Far Eastern University – Nicanor Reyes Medical Foundation
Surgery A – Shock
EVOLUTION IN UNDERSTANDING SHOCK
 Shock – the failure to meet the metabolic needs of the cell and
the consequences that ensue
 Initial cellular injury is reversible
 Irreversible if tissue perfusion is prolonged or severe,
compensation is no longer possible
 Clinical manifestations of physiologic responses are the leads for
the diagnosis of shock and guides for the management and
treatment
 Hemodynamic parameters (BP, HR) are insensitive measures of
shock
 General approach in the management of shock:
 Assuring a secure airway with adequate ventilation
 Control of hemorrhage in the bleeding patient
 Restoration of vascular volume and tissue perfusion
Historical Background
 Cluade Bernard (mid-19th century) – organism attempts to
maintain constancy in the internal environment against external
forces that attempt to disrupt the “milieu interieur”
 Walter B. Cannon
 Coined the term homeostasis, an organism’s ability to
survive was related to maintenance of homeostasis.
 Described the “fight and flight response”, generated by
elevated levels of catecholamines in the bloodstream.
 Propose that initiation of shock was due to a disturbance of
the nervous system that resulted in vasodilation and
hypotension
 Proposed that secondary shock with capillary permeability
leak was caused by a “toxic factor” released from the tissue
 Alfred Blalock – stated that shock in hemorrhage was associated
with reduced cardiac output due to volume loss and not by a toxic
factor.
He also proposed four categories of shock:
1. Hypovolemic – most common, results from loss of circulating
blood volume
2. Vasogenic (Septic) – results from decreased resistance within a
capacitance vessels, seen in sepsis
3. Neurogenic – form of vasogenic shock in which the spinal cord
injury or spinal anaesthesia causes vasodilation due to acute loss
of sympathetic vascular tone
4. Cardiogenic – results from failure of the heart as a pump, seen in
arrhythmias or acute myocardial infarction
Overtime, two additional types of shock were added:
5. Obstructive – form of cardiogenic shock, results from
mechanical impediment to circulation leading to depressed
cardiac output rather than primary cardiac failure (pulmonary
embolism and tension pneumothorax)
6. Traumatic – soft tissue and bony injury leads to the activation of
inflammatory cells and the release of circulating factors that
modulate the immune response. The effects of tissue injury are
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combined with the effects of hemorrhage creating a more
complex and amplified deviation from homeostasis
 Wiggers, 1947 – developed a sustainable, irreversible model of
hemorrhagic shock based on uptake of shed blood into a reservoir
to maintain a set level of hypotension
 G. Tom Shires – demonstrated that a large extracellular fluid
deficit, greater than could be attributed to vascular refilling alone,
as seen in severe hemorrhagic shock
 Third spacing – phenomenon of fluid redistribution after
major trauma involving blood loss. The translocation of
intravascular volume into the peritoneum, bowel, burned
tissues or crush injury sites
 These studies formed the scientific studies for the current
treatment of hemorrhagic shock with RBC and LR or isotonic
saline
 Acute fulminant pulmonary failure – an early cause of death after
successful surgery to control hemorrhage
 Initially called DaNang lung or shock lung
 Recognized as acute respiratory distress syndrome (ARDS)
 Core principles in the management of critically ill or injured
patient:
a. Definitive control of the airway must be secured
b. Control of active hemorrhage must occur promptly
c. Volume resuscitation with blood products with limited
volume of crystalloid must occur while operative control of
bleeding is achieved
d. Unrecognized or inadequately corrected hypoperfusion
increases morbidity and mortality
e. Excessive fluid resuscitation may exacerbate bleeding
Current Definitions and Challenges
 Shock consists of inadequate tissue perfusion marked by:
 Decreased delivery of required metabolic substrates
 Inadequate removal of cellular waste products
 Involves failure of oxidative metabolism (defects of O2 delivery,
transport and utilization)
 Focus on determining the cellular events that often occur in
parallel to result in organ dysfunction, shock irreversibility and
death
PATHOPHYSIOLOGY OF SHOCK
 Regardless of etiology, initial physiologic responses in shock are
driven by:
 Tissue hypoperfusion
 Developing cellular energy deficit
 Imbalance between cellular supply and demand leads to neuro-
endocrine and inflammatory responses, of which, the magnitude
is proportional to the degree and duration of shock
 Specific responses will differ based on the etiology of shock (e.g.
