential contraindications: an active alcoholic
370 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
372
Safety, Quality, Scoring Systems, and Legal Issues in Critical Care 373
systems theory suggests that the use of algorithms, check- errors, and automatically crosschecking for patient drug
lists, and team-based practice creates a more optimal envi- allergies and sensitivities, end-organ dysfunction and dos-
ronment for error prevention. Decision-support systems ing, and drug interactions. Electronic medical records can
also include the availability of information at the point of potentially increase patient safety by delivering accurate
prescribing, such as PDAs, intranet and internet access, and legible medical information to many health care
and reference texts. Multiple levels of verification include providers simultaneously at any point of care. Decision
nurses, pharmacy, and colleagues. According to the support systems (DSSs) include digitalized reference mate-
Agency for Health Care Research and Quality, adverse rials, formularies, internet access to search engines, and
drug events (ADEs) cause approximately 777,000 injuries guidelines and protocols available at the point of care
and deaths annually and cost $1.5 million to $5.6 million through digital area networks. DSSs can also automatically
annually per hospital depending on hospital size. In addi- initiate physical/occupational therapy evaluations, social
tion, ADEs increase hospital length of stay by 8–12 days work consultations, and discharge planning, for example.
per patient affected and increase hospitalization cost by up Crew resource management (CRM), originally called
to $24,000 per event. Medication dosage errors account cockpit resource management, is a model of active team
for 28% of all hospital-related errors. The Institute of participation at all levels of decision-making. In essence,
Medicine has highlighted the problem and proposed based on the safety practices of airlines, “any crew mem-
changes. Hospitals that do not proactively implement ber can question or stop takeoff.” CRM is based on the
plans to reduce medical error will risk losing market share concepts of situational awareness, interpersonal com-
and increase their medical–legal liability. Examples of prac- munications, and standard operating procedures, and
tical implementations of safety measures include resident debriefing to optimize operational integrity and safety.
work hours and supervision requirements, computerized Fully trained and credentialed providers and appropriate
position order entry and point-of-care decision support sys- staffing ratios are important to outcomes.
tems, and communication facilitation models such as crew Leadership defines the culture. The impact of leader-
resource management. Medical errors are also common in ship style, attitude, commitment, and willingness to
CCM, perhaps as a result of the intensity of care. The team adhere to the team model of critical care is fundamental
model of critical care practice is a key component of the to nurturing a culture of safety and quality. Continuous
“culture of safety” and encourages collaboration and input. learning is essential. Medicine and especially critical care
is a field where significant changes and advances occur
PEARLS frequently. Distillation of information and a dedication
to education in both academia and private practice alike
Examples of Patient Safety Improvement is a key component of safety and quality.
Opportunities Data also reveal that patient safety varies in the same
● Adverse drug reactions (ADRs)
institution between days, nights, and weekends. There
● Venous thromboembolism (VTE)
● Stress-related gastrointestinal bleeding is a significantly higher incidence of errors, slower
● Unplanned extubations response to critical incidents, and poorer outcomes dur-
● Ventilator weaning protocols ing “off-shifts.” Fatigue impairs data assimilation and
● Sedation and pain management protocols decision-making ability. Although standard operating
● Falls, restraints, and related injuries procedures and other support systems can mitigate the
● Failure to honor patient DNR preferences effects of fatigue, the imposition of mandatory rest times
● Communication issues
is becoming uniform practice.
● Wrong surgery/site
● Informed consent
● Abnormal laboratory or radiology results
● Nosocomial infections QUALITY
● Ventilator-associated pneumonia (VAP)
● Central venous catheter-related infections A precise definition of “quality” is elusive but may be
● Surgical site infections best defined as an error rate, although both frequency and
● Contrast-induced nephropathy magnitude of errors must be considered. Maximization of
● Malnutrition and related complications
● Unanticipated mortality
quality may be considered to represent minimization of
the variation from an accepted standard. Health care
reform of any nature must be based in a delivery system
Computerized physician order entry (CPOE) is a com- based in data and information. The challenge is to deter-
puterized order entry system whereby physicians and mine what is sufficiently important to be measured
other licensed providers enter medication and plan-of- and how best to measure it. Measurement is the basis
care orders directly into a computer terminal. CPOE has for any systematic safety or quality program; thus, there
an impact on patient safety by eliminating transcription is an overlap between the concepts of safety and
374 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
INTENSIVE CARE UNIT SCORING ● Glasgow Coma Scale (GCS) for central nervous
SYSTEMS system injuries
● Child–Pugh Score for cirrhosis
● Ranson’s Criteria for pancreatitis
Scoring systems have been developed in response to
● Lung Injury Score (LIS) for respiratory failure
a need for comparative analysis of patient outcomes
within a single institution over time and to assess the
impact of continuous quality improvement (CQI), and
for inter-institutional analysis to identify best practices.
Scoring systems are also used to estimate prognosis and range of diseases, be clinically credible, be capable of
outcome, to justify triage decisions, and to optimize measuring severity at multiple points along the care con-
resource allocation. tinuum, be relatively easy to implement, and provide
Many commonly accepted medical practices have statistically valid information. All predictive indices cur-
been implemented which had not been subjected to rig- rently in use have a false classification rate of 10–15%.
orous scientific clinical investigation. The lack of con- Therefore, 10–15% of patients predicted to survive will
vincing evidence supporting the efficacy of interventions die, and vice versa.
or medical therapies has resulted in diverse individual Data can be quantitative, quantal, or qualitative.
practitioner beliefs or practices with large variations in Quantitative data refers to measured quantities. Quantal
clinical outcome. Increasingly, these beliefs are being data refers to attributes that may be classified.
questioned and challenged in large prospective random- A distribution curve is a frequency distribution of the
ized multicenter clinical trials resulting in accepted incidence of specific values. A normal or Gaussian curve
evidence-based standards. Theoretically, each and every has values evenly distributed around the mode; a multi-
intervention used in intensive care should be subjected modal curve is a frequency distribution curve with more
to randomized controlled trials to determine its clinical than one mode. Many populations are normally distrib-
effectiveness. uted but many critical care populations cannot be
Data-driven evidence-based practices are supplanting described using a normal distribution curve.
traditional teachings. ICU scoring systems allow fairly However, the fundamental issue regarding mortality
accurate predictions regarding clinical outcomes in pop- and survival is the appropriate time interval (30 days,
ulations of patients but cannot accurately and reliably 6 months, 5 years, etc.) at which the endpoint represents
predict the probability of individual survival. a valid quality indicator.
A scoring system describes the association between an Applications of scoring systems include comparative
independent variable such as case mix or severity of illness audit, evaluative research, development of standards,
and a dependent variable such as survival or functional and clinical care. Limitations of scoring systems include
status. A scoring system is developed using retrospective data accuracy, population sampling, data interpretation,
outcome data from large populations of patients and is a and clinical applicability.
mathematical model capable of being prospectively applied Examples of critical care scoring systems include
to new populations to predict outcome. Development of organ-specific measures (Box 36-3) and general severity-
the scoring system is accomplished through multiple of-illness scoring measures.
logistic regression analyses which describe the strength The Glasgow Coma Scale (GCS) is an example of a sim-
of the association between combinations of independent ple scoring system used for the assessment of the extent of
variables while simultaneously accounting for the effects coma in patients based on eye opening (4), verbal
of other independent variables in the system. response (5), and motor response (6). The scale is
Scoring systems are most commonly used for research weighted in favor of motor response. The total GCS is the
studies and for general inter-institutional comparisons. sum of each category and ranges from a minimum of 3 to
The use of scoring systems for inter-institutional out- a maximum of 15. GCS applications include prehospital
come and performance comparisons is very controversial triage and assessment of clinical change based on serial
both because of the unknown underlying assumptions in examinations. The GCS is an example of a descriptive scor-
the statistical modeling and because outcomes other ing system which later evolved into a correlate of out-
than survival and mortality are important. Descriptors of come. The GCS is incorporated into most contemporary
outcomes include measures such as mortality, morbidity, general severity scoring systems including Acute
functional status, quality of life, and cost. Physiology and Chronic Health Evaluation (APACHE) II
A scoring system must function independently of and III, Simplified Acute Physiology Score (SAPS) II, and
treatment, be disease specific and yet function over a Mortality Probability Model (MPM) II (Box 36-4).
376 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
in DNR status to comfort care DNR. Brain death is a statu- Additionally, digitally stored information is vulnerable to
torily defined definition of death. The Uniform Brain threats such as worms, viruses, and Trojan horses which
Death Act (1978), the Uniform Determination of Death can eradicate digital data or compromise their security.
Act (1980), state legislation, and case law are all important HIPAA is characterized by three intra-related parts: (1)
considerations to the development of policy. Since state the administrative simplification provisions; (2) the pri-
laws regarding brain death determination are not uniform, vacy rule, which sets security standards and policies; and
policy should be developed with the advice of counsel. (3) the security rule which governs relationships
between health-care business associates. HIPAA
increases the level of control that individual patients
Triage and Rationing of Services have over their personal health information (PHI) by
Triage refers to the prioritization of resource alloca- requiring notice regarding the proposed uses of their
tion to the individuals most acutely in need. Where personal information, allowing patients the right to
scarce resources preclude an appropriate level of care to inspect, amend, and copy medical records, receive an
a critically ill patient, considerations for an appropriate accounting of disclosures of their PHI, and also restrict
transfer must be made. Triage in the ICU is common- the use of their information. HIPAA privacy regulations
place and is often based on a subjective assessment of protect only that health information which is indivi-
severity of illness and requirements for therapeutics and dually identifiable. De-identified data, on the other
monitoring. Triage should probably be accompanied by hand, can be used or shared, generally without restric-
an objective measure of severity of illness if possible. tions, for research, organizational strategic planning, and
teaching.
The penalties for violation of HIPAA provisions are
The Health Insurance Portability and strict. The Office of Civil Rights has the authority to
Accountability Act: HIPAA receive and investigate complaints, and the United States
Respect for the privacy and confidentiality of Department of Justice imposes penalties at $100 per
patients’ medical information is a well-established prin- violation to a maximum of $25,000 per year for each
ciple of both medical ethics and health law. A respect for violation. Intentional or malicious disclosures which fall
each patient’s individual rights and dignity is essential to under the category of criminal violations range from
ensure trust and to promote the integrity and the com- $50,000 to $100,000 and up to five years in prison for
pleteness of health information disclosure within the false pretenses; and $250,000 and 10 years in prison if
scope of the physician–patient relationship. A “fiduciary the information is sold for commercial advantage, per-
duty” is one which a professional owes to a patient ben- sonal gain, or malicious harm.
eficiary, by virtue of knowledge, training, and experi-
ence. Fiduciary principles impose a heightened duty of
loyalty, integrity, and devotion upon professionals. The Billing, Coding, the False Claims Act
physician’s duty of confidentiality dates from the The economic realities of practice management
Hippocratic Oath, is codified within the Principles of require not only the highest possible level of quality in
Medical Ethics of the American Medical Association, and patient care, but also an analysis of costs and reimburse-
has been reiterated in legislative statutes such as the ment to achieve an optimum balance between revenue
Federal Privacy Act of 1974, in the Guiding Principles of and expenses without compromising quality. Critical
the Joint Commission for the Accreditation of Health care is defined by the U.S. Health Care Financing
Care Organizations (JCAHO), and, most recently within Administration (HCFA) to be the direct delivery by physi-
HIPAA. Multiple levels of law govern the privacy of cians of medical care for a critically ill or critically
health-care information and existing civil causes of injured patient. Critical illness or injury acutely impairs
action can include breach of privacy, breach of confi- the function of one or more vital organ systems such that
dentiality, breach of contract, breach of loyalty, and there is a high probability of a sudden and clinically sig-
other statutory violations. nificant deterioration by which survival of the patient is
The broad goals of HIPAA are to: (1) increase the effi- jeopardized. A high level of professional preparedness is
ciency of electronic health-care transactions; (2) ensure necessary to intervene urgently. Critical care also involves
the continuity of an employee’s health insurance cover- frequent assessment, and high complexity decision-mak-
age during the process of changing jobs; and (3) man- ing to assess, manipulate, and support vital organ func-
date widespread privacy protection measures for tions. ICU admission in itself is insufficient justification for
ensuring the security of individually identifiable health claiming reimbursement for critical care services unless
information. HIPAA is increasingly necessary as “elec- other explicit criteria of medical necessity, physician
tronic data interchange” (EDI) is used to transmit per- attendance, and therapeutic complexity are met as well
sonal health information via electronic and digital media. as documented. Additionally, the standard for procedural
380 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
supervision is such that the attending physician must be Classen DC, Pestotnik SL, Evans RS et al: Adverse drug events
physically present and immediately available in the case in hospitalized patients. JAMA 277:301–306, 1997.
of difficulty. Although otherwise credentialed residents Cook DJ: Evidence-based critical care medicine: a potential
may be sufficiently technically proficient to perform tool for change. New Horizons 6:20–25, 1998.
independently, the requirements for procedural billing Iezzoni LI: The risks of risk adjustment. JAMA; 278:1600–1607,
are more stringent. Misrepresentation of patient care 1997.
rendered in a teaching hospital setting as ‘supervised’ Institute of Medicine: Crossing the Quality Chasm: A New
when in fact it was not closely supervised, represents Health System for the 21st Century, Washington, DC:
fraudulent billing and is subject to civil and/or criminal National Academy Press, 2001.
penalties. Since hospitals are reimbursed independently Institute of Medicine: To Err is Human: Building a Safer
by the Centers for Medicare and Medicaid Services Health System, Washington, DC: National Academy Press,
(CMS) for resident teaching, hospitals and providers may 2000.
not bill for services provided independently by residents Layde PM, Maas LA, Teret SP et al: Patient safety efforts should
alone. Also, time spent teaching residents cannot be focus on medical injuries. JAMA 287:1993–2001, 2002.
claimed toward critical care time unless the physician Marshall JC, Cook DJ, Christou NV et al: Multiple Organ
and residents are together directly engaged in patient Dysfunction Score: a reliable descriptor of a complex clin-
care. Billing for critical care services requires diagnostic ical outcome. Crit Care Med 23:1638–1652, 1995.
codes which must match the verbiage documented Szalados JE: Critical care medicine: essentials of the reimburse-
within the medical record. Thus, documentation is the ment process. NYSSA Sphere 53:22–28, 2001.
key to accurate and timely claims review and payment Szalados JE. Health information privacy and HIPAA: The Health
by insurers, defensibility in the event of a bad outcome, Insurance Portability and Accountability Act. Curr Rev Clin
and a pivotal tenet to billing compliance standards. The Anesth 25(1):1–16, 2004.
submission of claims for any component of critical care, Szalados JE. Age and functional status as determinants of inten-
procedure, or other evaluation and management for sive care unit outcome: sound basis for health policy or tip
which the attending physician was not directly present of the outcomes iceberg? Crit Care Med 32(1):291–293,
may constitute fraud and abuse under the False Claims 2004.
Act. Submission of a bill for services at a level of service Szalados JE. Intensive care unit resource utilization by Medicare
greater than that which was actually provided represents patients: margin and mission meet public policy and
“up-coding;” whereas, submission of a claim a level of practice economics. Crit Care Med 32(11):2351–2352,
service lower than that actually provided represents 2004.
“down-coding.” Both up-coding and down-coding repre- Szalados JE. Do Not Resusciate and end-of-life care issues:
sent mis-coding and are both illegal. Although, the False clinical, ethical, and legal principles. Curr Rev Anesth
Claims Act has traditionally been enforced by the 24(5): 47–53, 2003.
government against hospitals and providers in the set-
ting of inappropriate billing for services rendered to Internet Resources
Medicare patients, there is an increasing trend towards Agency for Healthcare Research and Quality: www.ahrg.org
monitoring for billing fraud, and enforcement action, by American Board of Quality Assurance and Utilization Review
private insurers. Physicians: www.abqaurp.org
Other issues within the scope of health-care fraud and
American College of Legal Medicine: www.aclm.org
abuse include restrictions on self-referral under the Stark
American Health Quality Association: www.ahqa.org
Law, and the relationships between physicians and hos-
pitals under the “anti-kickback” statute. Leapfrog: www.leapfroggroup.org
National Committee for Quality Assurance: www.ncqa.org
SELECTED READING Project Impact: www.sccm.org/pi
Role of Scoring Systems increase in risk of death in ICUs include increasing age,
Types of Scoring Systems greater severity of illness, emergency surgery, and
Scoring Systems Based on Resource Utilization presence of concurrent severe medical conditions.
Scoring Systems Based on Physiologic Derangement Accounting for such patient characteristics or “case
Acute Physiology and Chronic Health Evaluation mix” is essential for proper comparisons of outcome.
Simplified Acute Physiology Score Outcome is usually measured as death before discharge
Mortality Probability Models from hospital after critical care. The role of scoring sys-
Trauma Scoring Systems tems is based on the quantification of case mix and the
Morbidity Scores development of mathematical models to estimate proba-
Shortcomings in Selecting a Scoring System bilities of outcome for ICU patients. The association
Summary between the independent variables (case mix) and the
dependent variable (death) is described in the form of a
Critical care consumes a disproportionate share of multiple logistic regression model. Applying the model,
hospital resources. While intensive care unit (ICU) beds the probability of death before discharge from hospital
comprise between 5 and 10% of total hospital beds, criti- after critical care can be estimated for each patient and
cal care accounts for as much as 25–34% of total hospital summed for all patients to yield the expected hospital
costs. Quality and cost of care are emerging as growing death rate for the group of patients. The expected hos-
concerns among health care buyers, policy makers, regu- pital death rate can then be compared with the actual
lators, and the public at large. As a result there is increased hospital death rate. Standardized mortality ratio (SMR) is
scrutiny and pressure to improve ICU care processes and the ratio of actual to expected deaths. SMR can be used
outcomes. Critical care, by virtue of its high cost, high as a measure of quality of different providers or ICUs.
complexity, and high mortality, lends itself to measure- An SMR greater than 1.0 may reflect poor care and an
ment of ICU performance and quality of care. Given the SMR of less than 1.0 may reflect good care.
relatively high mortality in ICU patients, death is a sensitive The major roles of ICU scoring systems include the
and meaningful measure of outcome. Therefore, mortality following:
still remains a “gold standard” as an outcome measure for ● Perform comparative audits. As mentioned above,
critically ill patients. Scoring systems have been developed the use of case-mix-adjusted outcomes as a measure
in response to an increasing emphasis on the evaluation of clinical effectiveness of ICUs assumes that an
and monitoring of critical care services. SMR of >1.0 may reflect poor care and an SMR of
<1.0 may reflect good care. Local clinical audits
must be performed to explain the reasons for any
ROLE OF SCORING SYSTEMS unexpected results. Severity models (Box 37-1) have
been widely used as the basis for public report
The purpose of scoring systems in ICUs is to take into cards. Managed care organizations and group
account the characteristics of patients that could affect practices are keenly interested in outcomes
their risk of a particular outcome and account for factors reporting.
that are outside the control of those providing the care. ● Perform evaluative research. Scoring systems have
Various patient-related factors associated with an been used to aid risk stratification in randomized
381
382 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
+4 +3 +2 +1 0 +1 +2 +3 +4
1. Temperature, rectal (°C) ≥41 39–40.9 38.5–38.9 36.0–38.4 34–35.9 32–33.9 30–31.9 ≤29.9
2. Mean arterial pressure = ≥160 130–159 110–129 70–109 50–69 ≤49
(2 × diastolic + systolic)/3
3. Heart rate (ventricular response) ≥180 140–179 110–139 70–109 55–69 40–54 ≤39
4. Respiratory rate (nonventilated ≥50 35–49 25–34 12–24 10–11 6–9 <5
or ventilated)
5. Oxygenation, A-aDO2 or
PaO2 (mmHg)
(a) FIO2 > 0.5: record A-aDO2 ≥500 350–499 200–349 <200
(b) FIO2 < 0.5: record PaO2 >70 61–70 55–60 <55
6. Arterial pH (if no ABGs record ≥7.7 7.6–7.69 7.5–7.59 7.33–7.49 7.25–7.32 7.15–7.24 <7.15
serum HCO3 below*)
7. Serum sodium ≥180 160–179 155–159 150–154 130–139 120–129 111–119 ≤110
8. Serum potassium ≥7 6–6.9 5.6–5.9 3.5–5.4 3–3.4 2.5–2.9 <2.5
9. Serum creatinine (mg/dl); double ≥3.5 2–3.4 1.5–1.9 0.6–1.4 <0.6
point for acute renal failure
10. Hematocrit (%) ≥60 50–59.9 46–49.9 30–45.9 20–29.9 <20
11. White blood cell count ≥40 20–39.9 15–19.9 3–14.9 1–2.9 <1
12. Glasgow Coma Scale 15 – GCS
(score = 15 − actual GCS)
A. Total acute physiology Sum of the 12 individual variable points =
score (APS)
*Serum HCO3 (venous, mmol/l); <52 41–51.9 32–40.9 22–31.9 18–21.9 15–17.9 <15
not preferred, use if no ABGs
Eyes open Verbal – nonintubated Age Points If any of the 5 CHE categories A + B + C (A = APS points,
is answered with “yes” give + B = age points, C = chronic
4 – spontaneously 5 – oriented and <44 0
5 points for nonoperative or health points)
3 – to verbal stimulus converses 45–54 2
emergency postoperative
2 – to painful stimulus 4 – disoriented 55–64 3
patients
1 – no response and talks 65–74 5
Liver Cirrhosis with Total APACHE II Score =
3 – inappropriate >75 6
PHT or
words
encephalopathy
2 – incomprehensible
Cardiovascular Class IV angina or
sounds
at rest with
Motor response 1 – no response
minimal self-care
6 – to verbal command activities
Verbal – intubated
5 – localizes to pain Pulmonary Chronic hypoxemia
5 – seems able to talk
4 – withdraws to pain or hypercapnia or
3 – questionable
3 – decorticate polycythemia of
ability to talk
2 – decerebrate PHT > 40 mmHg
1 – generally
1 – no response Kidney Chronic peritoneal
unresponsive
or hemodialysis
Immune Immune
compromised host
Score
Organ System 0 1 2 3 4
* The PO2/FIO2 ratio is calculated without reference to the use or mode of mechanical ventilation, and without reference to the use or level of positive end-expiratory
pressure.
† The serum creatinine concentration is measured in μmol/l without reference to the use of dialysis.
‡ The serum bilirubin concentration is measured in μmol/l.