cardiovascular response driven by the sympathetic nervous system
is blunted in neurogenic or septic shock)

 Organ specific responses aims to maintain perfusion in the
cerebral and coronary circulation and is regulated at multiple
levels including:
 Stretch receptors and baroreceptors in the heart and
vasculature (carotid sinus and aortic arch)
 Chemoreceptors
 Cerebral ischemia responses
 Release of endogenous vasoconstrictors
 Shifting of fluid into the intravascular space
 Renal absorption and conservation of salt and water
 Pathophysiologic responses vary with time and in response to
resuscitation
 Compensated phase – e.g. in hemorrhagic shock, the body can
compensate for the initial loss of blood volume through the
neuroendocrine response to maintain hemodynamics
 Decompensation phase – continued hypoperfusion, which may
be unrecognized, ongoing cellular death and injury
 Microcirculatory dysfunction, parenchymal tissue damage and
inflammatory cell activation can perpetuate hypoperfusion
 Ischemia or reperfusion injury often exacerbates the initial result
 Vicious cycle of shock – compromise function at the organ system
level due to untreated damage at the cellular level
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 Irreversible phase of shock
 Persistent hypoperfusion results in further hemodynamic
derangements and cardiovascular collapse
 Develop quite insidiously and may only be obvious in
retrospect
 Extensive parenchymal and microvasculature injury that
volume resuscitation fails to reverse process and will
eventually lead to death
 Modified Wiggers model in animals representing the phases of
compensation, decompensation and irreversible phases of
hemorrhagic shock:
Neuroendocrine and Organ Specific Responses to Hemorrhage
 Goal of neuroendocrine response is to maintain perfusion to the
heart and brain, even at the expense of the other organ systems
 Peripheral vasoconstriction occurs and fluid excretion is inhibited
 Mechanisms involved:
 Autonomic control of peripheral vascular tone and cardiac
contractility
 Hormonal response to stress and volume depletion
 Local microcirculatory mechanisms that are organ specific
and regulate regional blood flow
 Initial stimulus is loss of circulating blood volume in hemorrhagic
shock
 Other stimuli that can cause response: pain, hypoxemia,
hypercarbia, acidosis, infection, change in temperature,
emotional arousal or hypoglycemia
 Magnitude of the response is based on the volume of blood lost
and the rate at which it is lost
Afferent Signals
 Impulses transmitted from the periphery and processed within the
central nervous system and activates reflexive efferent impulses
 Designed to expand plasma volume, maintain peripheral
perfusion and tissue O2 delivery and restore homeostasis
 Initiate the body’s intrinsic adaptive responses and converge in
the CNS originating from a variety of sources:
1. Spinothalamic Tracts
 Transmits the sensation of pain
 Resulting in activation of the hypothalamic-pituitary-adrenal
axis and autonomic nervous system inducing direct sympathetic
stimulation of the adrenal medulla to release catecholamines
2. Baroreceptors
 Volume receptors sensitive to changes in both chamber
pressure and wall stretch present within the atria of the heart,
activated with low volume hemorrhage or mild reductions in
right atrial pressure
 Receptors in the aortic arch and carotid bodies respond to
alterations in pressure or stretch of the arterial wall,
responding to larger reductions in intravascular volume or
pressure
 Normally inhibits induction of the ANS, but when activated,
these receptors diminish their output, dis-inhibiting the ANS,
increasing ANS output via sympathetic activation at the
vasomotor centers producing centrally mediated constriction of
peripheral vessels
3. Chemoreceptors
 Found in the aorta and carotid bodies and sensitive to changes
+
in O2 tension, H ion concentration and CO2 levels
 Stimulation results to vasodilation of the coronary arteries,
slowing of the heart rate, and vasoconstriction of splanchnic
and skeletal circulation
4. Variety of protein and non protein mediators
 Produced at the site of injury as part of the inflammatory
response
 Histamine, cytokines, eicosanoids and endothelins
Efferent Signals
1. Cardiovascular Response – results from neuroendocrine and ANS
response to shock and constitute a prominent feature of the
body’s adaptive response mechanism and clinical signs and
symptoms of the patient in shock
 Hemorrhage results in diminished venous return and decreased
cardiac output
 Compensated by increased cardiac heart rate and contractility
and venous and arterial vasoconstriction
 Stimulation of sympathetic fibers innervating the heart leads to
activation of β1 adrenergic receptors increasing heart rate and
contractility
 Increased myocardial O2 consumption occurs due to increased
workload, thus O2 supply must be maintained to prevent
development of myocardial dysfunction
 Direct sympathetic stimulation of the peripheral circulation via
activation of α1 receptors on arterioles induces vasoconstriction
causing compensatory increase in systemic vascular resistance and
BP
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 Due to non-uniformity of arterial vasoconstriction, marked
redistribution of blood flow results
 Selective perfusion to tissue occurs due to variations in arteriolar
resistance, blood shunted away from less essential organ beds (e.g.
intestine, kidney and skin)
 In the brain and heart, autoregulatory mechanisms attempt to
preserve blood flow despite decrease in cardiac output
 Direct sympathetic stimulation also induces constriction of venous
vessels, decreasing capacitance and accelerates blood return to
central circulation
 Increased sympathetic output induces catecholamine release from
the adrenal medulla and peaks within 24-48 hours of injury then
return to baseline
 Persistent elevation of catecholamine levels suggest ongoing
noxious afferent stimuli
 Catecholamine effects on tissue:
 Stimulation of hepatic glycogenolysis and gluconeogenesis
 Increase skeletal muscle glycogenolysis
 Suppression of insulin release
 Increased glucagon release
2. Hormonal Response – activation of the ANS and the hypothalamic-
pituitary-adrenal axis
a) ACTH and Cortisol
 Shock stimulates the hypothalamus to release corticotropin-
releasing hormone resulting to the release of ACTH by the
pituitary