§ The pressure-adjusted heart rate (PAR) is calculated as the product of the heart rate (HR) and the ratio of the right atrial (central venous) pressure (RAP) to the mean
** The Glasgow Coma Score is preferably calculated by the patient’s nurse, and is scored conservatively (for the patient receiving sedation or muscle relaxants, normal
function is assumed, unless there is evidence of intrinsically altered mentation).
to the MOD scores in most organs, except for cardiovas- goodness-of-fit (calibration and discrimination) of the
cular dysfunction. The SOFA score utilizes a combina- mathematical model used to estimate outcome.
tion of hypotension and requirement for specific Discrimination, or the ability of a model to distinguish
vasoactive drugs (Table 37-4). between a patient who will die and one who will live,
is usually measured by the area under the measured
receiver operator characteristic (ROC) curve. The total
SHORTCOMINGS IN SELECTING area under the curve is a good summary measure of pre-
A SCORING SYSTEM dictive ability. Calibration compares the observed mor-
tality with that predicted by the model within severity
APACHE II remains the most widely used and recog- strata. Validity is the ability of the score to measure fully
nized scoring system. The URL http://www.sfar.org/ what it is intended to measure, and includes construct,
scores2/apache22.html can be used to download APACHE content, and criterion validity. There is no “gold standard”
II. The criteria for selection of a scoring system should to use as the basis for establishing the validity of scoring
be based on the accuracy (validity and reliability) and systems. Reproducibility is the ability of the score to be
SOFA Score
Variable 0 1 2 3 4
389
390 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
state and cultural background may influence subjective with renal insufficiency due to the accumulation of
perception of pain. Therefore, the provider must assess active metabolites. PCA can be used with epidural infu-
the patient in order to determine the severity of pain and sions with combination techniques of local anesthetics
course of treatment. Numeric pain scales and Visual and opioids or with local and opioid infusions inde-
Analog Pain scales (VAS; 0 being no pain and 10 being pendently. Naloxone 40 μg IV may be repeated as
the worst pain ever noted) can assist in the treatment of needed to reverse respiratory depression; care should be
pain by helping patients quantify their pain. taken, as rapid reversal has been associated with cate-
In addition to incisional pain, a patient may complain cholamine release and pulmonary edema.
of nonsurgical pain, which must be elucidated before
aggressive treatment is initiated. A headache, sore throat
from airway instrumentation, and limb or back pain from Nonsteroidal Anti-inflammatory Drugs
prolonged positioning may distract the provider from The role of nonsteroidal anti-inflammatory drugs
adequate incisional pain relief. (NSAIDs) has changed as more anesthesiologists pursue
regimens that can supplement or replace opioids, and
thus decrease the incidence of opioid side effects.
Narcotics Effective as an analgesic, NSAID inhibition of cyclo-
Opioids are considered the mainstay for treatment for oxygenase (COX) expression has been associated with
early postoperative pain. Opioids are potent analgesics reduction of inflammatory mediators on peripheral noci-
that control moderate to severe postoperative pain. ceptors to promote preemptive analgesia. The use of
Binding to mu, kappa, and delta receptors spinally and NSAIDs has increased recently as studies have found
supraspinally, opioids may cause respiratory depression, equal efficacy between doses of NSAIDs and opioids
pruritis, nausea and vomiting, over-sedation, urinary without many of the deleterious central effects.
retention, and prolongation of postoperative ileus. Unfortunately, unlike opioids, there is a ceiling effect
Opioids such as fentanyl (12.5 to 50 μg), hydromor- with NSAIDs. Contraindications to NSAID use include
phone (0.125 to 0.5 mg), meperidine (10 to 25 mg), or history of allergy, renal insufficiency, peptic ulcer dis-
morphine (1 to 4 mg) may be cautiously intravenously ease, and platelet dysfunction. There has been great
titrated at five-minute intervals until an adequate anal- concern over the COX2 inhibitor agents over the last
gesic level is reached or respirations are 10 or less per year. The majority have been withdrawn from use.
minute. Although fentanyl has a quick onset (1 to 2 min- There may be increased risk for cardiovascular events.
utes) and rapid peak effect (3 to 5 minutes), its short We therefore recommend that they not be used until
duration of action compared with morphine results in further evaluation and risk benefit studies by the FDA.
higher pain scores and more need for oral analgesia
when patients recover in phase II. In the face of residual
postoperative sedation, PACU nurses should be acutely Local Anesthetics
aware of respiratory depression and titrate opioid therapy Local anesthetics block sodium channels and prevent
carefully for patient comfort. Preoperative neuraxial the transmission of electrical nerve impulses and are
morphine may last up to 24 hours (0.1 to 0.4 mg widely recognized as effective agents in perioperative
intrathecal, 3 to 5 mg epidural) and delivers good pain and postoperative pain management. Local anesthetics
control in the recovery room. Pruritis and nausea are can be utilized at various sites for analgesia. In addition
common side effects with opioid therapy and can be to nerve blocks performed by the anesthesiology team,
treated with nalbuphine and antiemetics, respectively. intraoperative infiltration of incisions and joints by
Intrathecal water-soluble opioids such as morphine may surgeons can reduce postoperative pain. Those at high
cause respiratory depression in the late postoperative risk for potential pulmonary complications can benefit
period. Recently, more research has demonstrated good from intercostal nerve blocks with local anesthetic seen
pain control with intra-articular opioids placed by sur- commonly in thoracic and upper abdominal procedures.
geons at the completion of their procedures, with or Extremity nerve blocks (e.g., interscalene, axillary, supra-
without local anesthetics. Patient-controlled analgesia clavicular, and sciatic) provide excellent pain control
(PCA) most commonly involves a preprogrammed sys- that will last many hours beyond the patient’s time in the
tem of continuous and/or incremental dosage of opioids PACU. Many patients without adequate pain control may
with a set lockout interval. PCA is often started in the be offered a nerve block in the PACU. Ultrasound guided
PACU, where nurses can evaluate and initiate loading blocks can be performed accurately and efficiently, with
doses. PCA increases patient satisfaction and decreases a lower incidence of complications. The toxicity of local
opioid requirement compared to scheduled regimens. anesthetics is reflected in the central nervous and cardio-
Morphine and meperidine should be avoided in patients vascular systems. With careful management and vigilant
Common Postanesthesia Care Unit Problems 391
dosing of local anesthetics, especially in the pediatric The blockade of these receptors is the mainstay in the
and geriatric populations, seizures and cardiac arrhyth- treatment of PONV.
mias can be minimized. These potential toxicities are
generally due to intravascular or inadvertent intrathecal
injection. Neuraxial anesthesia involving the placement Risk Factors
of local anesthesia into intrathecal, epidural, or caudal The risk factors involved in PONV can be subdivided
space can be performed throughout the perioperative into three areas: patient, surgery, and anesthesia. Patient-
period to help manage postoperative pain. Side effects related factors include female gender, nonsmoking
include hypotension secondary to sympathectomy status, and previous history of PONV or motion sickness.
and difficulty ambulating due to motor blockade and School-age children have a higher incidence than adults,
loss of proprioception. Analgesia is enhanced when whereas younger infants have a lower incidence.
narcotics are added to local anesthetics in neuraxial The type and duration of surgery are associated with
blockade. Safety with caudal anesthesia with the pedi- the rate of PONV. Surgery with an increased incidence
atric population has been well documented in the one-shot of PONV includes craniotomy; ear, nose, and throat pro-
bolus or continual infusion, with close observance to cedures including tonsillectomies and adenoidectomies;
dosing. ophthalmic, including strabismus surgery; major breast;
laparoscopic, especially gynecologic; laparotomies; and
orthopedic/shoulder operations. There is a 60% increase
NAUSEA AND VOMITING in the incidence of PONV for each 30-minute increase in
surgical duration.
Postoperative nausea and vomiting (PONV) remains Anesthetic-related factors can be divided into pre-
the most common complication in the immediate post- operative, intraoperative, and postoperative management.
operative period. Many patients acknowledge that Perioperative opioids have been associated with two to
PONV is the most distressing complication involved four times the incidence of PONV. However, inadequate
with the surgical experience, often more distressing analgesia in the perioperative period can cause increased
than postoperative pain. The incidence of PONV has PONV. Intraoperatively, the use of nitrous oxide has
been found to be as high as 30–50% in the first 24 hours been shown to increase PONV, especially in the later
following surgery. As the number of ambulatory surgery postoperative period. The diffusion of nitrous oxide to
centers and outpatient procedures continue to rise, the the middle ear and bowel, stimulating the vestibular
management of PONV becomes increasingly more apparatus and bowel distention, activates the dopamin-
important to both patients and the health care system. ergic receptors in the cortical medullary system and
Delays in discharge, risk of pulmonary aspiration, endogenous cerebrospinal opioids from bowel disten-
increased cost of nursing and medical care, and the tion. Modern volatile anesthetics increase the incidence
potential for unanticipated hospital admission following of PONV, although less than previously used ether and
ambulatory surgery erode the cost savings of outpatient cyclopropane. When propofol is used as an induction
surgery. The debate continues regarding the timing and and maintenance agent, it reduces PONV in the early
the efficacy of the many modalities for the prevention postoperative period with less benefit approximately
and treatment of PONV. 6 hours postoperatively. Propofol in low bolus doses
Nausea involves the subjective sensation of discom- (20 mg IV) in the PACU has been shown to assist in
fort often associated with vomiting, but may occur inde- the treatment of PONV. Reversal of neuromuscular
pendently caused by impulses from the gastrointestinal blocking drugs (NMBDs) with anticholinesterases, such
tract or from the cerebellum with motion sickness. as neostigmine and edrophonium, increases gastric
The physiology of vomiting involves an intricate com- motility and may increase PONV. PONV is more common
munications network centering on the emetic center at doses greater than 2.5 mg of neostigmine. Because
located in the lateral reticular formation in the medulla. anticholinergic medications are routinely given with
Afferent inputs involve chemical mediators from the anticholinesterases to reduce their muscarinic actions,
chemoreceptor trigger zone, solitary tract nucleus, there are reports that the use of tertiary agents like
vestibular apparatus, cerebellum, and higher cortical atropine, which cross the blood–brain barrier, may cause
areas, as well as input from the gastrointestinal system. less PONV than those that do not (glycopyrrolate).
Efferent impulses are transmitted through the vagus, Recent research has found that oxygen at 80% during
phrenic, and spinal nerves and coordinate the diaphragm and possibly two hours following laparoscopic gyneco-
and abdominal musculature in the act of vomiting. The logic surgery results in a twofold reduction in nausea
central chemical receptors involved include dopamin- and vomiting compared to 30% oxygen. It is thought that
ergic, muscarinic, serotoninergic, histaminic, and opioid. hyperoxia decreases dopamine release by the carotid
392 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
bodies and decreases serotonin release by the intestines Administration, due to anecdotal reports that found the
in periods of ischemia. prolongation of QTc interval and fatal arrhythmias; one
Although not conclusive, administration of intra- should consider alternatives in patients with a prolonged
venous fluids above maintenance rates (20 ml/kg) to QT interval or at high risk of arrhythmias.
ensure proper hydration reduces PONV. Dehydration, Promethazine and prochlorperazine are direct-acting
orthostatic hypotension, and dizziness can all promote dopamergic antagonists that work directly on the CTZ.
postoperative emesis. Even at low doses, they appear to be very effective for
Postoperatively, there are numerous stimuli that PONV but are associated with sedation and extra-
may cause PONV. Following a general anesthetic, the pyramidal side effects.
vestibular apparatus may become sensitized by diffusion
of nitrous oxide into the middle ear, causing emesis. Histamine H1 Antagonists
Movement of those individuals by stretcher, wheelchair, Commonly used in regimens for chemotheraputic-
or ambulation may cause PONV, especially in those indi- induced nausea and vomiting, the histamine H1 receptor
viduals that received opioids. Environmental factors can antagonists are weakly antiemetic. Due to their low cost,
reduce the incidence of PONV, especially those with a H1 blockers have found resurgence in interest as
history of previous PONV or motion sickness. A quiet antiemetic medication. Common side effects include seda-
environment with minimal activity may prevent and tion that may not be suitable for the postoperative period.
reduce emesis.
Muscarinic Antagonists
Receptors in the vestibular apparatus include mus-
Agents carinic and histaminic receptors. Although many studies
There are a number of agents available in the preven- extrapolate the use of anticholinergics from the premed-
tion and treatment of PONV. There are opposing views ication period, atropine can cause irritable behavior, dry
regarding treatment of PONV prophylactically or with mouth, and blurred vision. Transdermal scopolamine,
rescue medication. The cost effectiveness, side effect if placed well before the preoperative period, has
profile, and patient satisfaction must be considered, been shown to lessen PONV, especially in patients
especially as newer and more expensive antiemetic receiving epidural opioids as well as children using a
agents are being developed and used regularly. morphine PCA.
Pretreating patients at low risk for nausea and vomiting
is not cost effective; however, many providers agree that Serotonin Antagonists
high-risk patients undergoing operations with a high Ondansetron is the prototypical serotonin antagonist
likelihood of emesis should be treated aggressively with and although it has structure similar to metoclopramide,
multiple agents. We will focus on each medication as a it has no affinity at the dopamine receptor. Multiple
treatment for emesis and/or nausea, and the potential for studies have shown that ondansetron used to treat
effective combination therapy. PONV is effective at a 1 mg dose and is effective in the
prevention of PONV at a 4 mg dose. Many believe that
Dopamine Antagonists ondansetron is more consistently an antiemetic than an
Metoclopramide antagonizes central dopamine recep- antinausea agent. Side effects include headache, light-
tors and at high doses antagonizes 5-HT3 receptors. headedness, dizziness, increased liver enzymes, and con-
Although it is not recommended to treat or prevent stipation. Ondansetron has been noted to be effective in
PONV because of its minimal antiemetic effect, meto- children at a dose of 50 μg/kg. Although increasingly
clopramide increases lower esophageal sphincter tone expensive, other agents in this class include granisetron
and motility through interactions of dopaminergic and 40 μg/kg and dolasetron 12.5–50 mg.
cholinergic receptors. Droperidol interacts though
heterocyclic, neuroleptic central dopaminergic receptors Corticosteroids
and is known to cause adverse effects similar to meto- Although its exact mechanism of action is unknown,
clopramide, including sedation, lethargy, agitation and dexamethasone is an effective antiemetic at a dose
extrapyramidal symptoms. These effects can be mini- 150 μg/kg for children and 8–10 mg for adults if
mized by the use of lower dosing (0.625–1.25 mg) in given prior to incision. There is no proven benefit of
adults; its low cost and high efficacy make it an attractive dexamethasone in the PACU.
agent. Droperidol is contraindicated in patients with
Parkinson’s disease. Droperidol can be effectively dosed
at 50–75 μg/kg in children. Droperidol has been much Postanesthesia Care Unit Regimens
discussed with regards to the “black box” warning that After receiving a patient in the PACU with PONV, the
was provided recently by the US Food and Drug care provider must examine the patient at the bedside and
Common Postanesthesia Care Unit Problems 393
blockade including train-of-four ratio, sustained tetanus, aspiration, trauma, massive transfusion, sepsis, and acute
and sustained head lift for 5 seconds. The ideal train-of- respiratory distress syndrome.
four ratio of >0.7 is not practical in the operating suite. Pulmonary embolus would be suspected in a patient
Due to increased use of shorter-acting neuromuscular with pleuritic chest pain, dyspnea, tachypnea, and
agents and more commonplace use of nerve stimulators, decreases in PaO2. Pulmonary hypertension, right-sided
adequate reversal is more reliable and less postoperative heart strain on ECG, elevated central venous pressures,
residual blockade and upper airway obstruction is and systemic hypotension may be apparent in those
observed in the PACU. patients with a large pulmonary embolus. Patients at
Incisional thoracic and abdominal pain results in high risk include those who have been on prolonged
shallow rapid breathing and may result in a decrease in bed rest prior to surgery. Petechiae may be present in
the forced vital capacity/vital capacity (FVC/VC) ratio patients with fat emboli, which may occur after long
postoperatively. Upper abdominal surgery will reduce bone fractures.
diaphragm excursion musculature and decrease abdom- Pneumothorax should be high on the differential
inal assistance to breathing, converting the work of diagnosis of hypoxemia in cases following central line
breathing to the intercostals musculature. Pain can also placement, brachial plexus blockade, intercostal nerve
prevent the coughing and deep breathing that blocks, trauma including rib fractures and chest tube
is required to clear secretions and open closed airways. placement, procedures which involve the head and
neck, and diaphragm, especially in the retroperoneum.
In addition to rarely causing a pneumothorax, upper
V/Q Mismatch extremity blocks may cause hypoxia from phrenic nerve
Ventilation/perfusion mismatch may cause hypoxia paralysis.
or hypercarbia in the PACU. Shunt (low ventilation
relative to perfusion) will cause a more significant
hypoxemia, whereas deadspace (high ventilation relative
to perfusion) may additionally cause hypercarbia. Evaluation
Intraoperatively, patient positioning will potentially Hypoxemia may present as hypertension, hypotension,
worsen V/Q mismatch prior to surgical intervention. tachycardia, bradycardia, agitation, or cardiac dysrhyth-
Nondependent areas of lung will be well ventilated but mias. These signs and symptoms are nonspecific and may
poorly perfused, while dependent areas will have better be subtle; thus, the pulse oximeter should be continued
perfusion. These changes will linger into the early post- throughout the PACU period. Pulse oximeters are accu-
operative period and may cause hypoxemia. rate in the range 70–100%, although they require pul-
Postoperative atelectasis can occur from bronchial satile blood flow for differentiation of oxygenated and
obstruction due to secretions or blood in the airway, or deoxygenated blood and are unreliable in periods of
poor inspiratory effort. This can occur in a segmental or hypovolemia, hypothermia, and peripheral vasoconstric-
diffuse pattern. Right to left intrapulmonary shunting tion. Pulse oximeters are poor monitors of other clini-
will occur and the patient will develop a decreased func- cally important species of hemoglobin (Hb), including
tional residual capacity and smaller airway volumes, which Met-Hb and carboxy-Hb, which may cause unreliable
increase airway collapse. Upper abdominal and thoracic readings. If in doubt, the clinician should draw an arte-
procedures will commonly cause significant postoperative rial blood gas and measure the partial pressure of oxygen
atelectasis. Following thoracic cases with endobronchial directly. The arterial blood gas will reveal the patient’s
intubation, collapse of a patient’s lung is a source of major oxygenation and ventilation status. In addition to careful
atelectasis and if not corrected intraoperatively will be lung auscultation, a chest x-ray will help define the
difficult to manage in the PACU without positive pressure etiology of a patient with suboptimal oxygenation
ventilation to open up the collapsed airways. despite supplemental oxygen and a reasonable respira-
Pulmonary edema may cause hypoxia in the PACU. tory rate and tidal volume.
Pulmonary edema is most common in patients with a
decreased left ventricular ejection fraction, severe valvular
disease, or myocardial ischemia, especially in the setting Treatment
of acute rises in afterload or heart rate. Healthy patients Many of the above diagnoses can be treated quickly
with airway obstruction and hypoxia after extubation with supplemental oxygenation. Concentrations of
can develop negative pressure pulmonary edema from 30–60% generally will correct mild to moderate hypox-
the sustained reduction in interstitial hydrostatic pres- emia. Although this may help correct arterial hypoxemia
sure. Pulmonary edema may also be due to increased temporarily, the practitioner must evaluate the patient
capillary permeability after pulmonary injury, including and treat the underlying cause of hypoxemia.
Common Postanesthesia Care Unit Problems 395
Airway obstruction requires expeditious correction. antibiotics or magnesium therapy as well as hypokalemia
Loud snoring and/or inspiratory stridor characterize partial or metabolic acidosis. Second, altered pharmacokinetics
obstruction. Total obstruction is characterized by lack of air with hypothermia and liver or renal failure will cause
exchange and loss of breath sounds. The patient will com- delayed metabolism or excretion of certain neuromuscular
monly attempt to use all respiratory musculature to assist in agents. Third, pharmacologic reversal of the neuromus-
respirations. Nasal flaring, retractions of the substernal cular blockade may have been inadequate, causing pro-
notch as well as intercostal muscles, and increased longed paralysis in the PACU. Fourth, the patient may
diaphragmatic/abdominal excursions, which may perform inadvertently receive a neuromuscular block bolus in the
paradoxically to chest movement, may occur. These PACU when a previously obstructed IV line is cleared.
patients should receive supplemental oxygen while correct- Patients with residual neuromuscular blockade must be
ing the obstruction. The patient’s head should be extended quickly treated with supplemental oxygenation, additional
and jaw thrust forward to assist in pulling the tongue for- antagonist, if indicated, and ventilatory support as needed.
ward from the posterior pharynx. If needed, an oropharyn- Wheezing, rales, diminished bronchial sounds, and
geal or nasopharyngeal airway should be placed to ensure a rhonchi may be present in many forms of ventiliation/
patent airway down to the vocal cords. The nasal airway perfusion defects. Increased inspired oxygen concentra-
may be better tolerated in the lightly sedated patient. tion will overcome many of these defects, especially in
Continuous positive airway pressure may be successful in patients with known preoperative obstructive or restric-
some patients. If the obstruction is not relieved, one must tive lung disease. Bronchospasm should be treated with
then consider problems with the larynx. Laryngospasm is nebulized inhaled beta agonists or through metered dose
treated with the head tilt and jaw thrust maneuver, as well inhalers for intubated patients. Right to left shunting,
as manual pressure at the angle of the mandible and posi- including atelectasis, may not significantly improve with
tive pressure ventilation with a tight fitting bag and face- increased oxygen concentration. In intubated patients
mask with 100% oxygen. Suction if secretions or blood is simple atelectasis without potentially catastrophic com-
suspected. If the laryngospasm does not resolve, a small plications (i.e., lobar collapse, mainstem intubation, pul-
amount of IV succinylcholine (10–20 mg) should be monary edema, aspiration) may easily be corrected with
administered to assist in the relaxation of the cords. If simple maneuvers performed in the PACU. Humidified
unsuccessful, endotracheal intubation may be necessary to gases, lung opening procedures, and administration of
reestablish adequate ventilation. While intubating, one continuous airway pressures and positive end-expiratory
should observe the vocal cords closely for edema or pressure may be necessary to reinflate closed lung units.
trauma. Laryngeal edema may be treated with humidified Pulmonary edema of cardiac and noncardiac origin may
inspired gases and nebulized racemic epinephrine. be treated with diuretics, vasodiliators, and dialysis, if
Although not of immediate relief, dexamethasone 0.5 mg/kg necessary, in renal failure patients. Positive pressure ven-
IV can be given in cases of laryngeal edema. tilation may be indicated in cases of unresponsive severe
Residual opioid effects can be treated by the adminis- hypoxemia or respiratory acidosis. Intubation and venti-
tration of naloxone. Naloxone 40 μg every 2 minutes will lation with positive pressure ventilation will improve
allow the practitioner to titrate the opioid reversal to ade- oxygenation by expanding lung volumes. Continued
quate ventilation without completely antagonizing the ventilatory support may be necessary until definitive
analgesic effects following surgery. Poor titration will not treatment is identified.
only cause pain but activate the sympathetic nervous sys- Following aspiration, gastric contents must be quickly
tem, including hypertension, nausea and vomiting, pul- removed from the airway in the orophayrnx with thor-
monary edema, and myocardial ischemia. Naloxone has a ough suctioning. To protect the patient’s airway, a rapid
much shorter half-life than most narcotic medications sequence intubation with cricoid pressure will prevent
provided for analgesia; therefore, patients must be moni- further aspiration. The newly placed endotracheal
tored closely following dosing for renarcotization. tube should be quickly suctioned to prevent passing of
The evaluation of a patient with suspected neuromus- foreign material to the distal airways. 100% oxygen and
cular blockade should include a sustained head lift for positive pressure ventilation should be started as soon
5 seconds, vigorous hand grasping, and adequate vital as possible following the above maneuvers to avoid
capacity. Double vision and difficulty swallowing may also transient hypoxia.
occur. Neuromuscular blockade can be evaluated in a
moderately sedated patient with a nerve stimulator by test-
ing for acceptable response with no fade to a sustained TEMPERATURE ABNORMALITIES
tetanus. There are generally four reasons for residual neuro-
muscular blocking drugs. First, conditions that poten- Patients that arrive in the PACU with a temperature less
tiate neuromuscular blockers include aminoglycoside than 35°C are associated with a 30% increase in PACU
396 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
duration. Factors involved in heat loss include radiation, metabolize drugs are temperature sensitive and will be
convection, cutanous vasodilation, evaporative loss from affected by hypothermia. These medications include
the surgical field, and sweating. In addition, infusion of muscle relaxants and volatile and intravenous agents.
room temperature intravenous fluids or cold blood prod- The duration of vecuronium is nearly doubled in patients
ucts will contribute to heat loss. Although cool room with a reduction of 2°C of core temperature, and
temperature greatly contributes to hypothermia, anes- atracurium at 3°C below core temperature will have an
thetic-induced reduction in thermoregulatory control of increase in duration of about 60%. Tissue solubility of
a patient will add to postoperative hypothermia. Mild volatile agents increases with hypothermia. This will cause
hypothermia is generally defined as 34–36°C. greater uptake by the body at lower temperatures, and,
Complications with hypothermia have been exten- therefore, longer exhalation times to recover. Intravenous
sively studied. Notable are myocardial ischemia, coagu- propofol and fentanyl will have concentrations approxi-
lopathy, wound infection/healing, prolonged drug mately 10% and 5% greater, respectively, for every 1°C
effects, increased recovery times, and thermal discom- drop in temperature. These factors are related to the delay
fort. Upon emergence of general anesthesia, shivering in discharge of patients from recovery units.
may cause a large increase in oxygen demand. This may Thermal discomfort is notable for patients with mild
not directly cause hypoxia, but with an increased shunt hypothermia. Many patients in the recovery room will
fraction, the patient will likely become hypoxemic. As complain more about feeling cold than pain. Other con-
the patient attempts to regain thermostatic equilibrium cerns with hypothermia include hypokalemia and unre-
following a procedure, oxygen consumption will liable pulse oxygenation due to vasoconstriction.
increase and cause cardiac output and CO2 production Many PACUs will not discharge patients until their
to increase. Oxygen consumption may increase as much temperature reaches 36°C. Treatment involves an envi-
as 400–500% above baseline cardiac consumption, caus- ronment that provides a source of warming and prevents
ing a significant decrease in mixed venous oxygen satu- heat loss. Warming intravenous fluids will not actively
ration. Postoperative cold-induced hypertension in the warm patients, but rather sustain normothermia for a
elderly is associated with a threefold increase in nor- patient. Active cutaneous insulation and a forced air
epinephrine concentrations, which could lead to myo- warming system will provide adequate warming. Most
cardial ischemia. forced air systems include a powered heat blowing unit
Elderly patients with prolonged surgery have an as well as a cover. These disposable covers warm patients
increased likelihood of being transferred to the PACU through convection and radiant heat. Convection loss is
hypothermic. These patients are three times more likely to common in the operative suite and is the most common
have hypothermic-related myocardial ischemia or ven- source of heat loss, as cold air passing over skin will pro-
tricular arrhythmias. Platelet function, clotting factor mote loss, as seen with wind chill. A warming blanket
enzyme function, and fibrinolytic activity are three general passing warm air over skin will increase heat gain. Radiant
mechanisms that may cause hypothermia-induced coagu- heat loss will be reduced, as the warm covering will
lopathy. Platelet numbers are not affected by hypothermia replace the cool surfaces of the operating suite and PACU.
directly; however, platelet function is seriously impaired.
Coagulation tests are completed at 37°C even if the
patient’s temperature is much lower; therefore, prothrom- Hyperthermia
bin and partial thromboplastin times will not be prolonged Iatrogenic hyperthermia is usually due to vigorous
by hypothermia. Fibrinolysis appears to remain normal in warming without monitoring by the anesthesiologist.
mild hypothermia; however, the inability adequately to The differential diagnosis of hyperthermia includes
form clot may be the cause of coagulopathy. sepsis, inflammation, endocrine abnormalities, central
Wound infections have been a concern for both nervous system abnormalities, drug effects, and ineffec-
surgeons and anesthesiologists. Hypothermia can cause tive heat loss.
complications related to poor healing in two ways. Sepsis may cause hypotension and systemic vasodila-
First, hypothermia causes thermoregulatory vasocon- tion in a febrile patient. Inflammation mediated through
striction. Vasoconstriction markedly decreases oxygen cytokines will cause a systemic inflammatory reaction
tension to subcutaneous tissues, which directly correlates that will present with hyperthermia. Transfusion reac-
with wound infections. Second, mild hypothermia impairs tions related to immune reactions of incompatible blood
normal immune function, especially T-cell-mediated anti- products will cause a febrile reaction, hemolysis, and a
body and neutrophil oxidative bactericidal activities. leukoagglutinin reaction.
Reduced free oxygen radicals, which are oxygen depend- Endocrine abnormalities include catecholamine
ent, is notable in areas of vasoconstriction and hypoxia. excess, such as pheochromocytoma, thyroid storm,
The pharmacokinetics of many anesthetic-related Addisonian crisis, and cocaine or amphetamine use.
drugs are retarded in hypothermia. Many enzymes that There are several central nervous system sources of
Common Postanesthesia Care Unit Problems 397
hyperthermia, including trauma, in which hypothalamic ● Treatment of hyperkalemia if needed, e.g., insulin
injury can result in an elevated thermoregulatory set (10 units regular IV and glucose 50 ml D50).
point, intoxication, or postoperative delirium (resulting ● Monitoring urine to ensure adequate output, with
Anticholinergics and medications with similar actions ● Monitoring for arrhythmias, electrolytes, arterial
hypothermia will reduce minimum alveolar concentra- insufficiency and malnutrition. Rapid infusion of blood
tion in those patients. products decreases ionized calcium due to binding with
Narcotics and benzodiazepines may be reversed with citrate. Hypocalcemia is exaggerated by alkalosis, such
nalaxone and flumazenil (0.2 mg IV every minute, up to as in a patient hyperventilating due to pain. Signs and
1 mg total), respectively, but barbiturates, anticholiner- symptoms include confusion, seizures, and coma.
gics, psychotropic drugs, and alcohol have no specific Dysrhythmias including QT prolongation and decreased
antagonists. Physostigmine (1.25 mg IV) has been used cardiac contractility are commonly seen. Tetanus may
with variable success as a nonspecific treatment of also occur as well as laryngeal and diffuse muscle spasm.
delayed arousal. Treatment includes IV fluid hydration, correction of
respiratory alkalosis, and replacement with intravenous
calcium.
Metabolic Abnormalities
Many metabolic and electrolyte abnormalities in the
anesthetized patient will not become apparent until Neurologic Events
emergence from general anesthesia, presenting as Postoperative confusion may occur from intraopera-
decreased mental status or delayed emergence. Hypo- tive neurologic events such as cerebral ischemia,
glycemia, hyponatremia, and hypocalcemia are common seizures, and embolic or thrombotic events. Prolonged
disturbances that necessitate evaluation in the PACU. hypotension during anesthesia will have deleterious
A notable substrate for the brain to metabolize is glu- effects on perfusion and cerebral blood flow. Although
cose, and it is well known that hypoglycemia will cause the brain autoregulates to maintain constant perfusion
confusion and potentially coma. Those patients at high- at a mean arterial pressure range of 50–150 mmHg,
est risk for abnormalities include patients with diabetes patients who are above and below these values will have
mellitus who take insulin or oral hypoglycemics, patients cerebral perfusion that is pressure dependent. This
with hepatic dysfunction (low glycogen stores), and curve is shifted to the right in patients with hypertension
patients who have endocrine dysfunction including and cerebral hypoperfusion may occur without signifi-
hypothyroidism, hypopituitarism, and insulinomas. cant hypotension. Patients with existing cerebrovascular
Glucose test strips can quickly evaluate for hypoglycemia, disease have even less tolerance to hypotensive events,
which can be easily treated with intravenous 50% dex- as stenotic areas decrease perfusion to already suscepti-
trose. Severe hyperglycemia may cause decreased arousal; ble areas of the brain.
however, nonketotic hyperosmolar hyperglycemic Embolic phenomena may occur during carotid
coma takes days to develop and would rarely present in endarterectomy, sitting craniotomy (paradoxical emboli
the PACU, unless in patients who were debilitated prior if patent foramen ovale), or in patients with longstand-
to presenting for surgery. ing atrial fibrillation. Those with localized motor deficits
Hyponatremia can be seen related to multiple events, on examination indicating a possible ischemic or hem-
including free water absorption following transurethral orrhagic event must be evaluated appropriately with
resection of the prostate (TURP), hysteroscopy, and imaging and/or neurologic evaluation.
syndrome of inappropriate antidiuretic hormone release Any neurosurgical procedure will have the potential for
(SIADH). Pulmonary carcinomas commonly secrete seizure activity, as foci are potentially created with manip-
antidiuretic hormone (ADH). Positive pressure ventila- ulation of the brain. Generally, those being treated for
tion and stress following a surgical procedure also seizures will already have a depressed mental status due to
cause SIADH. Neurologic evaluation of patients with the disease itself or seizure medications. Many anesthetic
TURP procedures performed under spinal anesthesia agents are indicated in the treatment of seizures including
can be easily observed; however, the free water absorp- benzodiazepines and barbiturates; however, certain
tion of glycine-based irrigating solution during general intravenous agents have the potential for lowering
anesthesia is more difficult to evaluate. Depending on the seizure thresholds, including methohexatol and keta-
degree of hyponatremia, confusion, seizures, dysrhyth- mine. The postictal state can be treated conservatively
mias, and coma can occur. Acute, severe hyponatremia including protection of the airway, maintenance of
may be treated quickly with infusion of hypertonic saline, hemodynamic stability, and treatment with phenytoin.
but minimally symptomatic hyponatremia may be cor- Although muscle relaxants will stop physical muscle
rected slowly with normal saline and furosemide. Chronic activity, brain metabolic activity will continue and must
hyponatremia should not be rapidly corrected due to the be treated accordingly.
risk of central pontine myelinolysis. If the above diagnoses are ruled out, and postopera-
Hypocalcemia may occur following thyroidectomy tive delirium continues, sedation and/or psychotropic
or parathyroidectomy and in patients with pancreatic agents may be needed to manage the uncooperative
Common Postanesthesia Care Unit Problems 399
patient. Benzodiazepines, barbiturates, and haloperidol continues to be unarousable, check for iatrogenic causes
are agents of choice. Both benzodiazepines and barbitu- including residual propofol in the intravenous line, agents
rates have sedative effects and may potentially interfere given to the patient for nausea, or anxiolysis prior to the
with further examination of the patient; however, short procedure. Blood glucose should be checked and
haloperidol is a butyrophenone neuroleptic agent and electrolytes drawn and evaluated. Hypoglycemia should
can be used in cases of extreme delirium, agitation, and immediately be corrected with D50 and monitored
disorientation. Haloperidol is a dopamine antagonist closely. Hyponatremia can cause central nervous system
with minimal amounts of sedation and cardiac depres- (CNS) depression following a TURP, which can be
sive effects and can be given 5.0 mg IM or 2.5 mg IV prn. corrected with normal saline. Another CNS abnormality
Side effects include dysrhythmias, acute dystonic reac- which may be evaluated if indicated from the
anesthesiologist’s record of the procedure is a prolonged
tions, extrapyramidal symptoms reversed by diphen-
hypotensive period following the spinal and an ischemic
hydramine, tarditave dyskinesias, and NMS. event in a patient with hypertension and diabetes and
most likely cerebrovascular disease. Neurologic
evaluation and imaging studies would then be indicated
in this case, especially if the patient exhibited localizing
CASE STUDY motor deficits.
The case is a 78-year-old male, with longstanding
diabetes mellitus, hypertension, s/p TURP under spinal
anesthesia. The patient is somnolent upon arrival in the
PACU and the report received by the anesthesiology SELECTED READING
resident is that the patient received a bupivicane spinal,
3 liters LR and a propofol infusion because the patient Gan TJ, Meyer T, Apfel CC et al: Consensus guidelines for man-
“did not want to hear anything.” As the anesthetist aging postoperative nausea and vomiting. Anesth Analg
prepares to leave for the next patient it is quickly 97(1):62–67, 2003.
stated that the propofol infusion was discontinued Goll V, Akca O, Greif R et al: Ondansetron is no more effective
approximately 5 minutes prior to the completion of the than supplemental intraoperative oxygen for prevention
procedure and the patient has been “sleepy” since. of postoperative nausea and vomiting. Anesth Analg
Notable on preoperative evaluation is that the patient 92:112–117, 2001.
does not remember if he had taken his insulin at night Kissin I: Preemptive analgesia [Clinical Concepts and
or in the morning, but finger stick blood glucose on Commentary]. Anesthesiology 93:1138–1143, 2000.
the morning of surgery was 92. Your evaluation finds
McCrory CR, Lindahl SG: Cyclooxygenase inhibition for post-
an elderly gentleman, somnolent, unarousable, BP
operative analgesia. Anesth Analg 95:169–176, 2002.
100/45 P 98, RR 10 SpO2 99% on 3L NC. How would
you evaluate this patient? Rosenbaum HK, Miller JD: Malignant hyperthermia and
This is an elderly patient with multiple medical myotonic disorders. Anesthesiol Clin North Am 20:3, 2002.
problems presenting to the PACU with prolonged Sessler DI: Complications and treatment of mild hypothermia.
somnolence. His preoperative history appears unreliable Anesthesiology 95:531–543, 2001.
and his baseline mental status may not be completely Tramer MR: A rational approach to the control of postoperative
normal. Even so, following his procedure under spinal nausea and vomiting: evidence from systematic reviews.
anesthesia and propofol, the patient should be more Parts I and II. Acta Anaesthesiol Scand 45:4–19, 2001.
arousable. His vital signs, oxygenation, and ventilation
appear stable. After evaluating the airway, if the patient Watcha MF: Postoperative nausea and emesis. Anesthesiol Clin
North Am 20:3, 2002.
39
CHAPTER Pulmonary Surgery
Postoperative Care
SANJEEV V. CHHANGANI, M.D., M.B.A.
400
Pulmonary Surgery Postoperative Care 401
CLINICAL CAVEAT
The combination of acute mediastinal shift and
Suction Water seal Drainage gastric dilatation in a postpneumonectomy patient
control collection represents impending respiratory failure and must be
Figure 39-1 Chest tube drainage system showing three recognized and relieved immediately.
chambers for fluid collection, water seal, and suction control.
404 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
A B
Figure 39-2 A chest radiograph taken immediately after right pneumonectomy. Panel A shows mediastinal shift to left. Panel B shows
mediastinum returned to midline after aspiration of 1 liter of air from the right hemithorax (postpneumonectomy space).
ANTICHOLINERGIC AGENTS
Atropine sulfate 2.5–5 mg in 3 ml Nebulized 1 mg/ml
NaCl q 4–6 h
Glycopyrrolate 0.2 mg in 3 ml NaCl Nebulized 0.2 mg/ml
q6h
Ipratropium bromide 0.5 mg in 3 ml NaCl Nebulized 0.02% solution
q 4–6 h
2–4 puffs q 4–6 h MDI 18 μg/MDI dose
CORTICOSTEROIDS
Hydrocortisone 2 mg/kg or IV 50 mg/ml
2 mg/kg then IV
0.5 mg/kg/h Continuous
infusion
Methylprednisolone 60–125 mg q 6–8 h IV/PO 40, 62.5 mg/ml
Dexamethasone 4 mg q 6–8 h IV/PO 4 mg/ml Prophylactic for airway swelling
MUCOLYTIC AGENTS
N-acetylcysteine 3 ml of 20% solution Nebulized 10, 20% solution Use after nebulized β-agonist
q 6–8 h
Guaifenesin 100–400 mg q 6 h PO 100 mg/5 ml
NONSPECIFIC AGENTS
Helium/oxygen 70/30, 80/20 mixture Face mask Decreases turbulence of airflow via
mixture inhalation narrow airway
MDI, metered dose inhaler; SVT, supraventricular tachycardia; IV, intravenous; PO, oral; h, hours.
stress, reduce post-op pulmonary complications, and must be carefully balanced against the risk of sedation,
limit chronic post-thoracotomy pain syndrome. Post- hypoventilation, and cough inhibition.
thoracotomy analgesia begins with a thorough discussion
of post-op events and course and analgesia choices. Nonsteroidal Anti-inflammatory Drugs
Typically, a multimodal analgesia regimen provides supe- Nonsteroidal anti-inflammatory drugs (NSAIDs) block
rior pain control compared to any single technique. the synthesis of prostaglandins by inhibiting the enzyme
cyclooxygenase. NSAIDs may be used for controlling
Intercostal Nerve Block ipsilateral shoulder pain after thoracotomy in patients
Before thoracotomy is closed, intercostal nerve with epidural analgesia. Gastrointestinal bleeding and
blocks with 0.25% bupivacaine with epinephrine can decreased creatinine clearance are potentially serious
reduce post-op pain and opioid requirement. side effects of NSAIDs. These drugs must be avoided
in elderly patients and patients with preexisting renal
Systemic Opioids disease, hypovolemia, and congestive heart failure.
Systemic opioids are generally given as part of a mul-
timodal analgesia regimen, including nerve block and Paravertebral Block
nonopioid analgesics. Patient-controlled analgesia pro- Paravertebral block can be established by a catheter
vides better patient satisfaction. The benefit of analgesia placed surgically, at the time of thoracotomy, into the
406 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
paravertebral space. Analgesia is usually supplemented heart disease, congestive heart failure, advanced age), pres-
with systemic opioids and NSAIDs. In spite of its sim- ence of triggering factors (atrial extrasystoles, increased
plicity, paravertebral block carries a failure rate of sympathetic stimulation, acute atrial stretch), and surgical
approximately 10%. factors (atrial trauma, heightened sympathetic tone,
inflammatory response).
Interpleural Analgesia A variety of drugs have been used to prevent post-op
After thoracotomy, dilution of local anesthetic with AF. Routine use of digoxin should be discouraged due to
blood and loss of local of local anesthetic into the chest its lack of proven efficacy to prevent post-op AF. In a
tube reduces the efficacy of interpleural block. recent double-blind, placebo-controlled trial, Amar
showed that diltiazem was effective in reducing AF by
Epidural Analgesia 50% in thoracic surgery patients. The rate of AF remains
A thoracic epidural catheter provides effective and high despite extensive use of prophylactic beta-blockers.
reliable post-thoracotomy analgesia and has been shown The routine use of amiodarone is not recommended due
to be associated with decreased risk of post-thoracotomy to its high cost and concern about pulmonary toxicity
respiratory complications and potentially improved in thoracic surgery patients. The treatment of post-
outcome. The optimal site of insertion of the thoracic thoracotomy arrhythmias must begin with correction of
epidural catheter should be at the level of surgical incision. reversible factors such as respiratory failure and hypox-
We use a mixture of 0.1% bupivacaine and 4 μg per ml fen- emia, pain, and electrolyte imbalance. The initial goal is
tanyl for epidural infusion at 6–10 ml per hour. A properly to establish hemodynamic stability, obtain a 12-lead ECG
functioning thoracic epidural catheter is extremely valu- for diagnosis, and control the ventricular response.
able for post-thoracotomy analgesia in patients having Patients with severe hypotension or signs of organ
lung volume reduction surgery or pneumonectomy. hypoperfusion must be emergently electrically car-
Epidural opioids may potentially cause urinary retention dioverted using synchronized DC cardioversion.
and delayed gastric emptying. One of the common con- Adenosine is used to treat PSVT and delineate the under-
cerns among surgeons of epidural analgesia is that it can lying arrhythmia. Recent evidence from cardiac surgery
potentially cause hypotension requiring excessive fluid suggests that rate-controlling strategy may be superior to
administration. rhythm control. Beta-blockers (esmolol and metoprolol)
Whether thoracic epidural analgesia reduces post- or calcium channel blockers (verapamil and diltiazem)
thoracotomy mortality is still a controversial topic. Current are commonly used rate-controlling drugs. Calcium
evidence, however, suggests that epidural analgesia channel blockers are avoided in patients with pre-
can reduce post-op respiratory complications, decrease excitation arrhythmia (Wolff-Parkinson-White syndrome).
perioperative myocardial infarction, and reduce the Caution should be exercised with beta-blockers in
incidence of thromboembolic events. patients with known ventricular dysfunction and severe
COPD. Pharmacologic conversion to sinus rhythm, if
considered, must be used within 48 hours of AF due to
Management of Arrhythmia the risk of developing left atrial thrombus with persistent
Atrial tachyarrhythmias are common in a post- AF and potential embolic complication with restoration
thoracotomy patient, with incidence ranging from 9 to of sinus rhythm. The examples of converting drugs include
33%. The major arrhythmia in this population is atrial fib- ibutilide, amiodarone, flecainide, and propafenone.
rillation (AF), followed by paroxysmal supraventricular Prophylactic magnesium administration before using any
tachycardia (PSVT), atrial flutter (A-Flutter), and multi- of these drugs will reduce the risk of torsades de pointes.
form atrial tachycardia (MAT). The incidence of nonsus- The potential for thromboembolic complications increases
tained ventricular tachycardia is approximately 15%. if AF persists beyond 48 hours. Anticoagulation, using
The incidence of AF increases with amount of lung aspirin, heparin, or warfarin, is considered after weighing
tissue removed (12–25% after lobectomy, 20–30% after the risk of post-op bleeding.
pneumonectomy, and up to 40% after resection of malig-
nant pleural mesothelioma) and advanced age (60 years
or older). The onset of AF is greatest 2–3 days after
thoracic surgery, with the majority reverting to sinus MANAGEMENT OF SPECIAL CONDITIONS
rhythm with appropriate therapy. Common clinical pre-
sentations of AF include dyspnea, palpitation, dizziness, Postpneumonectomy Pulmonary Edema
and shortness of breath. With respect to the development The syndrome of postpneumonectomy pulmonary
of hypotension, younger patients tend to tolerate AF better edema (PPPE) refers to the development of an acute
than older patients. The proposed mechanisms of peri- lung injury (ALI) or acute respiratory distress syndrome
operative AF include preexisting atrial pathology (valvular (ARDS) characterized by severe and often fatal pulmonary
Pulmonary Surgery Postoperative Care 407
edema of unknown etiology. In spite of an increased approach, supplemental oxygen to prevent hypoxemia
awareness over the last two decades, a precise definition during rest, sleep, and exercise, avoiding long periods
and pathogenesis of PPPE is lacking. The reported inci- with the residual lung in the dependent position, and
dence of PPPE ranges from 2.5% to 14%. The incidence lung protective ventilation with or without inhaled
is greater after right pneumonectomy. It is universally nitric oxide in patients requiring intubation. High-dose
fatal if unrecognized. It accounts for the majority of in- steroids may be considered in patients with a recent
hospital mortality following lung resections. PPPE history of radiation or chemotherapy.
remains an equally challenging clinical problem for sur-
geons, anesthesiologists, and intensivists alike.