 ACTH stimulates the adrenal cortex to release cortisol
 Functions of Cortisol:
 Acts synergistically with epinephrine and glucagon to
induce a catabolic state
 Stimulates gluconeogenesis and insulin resistance resulting
in hyperglycemia as well as muscle cell protein breakdown
and lipolysis to provide substrates for hepatic
gluconeogenesis
 Causes retention of sodium and water by the nephrons of
the kidney
 In severe hypovolemia, ACTH secretion occurs independently of
cortisol negative feedback inhibition
b) Renin-Angiotensin-Aldosterone System (RAAS)
 Renin-angiotensin system is activated in shock
 Renin is released from the juxtaglomerular cells and the release is
caused by:
 Decreased renal artery perfusion
 β adrenergic stimulation
 Increased renal tubular sodium concentration
 Renin catalyzes the conversion of angiotensinogen (from the liver)
to angiotensin I which is then converted to angiotensin II by
angiotensin-converting enzyme (ACE) which is produced by the
lungs
 Angiotensin I has now significant functional activity
  Angiotensin II – potent vasoconstrictor of both splanchnic and
peripheral vascular beds. It also stimulates secretion of
aldosterone, ACTH and ADH
 Aldosterone – a mineralocorticoid that acts on nephron to
promote reabsorption of sodium and (as a consequence) water
 Potassium and hydrogen ions are lost in the urine in exchange for
sodium
c) Anti-Diuretic Hormone (ADH) or Arginine Vasopressin
 Released by the pituitary in response to:
 Hypovolemia
 Changes in circulating blood volume sensed by
baroreceptors and left atrial stretch receptors
 Increased plasma osmolality detected by hypothalamic
osmoreceptors
 Epinephrine, angiotensin II, pain and hyperglycemia increases
production of ADH
 Levels remain elevated for about 1 week after initial insult
 Acts on distal tubule and collecting duct of the nephrons to:
 Increase water permeability
 Decrease water and sodium losses
 Preserve intravascular volume
 In hypovolemic state, acts as a potent mesenteric vasoconstrictor,
shunting circulating blood away from splanchnic organs
 In shock state, may contribute to intestinal ischemia and
predispose to intestinal mucosal barrier dysfunction
 Increases hepatic gluconeogenesis and increases hepatic
glycolysis
 In septic states, endotoxin directly stimulates arginine vasopressin
independent of blood pressure, osmotic or intravascular volume
changes
 Proinflammatory cytokines also contribute to its releases
 Patients on chronic therapy with ACE inhibitors have low plasma
levels of ADH and has more risk of developing hypotension and
vasodilatory shock with open heart surgery
Circulatory Homeostasis
a) Preload
 At rest, majority of blood volume is within the venous system
 Venous return to the heart generates ventricular end-diastolic
wall tension, a major determinant of cardiac output
 Venous capacity immediately corrects alterations in blood
distribution due to gravitational shifts
 During decreased arteriolar flow, there is active contraction of the
venous smooth muscle and passive elastic recoil in the thin-walled
systemic veins, subsequently increasing venous return to the
heart and maintaining vascular filling
 Alterations in cardiac output in normal heart rate are due to
changes in preload
 Increase in sympathetic tone produces a dramatic reduction in
splanchnic blood volume but with minor effect on skeletal muscle
beds
 Normal circulating blood volume is maintained by the kidney’s
ability to manage salt and water balance with external losses
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 Acute responses to intravascular volume include:
 Changes in venous tone
 Systemic vascular resistance
 Intrathoracic pressure
 Net effect of preload on cardiac output is influence by cardiac
determinants of ventricular function (e.g. coordinated atrial
activity and tachycardia)
b) Ventricular Contraction
 Frank-Starling curve – describes the force of ventricular
contraction as a function of its preload
 Relationship is based on force of contraction determined by initial
muscle length
 Intrinsic cardiac disease will shift the curve to the left and alter
mechanical performance of the heart
 Cardiac dysfunction is seen in burns, hemorrhagic, traumatic and
septic shock
c) Afterload
 Force that resists myocardial work during contraction
 Arterial pressure is the major component and influences the
ejection fraction
 Determined by precapillary smooth muscle sphincters
 Blood viscosity increases vascular resistance
 As afterload increases, stroke volume is maintained by increasing
of preload
 In shock, after load is impeded
 Stress response increases heart contractility and heart rate
d) Microcirculation
 Plays an integral role in regulating cellular perfusion and
influenced in response to shock
 Microvasculature bed is innervated by the sympathetic nervous
system and has a profound effect on the larger arterioles
 In hemorrhage, this vessels constrict but on septic or neurogenic
shock, they dilate
 Flow in the capillary bed is heterogeneous in shock states,
secondary to multiple local mechanisms:
 Endothelial cell swelling
 Dysfunction
 Activation marked by recruitment of leukocytes and
platelets
 In hemorrhagic shock, correction of hemodynamic parameters
and reperfusion of O2 leads to restoration of O2 consumption and
normal O2 tissue levels
 In sepsis, regional tissue dysoxia often persists, despite similar
restoration. Response to limit O2 consumption by the tissue
parenchymal cells is an adaptive response to inflammatory
signaling and decreasing perfusion
 Pathophysiologic response of microcirculation in shock:
 Failure of integrity of the endothelium of the
microcirculation – due to dysfunction of energy-dependent
mechanisms
 Intracellular swelling – multifactorial
  Extracellular fluid deficit – due to decreased capillary
hydrostatic pressure secondary to changes in blood flow
and increased cellular uptake of fluid
 Capillary leak – dysfunction is secondary to activation of
endothelial cells by circulating inflammatory mediators
generated in septic or traumatic shock
 No-reflow – capillary occlusion that persist after resuscitation due
to endothelial swelling, capillary leak and increase leukocyte
adherence
 Hemorrhagic shock produces fewer capillaries with no-reflow and
lower mortality
METABOLIC EFFECTS
 Cellular metabolism is based on the hydrolysis of ATP
 Splitting of the phosphoanhydride bond of the terminal or