The diagnosis of PPPE is based on high index of Bronchopleural Fistula
suspicion and exclusion of factors known to cause Air leak via a chest tube is initially common after
ALI/ARDS. Among several conditions, the differential lobectomy or segmental resection due to transection of
diagnoses include aspiration pneumonitis, pneumonia, small airways. With proper drainage via chest tube(s),
cardiogenic pulmonary edema, pulmonary embolism, moderate suction (20–30 cmH2O), physiotherapy, and
extrapulmonary sepsis, and drugs (amiodarone) and blood ambulation, the initial air leak normally subsides over
transfusions. The onset of symptoms usually occurs 3–4 days. The development of a bronchopleural fistula
between post-op day 2 and 4, although radiologic findings (BPF) due to bronchial-stump disruption after pul-
may be seen earlier. Among many factors involved in the monary surgery is a serious complication. The etiologies
pathophysiology of PPPE, volume overload still remains of BPF include surgical reasons (poor suturing or sta-
an important topic of controversy between surgeons and pling techniques or bronchial ischemia due to poor dis-
anesthesiologists and has led to the dictum “Don’t drown section) or post-op necrosis due to infection or tumor in
the down lung.” The probable etiologies involved in the the stump. Prompt re-operation and closure of the fistula
pathophysiology of PPPE include fluid overload, lung lym- are recommended for early bronchial-stump disruption.
phatic injury, endothelial damage, increased pulmonary High-frequency jet ventilation (HFJV) or one-lung venti-
capillary pressure, hyperinflation of the lung, and right lation using a double-lumen tube may be required to
ventricular dysfunction. The role of oxygen toxicity and facilitate healing and maintain adequate oxygenation and
cytokines in PPPE is unclear. ventilation.
Temporizing measures include discontinuing suction, are added when appropriate, to maintain mean arterial
placing the patient in the lateral decubitus position with pressure. Inotropic agents are needed to support cardiac
the operative hemithorax uppermost, and minimizing output in recipients with preexisting right ventricular dys-
PEEP and airway pressures in intubated patients. function. Vasodilators such as prostaglandin E1 are used to
control elevated pulmonary artery pressure, especially if it
was being used preoperatively. Because of alterations in
Lung Transplantation pulmonary capillary permeability, disordered fluid clear-
The major concerns relating to the post-op care of ance related to disruption of pulmonary lymphatics, and
lung transplant recipients are hemodynamic and fluid therefore propensity to develop pulmonary edema, fluid
management, respiratory management, management of administration is generally kept to a minimum. Blood and
renal function, ischemia reperfusion injury, allograft blood component replacement is undertaken as necessary.
rejection, nutrition, and sepsis. Echocardiography is useful in evaluating cardiac function
and pericardial tamponade in an unstable patient.
Respiratory Management and
Mechanical Ventilation Ischemia Reperfusion Injury
After lung transplant, recipients have impaired cough and Allograft Rejection
reflexes due to the disruption of afferent nerve fibers The release of superoxide anions and oxygen free rad-
and thus have difficulty mobilizing respiratory secre- icals and subsequent activation of neutrophils following
tions. Aggressive pulmonary toilet is crucial. Frequent reperfusion of the ischemic lung ultimately leads to
airway suctioning and inhaled bronchodilators are uti- increased capillary permeability, interstitial alveolar
lized in patients on or off the ventilator. After extuba- edema, altered vascular tone, and dysfunction of type-II
tion, early ambulation, cough and deep breathing pneumocytes. Clinically, lung injury induced by
maneuvers, and bronchodilators help mobilize secre- ischemia-reperfusion is characterized by nonspecific
tions and prevent atelactasis. alveolar damage, pulmonary edema, and progressive
In uncomplicated cases most lung recipients can be hypoxemia within 72 hours of lung transplantation.
extubated 24–36 hours after surgery. Adequate oxy- Signs of resolution are usually apparent by day 4 and
genation is assured with supplemental oxygen and PEEP complete resolution is usually seen by day 14. If severe
and PaCO2 and pH adjusted based on minute ventilation. enough, it can lead to primary graft failure. Treatment is
In general, during mechanical ventilation, lung pro- generally supportive and includes lung protective venti-
tective ventilation using small tidal volumes (6 ml/kg lation both during and immediately after surgery to pro-
adjusted body weight) and PEEP with close attention tect the injured lung and prevent further worsening of
to prevent dynamic hyperinflation (auto-PEEP) is used. acute lung injury and diuretics. Inhaled nitric oxide may
Recipients who were hypercapnic before remain so be useful in the treatment of ischemia reperfusion injury
until medullary respiratory center readjusts over several by improving ventilation-perfusion mismatch without
weeks. At times, hyperinflation of a more compliant lung affecting systemic vascular resistance.
in a single-lung recipient with conventional ventilation Acute rejection usually presents on days 4–5 following
necessitates differential lung ventilation utilizing a double- surgery and presents as worsening gas exchange, pul-
lumen endobronchial tube. Unrecognized hyperinflation monary infiltrates, and pulmonary hypertension. A trans-
can result in mediastinal shift and hemodynamic com- bronchial or open lung biopsy is required for definitive
promise. Weaning from the mechanical ventilator is diagnosis. Current immunosuppressive regimens are based
initiated when the patient is warm, hemodynamically on the use of cyclosporine, azathioprine, and prednisone
stable, and arterial blood gases show adequate oxygena- as the mainstay of therapy after lung transplantation.
tion and ventilation using inspired oxygen 0.4 or less. Immunosuppressive agents are continued and inhaled
A short trial of spontaneous breathing is performed nitric oxide is used to decrease pulmonary vascular resist-
using pressure support ventilation and pulmonary ance without altering systemic resistance. Primary graft
mechanics (negative inspiratory force and vital capacity) failure from ischemia-reperfusion may be so severe that
are measures prior to extubation. Weaning may be ham- it necessitates extracorporeal membrane oxygenation
pered by emergence of infection, phrenic nerve injury (ECMO) to support the patient until injury improves.
secondary to surgical procedure, ischemia reperfusion
injury, and preexisting nutrition deficiency. Management of Renal Function
Fluid restriction and diuretic and vasopressor use in
Hemodynamic and Fluid Management conjunction with the use of nephrotoxic immunosup-
The goals of hemodynamic and fluid management in a pressive and antimicrobial medications can lead to the
lung transplant recipient are to ensure adequate organ per- development of acute renal failure in the post-op period.
fusion and prevent pulmonary edema. Vasoactive agents Dosing of all medications must be based on alteration in
Pulmonary Surgery Postoperative Care 409
creatinine clearance. Low-dose nicardipine has been initial clue to the presence of myocardial contusion.
shown to be reno-protective in transplant recipients Aortography remains the “gold standard” for diagnosis of
taking immunosuppressive agents. Some degree of renal traumatic aortic injury in a hemodynamically stable
insufficiency persists in these patients. patient. Bronchoscopy is the diagnostic test of choice in
tracheobrochial trauma. The role of videothoracoscopy
Nutrition in the treatment and management of thoracic trauma
Stress ulcer prophylaxis is routinely used. Nutrition is patients has been expanding. The current indications
a very important issue in lung transplant recipients. In for videothoracoscopy include evaluation of suspected
general, enteral nutrition is desired. Metoclopramide can diaphragmatic and mediastinal injuries, removal of foreign
be used to treat gastroparesis, which is quite common in bodies, evaluation and treatment of persistent leaks and
lung transplant recipients. Laxatives are used for regulation bleeding, and evacuation of a retained hematoma.
of bowel function.
Management
Sepsis Rib Fractures and Flail Chest
Sepsis can be another problem in these patients. Simple rib fractures can be successfully treated with
Prophylactic antimicrobials are important in preventing analgesics. Intercostal, interpleural, or epidural analgesia
post-op infections. Common infections that are likely can be used in a high-risk patient. A flail chest occurs when
include bacterial pneumonia around day 2–3, acute the fracture of ribs at multiple locations produces discon-
rejection around day 4–6, and cytomegalovirus pneu- tinuity of a segment of thoracic wall and paradoxical
monitis at week 4 following the surgery. Bacterial, viral, motion with respiration. This results in increased work of
and fungal prophylaxis is based on culture data from the breathing, decreased vital capacity, and hypoxemia due to
donor lung. After 1 month, trimethoprim-sulfamethoxazole V/Q mismatch. Invariably there is underlying pulmonary
is given as a prophylaxis against Pneumocystis carinii contusion in patients with flail chest. It is the underlying
and acyclovir against herpes simplex virus. pulmonary contusion that plays the greater role in the
patient’s inability to oxygenate and ventilate. Key in the
management of flail chest is pain relief. Conservative man-
Thoracic Trauma agement including supplemental oxygen, epidural analge-
Thoracic trauma accounts for 25% of all trauma sia, and pulmonary physiotherapy may be used in patients
deaths in the USA. With blunt or penetrating injury the with mild flail chest. Arterial blood gases may be drawn to
basic principles of resuscitation are rapid restoration of monitor gas exchange. The patient with severe flail chest
airway, supplemental oxygen, needle decompression of and pulmonary contusion requires mechanical ventilator
a suspected tension pneumothorax, and coverage of an support using lung protective ventilation strategy, along
open pneumothorax wound. with adequate pain control, sedation, and careful attention
to fluids. Pulmonary contusions are common after blunt
Diagnosis thoracic trauma and may progress to full-blown ARDS.
The initial evaluation is directed at diagnosing and Cardiac Contusion
treating life-threatening injuries related to the airway and Patients sustaining massive blunt chest trauma, with
cardiopulmonary system. A secondary survey should be ECG abnormalities, and with a positive “steering wheel
rapidly done to search for other injuries. A combination sign” on the anterior chest should be investigated for car-
of radiologic and clinical procedures is usually required diac contusion. Patients with normal ECG can be man-
to clearly define the nature and extent of thoracic injury. aged on the regular ward. Stable patients with abnormal
Despite its limitations, the initial chest radiograph repre- ECG should be admitted to a telemetry ward. All patients
sents the most important diagnostic tool in patients with with unstable hemodynamic status must be admitted to
thoracic trauma. Presence of pneumothorax, hemothorax, the ICU. Antiarrhythmic and inotropic support is used for
and rib fractures may be identified. A wide mediastinum the treatment of arrhythmias and cardiogenic shock.
on chest radiograph may indicate traumatic aortic injury. Tracheobronchial Injuries
A computerized tomography scan of the chest is useful in Tracheobronchial injuries may be suspected in
diagnosing mediastinal hemorrhage, pulmonary contusion, patients with thoracic trauma who develop massive sub-
and aortic rupture. Transesophageal performed intra- cutaneous and mediastinal emphysema or continuous air
operatively may help in diagnosing traumatic aortic leak via chest tube. Laryngeal and tracheal injuries can
injury, traumatic rupture of the ventricular septum, car- be managed by endotracheal intubation with the cuff
diac tamponade, or wall motion abnormality seen with below the level of injury. HFJV can be used in to mini-
myocardial contusion in a hemodynamically unstable mize airway pressure and inspiratory peak pressures to
patient. A 12-lead ECG is required in monitoring all decrease the likelihood of suture line dehiscence after
trauma patients. Unexplained arrhythmia may be an repair of distal tracheobronchial injury.
410 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
SELECTED READING
SUMMARY
Alvarez JM: Postpneumonectomy pulmonary edema. In Slinger P,
editor: Progress in Anesthesia, Philadelphia: Lippincott
The optimum post-op care of pulmonary surgery
Williams & Wilkins, 2004, pp 187–220.
patients is challenging. Respiratory complications repre-
sent the major cause of post-op morbidity and mortality Amar D: Posthoracotomy arrhythmias. In Slinger P, editor:
Progress in Anesthesia, Philadelphia: Lippincott Williams
in this group of patients. Preoperative teaching in smoking
& Wilkins, 2004, pp 247–266.
cessation and pulmonary physiotherapy goes a long way
in the prevention of post-op respiratory complications. Pennefather SH, Russell GN: Postthoracotomy analgesia: recent
advances and future directions. In Slinger P, editor:
Integral to routine post-op care of pulmonary surgery
Progress in Anesthesia, Philadelphia: Lippincott Williams
patients is good pain control. PPPE is universally fatal if
& Wilkins, 2004, pp 163–186.
unrecognized. The post-op period in patients with pul-
Slinger PD: Thoracic anesthesia. Anesth Analg 98(3 Suppl):
monary trauma and transplant equally presents with
A116–122, 2004.
unique challenges.
40
CHAPTER Hemodynamic
Instability in the
Recovery Room
D. JAY DUONG, M.D.
STEWART J. LUSTIK, M.D.
411
412 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
complications, such as patients with chronic hyperten- filling, resulting in a reduced stroke volume and cardiac
sion, atherosclerotic disease of the coronary or carotid output.
arteries, stenotic valvular disease, or increased intra- Stroke volume is defined as the end-diastolic volume
cranial pressure. Compensatory mechanisms act to pre- minus the end-systolic volume, or the volume of blood
serve perfusion to vital organs; signs or symptoms of ejected with each ventricular contraction. Stroke vol-
end-organ hypoperfusion, such as altered mental status, ume is reduced if there is a decrease in preload or con-
indicate the compensatory mechanisms are inadequate tractility. Preload is the myocardial tension at the end of
to overcome the degree of hypotension. Tissue hypoxia diastole and may be estimated using multiple tech-
results in anaerobic metabolism and a lactic acid-induced niques. Ventilation-induced systolic pressure variation of
metabolic acidosis and electrolyte derangements. If not greater than 15 mmHg accurately diagnoses low preload.
treated, vital organ dysfunction can result, and a cycle of Pressure in the left ventricle can be indirectly measured
decompensation may ensue. by the central venous pressure (CVP) or pulmonary cap-
illary wedge pressure (PCWP). However, these pressure
measurements may not accurately reflect left ventricular
Determinants of Blood Pressure volume due to valvular heart disease or decreased left
To understand and control blood pressure one needs ventricular compliance. The right ventricular ejection
to understand the underlying physiology. Blood pressure fraction catheter uses a rapid thermistor and electro-
(BP) is related to cardiac output (CO) and systemic vas- cardiogram electrodes to calculate end-diastolic volume
cular resistance (SVR) by the following equation: without interference from ventricular hypertrophy or
valvular disease. Preload is more accurately assessed
BP = CO × SVR (40-1)
using echocardiography, where the ventricular filling
This relationship is derived from rearranging the basic volume is directly visualized.
flow equation: The amount of venous blood return to the ventricle
and the venous vascular tone determine preload. The
Q = ΔP/R or ΔP = Q × R (40-2)
most common cause of inadequate preload is hypo-
where ΔP is the pressure difference between two points volemia due to blood loss or inadequate fluid resuscitation.
(mmHg), Q is the flow rate (volume/time), and R is the Impaired venous return can also be due to mechanical
resistance to flow (mmHg × time/volume). This equation impedance such as positive pressure ventilation, diastolic
is a variant of Ohm’s law. When applied to human dysfunction, inadequate ventricular filling time, stenotic
circulation, ΔP represents blood pressure, Q describes valvular disease, abdominal compartment syndrome,
cardiac output, and R is analogous to systemic vascular pulmonary embolus, tension pneumothorax, or cardiac
resistance. Equation 40-1 demonstrates that a decrease in tamponade.
blood pressure must be caused by either a decrease in Contractility is the peak isometric tension that a
cardiac output or a decrease in SVR. cardiac muscle can generate for a fixed fiber length. The
The output of the left ventricle may be measured by heart contracts more vigorously when the end-diastolic
themodilution using a pulmonary artery catheter, which volume increases. This relationship is known as the
approximates right ventricular output and when aver- Frank–Starling law of the heart. Contractility is affected
aged over a period of time must be equal to left ventric- by cardiac ischemia, the sympathetic tone, viable muscle
ular output. Cardiac output is directly related to heart mass of the ventricle, and inotropic drugs (e.g., dopamine,
rate (HR) and stroke volume (SV): dobutamine, epinephrine, milrinone).
Blood pressure is also directly related to the SVR as
CO = HR × SV (40-3)
shown in Equation 40-1. The factors that determine the
Normal resting heart rate in the adult is 60–100 beats resistance to fluid flow are described by Poiseuille’s
per minute. In patients with noncompliant ventricles equation:
(e.g., neonates or patients with left ventricular hypertro-
R = 8Lη/πr4 (40-4)
phy) HR is the primary determinant of cardiac output.
Heart rate is regulated by the autonomic nervous system where L is the length of the tubing, η is the viscosity of
and influenced by hormones, such as thyroid hormone. the fluid, and r is the radius of the tubing. Poiseuille
A slow heart rate is desirable in patients with coronary initially described this relationship for the flow of liquids
artery disease, but significant bradycardia may result through a glass tube. This relationship is applicable to the
in a low cardiac output. A rapid heart rate increases myo- flow of blood in the circulatory system. The length of the
cardial oxygen demand and decreases diastolic time, and, vascular tubing can be considered to be a fixed variable.
thus, perfusion of the myocardium (the left ventricle The viscosity of the blood, although it can be altered
receives most of its perfusion during diastole). Decreased by hemoconcentration or hemodilution, is not regulated
diastolic time also may prevent adequate ventricular by the body on a minute-to-minute basis. Changing the
Hemodynamic Instability in the Recovery Room 413
radius through vasoconstriction or vasodilation is the be wise to check the blood pressure in the other upper
primary means by which the body regulates vascular extremity, particularly in patients with peripheral vascu-
resistance, and, therefore, blood pressure. One can see lar disease that may have occlusions proximal to the cuff
from Equation 40-4 that if the radius is decreased or arterial line. A careful review of the patient’s history
by one-half, the resistance increases sixteen fold. This and intraoperative course will help determine if additional
relationship holds for lamellar flow, where the maxi- monitoring is needed prior to treatment.
mum velocity of the fluid is at the center and zero at The most common cause of postoperative hypoten-
the walls. When there is a narrowing of the tubing such sion is decreased preload from hypovolemia. Causes
that lamellar flow becomes turbulent, the resistance to include inadequate replacement of intraoperative blood
flow is even higher than that predicted by Poiseuille’s loss, postoperative bleeding, urinary losses, and third
equation. One can therefore appreciate that small changes spacing of fluid. A simple test for hypovolemia is to use
in the vessel diameter can have significant impact on positional maneuvers that utilize gravity to augment
resistance. venous return to the heart. Placing a patient in the
Afterload is the ventricular wall tension during systole Trendelenburg position can autotransfuse up to two
caused by the forces that oppose muscle fiber short- units of blood volume. A rise in blood pressure suggests
ening. Afterload is proportional to arterial blood pres- hypovolemia. Another useful test is to administer rapidly
sure and the chamber dimension, shape, and wall 250 ml of a crystalloid solution. If invasive monitoring
thickness. SVR can be readily altered and approximates is present, a rise in blood pressure with only a small
afterload. The pulmonary artery catheter can be used to increase in CVP or PCWP is suggestive of a hypovolemic
calculate SVR: state. This is followed by further fluid resuscitation as
indicated. Vasopressors and positive inotropic agents are
MAP − CVP not indicated in this setting, except as a temporary
SVR = × 80 (40-5)
CO means of treatment until intravascular volume can be
adequately restored. Hypotension because of obstruc-
where MAP is mean arterial pressure; the units for SVR tion to venous return (e.g., cardiac tamponade) will
are dyns/cm5. often respond to fluid therapy, but the definitive treat-
SVR is regulated by the autonomic nervous system ment is eliminating the impedance.
and affected by inflammatory processes and tempera- If a fluid challenge results in rapidly rising filling pres-
ture. A decreased sympathetic tone can be due to vaso- sures without much improvement in blood pressure,
dilating properties of some medications or direct spinal then the heart may be failing and further administration
cord inhibition of sympathetic nerves from intrathecal of fluids may be of little benefit. The pulmonary artery
or epidural local anesthetics. Neurogenic shock, liver catheter (PAC) will indicate an elevated PCWP and SVR
failure, spinal cord injury, carotid sinus dysfunction (S/P with a low cardiac output. Causes of cardiac dysfunction
carotid endarterectomy), and adrenal insufficiency can include hypocalcemia and myocardial infarction.
also result in a low SVR. Systemic inflammation, such as Hypocalcemia should be suspected in any patient that
sepsis or anaphylaxis, involves circulating factors that received a large amount of blood products, especially in
cause vasodilation. Bacteremia from urogenital procedures patients with liver dysfunction who will not efficiently
has caused fever and hypotension in the recovery room. metabolize citrate. If the ionized calcium level is low,
Hyperthermia from excessive warming or malignant intravenous calcium may correct the hypotension. Acute
hyperthermia results in temperature-related vasodilation. ST elevation indicates coronary artery occlusion and
Treatment is geared toward correcting the underlying requires immediate and aggressive treatment (see Case
cause and, if needed, instituting pharmacologic agents Study box) including supporting blood pressure with
that augment vascular tone. Alpha-agonists are successful inotropic agents in hypotensive patients. In contrast to
at increasing SVR and blood pressure, but the vasocon- ST elevation, new ST depression on the EKG may indi-
striction may lead to decreased perfusion of vital organs. cate cardiac ischemia secondary to the hypotension and
the diastolic pressure should be raised (using phenyle-
phrine) rather than employing the usual steps to maxi-
Management of Hypotension mize oxygen supply/demand (using beta-blockers and
The management of hypotension begins with the nitroglycerin). Other reversible causes of myocardial
elimination of erroneous blood pressure measurements, depression include acidosis and hypothermia.
such as those caused by too large a cuff or calibration of A failure of hypotension to respond to a volume load
a transducer above the level of the heart. An overdamped may also be due to a significantly reduced SVR (Table 40-1).
waveform can result in a falsely low systolic blood pres- The PAC helps differentiate low SVR conditions from
sure; the MAP should be used in guiding therapy. It may patients with decreased preload or decreased contractility.
414 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Phenylephrine Alpha-adrenergic agonist Children: 1–30 μg/kg/dose every 10–15 minutes; May see reflex bradycardia
0.1–0.5 μg/kg/minute infusion.