γ-phosphate from ATP is the source of energy for most
processes
 Majority of ATP is generated in our bodies through aerobic
metabolism in the process of oxidative phosphorylation in
the mitochondria
 Process is dependent on O2 availability which serves as
final electron acceptor in the electron transport chain
 As O2 tension decreases, oxidative phosphorylation decreases and
generation of ATP is slowed down
 Dysoxia – a state where O2 delivery is severely impaired that
oxidative phosphorylation cannot be sustained
 Cells shift to anaerobic metabolism and glycolysis to generate
ATP when oxidative phosphorylation is insufficient
 Occurs via breakdown of cellular glycogen storage to
pyruvate
 Glycolysis is not an efficient process, only 2 mol of ATP is
produced from 1 mol of glucose
 Complete oxidation produces 38 mol of ATP per 1 mol of glucose
 Under hypoxic conditions, in anaerobic metabolism, pyruvate is
converted in to lactate leading to intracellular metabolic acidosis
Consequences that are Secondary to Metabolic Changes:
 Depletion of ATP potentially influence all ATP-dependent cellular
processes, including:
 Maintenance of cellular membrane potential
 Synthesis of enzymes and proteins
 Cell signaling and DNA repair mechanisms
 Decreased intracellular pH influences vital cellular functions,
including:
 Normal enzyme activity
 Cell membrane ion exchange
 Cellular metabolic signaling
 Changes will lead to changes in gene expression within the cell
 Acidosis leads to changes in calcium metabolism and signaling
Effects of Catecholamines:
 Processes increased by catecholamines:
 Hepatic glycogenolysis
 Gluconeogenesis
Page 5 of 15
 Ketogenesis
 Skeletal muscle protein breakdown
 Adipose tissue lipolysis
 Cortisol, glucagon and ADH also contribute to the catabolism
during shock
 Epinephrine induces further release of glucagon and inhibits
release of insulin resulting to:
 Catabolic state with glucose mobilization
 Hyperglycemia
 Protein breakdown
 Negative nitrogen balance
 Lipolysis
 Insulin resistance during shock and injury
 The underuse of glucose by peripheral tissues preserve it for the
glucose-dependent organs such as heart and brain
Cellular Hypoperfusion
 Crowell, 1961 – hypoperfused cells and tissues experience what
has been termed “oxygen debt”
 The O2 debt is the deficit in tissue oxygenation over time that
occurs in shock
 Measurement of O2 deficit uses calculation of difference between
the estimated O2 demand and the actual value obtained for O2
consumption
 Magnitude of the O2 debt correlates with the severity and
duration of hypoperfusion
 Surrogate values for measuring O2 debt include base deficit and
lactate levels
Changes in Cellular Gene Expression
 The DNA binding activity of a number of nuclear transcription
factors is altered by hypoxia and production of O2 or nitrogen
radicals which are produced by shock
 Other gene products increased by shock:
 Heat shock proteins
 Vascular endothelial growth factor (VEGF)
 Inducible Nitric Oxide Synthase (iNOS)
 Heme oxygenase-1
 Cytokines
 They alter gene expression in specific target cells and tissues
 Involvement of multiple pathways emphasizes the complex,
integrated and overlapping nature of the response to shock
IMMUNE AND INFLAMMATORY RESPONSE
 Complex set of interactions between circulation soluble factors
and cells that arises in response to trauma, infection, ischemia,
toxic or autoimmune stimuli
 Failure to adequately control the activation, escalation, or
suppression of the inflammatory response can lead to systemic
inflammatory response syndrome and potential multiple organ
failure
 Innate and adaptive branches of immunity work in unison to
respond in a specific and effective manner to challenges in an
organism’s well-being
 Alterations in the activity of the innate system can be responsible  Coagulation and kinin cascades impact the interaction of
for the development of shock and pathophysiologic sequel of endothelium and leukocytes
shock
 Host inflammatory response – a variety of metabolic changes
induced by predominantly paracrine mediators that gain access to
the systemic circulation
 Mechanisms that lead to the activation of the active inflammatory
and immune response:
 Release of bioactive peptides by neurons in response to
pain
 Release of intracellular molecules by broken cells (e.g.
heat shock proteins, mitochondrial products, heparan
sulphate, high mobility group box 1 and RNA)
 Danger signaling – endogenous molecules are capable of signaling
the presence of danger to surrounding cells and tissues and these
molecules are called damage-associated molecular patterns
(DAMPs), as proposed by Matzinger
 DAMPs – recognized by cell surface receptors to effect
intracellular signaling that primes and amplifies the immune
response

Cytokines / Chemokines
 Immune response to shock encompasses the elaboration of
mediators with both pro and anti-inflammatory properties
 Innate immune response can help restore homeostasis, or if
excessive, it can promote cellular and organ dysfunction

 Pattern Recognition receptors (PRRs) – Toll-like receptors (TLRs)

and receptor for advanced glycation end products
 Pathogen-associated molecular patterns (PAMPs) – bacterial
products first recognized by TLRs and PRRs
 PRR activation leads to intracellular signaling and release of
cellular products including cytokine:

1. Tumor Necrosis Factor Alpha (TNF – α)

 One of earliest potent proinflammatory cytokines released in
response to injurious stimuli
 Released by:
 Monocytes
 Macrophages
 T-cells
 Peaks within 90 minutes of stimulation and returns to baseline
by 4 hours
 Release and production may be induced by:
 Bacteria or endotoxin and leads to development of
 Mast cells – sentinel responders that release histamines,
shock and hypoperfusion (most commonly observed in
eicosanoids, tryptases and cytokines before recruitment of
septic shock)
leukocytes into sites of injury
 Hemorrhage
 These mediators amplify the immune response and cause
 Ischemia
leukocytes to release platelet activating factor

Page 6 of 15
  Functions of TNF-α:  Contributes to lung, liver and gut injury after hemorrhagic
 Produce peripheral vasodilation shock
 Activate release of other cytokines  Play a role in development of diffuse alveolar damage and
 Induce procoagulant activity ARDS
 Stimulate a wide array of cellular metabolic changes  Along with IL-1, they are:
 TNF-α levels correlate with mortality in models of hemorrhage  Mediators of hepatic acute phase response to injury
 Increase in serum TNF-α levels in trauma patients is less than  Enhance the expression and activity of complement, C-
in septic patients reactive protein, fibrinogen, haptoglobin, amyloid A and
 During stress response, it contributes to muscle protein α1-antitrypsin
breakdown and cachexia  Promote neutrophil activation

2. Interleukin 1 (IL-1) 5. Interleukin 10 (IL-10)

 Actions similar to TNF-α  An anti-inflammatory cytokine that may have
 Short half life of 6 minutes immunosuppressive properties
 Primarily acts in paracrine fashion to modulate local cellular  Production is increased after shock and trauma
responses  Associated with depressed immune function and increased
 Produces a febrile response to injury by activating the susceptibility to infections
prostaglandins and causes anorexia by activating the satiety  Secreted by T-cells, monocytes and macrophages
center  IL-10 inhibits:
 Augments the secretion of:  Pro-inflammatory cytokine secretion
 ACTH  O2 radical production by phagocytes
 Glucocorticoids  Adhesion molecule expression
 β-endorphins  Lymphocyte activation
 Stimulate the release of other cytokines:
 IL-2 6. Chemokines
 Il-4  Specific set of cytokines that have the ability to induce
 IL-6 chemotaxis of leukocytes
 IL-8  Bind to specific chemokines receptors and transducer
 Granulocyte-macrophage colony-stimulating factor chemotactic signals to leukocytes
 Interferon-γ  Involved in:
 Immune system development
3. Interleukin 2 IL-2)  Immune surveillance
 Produced by activated T-cells in response to variety of stimuli  Immune priming
and activates other lymphocytes subpopulations and natural  Effector response
killer cells  Immune regulation
 Role is still not confirmed in shock, current postulates include:
 Increased IL-2 secretion promotes shock-induced tissue Complement
injury and the development of shock  Activated by injury, shock and severe infection
 Depressed IL-2 contributes to depression in immune  Contributes to host defence and pro-inflammatory activation
function after hemorrhage that increases the  Significant consumption occurs after hemorrhagic shock
susceptibility of patients who develop shock to suffer  In trauma patients, degree of complement activation is
infections proportional to the magnitude of injury and may serve as a
 Overly exuberant pro-inflammatory activation marker for severity of injury
promotes tissue injury, organ dysfunction and immune  In septic shock patients, activation of complement pathway with
suppression elevations of activated complement proteins, C3a and C5a
 Temporal changes in the production of mediators (increased  Activation of complement cascade can contribute to the
or depressed levels) of IL-2 are probably important in the development of organ dysfunction
progression of shock  Activated complement factors (C3a, C4a and C5a) are potent
mediators of:
4. Interleukin 6 (IL-6)  Increased vascular permeability
 Elevated in response to shock, major operative procedures  Smooth muscle contraction
and trauma  Histamine and arachidonic acid by-product release
 Elevated levels correspond with mortality in shock states  Adherence of neutrophils to vascular endothelium

Page 7 of 15
 Acts synergistically with endotoxin to induce the release of TNF-α
and IL-1
 Development of ARDS and MODS in trauma patients correlates
with intensity of complement activation
Neutrophils
 Neutrophil activation is an early even in the upregulation of the
inflammatory response
 First cells to be recruited at the site of injury
 PMNs remove infectious agents, foreign substance and nonviable
tissue through phagocytosis
 Activated PMNs and their products may produce cell injury and
organ dysfunction
 Generate and release a number of substances that may induce
cell or tissue injury, such as:
 Reactive O2 species
 Lipid peroxidation products
 Proteolytic enzymes
 Vasoactive mediators
 Oxygen free radicals induce lipid peroxidation, inactivate enzymes
and consume antioxidants
 Ischemia-reperfusion activates PMNs and causes PMN-induced
organ injury
Effects of the Vascular Endothelium to the Leukocytes:
 The vascular endothelium contributes to the regulation of blood
flow, leukocyte adhesion and coagulation cascade
 Extracellular ligands (e.g. intercellular adhesion molecules,
vascular adhesion molecules and selectin) are expressed on the
surface of endothelial cells and are responsible for leukocyte
adhesion
 The interaction allows activated neutrophils to migrate into the
tissues to combat infection
Cell Signaling
 Signaling pathways are altered by changes in:
 Cellular oxygenation
 Redox state
 High-energy phosphate concentration
 Gene-expression
 Intracellular electrolyte concentration induced by shock
 Cells communicate with the external environment through cell
surface receptors, which when bound by a ligand, transmit their
information to the interior of the cell through various signaling
cascades
 These pathways may alter specific enzymes, expression or
breakdown of important proteins or affect intracellular energy
metabolism
 Intracellular calcium (Ca ) concentrations regulate many aspects
2+
2+ 2+
of cellular metabolism and changes of Ca levels and Ca
transport are seen in shock
 Alterations of Ca2+ regulation may lead to:
 Direct cellular injury
 Changes in transcription factor activation
Page 8 of 15
 Alterations in the expression of genes important in
homeostasis
 Modulation of the activation of cells by other shock-
induced hormones or mediators
Effects of Oxygen Radicals on the Intracellular Signaling Cascade
 Intracellular signaling cascade consists of a series of kinase that
transmit and amplify the signal through phosphorylation of target
proteins
 The O2 radicals produced during shock and intracellular redox
state are known to influence the activity of components of the
intracellular cascade, such as:
 Protein tyrosine kinase
 Mitogen activated kinase
 Protein kinase C
 O2 radicals also regulate the activity of transcription factors for
gene expression such as:
 Factor-κB
 APETALA1
 Hypoxia-inducible factor 1
 Oxidant-mediated direct cell injury is one consequence of the
production of O2 radical during shock
Effects of Shock on Gene Expression
 Changes in gene expression are critical for adaptive and survival
cell signaling
 Polymorphisms in gene promoters are likely to contribute to
significantly carried responses to similar insults
 Similarities in genomic responses between different injuries
revealed a fundamental human response to stresses involving
dysregulated immune response
FORMS OF SHOCK
A. HYPOVOLEMIC / HEMORRHAGIC SHOCK
 Most common cause of shock is loss of circulating volume
from hemorrhage
 Acute blood loss results in reflexive decreased baroreceptors
stimulation resulting in:
 Decreased inhibition of vasoconstrictor centers in the
brain stem
 Increased chemoreceptor stimulation of vasomotor
centers
 Diminished output from atrial stretch receptors
 Changes increases vasoconstriction and peripheral arterial
resistance
 Hypovolemia induces induces sympathetic stimulation leading
to:
 Epinephrine and Norepinephrine release
 Activation of the renin-angiotensin cascade
 Increased vasopressin release
 Peripheral vasoconstriction is prominent
 Lack of sympathetic effects on cerebral and coronary vessels
and local autoregulation promote maintenance of cardiac and
CNS blood flow
Diagnosis:
 A secure airway must be confirmed or established and volume
infusion is initiated while the search for cause of hypotension is
pursued
 Shock in trauma or post-op patients is presumed to be due to
hemorrhage until proven otherwise
 Clinical signs of shock is evident by:
 Agitation
 Cool clammy extremities
 Tachycardia
 Week or absent peripheral pulses
 Hypotension
 Tachycardia or hypotension represents both significant blood loss
and physiologic decompensation
 Clinical and physiologic responses to hemorrhage has been
classified according to the magnitude of volume loss:
 <15% of the circulating blood volume may produce little in
terms of obvious symptoms
 <30% of circulating volume may result in mild tachycardia,
tachypnea and anxiety
 >30% of circulating volume shows hypotension marked by
tachycardia and conduction
 >40% of circulating blood volume is immediately life
threatening and requires operative control of bleeding
 Medications may promote bleeding or mask the compensatory
responses to bleeding
 Factors that decreases the elderly patient’s ability to tolerate
hemorrhage:
 Medication
 Atherosclerotic vascular disease
 Diminishing cardiac compliance with age
 Inability to elevate heart rate or cardiac contractility in
response to hemorrhage
 Overall decline in physiologic reserve
 A systolic BP of <110 mmHg is a relevant definition of
hypotension and hypoperfusion based on increasing rate of
mortality below this pressure
 Serum lactate and base deficit are measurements that are helpful
to both estimate and monitor the extent of bleeding and shock
 Amount of lactate produced is an indirect marker of tissue
hypoperfusion, cellular O2 debt and severity of hemorrhagic
shock
Page 9 of 15
 Base deficit values derived from ABG analysis provides an indirect
stimulation of tissue acidosis from hypoperfusion
 Lack of depression of initial hematocrit level does not rule out
substantial blood loss or ongoing bleeding
 Patients with penetrating injuries who are in shock require
operative intervention
 Blood loss sufficient to cause shock is generally of a large volume
and limited number of sites can harbour sufficient extra vascular
blood volume to induce hypotension:
 External cavity
 Intrathoracic cavity
 Intra-abdominal cavity
 Retroperitoneal cavity
 Long bone fractures
 GI tract is considered a site for blood loss in non trauma patients
 Injuries to major arteries or veins with associated open wounds
may cause massive blood loss rapidly
 Direct pressure must be applies and sustained to maintain
ongoing blood loss
 Internal blood loss is suspected when major blood loss is not
visible in a trauma setting
 Each pleural cavity can hold 2 to 3L of blood and can be a site of
significant blood loss, for confirmation of hemothorax:
 Unstable patients – diagnostic and therapeutic tube
thoracostomy
 Stable patients – chest radiograph
 Major retroperitoneal hemorrhage occurs in association with
pelvic fractures and is confirmed by pelvic radiograph
 Intraperitoneal hemorrhage is the most common source of blood
loss inducing shock and rapidly identified by diagnostic ultrasound
or peritoneal lavage
 Physical examination is insensitive and unreliable, large volumes
of intraperitoneal blood may be present before PE findings are
apparent
 Findings with intra-abdominal hemorrhage include abdominal
distension, tenderness and visible wounds
 Hemodynamic abnormalities generally stimulate a search for
blood loss before appearance of obvious abdominal findings
 Patients who suffered blunt trauma who are hemodynamically
stable or normal vital signs should undergo computed
tomography
Treatment:
 Control of ongoing hemorrhage is an essential component of the
resuscitation of the patient in shock
 Treatment is instituted concurrently with diagnostic evaluation to
identify a source
 Patients who fail to respond to initial efforts should be assumed
to have ongoing active hemorrhage from large vessels and require
prompt operative intervention
 Appropriate priorities in patients:
 Secure the airway
 Control the source of blood loss
 Intravenous volume resuscitation
 Rapid treatment is essential and diagnostic laparotomy or
thoracotomy may be indicated
 Actively bleeding patient cannot be resuscitated until control of
ongoing hemorrhage is achieved
 Damage control resuscitation – begins in the emergency
department and continues into the operating room up to the ICU,
 Initial resuscitation is limited to keep SBP around 80 to 90
mmHg
 Prevent renewed bleeding from recently clotting vessels
 Resuscitation and intravascular volume resuscitation are
accomplished with blood productions (RBC, fresh frozen
plasma and platelets in equal numbers) and limited
crystalloids
 Attempts to increase blood pressure with uncontrolled sources of
hemorrhage is counterproductive, increasing bleeding and higher
mortality
 Attempts to restore normal blood pressure with fluid infusions or
vasopressors were rarely successful and resulted to more
bleeding and higher mortality
 Conclusions in the setting of uncontrolled hemorrhage:
 Any delay in surgery for control of hemorrhage increases
mortality
 With uncontrolled hemorrhage attempting to achieve
normal BP may increase mortality particularly with
penetrating injuries and short transport times
 A goal of SBP 80 to 90 mmHg may be adequate in the
patient with penetrating injury
 Profound hemodilution should be avoided by early