Adults: 100–500 μg/dose every 10–15 minutes;
100–180 μg/minute initial infusion rate, followed
by 40–60 μg/minute maintenance rate
Ephedrine Releases tissue stores Children: 0.1–0.3 mg/kg/dose Longer acting, but less potent
of epinephrine Adults: 5–25 mg/dose than epinephrine
Epinephrine Alpha- and beta- Children: 0.05–0.1 μg/kg/minute infusion; titrate
adrenergic agonist as needed
Adults: 1–10 μg/minute infusion
Norepinephrine Alpha- and beta- Children: 0.05–0.1 μg/kg/minute infusion; Requires cautious monitoring
adrenergic agonist titrate as needed for extravasation
Adults: 1–10 μg/minute infusion
Dopamine Dopaminergic and 1–20 μg/kg/minute, up to 50 μg/kg/minute; Hemodynamic effects are
adrenergic agonist titrate as needed dose-dependent
Vasopressin Antidiuretic hormone Children: 0.002–0.005 units/kg/minute; Water intoxication requires
analog titrate as needed discontinuation of the drug
Adults: 0.2–0.4 units/minute; titrate as needed
Calcium chloride Electrolyte supplement Children: 10–20 mg/kg/dose Used in hypocalcemic
Adults: 500–1000 mg/dose states to improve
myocardial contractions
Hemodynamic Instability in the Recovery Room 415
Esmolol Beta-adrenergic Children: limited information Short acting. All beta-blockers must be used
blocker Adults: 500 μg/kg over 1 minute loading cautiously in patients with bronchospastic
dose; 50–200 μg/kg/minute maintenance disease or acute congestive heart failure
Metoprolol Beta-adrenergic Adults: 5 mg/dose every 2 minutes, Beta-blockers can mask the signs and
blocker up to 3 doses symptoms of hypoglycemia
Labetalol Beta-adrenergic Adults: 0.25 mg/kg/dose; 2 mg/minute Blocks alpha- and beta-adrenergic
blocker infusion, titrate as needed receptor sites
Diltiazem Calcium channel Adults: 0.25 mg/kg over 2 minutes loading Use cautiously in hepatic/renal impairment
blocker dose; 5–15 mg/hour maintenance
Hydralazine Arteriole vasodilator Children: 0.1–0.2 mg/kg/dose Half-life is prolonged in renal disease
Adults: 10–20 mg/dose
Enalaprilat Angiotensin converting 1.25 mg/dose May impair renal function
enzyme inhibitor
the dysrhythmia. If the rhythm is not corrected with course was uncomplicated. Estimated blood loss was
treating reversible causes, attempts to convert atrial 300 ml, and she received 3000 ml of crystalloid.
fibrillation or atrial flutter to normal sinus rhythm with She was extubated at the end of the case, and was
amiodarone may be successful. To control the ventricu- transferred to the PACU in stable condition.
lar rate, pharmacologic intervention involves slowing the After 35 minutes in the PACU she complained of
AV node with beta-blockers, calcium channel blockers, or chest pressure and dyspnea. Her vital signs were
digoxin. These medications should be avoided in patients BP 145/86, HR 102, RR 24, O2 sat 92% on room air.
with Wolf-Parkinson-White syndrome and digoxin should Telemetry revealed ST segment elevation. Physical
be used cautiously in patients with hypokalemia. examination revealed a woman in moderate discomfort.
Ventricular tachycardia and fibrillation are commonly Lung examination was notable for new bibasilar
crackles. Heart examination was notable only for
caused by acute myocardial infarction or ischemia. These
tachycardia. A repeat 12-lead EKG showed sinus
rhythms are managed and treated as outlined in the tachycardia with 2 mm ST segment elevation in
advanced cardiac life support guidelines. Ventricular leads II, III, and aVF consistent with an acute inferior
tachycardia that is unstable should be treated immedi- myocardial infarction. Treatment was immediately
ately with cardioversion, followed by drug therapy. initiated while cardiology was consulted. She was given
Electrolyte and metabolic derangements should be 4 liters/minute of oxygen via nasal canula and her pulse
promptly sought and corrected. Those without significant oxymetry improved to 100%. She was also given
symptoms or hemodynamic instability may be treated nitroglycerin 0.3 mg × 3 sublingually with mild
with antiarrhythmic agents (amiodarone, lidocaine, or improvement in her chest pressure. This was followed
procainamide) and correction of underlying triggers. by morphine 4 mg IV × 2 with good pain relief. Aspirin
Patients with recurring ventricular tachyarrhythmias 325 mg PO and metoprolol 5 mg IV × 3 were
administered. Stat labs for hematocrit, electrolytes,
may develop cardiac death. Recurrence can be pre-
and cardiac enzymes were sent. Chest x-ray was clear.
vented by continuous infusion of an effective anti- Heparin and thrombolytics were not administered
arrhythmic agent. due to concerns about bleeding. She was taken
emergently to the cardiac catheterization lab where
she successfully underwent angioplasty of her right
CONCLUSION coronary artery.
The transport from the operating room to the inten- Communication between the surgical team and criti-
sive care unit (ICU) is a crucial time in the critically ill cal care team is one of the most important aspects of
patient’s care. In the operating room patients are man- postoperative transport of the patient. Whether the
aged one-to-one by an anesthesia care provider with full patient is expected in the ICU after surgery or the need
monitors. There is rapid access to emergency drugs, air- develops intraoperatively, contact with the ICU team
way management equipment, IV infusion equipment, etc. should be made well in advance of patient transport.
In the ICU, the ICU team with 1:1 or 1:2 nursing coverage Issues discussed should include the surgical procedure,
manages patients. During transport from the operating past medical history, blood loss, volume/product/vaso-
room to the ICU, these conditions may not exist. Optimal pressor requirements, IV access, any significant intraoper-
management of these patients during transport requires ative events, and special monitors (arterial line, Swan-Ganz
excellent communication between the operating room catheter, etc.). In addition, anticipated postoperative
and ICU. In addition, conditions must be established that ventilator requirements should be discussed. Ideally, the
will provide for the safest possible transfer from the communication between the operating room and ICU
operating room to the ICU. should be physician to physician. However, it is impor-
Before any discussion of transfer, clearly the need for tant that the ICU physician communicate with the ICU
a critical care bed must be established. This is not a trivial nursing staff about the patient.
point. We all desire the optimal care for our patients.
Unfortunately, ICU beds are often in short supply. Often
the intensivist is faced with discharging a patient who EQUIPMENT NEEDS FOR TRANSPORT
would benefit from more time in the ICU in order to
admit a new patient. The decision to admit a patient to JACHO requirements for the ICU include having
the ICU should be made jointly between the surgical and uniform monitor requirements for all ICUs for patient
anesthesiology teams. Clearly, a patient who requires transport. At our institution, the monitors include EKG
more than a few hours of postoperative ventilatory sup- monitoring, pulse oximetry, and blood pressure moni-
port will need an ICU bed. These include those with toring. A defibrillator must be available. Since the patient
large blood losses, evolving sepsis, long procedures with transporting to the ICU from the operating room is an
associated airway edema, etc. Patients who are extubated ICU patient, transport should be accomplished at a min-
but have very marginal pulmonary function, are at high imum with the above monitors. If patient requirements
risk for respiratory failure and will need an ICU bed. exceed the minimum required (such as pulmonary artery
There are patients who require intensive neurologic or pressure monitoring, intracranial pressure monitoring,
vascular monitoring that can only be accomplished in an etc.), then they should be used. Beyond monitors, the
ICU. As soon as the need for an ICU bed is established, physician transporting the patient should be prepared to
418
Postoperative Transport to the Intensive Care Unit 419
Box 41-1 SMH Department of Anesthesiology Guidelines for the Transfer of Intensive
Care Unit Patients to and from the Operating Room
Continued
420 CRITICAL CARE: THE REQUISITES IN ANESTHESIOLOGY
Box 41-1 SMH Department of Anesthesiology Guidelines for the Transfer of Intensive
Care Unit Patients to and from the Operating Room—Cont’d
INTRAOPERATIVE
A. When it becomes clear that an ICU admission will be required, contact one of the following individuals to arrange for a bed.
1. Adult, noncardiac: critical care fellow on call.
2. Pediatric: PICU attending.
3. Neonates: NICU attending.
B. Make sure that an ICU bed with monitor and defibrillator is available for the end of the procedure.
POSTOPERATIVE
A. Direct transfer to the ICU.
1. Anesthesia care provider to contact ICU immediately prior to leaving the operating room.
2. Anesthesia care provider will accompany the patient to the ICU.
3. Full monitors and defibrillator for transfer.
4. Direct sign out by anesthesia care provider to ICU team member detailing the operative course.
B. PACU admission prior to ICU admission.
1. Certain situations dictate admission to PACU first (vascular checks, neurologic examinations, etc.).
2. Anesthesia care provider will accompany the patient to the PACU and give sign out to the PACU nurse.
3. Anesthesia care provider will contact the ICU physician to give sign out and transfer care as soon as feasible.
4. For transfer to the ICU, a PACU nurse will accompany the patient with full monitors and defibrillator.
5. Direct sign out to ICU team member detailing the perioperative course.
C. Indirect transfer to the ICU.
1. Certain situations require procedures/studies outside of the operating room prior to transfer to the ICU (e.g., CT,
MRI, angiography).
2. Unless continued anesthesia is required, the anesthetist will not accompany the patient to an “off site” location.
3. As soon as the need for the study/procedure is known, the ICU attending should be contacted to arrange for
critical care nursing coverage during the procedure and thereafter. The ICU attending, in collaboration with the
ICU and/or PACU nurses will arrange for coverage of the patient during the procedure.
4. The place where care will be transferred will be arranged by mutual agreement between the anesthesia and
critical care teams.
5. If no ICU or PACU nurse is available, remain in the operating room.
D. ICU patients boarding in the PACU.
1. When an ICU bed in not available, the patient will be boarded in the PACU.
2. The critical care attending and ICU team will be responsible for the patient’s care.
E. Nursing coverage in either the ICU or PACU is not available. The patient will remain in the operating room under the
care of the anesthesiology team.
Department of Anesthesiology, University of Rochester, Rochester, New York.
Index
Please note as the subject of this book is critical care, all entries refer to this unless otherwise stated. Entries followed by “f” and “t” denote figures
and tables respectively.
421
422 INDEX
acute respiratory distress syndrome (ARDS) adverse events, root cause analysis 374 alpha-blockers 140
(Continued) afterload (outflow resistance) 30, 31f, 413 drug interactions 148
in hepatic disease 292 measures 32 pheochromocytoma treatment 246
hypercapnic respiratory failure 14 “against medical advice” (AMA) 377 stroke management 199
management 178–179 Agent 15 358 alphaviruses 356
mortality 178 agitation see also sedation/sedatives aluminum hydroxide 54
open lung concept 178–179 drug-related 124, 124t alveolar–capillary unit
pathology 177 evaluation 123–124 hypoxemia and 11–12, 13f
postpneumonectomy 406 scales 125, 125t ventilation–perfusion 33
risk factors 176, 177 AIDS see HIV/AIDS alveolus
thermal injury/smoke inhalation 348 airway ARDS pathology 177
ventilation and 176, 178, 185–186 assessment, primary survey 338, 339–340 oxygen tension gradient 11–12, 13f
Acute Respiratory Distress Syndrome Network disease, pneumonia management in 173 physiology 188f
(ARDS-NET) 178, 187 increasing mean pressure in 12–14 pressure in (PA) 33
acute respiratory failure (ARF) 11–15, see also ventilatory support type I cells 177
181–182 see also hypercapnia; management amantadine 56
hypoxemia ABCDE algorithm 328, 338 American Academy of Neurology, rt-PA use in
hypercapnic (type 2) 11, 14–15, 182t ischemic stroke 198 stroke 202
hypoxemic (type 1) 11–14, 182t postanesthetic 395 American Association for Surgery of Trauma
infection in 111, 112, 165 traumatic brain injury 221 (AAST), renal trauma classification
management see also ventilatory support obstruction 329–330, 329f, 330t
hypercapnia 14–15 chronic disease see COPD American College of Cardiology (ACC),
hypoxia 12–14, 14t hypercapnia 14 myocardial ischemia evaluation 143
nutritional support 110–112 hypoventilation 393 American College of Surgeons, advanced
acute tubular necrosis (ATN) 295, 307 management 395 trauma life support (ATLS) course 222,
see also acute renal failure (ARF) thermal injury/smoke inhalation 347–348 328, 338
acyanotic heart defects 150–152, 151t trauma 409 American–European Consensus Conference,
atrial septal defect 151 airway pressure-release ventilation (APRV) 186 ALI/ARDS definitions 77, 176
critical care in 155 alarm systems 16 American Heart Association (AHA)
patent ductus arteriosus 151–152 albumin Advanced Cardiac Life Support
ventricular septal defect 150–151 anion gap and 42 Protocol 27
acyclovir blood products 279 myocardial ischemia evaluation 143
dialysis and 315t burn pathophysiology 346 rt-PA use in stroke 202
pneumonia management 174 oncotic pressure and 69 American Medical Association, principles of
Adamsite 358 trauma management 343 Medical Ethics 379
Addisonian crisis 241 thermal injury 349 amino acids
adenosine albuterol immunonutrition 115
multifocal atrial tachycardia 82 pneumonia management 173 nutritional requirements 107–108
paroxysmal supraventricular tachycardia 83 postoperative pulmonary care 405t in renal failure 113
pulmonary surgery and 406 alcohol/alcoholism in sepsis 112
adenovirus infection 254 cirrhosis pathophysiology 286 see also aminocaproic acid 266
adrenal gland cirrhosis aminoglycoside antibiotics
functions 240–241 hypoglycemia 243 dialysis and 315t
hemorrhage 241 poisoning 362t pneumonia management 172–173
insufficiency 241–242 aldehyde gas 346–347 amiodarone
diagnosis 241–242 aldosterone, hypertension pathogenesis 138 multifocal atrial tachycardia 82
in HIV/AIDS 241 ALI see acute lung injury (ALI) pulmonary surgery and 406
presentation 64 alkali, burns 347 Torsade de pointes 84
primary, secondary and tertiary 241 alkalosis 68 ventricular fibrillation 79
treatment 242 chloride ions and 41, 68 Wolff–Parkinson–White syndrome 81
tumors 245–246 hyperkalemic 46 ammonia, serum levels in cirrhosis 291
adrenaline see epinephrine hypoalbuminemic 45 amniotic fluid embolus (AFE) 250
adrenalitis, in myxedema 238 ionized hypocalcemia 66 amoxycillin, dialysis and 315t
adrenergic receptors metabolic 41, 68 amphetamines, poisoning 362t, 364
α-2 agonists see alpha-2 agonists proteinaceous 45–46 amphotericin B, dialysis and 315t
α-blockers see alpha-blockers relative 67 amphotericin, liposomal, dialysis and 315t
beta-adrenergic agents respiratory 40 analgesia see also anesthesia; sedation/
arrhythmia induction 77 cardiac arrhythmias 416 sedatives; specific drugs
β-agonists 77, 173 metabolic acidosis compensation 67 agitation and anxiety 123, 124t
β-blockers see beta-blockers treatment 68 angina treatment 147
pneumonia management 173 Allen test 24 burn care 350–351
postoperative pulmonary care 405t allergies/allergic reactions ICP reduction 199, 228
adrenocorticotropic hormone (ACTH) 240 epinephrine in 93 inadequate 123
resistance 242 latex allergy 22–23 ketamine 130–131
stimulation tests 241–242 transfusion-related reaction 283t NSAIDs see nonsteroidal anti-inflammatory
adult live donor liver transplantation (aLDLT) allograft rejection 256 drugs (NSAIDs)
298 lung 408 opioid see opioids
Advanced Cardiac Life Support Protocol 27 alloimunization, platelet transfusion 281 patient-controlled 390
credentialing 374 alpha-2 agonists 131 postoperative 389–391
advance directives 367, 378–379 hypertension management 140, 198–199, post-thoracotomy 404–406
Advanced Trauma Life Support (ATLS) course 415 tolerance 389
328, 338 myocardial ischemia prevention 146 in traumatic brain injury 228
traumatic brain injury 222 stroke management 198–199 during vascular access 20–21
Index 423
blood count, hepatic disease 289 blood transfusion (Continued) brain (Continued)
blood gas analysis see also carbon dioxide; donation 273 traumatic injury see traumatic brain
oxygen fatality 282 injury (TBI)
acceptable values 182 gastrointestinal bleeding tumors 205
capnography 17, 18–19 management 301 brain death
postanesthetic 394 hypocalcemia and 51 criteria 370
pulse oximetry 17–18, 17f informed consent 71, 371 ethical issues 370
blood glucose Jehovah’s Witnesses 276, 284–285 legal issues 379
disturbance 62, 243–245 see also massive 281–282 brainstem, hemorrhage 206
hyperglycemia; hypoglycemia coagulopathy and 265 Brain Trauma Foundation 339
target level 243 special issues 282t brain tumors, intraparenchymal
blood pressure total blood volume replacement 275 hemorrhage 205
arterial waveform 25 optimal hematocrit 71 Brater’s syndrome 68
determinants 412–413 special transfusion needs 273–274 breathing see also entries beginning
elevated see hypertension trauma management 342 respiration/respiratory; lung
“fallacy of” 26f uncrossmatched RBCs, safety 276 assessment 339
low see hypotension blood urea nitrogen (BUN), pregnancy Cheine–Stokes respiration 218
massive blood transfusion and 281 changes 249 postanesthetic complications 393–395, 393t
mean arterial see mean arterial pressure “blue bloaters” 111 hypoventilation 393–394
(MAP) blunt trauma pregnancy 248
monitoring in the elderly 344 rate, poisoning 362t
invasive 24–26 renal 328 respiratory muscles 111, 190, 401
noninvasive 17, 19 B lymphocytes 255 spontaneous 111–112
poisoning 362t body fluid 59–60 see also electrolytes; water; thermal injury/smoke inhalation 347–348
pulse pressure 26 specific components thoracic trauma and 409
blood products 72, 273–285 see also blood balance 61 “breath stacking” 183, 184
transfusion cardiac output and 59–60, 59f bretylium, in hypothermia 57
alternatives 283–285 compartments 60, 60f British Anti-Lewisite (BAL) 357
clotting factors 273, 277t hypovolemia see hypovolemia bromocryptine, neuroleptic malignant
coagulopathy and DIC management 270–271 loss/redistribution syndrome treatment 56
contents 274t, 278t normal 61 bronchiectasis, thermal injury/smoke
cryoprecipitate 72, 273, 278–279 in pathology 61–67 inhalation 348
dosing guidelines 278t maintenance see fluid management bronchoalveolar lavage, ventilator-associated
protein contents 278t normal 60–61, 60f pneumonia diagnosis 169
donation 273 osmotic pressure 61 bronchodilators see also specific drugs
fresh frozen plasma 72, 273, 277–278 body temperature pneumonia management 173
dosing 278t anesthesia effects 55, 57, 395–397 ventilator weaning and 191
indications 277t circadian 54 bronchopleural fistula
immunoglobulins 273, 279 hyperthermia see hyperthermia pulmonary surgery complications 407
irradiation 274 hypothalamus and 397 radiography 403
leukoreduction 273–274 hypothermia see hypothermia bronchopneumonia 160, 161f
plasma derivatives 273, 279, 280t normal 54 bronchoscopy
platelets 72, 273, 279, 281 poisoning 362t thermal injury/smoke inhalation 347
storage 274t, 279 stroke patients 203 thoracic trauma 409
trauma management 342–343 in traumatic brain injury ventilator-associated pneumonia
use in liver transplantation 298 manipulating 229 diagnosis 169
blood purification, renal failure 315 monitoring 227 bronchospasm, evaluation/treatment 395
blood salvage 284 Bonanno catheter 321 Brønsted–Lowry acid definition 38
bloodstream infections (BSIs), catheter-related bone marrow transplantation 257–258 bubonic plague 355
see catheter-related infection case study 260 buffers, definition 38
blood substitutes 343 patterns of infection 257 burns see thermal injury
blood tests bones
hepatic disease 289 assessment 340 see also radiography
myocardial ischemia 147 fractures see fractures C
blood transfusion 69, 71–72, 273–285 botulinum toxin 365
see also blood products environmental threat 357 caffeine–halothane contracture test 55
ABO compatibility 275, 275t, 276 botulism 357 calcitonin, hypercalcemia treatment 52
anemia 69, 275–277 bowel see also intestines calcium 51–52, 66
autologous 273, 283–284 injury, suprapubic cystostomy 323 cardiac arrhythmias and 66, 76
choice of “trigger” irrigation, poisoning treatment 363 coagulopathy 269
consensus statements 281 bradyarrhythmias 77t, 84–85 drug interactions 51
critical care 276–277 postoperative 416 homeostasis 51
perioperative 276, 277t brain see also entries beginning hormonal regulation 240
coagulopathy management 270–271 cerebral/cerebro-; specific regions in hyperalbuminemia 67
complications 71–72, 282, 283t abscess(es) low see hypocalcemia
alloimmunization 281 in congenital heart disease (adult) 154 normal plasma levels 51
coagulopathy 264, 265, 281 in HIV/AIDS 259 raised see hypercalcemia
febrile 396 in congenital heart disease (adult) 154 calcium channel blockers 101
graft versus host reactions 71, 283t edema/swelling see cerebral edema angina treatment 147
hemolysis 72, 276, 283t herniation 207, 218 atrial fibrillation 81, 82t
hypothermia 72, 282 hypertension effects 139 hypertension management 140–141,
infectious 72, 159, 282 ICP monitor placement 235 415, 415t
leukoreduction and 274, 282 nontraumatic injury see stroke multifocal atrial tachycardia 82
426 INDEX
catheters see also specific types central venous catheters (CVCs) (Continued) cerebrospinal fluid (CSF) (Continued)
anaphylaxis induction 120 Seldinger technique 28, 29 elevated ICP 234