transfusion of RBC
 For patient with blunt injury, an SBP of 110 mmHg is more
appropriate
 Patients who respond to initial resuscitative effort but deteriorate
hemodynamically have injuries that require operative
intervention
 Patients who fail to respond to resuscitative efforts but with
control of hemorrhage have deteriorated to decompensate or
irreversible shock with peripheral vasodilation and resistance to
vasoressor infusion
 Crystalloids continue to be the mainstay fluid of choice during
resuscitation
 Hypertonic saline is evaluated as a resuscitative adjunct in
bleeding patients, and has the benefit of being
immunomodulatory and may contribute to the decreases of
incidence of ARDS and multiple organ failure
 Transfusion of RBC and blood products is essential for treatment,
recommendation in stable ICU patients aim for a target
haemoglobin of 7 to 9 g/dL
 Platelets should be transfused in the bleeding patient to maintain
9
counts above 50 x 10 /L
 Use of antifibrinolytic agents in bleeding patients is also
supported
 Development of hypothermia in the bleeding patient is associated
with acidosis, hypotension and coagulopathy
Page 10 of 15
 Hypothermia is an independent risk factors for bleeding and
death secondary to impaired platelet function and impairments in
coagulation cascades
B. TRAUMATIC SHOCK
 Systemic response after trauma, combining the effects of soft
tissue injury, long bone fractures and blood loss
 Multiple organ failure, including ARDS develop often in
trauma patient, rarely in pure hemorrhagic shock patient
 Hypoperfusion deficit is magnified by the pro-inflammatory
activation that occurs following the induction of shock
 At the cellular level, there is releases of DAMPs that initiates
cell signaling
 Examples of traumatic shock include:
 Small-volume hemorrhage with by soft tissue injury
 Any combination of hypovolemic, neurogenic,
cardiogenic and obstructive shock that precipitates
rapidly progressive proinflammatory action
Treatment:
 Focused on correction of the individual elements to diminish the
cascade of pro-inflammatory activation
 Prompt control of hemorrhage, adequate volume resuscitation to
correct O2 debt
 Debridement of nonviable tissue
 Stabilization of bone injures
 Appropriate treatment of soft tissue injuries
C. SEPTIC / VASODILATORY SHOCK
 Result of the dysfunction of the endothelium and vasculature
secondary to circulating inflammatory mediators and cells or
as a response to prolonged and severe hypoperfusion
 Hypotension results from failure of the vascular smooth
muscle to constrict appropriately
 Characterized by peripheral vasodilation with resultant
hypotension and resistance to treatment with vasopressors
 Plasma catecholamine levels are elevated and the RAAS
system is activated
 Represents the final common pathway for profound and
prolonged shock of any etiology
 Mortality rate for sepsis is 30 to 50%
  Septic shock is a by-product of the body’s response to
disruption of the host-microbe equilibrium, resulting in
invasive or server localized infection
 When immune response becomes systemic rather than
localized, manifestations of sepsis is evident, including:
 Enhanced cardiac output
 Peripheral vasoconstriction
 Fever
 Leukocytosis
 Hyperglycemia
 Tachycardia
 Vasodilatory effect are due to the upregulation of the
inducible isoform of nitric oxide synthase in the vessel wall
 This potent vasodilator (NOS) suppresses vascular tone and
renders the vasculature resistant to the effects of
vasoconstrictor agents
Diagnosis:
 The terms sepsis, severe sepsis and septic shock are used to
quantify the magnitude of the systemic inflammatory reaction
 Patients with sepsis have evidence of an infection, as well as signs
of systemic inflammation
 Severe sepsis is hypoperfusion with signs of organ dysfunction
 Septic shock requires presence of the severe sepsis, associated
with more significant hypoperfusion and systemic hypotension
 Fever, tachycardia, and tachypnea, signs of hypoperfusion such as
confusion, malaise, oliguria or hypotension is present in septic
shock
 An aggressive search for infection should be performed, including:
 Thorough physical examination
 Inspection of all wounds
 Evaluation of intravascular catheters
 Obtaining appropriate cultures
 Adjunctive imaging studies
Treatment:
 Begins with the assessment of airway and ventilation
 Severely obtunded patients require intubation and ventilation to
prevent respiratory collapse
 Fluid resuscitation and restoration of circulatory volume with
balanced salt solutions is essential (at least 30 mL/kg with the first
4-6 hours)
 Starch-based colloid solutions should be avoided
 Antibiotics should be tailored to cover the responsible organism
 IV antibiotics will be insufficient to adequately treat the infectious
episode in the settings of infected fluid collections, infected
foreign bodies and devitalized tissues
 Vasopressors may be necessary to treat patients with septic
shock
 Catecholamines are used more often, with norepinephrine being
the first line agent followed by epinephrine
 Arginine vasopressin is often added to norepinephrine for
patients that develop resistance to catecholamines
Page 11 of 15
 Dobutamine therapy is recommended for patients with cardiac
dysfunction as evidenced by high filling pressures and low cardiac
output
 Surviving Sepsis Campaign:
 Hyperglycemia and insulin resistance are typical in critically ill
and septic patients without diabetes mellitus
 Intensive insulin therapy reduced episodes of septicaemia by 46%,
reduced duration of antibiotic therapy, and decreased the need
for prolonged ventilatory support and renal replacement therapy
 Use of lower ventilatory tidal volumes compared to traditional
tidal volumes increases survival of patients with ARDS
 Additional strategies in ARDS management include higher levels of
positive end expiratory pressure (PEEP), alveolar recruitment
maneuvers and prone poisoning
 Hydrocortisone therapy cannot be recommended as routine
adjuvant therapy for septic shock, however, if SBP remains less
tan 90mmHg despite appropriate therapy, hydrocortisone at
200mg/d for 7 days in four divided doses or continous infusion
should be considered
 Other treatment like antiendotoxin antibodies, anticytokine
antibodies, cytokine receptor antagonists, immune enhancers, non
isoform-specific nitric oxide synthase inhibitor and O 2 radical
scavengers have been used but with no avail.