care 121 site preparation 119 hydrocephalus 218–219
central venous see central venous catheters ultrasound use 28–29 cerebrovascular disease 195–213
(CVCs) preparation 20 stroke see stroke
cystourethroscopy 319, 320, 321f site dressing 120 cervical spine, assessment 340, 341f
fluid flow through 27–28, 69, 71 uses/importance 26–28 Charcot Bouchard aneurysms, hemorrhage 205
French size 28, 319 central venous pressure (CVP) 28, 412 Chediak–Higashi syndrome 253
ICP monitors 235 monitoring 29–30 Cheine–Stokes respiration 218
impregnation of 120–121 trauma, monitoring 343 chemical incidents/weapons 354, 356–359
infection see catheter-related infection waveform 29, 30f agents 357–358, 365
pulmonary see pulmonary artery cephalic vein 27f antidotes 358, 359, 365
catheter (PAC) cephalosporin, hospital-acquired burns 347
radiological verification 23–24 pneumonia 167 management principles 358–359, 365
suprapubic cystostomy 321, 322f cerebellum chemotherapy, neutropenia 253
placement 322, 323f hemorrhage 206–207 chest drainage 403, 403f
thrombosis induction 24 herniation 218 chest physiotherapy, post-pulmonary
urethral 317, 318f infarction 197 surgery 404
urinary 332 neurological assessment 233 chest radiography
cation exchange, hyperkalemia treatment 50 cerebral aneurysms ARDS 177
cations, definition 61 anesthesia and 140 pneumonia diagnosis 160–161, 160f, 171
caudate, hemorrhage 206 intraparenchymal hemorrhage 205 “ground glass” appearance 171f
cavernous angiomas, hemorrhage 205 subarachnoid hemorrhage 208–209 “honeycomb” appearance 172f
cavitation, pneumonia 160 cerebral angiography 210 interpretation 174–175
CD4 cell counts 254 cerebral arteries post-pulmonary surgery 403, 404f
HIV/AIDS 258, 259 anterior circulation 196–197 thermal injury/smoke inhalation 347
CD8 cells 254 occlusion see ischemic stroke thoracic trauma 409
CD14 cells, sepsis pathophysiology 5 cerebral blood flow chickenpox, smallpox vs. 356
cefotaxime, dialysis and 315t anesthesia and 398 Child–Pugh score (CPS) 288, 288t
ceftazidime, dialysis and 315t anterior circulation 196–197 children, sedation in 130, 131
ceftriaxone autoregulation 219–220 chlorhexidine
dialysis and 315t carbon dioxide 220 catheter impregnation 120
hospital-acquired pneumonia 167 factors affecting 219, 220 catheter insertion 119
cefuroxime, hospital-acquired pneumonia 167 stroke and 203 chloride ions 65
cell-mediated immunity 254–255 cerebral perfusion pressure see cerebral acid–base physiology 41–42, 68, 69
in HIV/AIDS 258 perfusion pressure (CPP) hyperkalemia treatment 65
Centers for Disease Control (CDC), intracranial pressure see intracranial chlorine gas 358, 365
pneumonia definition 157 pressure (ICP) chloroacetophenone 358
Centers for Medicare and Medicaid Services obstruction/occlusion see ischemic stroke chloropicrin 358, 365
(CMS) 380 in trauma 219–221, 229 cholecystectomy, avoidance in cirrhosis 290
central (neurogenic) diabetes insipidus 242 anesthesia and 224 choledochocholedochostomy 297
central nervous system (CNS) see also brain; hyperemia 219 cholestasis, cirrhosis and 286, 287t
entries beginning neural/neuro- hypoperfusion 219 chronic lymphatic leukemia (CLL), humoral
hypertension effects 139 monitoring 226–227 defects 255
hypomagnesemia effects 52–53 vasospacticity 219 chronic obstructive pulmonary disease
infection vasoconstriction cascade 221 see COPD
complement deficiencies 255 vasodilation cascade 220–221 Chvostek’s sign 66
in HIV/AIDS 258, 259 cerebral edema 217–218 see also intracranial cingulate gyrus, herniation 218
humoral defects 255 hypertension ciprofloxacin
monitoring 233–236 cytotoxic 217, 218 anthrax 355
nontraumatic injury 195–213 glucose administration and 62 dialysis and 315t
postoperative events 398–399 hyponatremia 47 Y. pestis infection 355
traumatic injury interstitial 217, 218 circadian rhythm, body temperature 54
brain see traumatic brain injury (TBI) vasogenic 217, 218 circulation
spinal cord 340, 341f, 342 cerebral embolization assessment 339
central pontine demyelination 48, 64 in congenital heart disease (adult) 154 failure (shock) see shock
central venous catheters (CVCs) 19, 26–30 postoperative 398 hepatic disease and 292
complications cerebral hemorrhage 195, 204–212 ketamine-induced hyperdynamic
DVT 119 classification 196 response 131
infections see catheter-related infection congenital heart disease and 154 cirrhosis 286–299 see also fulminant hepatic
pneumothorax 23, 29, 109 intraparenchymal see intraparenchymal failure (FHF)
CVP monitoring 29–30, 30f hemorrhage cholecystectomy avoidance 290
fluid flow through 27–28, 69, 71 neurologic monitoring complication 235 classification 286, 288, 288t, 289t
French size 28 subarachnoid see subarachnoid clinical manifestations 290–296
insertion 27, 27f hemorrhage cardiovascular 292
in myocardial ischemia 146 cerebral ischemia see ischemic stroke coagulopathy 289, 296
parenteral nutrition 109 cerebral perfusion pressure (CPP) 199, 220, encephalopathy 290–292, 291t
peripherally inserted (PICC lines) 27 224, 229, 234 gastrointestinal 293–295
positioning/placement 21, 28–29, 118–119 in hepatic encephalopathy 291 immunologic 296
approaches 28, 28f, 119 cerebral salt wasting syndrome 212 pulmonary 292–293
infection prevention 118–120 cerebrospinal fluid (CSF) renal 295
malpositioning 23 analysis in HIV/AIDS 259 definition 286
radiological verification 23–24 drainage 228, 235 diagnostic studies 289–290, 290t
428 INDEX
Fick principle 32 fulminant hepatic failure (FHF) (Continued) gastrointestinal system 286–334 see also
fiduciary duty encephalopathy 290–292, 291t, 363, 369 specific components
advance directives and 378 gastrointestinal 293–295 bleeding see gastrointestinal bleeding
HIPPA 379 immunologic 296 enteral nutrition and 108
filovirus fevers 356 pulmonary 292–293 in hepatic disease 293–295
flail chest 409 renal 295 host defense role 252
flaviviruses 356 definition 286 in pregnancy 249
flecainide diagnostic studies 290t general systems theory 372–373
pulmonary surgery and arrhythmia 406 etiology 287–288, 287t genetic polymorphism
Wolff–Parkinson–White syndrome 81 drug toxicity see hepatotoxic drugs pneumonia pathogenesis 158
fluconazole, dialysis and 315t liver transplant in see liver transplantation sepsis predisposition 4
fluid balance 61 mortality 296 genitourinary trauma 328–333
fluid challenge 413 functional residual capacity (FRC), bladder 330, 332
sepsis 8, 8t post-thoracic surgery 404 renal 328–330
fluid management 59–72 see also blood fundamental critical care support, urethral 332–333
products; blood transfusion; electrolytes; credentialing 374 gentamicin
water fungal infection(s) see also specific magnesuria 65
acute renal failure 310 organisms/infections Y. pestis infection 355
hepatorenal syndrome 309 pneumonia 158t, 165–166, 166f Glanzmann’s thrombasthenia 264
cardiac output and 59–60, 59f furosemide Glasgow Coma Scale (GCS) 215, 222,
colloids see colloids hypercalcemia treatment 52 233–234, 339, 375, 383t
colloid vs. crystalloid controversy 279 hypertension management 415t subarachnoid hemorrhage grading systems
crystalloids see crystalloids fusiform aneurysms, hemorrhage 209 209, 210
diabetic ketoacidosis 244 futility 371 Glasgow Outcome Scale (extended) 232
nonketotic hyperosmolar syndrome 245 glomerular filtration
pneumonia treatment 171–172 fenoldopam effects 101–102
in pulmonary surgery 403 G rate assessment 307–308
lung transplants 408 glomerular nephritis, acute renal failure
purpose 59 GABA receptors, benzodiazepine and 311
in sepsis 7–8, 8t effects 128 glucagon, in postoperative bradycardia 416
stroke management 203, 211 gallstones, congenital heart defects (adult) glucocorticoids 240
triple-H therapy 202, 211 and 155 thyroid storm management 239
trauma 342–343 gamma-hydroxybutyrate (GHB), in traumatic brain injury management 229
brain injury 221–222, 230–231 poisoning 362t glucose
thermal injuries 348–350 gamma irradiation, blood products 274 blood level disturbance 62, 243–245
flumazenil 129, 398 gancyclovir diabetic ketoacidosis 243–244
in benzodiazepine poisoning 364 dialysis and 315t hyperglycemia see hyperglycemia
fluoroquinolones drug interactions 259 hypoglycemia see hypoglycemia
anthrax 355 gases nonketotic hyperosmolar syndrome
pneumonia management 173 blood see blood gas analysis 244–245
focused assessment with sonography for smoke inhalation 346–347 glycosuria in pregnancy 249
trauma 341, 342 gas exchange, assessment 401 hyperkalemia treatment 50, 65
Foley catheter 318f, 326, 332, 340 gastric decompression 340 metabolism
urethral trauma due to 319 gastric emptying, poisoning treatment 362 in acute pancreatitis 114
Fontan procedures 153, 154, 156 gastric lavage, poisoning treatment 362–363 in stroke patients 203
food, environmental threat and 360 gastric tonometry, trauma patients 338 nutritional requirements 107
forced expiratory volume in 1sec (FEV1) 401 gastric ulcers, NSAIDs and 301 sepsis pathophysiology 112
fractures gastritis, stress glutamine, immunonutrition 115
assessment 340 burns 351 glycogen 107
pelvis 332 prophylaxis in trauma 341 glycolysis, lactic acidosis 45
skull 216 gastroesophageal reflux, in pregnancy 249 glycoprotein receptors, coagulation role
thoracic 409 gastrointestinal bleeding 300–306 261–262, 262
traumatic brain injury and 216, 219 case study 305 glycopyrrolate, nerve gas antidote 365
Francisella tularensis, atypical pneumonia cirrhosis-associated 294 glycopyrrolate, postoperative pulmonary care
164 definitions 300 405t
Frank–Starling law 412 history 301 glycosuria, pregnancy 249
fraud 379–380 lower 300, 304–305 goiter 239
“free water” causes 301, 304–305 “golden hour” 337–342
contraindications 62, 69 differential diagnosis 304 graft-to-recipient standard liver volume ratio
deficit 49, 49t, 243 management algorithm 304f (GSLV) 298
glucose effects 62 presentation 304 graft-to-recipient weight ratio (GRWR), liver
French size 28, 319 NSAIDs and 301, 302 transplantation 298
fresh frozen plasma (FFP) 72, 273, 277–278 physical examination 301 graft versus host reactions
in acute renal failure 314 presentation 300 blood transfusions 71, 283t
coagulopathy and DIC management 270 resuscitation 300–301 reduction 274
storage 274t severity classification 300–301, 301t bone marrow transplantation 258
trauma management 342 trauma-related 232 Gram stain 161
fulminant hepatic failure (FHF) 286–299 upper 300, 301–303 granisetron, PONV prevention/treatment 392
see also cirrhosis differential diagnosis 303 granulocyte colony-stimulating factor (GCSF),
classification 286, 288, 289t management/treatment 302–303, 303f pneumonia management 173
clinical manifestations 290–296 presentation 301–302 granulocytes see polymorphonuclear
cardiovascular 292 prognosis 302 leukocytes
coagulopathy 289, 296 gastrointestinal mucosa, host defense 252 Grave’s disease 239
Index 433
guaifenesin, postoperative pulmonary heart failure (Continued) hemodynamic stabilization see also blood
care 405t enalaprilat 102 transfusion; fluid management
gut motor hypothesis 160 hyponatremia 48 in acute renal failure 310
catheter-related sepsis 21–22 hypertension and 139, 141 lung transplantation 408
gynecologic surgery, PONV and 391 hyponatremia 48 postoperative 411–417
nesiritide 102–103 sepsis management 7–8, 8t
sodium nitroprusside 98 catecholamines 90t
H vasodilator drug choice 103 VIP principles 7–8
ventricular function curve 30f hemofiltration
Haemophilus influenzae infection heart–lung interaction assessment 401 acute renal failure 312
bronchopneumonia 160 heart valves continuous veno-venous (CVVH) 312
community-acquired pneumonia 162, 163 bicuspid defects 153 intermittent extended 314
in HIV/AIDS 258 pulmonary stenosis 153 lactate metabolism 44–45
humoral defects 255 in tetralogy of Fallot 152 hemoglobin
ventilator-associated pneumonia 168 tricuspid agenesis 13 carboxyhemoglobin 18, 346
Haldol, neuroleptic malignant syndrome 55 in ventricular septal defects 151 spectrophotometry 17–18
haloperidol 130 heat stroke 54–55 extinction curves 17f
in postoperative delirium 399 Helicobacter pylori, gastrointestinal bleeding Hemolink 284
halothane 302 hemolysis
hepatotoxicity 287 helium/oxygen mixture, postoperative HELLP syndrome 250
postoperative hypoventilation 393 pulmonary care 405t hemolytic disease of the newborn 279
in traumatic brain injury 225 HELLP syndrome 250 transfusion-related reaction 72, 276, 283t
Hamburger shift 45 hematemesis, coagulopathies 267 hemolytic disease of the newborn 279
hand hygiene, catheter insertion 119–120 hematochezia hemoperfusion, poisoning treatment 363
Harris–Benedict equation 106, 351 coagulopathies 267 hemophilia(s)
Hashimoto’s thyroiditis 237 gastrointestinal bleeding 300, 302, hypocoagulation 264
headache 304, 305 management
intraparenchymal hemorrhage and 205 hematocrit cryoprecipitate 278
subarachnoid hemorrhage 209 congenital heart defects (adult) and DDAVP 278, 284
head injury see traumatic brain injury (TBI) 154–155 plasma derivatives 279, 280t
Head Injury Severity Score (HISS) 215, 222 gastrointestinal bleeding and 301 preoperative 264
Health Care Financing Administration optimal in ICU patients 71 Hemopure 284
(HCFA) 379 transfusion “trigger” 276 hemorrhage see also bleeding; hypovolemia
health care rationing 379 trauma patients 338 acute, signs 69
Health Insurance Portability and hematologic system 252–285 see also blood adrenal gland 241
Accountability Act (HIPPA) 379 coagulation 261–272 cerebral see cerebral hemorrhage
heart see also entries beginning congenital heart defects (adult) and coagulopathies 267
cardiac/cardio- 154–155 gastrointestinal see gastrointestinal bleeding
abnormalities immune-compromised host 252–260 obstetric 250
congenital see congenital heart defects pregnancy physiology 249 primary assessment 339
(CHD) hematoma(s) risk assessment 69
in HIV/AIDS 259–260 extradural 216 vascular access and 20
catheterization see central venous catheters renal 330 viral hemorrhagic fevers 356
(CVCs) subarachnoid hemorrhage 212 hemorrhagic stroke see cerebral hemorrhage
contractility 30, 412 subdural 217 hemostasis see also coagulation
disease see heart disease hematuria fibrinolysis 262
electrophysiology 74, 74f bladder trauma 332 primary 261–262
failure see heart failure renal trauma 328–329 secondary 262
functional measures 32 suprapubic cystostomy 323–324 surgical 271
hyperkalemia effects 65 urethral catheterization 319 “Henderson” equation 38
hypertension effects 138–139 hemicolectomy, diverticulosis management 304 Henderson–Hasselbalch equation 38–39, 67
ischemia see myocardial ischemia/infarction hemodialysis Hendex® 69
rate 30, 412 acute renal failure 312, 314 heparin
poisoning 362t drug prescription and 315t catheter insertion 120
trauma 409 lactate metabolism 44–45 coagulopathy/DIC management 270–271
valves see heart valves membranes, controversy 314 complications 24, 72, 264–265, 266, 270,
heart block 84–85 poisoning treatment 363 281, 313
ECG 84, 84f, 85 hemodynamic instability see also blood pres- in continuous renal replacement
first-degree 84, 84f sure; hypovolemia therapy 313
hyperphosphatemia 54 cardiac arrhythmias and 78 intraoperative ischemia management 148
PAC use 33 case study 417 ischemic stroke management 202
second-degree 84–85, 84f management see hemodynamic stabilization laboratory findings following use 268t
third-degree 84f, 85 monitoring see hemodynamic monitoring resistance 72
ventral septal defects 151 in recovery room 411–417 vascular access and 24
heart disease in sepsis 7–8 heparin-associated thrombocytopenia (HAT)
arrhythmias and 75t, 76 hemodynamic monitoring 16–36 see also 24, 72
congenital see congenital heart defects specific methods heparin-induced thrombocytopenia (HIT)
(CHD) blood pressure 17, 19, 24–26 24, 264–265, 281, 313
ischemic see myocardial ischemia/infarction general principles 19–24 assay 270
pulmonary surgery and 401–402 noninvasive 17, 19, 35 hypercoagulable states 266
heart failure pulse oximetry 17–18, 17f heparinoids, in continuous renal replacement
congestive renal trauma 330 therapy 313
coarctation of the aorta 153 vascular access see vascular access hepatic artery, in liver transplantation 297
434 INDEX
ischemic stroke (Continued) Klebsiella pneumoniae infection (Continued) Legionella pneumophilia infection
seizures 203–204 humoral defects 255 cell-mediated immunity and 254
surgical 204 lobular pneumonia 160 community-acquired pneumonia 163
thrombolysis 201–202, 204 neutropenia 253 hospital-acquired pneumonia 167
pathophysiology 196, 218 ventilator-associated pneumonia 168 lenticulostriate arteries, occlusion 197
subarachnoid hemorrhage and 211, 212 Korotkoff sounds, blood pressure leukoreduction 273–274, 282
symptoms/signs 196, 197 monitoring 19 leukotrienes, burn pathophysiology 346
transient ischemic attack (TAI) 154, 196 Kothary ABC/2 formula 207 levo-carbidopa, neuroleptic malignant
traumatic brain injury 218 K-phos, hypophosphatemia treatment 67 syndrome treatment 56
vertebrobasilar 197 Levophed 92
watershed infarcts 196, 197 Lewisite 357, 365
isoflurane L lidocaine (lignocaine)
postoperative hypoventilation 393 during vascular access 20
in traumatic brain injury 225 labetolol 100–101, 140, 415t ventricular fibrillation 79
isolation, disaster management 353 actions 100 life support see also resuscitation
isoniazid, hepatotoxicity 287 adverse effects 100–101 Advanced Cardiac Life Support Protocol 27
isovolemic hemodilution 284 characteristics 104t ATLS course 222, 328, 338
stroke management 198 withdrawal 378–379
in sympathomimetic poisoning syndrome 56 linezolid (Zyvox)
J laboratory tests hospital-acquired pneumonia 167
acute renal failure 308t ventilator-associated pneumonia 169
Jatene procedure 153 coagulopathies 268t, 267–269 lipid-lowering drugs, angina treatment 147
Jehovah’s Witnesses, blood transfusion and hepatic failure 289–290, 290t lipids
276, 284–285 liver disease 268t nutritional requirements 107
ethical issues 369 laceration nutritional support in renal failure 113
jejunostomy, total enteral nutrition 110 assessment 340 nutritional support in sepsis 112
Johns Hopkins University Scale, subarachnoid brain 216, 217 lipopolysaccharide-binding protein (LPB),
hemorrhage 210 scalp 216 sepsis pathophysiology 5
Joint Commission for the Accreditation of lacrimants 358 lipopolysaccharide (LPS), sepsis
health Care Organizations (JCAHO) lactate pathophysiology 5
Guiding Principles 379 acid–base balance and 35, 43–44 liposomal amphotericin, dialysis and 315t
postoperative transport 418 chemistry 42 lipotiechoic acid, sepsis pathophysiology 5
Joint National Committee on Prevention, excess see lactic acidosis Listeria monocytogenes infection
Detection, Evaluation and Treatment of hemodialysis/hemofiltration and 44–45 cell-mediated immunity and 254
High Blood Pressure, hypertension liver graft assessment 298 transplantation and 256
definition 137 lactated Ringer’s solution 42 liver see also entries beginning
jugular vein thermal injuries 348–349 hepatic/hepato-
cannulation 28, 119 trauma management 342 artificial 298, 315
oxygen saturation 18 lactic acidosis 43–44, 67–68 biopsy 290
cerebral blood flow and 226 artificial kidney and 44–45 disease see hepatic disease
monitoring in traumatic brain injury case study 46 failure see hepatic failure
226–227 septic shock 45 transplantation see liver transplantation
jugular venous bulb oximetry 18 tissue oxygen relationship 35 liver enzymes 289
junctional tachycardia 83 types/subtypes 67 liver transplantation 296–298
justice, medical ethics 368–369 lacunar infarcts 196, 197 in acetaminophen poisoning 363–364
justification 20 Laplace’s law 178 adult live donor 298
laryngeal mask airway 140 anesthesia 296–297
K laryngospasm, postanesthetic 395 artificial 298, 315
larynx contraindications 296t
Kayexelate, hyperkalemia treatment 50 injury 409 controversies 296, 298
Kernoan Woltman syndrome 218, 222 postoperative edema 395 ethical issues 369–370
ketamine 130–131 Lasix, hyperkalemia treatment 50 graft assessment 298
seizure association 398 latex allergy, vascular access and 22–23 graft failure 296
in traumatic brain injury 224–225 LD50 353 intraoperative phases
ketones, diabetic ketoacidosis 244 “lead-pipe” rigidity, neuroleptic malignant anhepatic 297
kidney see also entries beginning syndrome 55 neohepatic 297
renal/nephro-; urological procedures left bundle branch block (LBBB), venous preanhepatic 296–297
artificial 44–45 access and 20, 33 orthoptic 296–298
congenital heart defects (adult) and 155 left ventricular end diastolic pressure postreperfusion syndrome 297
failure see renal failure (LVEDP) 32 living wills
functional assessment 307–308 legal issues 376–380 ethical issues 367
in HIV/AIDS 260 advance directives and DNRs 370, 378–379 legal issues 378–379
hypertension and Anti-Kickback statute 380 lobular pneumonia 160, 160f
effects on 139 consent 377–378 local anesthesia
role in pathogenesis 138 False Claims Act 379–380 postoperative analgesia 390–391
injury mechanisms 310 Health Insurance Portability and during vascular access 20–21
stones, acute renal failure 309 Accountability Act 379 loop diuretics
trauma see renal trauma liability, minimization strategies 377 acute renal failure and 310–311
King’s College Hospital Criteria for FHF malpractice 376, 377 hypertension management 141
288, 289t negligence 376, 377 lorazepam 128, 129
Klebsiella pneumoniae infection procedural credentialing 19–20 low molecular weight heparin (LMWH)
catheter-related 118 Stark Law 380 coagulopathy/DIC management 270–271
community-acquired pneumonia 162 triage and rationing of services 379 laboratory findings following use 268t
438 INDEX
neurological examination 233–234 noninvasive ventilatory support 13, 14t, 15, 15t obstetric complications (Continued)
poisoning 362t nonketotic hyperosmolar syndrome (NKHS) hypertensive 250
trauma assessment 339, 340–341 244–245 thrombotic 250–251
in traumatic brain injury 222 diabetic ketoacidosis vs. 245 obstructive heart defects 151t, 153–154
neurological status 233, 339 nonmaleficence 368 coarctation of the aorta 153–154
neurologic monitoring 233–236 advance directives and 378 critical care in 156
body temperature 227 nonsteroidal anti-inflammatory drugs (NSAIDs) pulmonary stenosis 153
cerebral blood flow 226–227 burn care 350 obstructive pyelonephritis 326
cerebral perfusion pressure 234 gastric ulcers and 301 obstructive sleep apnea, postoperative
complications 226, 235 gastrointestinal bleeding and 301, 302 hypoventilation 393
electrophysiology 227, 235–236 liver disease and 294, 295 obturators, suprapubic cystostomy
examination 233–234, 339 mechanisms of action 128, 390 322f, 323
intracranial pressure 199, 225–226, postoperative analgesia 390 occipital lobe, hemorrhage 206
234–235, 292 post-thoracotomy analgesia 405 occult bleeding, coagulopathies 267
indications 226 sedation and 128 ocular bobbing 206
in stroke 199 nonstress test (NST), fetal monitoring 249 Ohm’s law 412
in traumatic brain injury 225–227 nonthyroidal illness syndrome 239–240 oliguria 60, 61
neuromuscular blockade 132–134 see also noradrenaline see norepinephrine definition 62
specific agents norepinephrine 91–92 thermal injury 349
clinical use adverse effects 92 oncotic pressure 69
indications 132 hypotension management 92, 414t definition 61
neuroleptic malignant syndrome 56 in sepsis/septic shock 8, 90t, 91–92, 97 ondansetron, PONV prevention/treatment 392
sympathomimetic poisoning 56 comparative studies 95–96t open lung biopsy, in ventilator-associated
complications 132, 133–134 drug of choice 94 pneumonia 169
respiratory 393, 395 tachycardia induction 91, 97 open lung concept 178–179
depolarizing drugs 132–133 normal saline (NS) 68–69 opioids 126–128 see also individual opioids
drug interactions 134 in traumatic brain injury 230 adverse effects 128
drug properties 133t normo-osmolar hyponatremia 48 management 127, 395
evaluation/treatment 395 nosocomial pneumonia 166–170 PONV association 391
nondepolarizing drugs 133 hospital-acquired 166–167 respiratory depression 390
tolerance 132 infectious disease (ID) services 167 agitation and anxiety 124t
in traumatic brain injury 228 pathogens 168t in cirrhotic patients 291
neurovegetative signs, subdural hematoma 217 ventilator-associated 167–170 inadequate analgesia 123
Neutra-Phos NSAIDs see nonsteroidal anti-inflammatory patient-controlled analgesia 390
hypercalcemia treatment 52 drugs (NSAIDs) pharmacology 126t
hypophosphatemia treatment 53, 67 nuclear incidents 359 poisoning 362t, 364
neutropenia nuclear magnetic resonance (NMR) postoperative pain management 390
antimicrobial therapy in 254 intraparenchymal hemorrhage 207 post-thoracotomy analgesia 405
definition 253 subarachnoid hemorrhage 210 reversal of effects 127, 395, 398
neutropenic fever 253 in traumatic brain injury 224 in traumatic brain injury 225, 228
neutrophils see polymorphonuclear leukocytes nuclear medicine, ventilation perfusion oral care agents, pneumonia management
next-of-kin 368 scintigraphy 401 173–174
nicardipine 101, 140–141 nucleotides, immunonutrition 115 oral surgery, blood loss 284
nifedipine nutrition see also malnutrition organic brain syndrome, neuroleptic
hypertension management 140–141 amino acids 107–108 malignant syndrome 55
stroke management 199 carbohydrates 107 organ of Zuckerkandl, tumors 245
nimodipine, subarachnoid hemorrhage and 211 energy/energy balance 106–107 organophosphates, poisoning 362t
nitrates 140 in ICU 106–116 organ-specific scoring systems 375
hydralazine 99–100, 104t, 140 acute pancreatitis 113–114 organ systems 135–334 see also individual
nitroglycerin see nitroglycerin burns patients 351 organs/systems
sodium nitroprusside see sodium enteral route 108–109, 110 in HIV/AIDS 259–260
nitroprusside immunonutrition 110, 114–115 sepsis and 4t, 5
stroke management 199 lung transplants 409 organ transplantation 256–257
nitric oxide parenteral route see parenteral nutrition antibiotic prophylaxis 257
ARDS management 179 perioperative 109–110 cell-mediated immunity dysfunction 254
arginine and 115 pneumonia 172 ethical issues 369–370
lung transplantation and 408 renal failure 113, 311 immunosuppression 408
pneumonia management 174 respiratory failure 110–112 infection following 254, 256–257
nitrogen balance 106 septic patients 112–113 patterns of 257
in renal failure 113 stroke patients 203 liver see liver transplantation
nitroglycerin 99, 140 trauma patients 110, 231 lung 408–409
characteristics 104t lipids 107 rejection 256, 408
heart failure, nesiritide vs. 103 status evaluation 106 success rates 256
hypertension management 415t nutritional status 106 orogastric tubes, cirrhosis-associated
intraoperative ischemia management 148 nutrition risk index (NRI) 106 GI bleeding 294
stroke management 199 orotracheal tubes 339
nitroprusside see sodium nitroprusside ortho-chlorobenzylidene-malononitrile
nitrous oxide O (CS gas) 358
PONV association 391 orthopedic surgery, postoperative pain 389
postanesthetic hypoxia 393 obesity, cirrhosis pathophysiology 286 orthoptic liver transplantation (OLT) 296–298
in traumatic brain injury 225 obstetric complications 249–251 oscillating ventilation, in hypoxemic
nodules, pneumonia 160 disseminated intravascular coagulation 263 respiratory failure 13–14
noninvasive blood pressure monitoring 19 hemorrhage 250 oscillometry 19
Index 441
osmolality pancuronium 132, 133 percutaneous nephrostomy 324, 324t, 325f, 326
calculation 48t postoperative hypoventilation 393 renal trauma 330
serum 60 properties 133t ureteral stent vs. 326–328, 327t
osmolarity pressure, definition 61 papillary necrosis, acute 326 percutaneous suprapubic cystostomy
osmole, definition 61 paracentesis, cirrhosis-associated ascites 293 catheterization 321–324, 321t, 326
osmotic diuresis 62 paracetamol see acetaminophen percutaneous transluminal coronary
hypernatremia 49 parapneumonic infiltrates 160–161, 161f angioplasty (PTCA) 144
ICP reduction parathyroid gland Perflubron 284
in stroke management 199 dysfunction perfluorocarbon solutions 284
in traumatic brain injury management hyperparathyroidism 52, 240 peribronchovascular infiltrates (interstitial
223, 228 hypoparathyroidism 54, 240 pneumonia) 160, 161f
osmotic pressure 61 hormones 51, 66, 240 pericardial tamponade, trauma assessment 341
outcome measures 372, 381 surgery, hypocalcemia 398 perioperative complications
in traumatic brain injury 232 parathyroid hormone (PTH) hypothermia 57
oxacillin-resistant Staphylococcus aureus calcium regulation 240 myocardial ischemia/infarction 143–149
(ORSA) 167 hypocalcemia and 51, 66 perioperative nutrition 109–110
ventilator-associated pneumonia 168 paravertebral block, post-thoracotomy peripherally inserted central catheters
oximes, nerve gas antidote 365 analgesia 405–406 (PICC lines) 27
oxygen parenchymal acute renal failure 308 peritoneal dialysis, acute renal failure 312, 314
administration see also ventilatory support pathogenesis 310 peritoneal lavage, trauma assessment 341
hyperbaric, CO poisoning 364 parenchymal liver disease 286, 287t peritonitis, bacterial 289, 296
PONV and 391–392 parenteral nutrition 109–110 cirrhosis 294–295
postoperative transport 419 acute pancreatitis 114 hepatorenal syndrome 309
thermal injury/smoke inhalation 347 total (TPN) 110 permanent pacemaker (PPM) 85–86
alveolar-arterial (A-a PO2) tension, catheter-related infection 118 persistent vegetative state (PVS)
hypoxemia 11–12 parietal lobe, hemorrhage 206 diffuse axonal injury 217
arterial tension (PaO2) 71 Parkland formula, thermal injuries 348–349 ethical issues 370
elderly trauma victims 344 paroxysmal supraventricular tachycardia petrolatum, burns care 350
in stroke 198 82–83, 82f phagocytosis, polymorphonuclear
in traumatic brain injury 221, 224 partial thromboplastin time (PTT) 268t, leukocytes 253
delivery (DO2) 30, 30f, 71 268, 277 pharmaceutical industry, ethical issues 371
cardiac output and 59 1:1 mixing studies 268–269 pharyngeal obstruction, postoperative
dopamine effects 91 hepatic disease 289 hypoventilation 393
lactic acidosis relationship 35 patent ductus arteriosus (PDA) 151–152 pH, definition 38
phenylephrine effects 93–94 patient(s) phenobarbital, poisoning 363
pregnancy 248 capacity 367, 370, 377 phenoxybenzamine 246
uptake (DO2–VO2) relationship 34–35, 35f comfort, during vascular access 20–21 phentolamine 246
demand, myocardial 144 competence 377 phenylephrine 93–94
hypoxemic respiratory failure 11–12 confidentiality/privacy laws 379 adverse effects 94
saturation (SaO2) consent issues see consent hypotension management 94, 414t
jugular oxygen monitoring 226–227 elderly see elderly patients intraoperative ischemia management 148
near infrared spectroscopy 227 management, scoring systems role 382 pheochromocytoma 245–246
pulse oximetry (SpO2) 17–18 safety 372–373 diagnosis 245
tissue oximetry 227 staff ratios 374 hypertension 138, 245
uptake (VO2) treatment refusal 377 treatment 140, 246
assessment 401 wishes, ethical issues 368 phlebitis, catheter-related 22
delivery (DO2–VO2) relationship 34–35 patient care phlebostatic axis 29
dopamine effects 91 individual 382 phlebotomy 71
maximal (VO2max) 401 misrepresentation 380 phosgene 357–358, 365
phenylephrine effects 93–94 patient positioning phosphate ions 53–54, 66–67
oxygen extraction ratio (O2 ER) 34 catheter insertion 21 acid–base balance 43
oxyhemoglobin 17, 18 urethral 318, 320f hypercalcemia treatment 52
hypotension management 413 hyperphosphatemia 51, 54, 67
percutaneous nephrostomy 325f hypophosphatemia 53–54, 66–67, 244
P stroke management 199 metabolic functions 53, 66
suprapubic cystostomy 323 physiotherapy, post-pulmonary surgery 404
pacemaker cells 74 in ventilator-associated pneumonia 170 physostigmine, anticholinergic syndrome
pacemakers see cardiac pacing ventilator weaning and 192 treatment 57
pain pediatric medicine, sedation in 130, 131 PICC lines (peripherally inserted central
abdominal 393 pelvis catheters) 27
burns 350–351 examination 340 “pink puffers” 111
control see analgesia fracture 332 piperacillin, dialysis and 315t
postoperative 389–391 trauma assessment 341–342 PIRO system 4–5, 4t
hypoventilation and 393 penetrating trauma, renal 328 pituitary hormones, TSH 237
post-thoracotomy 404–406 penicillin plague 355
scales 390 anthrax 355 plasma
palmar arch 27f Y. pestis infection 355 exchange (plasmapheresis), ARF 314
pamidronate, hypercalcemia treatment 52 penicillin-resistant Streptococcus pneumoniae proteins, acid–base physiology 45–46
pancreatitis (PRSP) 162 transfusion 72, 273, 277–278
acute pentamidine, Pneumocystis carnii infection 171 derivatives 273, 279, 280t
nutritional support 113–114 peptidoglycan, sepsis pathophysiology 5 indications for use 277t
sepsis 114 percutaneous gastronomy, enteral nutrition storage 274t
hypocalcemia 66 and 108 volume 60, 62
442 INDEX
plasmapheresis (plasma exchange), pneumonia (Continued) postanesthesia care unit (PACU) 389–420
acute renal failure 314 nosocomial 166–170, 168t see also anesthesia
plasminogen activator inhibitor (PAI-1) hospital-acquired 166–167 case study 399
assay 270 ventilator-associated 159, 167–170 common problems 389–399 see also
coagulation role 261 parapneumonic infiltrates 160–161, specific complications
plasminogen activator inhibitor 1 (PAI-1), 161f, 170 arousal 397–399
sepsis 7 pathogenesis 159–160 nausea and vomiting 391–393
plasminogen, coagulation role 261, 262 genetics 158 pain 389–391
platelet-activating factor (PAF), coagulation gut motor hypothesis 160 respiratory 393–395
role 261, 262 presentation 158 thermal 395–397
platelet function analyzer-100 (PFA-100) risk factors 159–160, 162, 163t hemodynamic instability 411–417
267–268 thermal injury/smoke inhalation 348 postoperative transport 418–420
platelets treatment 162–171 pulmonary surgery 400–410 see also
activation 261–262 adjunctive/supportive 171–174 pulmonary surgery
counts 267, 268t antibiotics see antibiotics post-hypercapnic syndrome 68
dysfunction Fine prediction rule/criteria 163t postoperative blood salvage 284
cardiopulmonary bypass 265 guidelines 157–158, 163, 164t postoperative nausea and vomiting (PONV)
drug-induced 270 nonantibiotic drugs 173–174 391–393
in hepatic disease 296 viral 158t, 164–165, 164f, 174 incidence 391
hypothermia 265 pneumonic tularemia 355 prevention/treatment
inherited abnormalities 264 pneumonitis, pneumonia vs. 158, 158f agents 392
storage 274t, 279 pneumothorax PACU regimens 392–393
substitutes 284 catheter-induced 23, 29 risk factors 391–392
transfusion 72, 273, 279, 281 postoperative V/Q mismatch 394 postoperative pain 389–391
coagulopathy/DIC management 271 radiography 23, 403 hypoventilation and 393
dosing 281 Poiseuille–Hagen formula 27, 69, 71 post-thoracotomy 404–406
trauma 342 Poiseuille’s equation 412 postoperative transport see transport issues
washing 274 poisoning 361–366 see also specific postpartum hemorrhage 250
plethysmography 17, 18 toxicities postpneumonectomy pulmonary edema
pleural effusion diagnosis 361–362 (PPPE) 406
in congenital heart disease (adult) 154 neurological signs 362t postreperfusion syndrome (PRS),
parapneumonic infiltrates 160–161, 161f “toxidromes” 361, 362t liver transplantation 297
ventilator-associated pneumonia 170 resuscitation/stabilization 361 postsynaptic potential (PSP) 235–236
Plicamycin (mithramycin), hypercalcemia treatment 362–363 post-thoracotomy pain syndrome 405
treatment 52 polycythemia, congenital heart defects (adult) posttraumatic stress disorder (PTSD)
Pneumocystis carnii infection 170–171, and 154, 156 natural disasters 354
171f, 172f polydipsia 64 sedation and 123
cell-mediated immunity and 254 nonketotic hyperosmolar syndrome 245 potassium iodide, radioactive iodine
in HIV/AIDS 170–171, 258, 259 PolyHeme 284 exposure 359
interstitial pneumonia 160 polymorphic ventricular tachycardia 83–84, potassium ions 49–51, 64–65
transplantation and 256 83f see also Torsade de Pointes cardiac arrhythmias and 50, 76
treatment 171 polymorphonuclear leukocytes 253–254 deficiency see hypokalemia
pneumocytes type II 177 dysfunction (neutropenia) drug interactions 50
pneumonectomy 403, 404f antimicrobial therapy in 254 excess see hyperkalemia
pulmonary edema 406–407 characteristics 253 functions 49
pneumonia fever 253 potassium phosphate, hypophosphatemia
in adults 157–175 infections associated 253 treatment 53, 67
ARDS and 165, 176, 179 polystyrene sulfonate, hyperkalemia potassium-sparing diuretics, hypertension
ARF and 111, 112, 165 treatment 50, 65 management 141
bronchopneumonia 160, 161f polyurethane dressings 120 Potts shunt, tetralogy of Fallot 152
causative organisms 157, 158t, 168t see polyuria, nonketotic hyperosmolar pralidoxime, nerve gas antidote 365
also specific organisms/infections syndrome 245 predicted postoperative forced expiratory
cavitation 160 portopulmonary hypertension, volume in 1sec (ppoFEV1) 401
CDC definition 157 hepatic disease 292 prednisolone, lung transplantation 408
cell-mediated immunity and 254 portosystemic encephalopathy preeclampsia 249, 250
classification 162–171 (PSE) 290–292 disseminated intravascular coagulation 263
community-acquired 162–164 acetaminophen poisoning 363, 369 pregnancy 248–251
atypical 158t, 163–164 grades 291, 291t disseminated intravascular coagulation 263
typical 158t, 162–163 lactulose therapy 291 fetal monitoring 249
diagnosis 160–162 raised ICP and 291–292 obstetric complications 249–251
nonradiologic 161–162, 162t, 163 positive end expiratory pressure (PEEP) hemorrhage 250
radiography 160–161, 160f, 161f, 171, auto-PEEP 183, 187, 188, 408 hypertension 250
171f, 172f, 174–175 in hypoxemic respiratory failure 13 thromboembolism 249, 250–251
ventilator-associated pneumonia 169 indications 188 physiological issues 248–249
differential diagnosis 158, 406 key effects 187 cardiorespiratory 248
fungal 158t, 165–166, 166f in lung transplantation 408 hematologic 249
in hepatic disease 292 postoperative, pulmonary surgery 404 renal/gastointestinal 249
in HIV/AIDS 258–259 postoperative transport 419 von Willebrand’s disease 264
in the immune-compromised 170–171, 171f thermal injury/smoke inhalation 348 pregnancy-induced hypertension (PIH) 250
interstitial (peribronchovascular) 160, 161f titration 187, 187f preload (venous return) 30, 412
lobular 160, 160f in traumatic brain injury 224 definition 29
lung transplantation and 409 ventilation–perfusion zone fluid administration and 59, 59f
nodular infiltrates 160 vulnerability 34 hypovolemia and 412
Index 443
preload (Continued) psychiatric intervention, natural disasters 354 pulmonary surgery (Continued)
measures 32 psychological considerations, ventilator pulmonary edema 406–407
Starling curves 32, 60 weaning 191–192 high-risk patients 401–402, 402t
prerenal acute renal failure 308 Pugin score (clinical pulmonary infection coexisting medical conditions 401–402
pathogenesis 310 score; CPIS) 170 respiratory assessment 401
pressure-controlled inverse ratio ventilation pulmonary artery lung opening procedure (LOP) 178–179
(PCIRV) 185–186 catheterization see pulmonary artery lung transplantation 408–409
pressure-control ventilation (PVC) 185 catheter (PAC) postanesthesia care 400–410
pressure-regulated volume control (PRVC) rupture 33 analgesia 404–406
185 pulmonary artery catheter (PAC) 30–35 arrhythmia management 406
pressure support ventilation (PSV) 185 anatomy 31f chest drainage 403, 403f
weaning 193 complications 32–33 chest radiography 403, 404f
primidone, poisoning, treatment 363 effectiveness 34 commonly used agents 405t
primum atrial defects 151 information obtained 32 fluid management 403, 408
primum non nocere, advance directives insertion 31 lung transplants 408–409
and 378 mechanical ventilation and 34 monitoring 402
prion disease, transfusion-related 72, 282 in myocardial ischemia 146 physiotherapy 404
procainamide “pseudo-wedging” 31–32 routine 402–406
ventricular fibrillation 79 in pulmonary surgery 402 specific conditions 406–409
Wolff–Parkinson–White syndrome 81 trauma 343 ventilatory support 404
prochlorperazine, PONV prevention/ ventilation–perfusion pressures 33–34, 33f thoracic trauma 409
treatment 392 waveforms 31f video-assisted 400
proinflammatory cytokines, sepsis 7 pulmonary artery occlusion pressure (PAOP) 32 pulmonary tularemia 355
promethazine, PONV 392 pulmonary capillary pressure (Pc) 33 pulse alternans 26
propafenone pulmonary catheter wedge pressure (PCWP) pulseless electrical activity 79–80, 80f
pulmonary surgery and arrhythmia 406 31f, 32, 34, 34f, 412 pulseless ventricular tachycardia 78–79
Wolff–Parkinson–White syndrome 81 pulmonary complications see also specific pulse oximetry
propanolol, atrial fibrillation 82t conditions physiology 17–18, 17f
propofol 129–130 congenital heart disease (adult) 154 postanesthetic 394
in hepatic encephalopathy 292 in hepatic disease 292–293 pulse pressure 26
PONV and 391 postoperative 393–395 pupillary responses
in traumatic brain injury 225, 228 evaluation 394 poisoning 362t
propylthiouracil 239 hypoventilation 393–394 traumatic brain injury 222
prostacyclin, pneumonia management 174 post-thoracic surgery 404, 406–407 purine bases, immunonutrition 115
protamine anticoagulation, in CRRT 313 in subarachnoid hemorrhage 212 purpura
protein(s) thermal injury/smoke inhalation 348 post-transfusion 264
catabolism, acute pancreatitis 114 treatment 394–395 thrombocytopenic 264, 281, 311
nutritional requirements 107–108 V/Q mismatch see ventilation/perfusion putamen, hemorrhage 206
in hepatic failure 108, 291 (V/Q) mismatch P wave 74, 74f, 78
in renal failure 113 pulmonary contusion 409 pyelography, renal trauma 329
in urine, pregnancy and 249, 250 pulmonary edema pyelonephritis
visceral, status 106 cardiogenic 406 emphysematous 326
protein C evaluation/treatment 395 obstructive 326
activated, coagulopathy/DIC in liver transplantation 298 pyrexia see fever
management 271 postoperative V/Q mismatch 394 pyrimidine bases, immunonutrition 115
deficiency 266 postpneumonectomy 406–407
sepsis pathophysiology 7 pulmonary embolism
protein S, deficiency 266 circulatory shock 31 Q
protein status, visceral 106 definition 250
Q fever 356
proteinuria, pregnancy 249, 250 hypercoagulable states 266
atypical pneumonia 164
Proteus spp. infections, ventilator-associated postoperative V/Q mismatch 394
QRS complex 74, 74f, 78
pneumonia 168 postpneumonectomy pulmonary edema
QT interval 74, 74f
prothrombinase complex, coagulation vs. 406
prolongation 75
role 262 in pregnancy 249, 250–251
drug-induced arrhythmia 77
prothrombin time (PT) 268t, 268, 277 in stroke 204
drugs causing 77t
1:1 mixing studies 268–269 in traumatic brain injury 231
Torsade de pointes 83, 83f, 84
hepatic disease 289 pulmonary Hantavirus syndrome 164
qualitative data 375
proton pump inhibitors pulmonary histoplasmosis 165, 166f
quality issues 367, 373–375
gastrointestinal bleeding 302 pulmonary hypertension
scoring systems role 382
pneumonia management 173 congenital heart defects (adult) 155
quantitative data 375
P-selectins, coagulation role 261 patent ductus arteriosus 151
quarantine, disaster management 353
pseudoacidosis 67 tetralogy of Fallot 152
quinine, poisoning, treatment 363
pseudohyperkalemia 50, 64 crisis 155
quinolones, pneumonia management 172
pseudohypocarbia 67 definition 292
pseudohyponatremia 48, 64 hepatic disease 292–293
pseudohypoparathyroidism 66 management 155 R
pseudohypoxemia 67 pulmonary stenosis 153
Pseudomonas aeruginosa infections pulmonary surgery “rabbit fever” 355
catheter-related 118 complications 404 radial artery 27f
neutropenia 253 bronchopleural fistula 407 cannulation 24, 25f
ventilator-associated pneumonia 168 cardiac arrhythmia 401–402, 406 radiation syndrome 359
Wegener’s granulomatosis 160 cardiac herniation 407–408 radioactivity, exposure 359
“pseudo-wedging” 31–32 lung torsion/infarction 407 radiocontrast nephropathy 311
444 INDEX
sedation/sedatives (Continued) Sepsis Occurrence in Acutely Ill Patients smoke inhalation see also thermal injury
muscle relaxants 132–134 (SOAP) 3 management principles
nonopioid analgesics 128 septic shock 31 see also anaphylaxis; sepsis airway/breathing 347–348
opioids see opioids gut motor hypothesis 21–22 fluid resuscitation and 349
evaluation and titration of drugs 124 hyperdynamic 91 pathophysiology 346–347
guidelines/protocols 126, 129 lactic acidosis 45 respiratory dysfunction 347–348
ICP reduction 199, 228 management, blood purification smoking, pneumonia risk 159
mechanical ventilation 182–183, 191 techniques 315 “sneaky PEEP” 13
neurological assessment and 233 pulse oximetry 18 Society of Critical Care Medicine (SCCM)
pediatric 130, 131 refractory 90, 94 Practice Parameters for Hemodynamic
poisoning 362t second hit hypothesis 22 Support of Sepsis in Adult Patients 89
scale(s) 124–126, 125t, 340–341 vasoconstrictive drugs 89–97, 90t see also sedation guidelines 129
trauma assessment and 340–341 individual drugs sodium bicarbonate
in traumatic brain injury 228 choice of 94–97 acidosis management 42–43
during vascular access 21 comparative studies 95–96t acute renal failure treatment 311
segmental wall motion defects (SWMAs), septic thrombosis, catheter-related 22 hyperkalemia treatment 51
TEE 36 sequential multichannel analyzer (SMA) 67 malignant hyperthermia treatment 397
seizures see also anticonvulsants Sequential Organ Failure Assessment (SOFA) rhabdomyolysis management 309
postoperative 398 5, 6t, 384–385, 385t sodium ions 47–49, 62–63
in stroke serotonin antagonists, PONV prevention/ deficiency see hyponatremia
hemorrhagic 208, 212 treatment 392 excess see hypernatremia
ischemic 203–204 serotonin syndrome 56, 397 fractional excretion 60
in traumatic brain injury 231 Serratia spp. infections, ventilator-associated sodium nitroprusside 98–99
Seldinger technique, CVC placement 28, 29 pneumonia 168 adverse effects 98
selective serotonin reuptake inhibitors (SSRIs), severe acute respiratory distress syndrome characteristics 104t
serotonin syndrome 56 (SARS) 179 hypertension management 140, 415t
Sellick maneuver 221 severity models 381, 382 mechanism of action 98
semipermeable polyurethane dressings 120 sevoflurane, in traumatic brain injury 225 pheochromocytoma treatment 246
Sengstaken–Blakemore (Minnesota) tube 302 sex hormones 240 stroke management 199
Senning procedure 152, 156 shock 60 in sympathomimetic poisoning syndrome 56
sensory aphasia, stroke and 197 acute respiratory distress syndrome 176 sodium phosphate, hypophosphatemia
sensory function, neurological assessment 233 cardiogenic 30–31 treatment 53, 67
sepsis 3–10 see also anaphylaxis; septic definition 30 sodium pump (Na+,K+ ATPase), hypokalemia
shock; specific infections drug treatment see vasopressors and 50
acid–base balance 45 gastrointestinal bleeding 301 sodium thiosulfate, thermal injury/smoke
acute pancreatitis 114 hypovolemic 30, 61 inhalation 347
acute renal failure 309, 310 lactic acidosis 35, 35f Soman 358
acute respiratory distress syndrome 176 resuscitation 301, 342–344 somatosensory evoked potentials, in traumatic
catheter-related 21–22, 22t see also septic see septic shock brain injury 227
catheter-related infection thermal injury (burn shock) 346 sorbitol, hyperkalemia treatment 50
definitions 3–4 shunt hypoxemia, physiology 11, 12, 13f sotalol, Wolff–Parkinson–White syndrome 81
diagnosis 3–5 sick euthyroid syndrome 239 sphygmomanometer 19
ACCP/SCCM classification 3 sick sinus syndrome, atrial septal defects spinal cord injury, assessment 340, 341f, 342
criteria 4t and 151 spirometry, post-thoracic surgery 404
PIRO system 4–5, 4t Silvadene 350, 350t spironolactone, hypertension management 141
SOFA assessment 5, 6t silver, catheter impregnation 120–121 splanchnic perfusion, dopamine effects 91
disseminated intravascular silver nitrate, burns care 350t spleen
coagulation 262 silver sulfadiazine 350, 350t community-acquired pneumonia and 163
hospital-acquired pneumonia 167 catheter impregnation 120 humoral immunity and 255
humoral defects and 255 Simplified Acute Physiology Score (SAPS) liver disease and 290
hyperthermia vs. 396 375, 376, 384 splenectomy, community-acquired
immune response 4–5, 4t, 5f single ventricle defects 153 pneumonia 163
incidence 3 Sin Nombre virus, pneumonia 164 spontaneous bacterial peritonitis (SBP),
insult 4, 4t sinoatrial (S-A) node 74 hepatic disease 289, 294–295, 296
lung transplants and 409 sinum cavernosum, injury 216 spontaneous breathing trials 193
management 7–9 sinus bradycardia 84, 416 sputum, pneumonia diagnosis 161–162
blood purification techniques 315 sinus rhythm 78 stable monomorphic ventricular tachycardia
catecholamines see catecholamines congenital defects 153 83, 83f
catheter-related infection 121–122 postoperative arrhythmia 416 staff-to-patient ratios 374
hemodynamic stabilization 7–8, 8t, 90t sinus tachycardia 416, 416t Stamy catheter set 321, 322f
immunomodulation 8–9, 9t sinus venosus atrial defects 151 standard base excess (SBE) 40–41
nutritional support 112–113 Site-Rite® 28 standardized mortality ratio (SMR) 381
massive blood transfusion and 281 6-minute walk test (6MWT) 401 standards of care 16–17
organ dysfunction 4t, 5, 6t, 7 skeletal hypertonus, remifentanil- staphylococcal enterotoxin B, terrorism
pathophysiology 5–7 induced 127 threat 357
coagulation 7 skin Staphylococcus aureus infections
glucose production 112 burns see thermal injury bronchopneumonia 160
inflammatory mediators 5, 7 host defense mechanism 252 catheter-related 21, 22, 118, 121
predisposition 4, 4t substitutes 350 hospital-acquired pneumonia 167
SIRS see systemic inflammatory response skull fracture 216 management 121
syndrome (SIRS) sleep apnea, postoperative methicillin-resistant (MRSA) 118, 167,
transfusion-related reaction 283t hypoventilation 393 168, 254
urinary tract 324, 326 smallpox 355–356 neutropenia 253
446 INDEX
Staphylococcus aureus infections (Continued) stroke (Continued) systemic inflammatory response 3–10
oxacillin-resistant (ORSA) 167 ischemia 198 sepsis and 4–5
staphylococcal enterotoxin B 357 ischemic see ischemic stroke systemic inflammatory response syndrome
vancomycin-resistant (VRSA) 168 stroke units 201 (SIRS)
ventilator-associated pneumonia 168 stroke volume 412 acute respiratory distress syndrome 176
Staphylococcus epidermis infections strong ion difference (SID) 40, 45 definition 3
catheter-related sepsis 21 strong ion gap (SIG) 45 disseminated intravascular coagulation 262
neutropenia 253 structural heart disease, arrhythmias and 75t, 76 pneumonia 158
Stark Law 380 ST segment 74, 74f predisposing factors 4
Starling curves 32, 60 ST-T complex 74, 74f systemic lupus erythematosus (SLE),
Starling–Landis equation 60, 69t subacute bacterial endocarditis (SBE) 151 laboratory findings 268t, 269
statins, angina treatment 147 subarachnoid hemorrhage 208–212 systemic vascular resistance (SVR) 412, 413
status epilepticus, in stroke 203 classification/grading systems 209–210 calculation 32
“steering wheel sign” 409 clinical symptoms/signs 209 in hepatic disease 292
stenting definition 208 low, causes 414t
stroke management 204 diagnostic workup 210
ureteral 326–327, 327t etiology/pathophysiology 208–209
sterile technique, vascular access 21 incidence 208 T
steroids see also specific drugs management 210–212
corticosteroids see corticosteroids medical complications 212 Tabun 358, 365
glucocorticoids see glucocorticoids neurologic complications 210–212 tachyarrhythmias
sex hormones 240 outcomes 211 atrial fibrillation see atrial fibrillation
in traumatic brain injury 229 subarachnoid space atrial flutter see atrial flutter
Stewart, Peter 37, 39 hemorrhage into see subarachnoid causes 416t
stomach see also entries beginning hemorrhage hypovolemia-induced 32
gastric/gastro- ICP monitors 235 junctional 83
“pumping” in poisoning 362 subclavian artery steal syndrome 197 norepinephrine-induced 91, 97
ulcers, NSAIDs and 301 subclavian vein, cannulation 28, 29, 119 paroxysmal supraventricular 82–83, 82f
Streptococcus pneumoniae infection subdural hematoma 217 in pneumonia management 172
community-acquired pneumonia 162, 163 subdural space, ICP monitors 235 polymorphic ventricular 83–84, 83f see
complement deficiencies 255 subglottic stenosis, thermal injury/smoke also Torsade de pointes
in HIV/AIDS 258, 259 inhalation 348 postoperative 416–417
hospital-acquired pneumonia 167 succinylcholine 132–133 stable monomorphic ventricular 83, 83f
humoral defects 255 complications 133 thermal injury 349
lobular pneumonia 160 malignant hyperthermia 55 ventricular (pulseless) 78–79
penicillin-resistant (PRSP) 162 laryngospasm treatment 395 ventricular fibrillation 78–79, 79f
ventilator-associated pneumonia 168 malignant hyperthermia 397 telangiectasis, intraparenchymal
Streptococcus viridans infection, properties 133t hemorrhage 205
neutropenia 253 sudden death, tetralogy of Fallot and 152 telemetry, postoperative monitoring 402
streptokinase, stroke management 201 suicide temporal lobe, herniation 218
streptomycin, Y. pestis infection 355 attempted, ethical issues 369–370 terbutaline, postoperative pulmonary care 405t
stress physician-assisted 378 terrorism 352 see also environmental threat
adrenal insufficiency 241–242 Sulfamylon (mafenide acetate), burns care bioterrorism 354–356
of anesthesia 139 350, 350t explosives 354
cardiac arrhythmias and 76 suprapubic cystostomy catheterization nuclear 359
fatty acid metabolism 114 321–324, 326 toxins/chemicals 356–359
gastrointestinal bleeding 301 complications 321, 323–324 tetanus toxin 357
hyperglycemia 243 equipment 321, 322f tetracycline
stress gastritis indications/contraindications 321t Coxiella burnetii 356
burns 351 technique 322, 323f pneumonia management 172
prophylaxis in trauma 341 urethral trauma examination 333 tetralogy of Fallot (TOF) 152
stress tests, adrenal insufficiency 241–242 supratentorial hemorrhage 206 thalamus, hemorrhage 206
stress ulcers supraventricular arrhythmias 77t, 80–83 theophylline, poisoning 362t, 363
in fulminant hepatic failure 294 atrial septal defects and 151 Therapeutic Intervention Scoring System
prophylaxis pulmonary surgery and 406 (TISS) 376, 382
acute renal failure management 311–312 surfactant 178 thermal injury 345–351 see also smoke
lung transplantation 409 ARDS pathology 177 inhalation
pneumonia management 173 replacement therapy 179 assessment 345–346
stroke 195–213 surgery see also specific types classification 345
classification 196 nutritional requirements during 109–110 electrical burns 349–350
congenital heart disease and 154 PONV incidence 391 epidemiology 345
definition 195 stress response 416 hypovolemic shock 346
epidemiology 195–196 Swan–Ganz catheter see pulmonary artery management principles
hemorrhagic 195, 204–212 catheter (PAC) airway/breathing 347–348
classification 196 swelling see edema analgesia 350–351
congenital heart disease and 154 sympathomimetic poisoning syndrome 56 circulation 348–350
intraparenchymal see intraparenchymal sympathomimetics, poisoning 56, 362t escharotomy 348, 348f
hemorrhage synchronized intermittent mandatory neutralization 347
subarachnoid see subarachnoid ventilation (SIMV) 184 nutritional support 351
hemorrhage syndrome of inappropriate ADH secretion “rule of nines” 348, 349f
hypertension and 139 (SIADH) 48, 64 topical agents 350, 350t
crisis 141 postoperative 398 wound care 350
hemorrhage 205, 207 in subarachnoid hemorrhage 212 pain 350–351
Index 447
traumatic brain injury (TBI) (Continued) triiodothyronine (T3) 237 urethroplasty 333
classification 215 drug interactions 238 urinalysis, renal trauma 328
Marshall’s 224 excess 239 urinary catheters 332
disability and 214 in hyperthyroidism 239 urinary tract see also specific regions
disseminated intravascular coagulation 263 in hypothyroidism 238 infection 324, 326
epidemiology 214–215 in sick euthyroid syndrome 239 cysturethroscopy and 320–321
evidence-based recommendations 340 trimethoprim-sulfamethoxazole (TMP-SMX) percutaneous nephrostomy 324
free water administration and 62, 69 Pneumocystis carnii infection 171 in stroke 204
hyperthermia in 227, 229 pneumonia management 172 lower, obstruction 326
intracranial hypertension 340 triple-H therapy upper, obstruction
management 221–225 ischemic stroke management 202 causes 326, 326t
airway 221 subarachnoid hemorrhage and 211 management 326–328
analgesia 228 tris-hydroxymethyl aminomethane (THAM), urine
anesthesia in 224–225 acidosis treatment 43, 68 alkalization, poisoning treatment 363
antithrombotic 231 Trousseau’s sign 66 analysis, renal trauma 328
approaches, controversy 229–230 T-tubes 193 in diabetic ketoacidosis 244
electrolyte management 230–231 tuberculosis flow obstruction, postrenal renal failure 309
emergency room 221 in HIV/AIDS 258, 259 output monitoring 16–17
fluid management 62, 69, 221–222, in the immune-compromised 170, 171f urokinase, stroke management 201
230–231 transplantation and 256 urological procedures 317–324, 317–334
gastrointestinal bleeding 232 tubular necrosis, acute (ATN) 307 see also individual techniques
general care 230–232 tularemia 355 cystourethroscopy 319–321, 320f, 321f
hypothermia 229 atypical pneumonia 164 nonoperative 328–333
ICU 225–227 tumor lysis syndrome bladder 332, 332f
of infections 231 hyperphosphatemia and 54 renal trauma 330, 331f
intracranial hypertension 222–223, hypocalcemia and 51 urethra 332f, 333
227–230 tumor necrosis factor (TNF) percutaneous nephrostomy 324, 324t,
multiple trauma 222 sepsis pathophysiology 7 325f, 326–328, 330
neuromuscular block 228 sepsis predisposition 4 suprapubic cystostomy 321–324, 321t,
nutritional support 231 surgery-induced changes 109 322f, 326
prehospital 221 tumors see also malignancy; specific tumors upper urinary tract obstruction 326–328
sedation 228 adrenal 245–246 ureteral stenting 326–327, 327t
seizures 231 cerebral 205 urethral catheterization 317–319, 318f,
surgery, indications for 224 organ of Zuckerkandl 245 318t, 319f
neurologic monitoring 225–227 pneumonia risk 160 urosepsis 324
cerebral blood flow 226–227 tumor lysis syndrome 51, 54
ICP 225–226 T wave 74, 74f
jugular oxygen saturation 226–227 typhilitis, neutropenia 253 V
near infrared spectroscopy 227
tissue oxygen 227 vagal maneuver, paroxysmal supraventricular
transcranial Doppler 227 U tachycardia 83
outcome 232 vagal stimulation, multifocal atrial
oxygen saturation and 227 ulcerative colitis, gastrointestinal tachycardia 82
primary damage and 215, 217 bleeding 305 Valsalva’s maneuver 416
pathophysiology ulnar artery 27f vancomycin
cerebral blood flow 219–221 ultrasound see also specific techniques catheter-related infection prevention 120
primary and secondary damage 215–219 CVC placement 28–29 dialysis and 315t
primary damage 215–217 fetal monitoring 249 hospital-acquired pneumonia 167
brain contusion/laceration 216, 217 hemodynamic monitoring 35–36 resistance 168–169
diffuse axonal injury 217 liver disease 290 in ventilator-associated pneumonia 168
extradural hematoma 216 stroke 200 vancomycin-resistant enterococcus (VRE)
intracerebral hematoma 217 trauma assessment 341, 342 168–169
scalp laceration 216 trauma monitoring 343 vancomycin-resistant Staphylococcus aureus
skull fracture 216 United Network for Organ Sharing (UNOS) (VRSA) infections 168
subdural hematoma 217 liver status 288, 289t variceal bleeding, cirrhosis-associated 294
scoring systems 222, 233–234, 339, 384 United States Department of Justice, HIPPA varicella zoster virus (VZV) infection
anatomic/pathologic 215 violation penalty 379 cell-mediated immunity and 254
Glasgow Coma Scale 215, 233–234, 339 United States Health Care Financing pneumonia 164
Head Injury Severity Score 215 Administration (HCFA) 379 Variola major virus 355–356
secondary damage 217–219 upper urinary tract obstruction 326–328 vascular abnormalities/malformations
brain shift/herniation 218 urapidil, stroke management 199 gastrointestinal bleeding 305
cerebral edema 217–218 ureteral stent placement, percutaneous intraparenchymal hemorrhage 205
extracranial lesions 219 nephrostomy vs. 326–328, 327t subarachnoid hemorrhage 208
hydrocephalus 218–219 urethra vascular access see also catheters; specific
ischemia 218 catheterization 317–319 sites
vasodilator drug choice 103 catheters 317, 318f analgesia/sedation 20–21
Trendelenburg position complications 318–319 arterial see arteries, cannulation
catheter insertion 21 indications 317, 318t central venous see central venous catheters
hypotension management 413 patient position 318, 320f (CVCs)
suprapubic cystostomy 323 technique 318–319, 319f complications
triage 379 dilatation, cysturethroscopy 320 infectious see catheter-related infection
tricuspid atresia 153 trauma 332–333 thrombotic 24
tricylic antidepressants, hepatotoxicity 287 management 332f, 333 credentialing 19–20
Index 449
vascular access (Continued) venous thrombosis video-assisted thoracic surgery (VATS) 400
general principles 19–24 DVT see deep vein thrombosis (DVT) videothoracoscopy, thoracic trauma 409
informed consent 20 subarachnoid hemorrhage 208 viral encephalitides 356
justification 20 veno-veno bypass (VVB), in liver viral hemorrhagic fevers 356
latex allergy and 22–23 transplantation 297 viral infection(s) see also specific
in liver transplantation 297 ventilate, infuse and pump (VIP) principle, organisms/infections
needlestick injuries 23 sepsis 7–8 cell-mediated immunity and 254
preparation 20 ventilation encephalitides 356
procedural positioning 21 alveolar-arterial oxygen 11–12, 13f hemorrhagic fevers 356
radiological verification 23–24 assessment 339, 401 hepatic disease 289
sterile technique 21 assisted see ventilatory support pneumonia 158t, 164–165, 164f, 174
thermal injury and 348 deadspace 14 transplantation and 256
wound dressing/care 22 sustainable 14 “viral priming” 159
vascular pulmonary disease, in hepatic voluntary 14 Virchow’s triad 250
disease 292 weaning criteria 192 virtue theory 370
vasculitis ventilation/perfusion (V/Q) mismatch 394 Visual Analog Pain Scale (VAS) 390
acute renal failure and 311 assessment 401 vital capacity, ventilatory weaning criteria 192
intraparenchymal hemorrhage 205 physiology 11, 12, 13f vital signs
vasoactive drugs 89–105 see also specific postoperative 394 in coagulopathy 270
drugs/drug types thoracic surgery 404 poisoning diagnosis 362t
in acute renal failure 309, 310 sodium nitroprusside-induced 99 vitamin D
infusion 27 ventilation–perfusion scintigraphy 401 calcium regulation 240
sepsis management 8 ventilation–perfusion zones 33–34, 33f deficiency 66
vasoconstrictive see vasopressors ventilator-associated pneumonia 159, 167–170 vitamin K deficiency
vasodilational see vasodilators diagnosis 169 hepatic disease 289, 296
vasoconstriction pathogens 168t laboratory findings 268t
cerebral blood flow 221, 229 treatment, controversy 169 plasma transfusion and 278
drugs inducing see vasopressors ventilator desynchronization, agitation and 124 volatile anesthetics
hypocapnic 220 ventilator-induced lung injury (VILI) 176, 178, arrhythmia induction 77
subarachnoid hemorrhage and 210–211 184, 185 hypothermia effects 396
vasoconstrictive drugs see vasopressors ventilatory support see also specific methods malignant hyperthermia 397
vasodilation agitation and 124 PONV and 391
cerebral blood flow 220–221, 229 in ARDS/ALI 176, 178, 185–186 volume overload, postpneumonectomy
drugs inducing see vasodilators case study 188 pulmonary edema 406
vasodilators 97–103 see also specific drugs indications 181–182 volume-targeted assist-control ventilation
characteristics 104t lung injury due to 176, 178, 184, 185 183–184
choice 103 lung recruitment 187–188, 188f vomiting
indications 97 mechanical see mechanical ventilation hypo-osmolar hyponatremia 48
lung transplantation 408 monitoring 17 intraparenchymal hemorrhage and 205
pulmonary 155 noninvasive 12–13, 15 poisoning treatment 362
sites of activity 98t clinical caveat 14t postoperative see postoperative nausea and
vasogenic cerebral edema 217, 218 controversy 15t vomiting (PONV)
vasopressin 97 pneumonia and 159, 167–170 von Willebrand’s disease 72, 263–264
asystole 80 postoperative, pulmonary surgery 404 management 278, 279, 280t, 284
in cardiogenic shock 97 respiratory failure von Willebrand’s factor
DDAVP see 1-deamino-8-D-arginine hypercapnic 15 assay 269
vasopressin (DDAVP) hypoxic 12–14 coagulation role 261
diabetes insipidus 242 ventricles (cerebral) VX 358
in hepatorenal syndrome 309 dilatation 218–219
hypotension management 414t drainage 228
in sepsis/septic shock 9, 97 ventricles (heart) W
ventricular fibrillation 79 arrhythmias see ventricular arrhythmias
vasopressors 89–97 see also function curves 30, 30f, 32 Waldström’s macroglobulinemia, humoral
specific drugs septal defects 150–151 defects 255
catecholamines see catecholamines single 153 Wallenberg syndrome 197
elderly trauma victims 344 ventricular arrhythmias 77t, 83–84 warfarin, catheter insertion 120
hyperthermia contraindication 54 postoperative 416 water 62–63
in pneumonia management 172 tachycardia (pulseless) 78–79 deficit
sepsis management 8, 89–97, 90t tetralogy of Fallot 152 calculation 49t, 243
vasopressin see vasopressin ventricular fibrillation 78–79, 79f diabetes insipidus 242
vasospasm, subarachnoid hemorrhage and ventricular function curve 30, 30f, 32 hypernatremia 49, 63, 64
210–211 ventricular septal defect (VSD) 150–151 environmental threat and 360
vecuronium 132, 133 ventricular tachycardia (pulseless) 78–79 “free”
hypothermia effects 396 verapamil contraindications 62, 69
properties 133t atrial fibrillation 82t deficit 49, 49t, 243
venous air embolism (VAE), catheter hypertension management 140–141 glucose effects 62
insertion 21 pulmonary surgery and 406 glucose administration and 62
venous angiomas, intraparenchymal verbal responses, GCS scoring 233 total body 60, 60f
hemorrhage 205 vertebral artery dissection 197 male vs. female 63
venous cannulation vertebrobasilar ischemia 197 “water-rat trapper’s disease” 355
central see central venous vesicants 357–358 watershed infarcts 196, 197
catheters (CVCs) Vibrio parahaemolyticus infection, Waterstone shunt, tetralogy of Fallot 152
femoral vein 28, 29 gastrointestinal bleeding 305 Wegener’s granulomatosis 160
450 INDEX