D. CARDIOGENIC SHOCK
 Circulatory pump failure leading to diminished forward flow
and subsequent tissue hypoxia, in the setting of adequate
intravascular volume
 Hemodynamic criteria:
 Sustained hypotension (SBP <90mmHg for at least 30
mins)
 Reduced cardiac index (<2.2 L/min per square meter)
 Elevated pulmonary artery wedge pressure (>15
mmHg)
 Mortality rate: 50 to 80%
 Acute, extensive MI is the most common cause and a smaller
infarction in a patient with existing left ventricular dysfunction
also may precipitate this type of shock
 Recognition of the patient with occult hypoperfusion is critical
to prevent progression to shock
 Early initiation of therapy to maintain BP and cardiac output is
vital
  Invasive cardiac monitoring is not generally necessary, but can be
useful to exclude right ventricular infarction, hypovolemia and
mechanical complications
 In blunt traumatic injury, hemorrhagic shock from intra-
abdominal bleed, intra-thoracic bleed and bleed from fractures
must be excluded
 Invasive hemodynamic monitoring with a pulmonary artery
catheter may uncover evidence of diminished cardiac output and
pulmonary artery pressure

Treatment:
 Intubation and mechanical ventilation often are requited, to
decrease work of breathing and facilitate sedation of the patient
 Treatment of cardiac dysfunction:
 Maintenance of adequate oxygenation
 The pathophysiology of cardiogenic shock involves a vicious  Judicious fluid administration to avoid fluid overload and
cycle of myocardial ischemia the causes myocardial development of cardiogenic pulmonary edema
dysfunction that results to more myocardial ischemia  Electrolyte abnormalities should be corrected
 When sufficient mass of the left ventricular wall is necrotic or  Pain is treated with IV morphine sulfate or fentanyl
ischemic and fails to pump, the stroke volume decreases  Dysrhythmias and heart block must be treated with anti-
 Myocardial diastolic function is impaired in cardiogenic shock arrhythmic drugs, pacing or cardioversion
as well  If profound cardiac dysfunction exists, inotropic support may be
 Decreased compliance results from myocardial ischemia, and indicated to improve cardiac contractility and cardiac output
compensatory increases in left ventricular filling pressure  Dobutamine – stimulates cardiac β1 receptors to increases
progressively occur cardiac output, but may:
 Diminished cardiac output in the face of adequate preload  Vasodilate peripheral vascular beds
may lead to under-perfused vascular beds and reflexive
 Lower total peripheral resistance
sympathetic discharge
 Lower systemic blood pressure through effects of β2
 Increased sympathetic stimulation of the heart may not be
receptors
relieved by increases in coronary artery blood flow in patients
 Dopamine stimulates β receptors at low doses and preferable to
with fixed stenosis of the coronary arteries
dobutamine in treatment of cardiac dysfunction in hypotensive
 Acute heart failure and diminished cardiac output decreases
patients
myocardial O2 delivery
 Tachycardia and increased peripheral resistance from dopamine
infusion may worsen myocardial ischemia
Diagnosis:
 Titration of both dopamine and dobutamine may be required for
 In evaluation of possible cardiogenic shock, other causes of
some patients
hypotension must be excluded (e.g. hemorrhage, sepsis,
 Epinephrine stimulates α and β receptors and may increases
pulmonary embolism, and aortic dissection)
cardiac contractility, may also have intense peripheral
 Signs of circulatory shock:
vasoconstrictor effects that can impair cardiac performance
 Hypotension
 Balancing the beneficial effects of impaired cardiac performance
 Cool and mottled skin
with the potential side effects of excessive reflex tachycardia and
 Depressed mental status peripheral vasoconstriction requires series assessment of tissue
 Tachycardia perfusion using indices such as:
 Diminished pulses  Capillary refill
 Cardiac exam may include dysrhytmia, precardial heave, distal  Character of peripheral pulses
heart tones  Adequacy of urine output
 Confirmation requires electrocardiogram and urgent  Improvement in laboratory parameters of resuscitation
echocardiography (pH, base deficit and lactate)
 Other diagnostic tests:  Phosphodiesterase inhibitors (amrinone and milrinone) may be
 Chest radiograph required on occasion in patients with resistant cardiogenic shock
 ABG  Patients whose cardiac dysfunction is refractory to cardiotonics
 Electrolytes may require mechanical circulatory support with an intra-aortic
 CBC balloon pump, inserted at the femoral artery (cut down or
 Cardiac enzymes percutaneous approach)

Page 12 of 15
 Preservation of existing myocardium and preservation of cardiac
functions are priorities of therapy for patients who suffered acute
MI
 Anticoagulation and aspirin are given for acute MI
 β blockers and ACE inhibitors are also pharmacological tools used
to control heart rate and myocardial O2 consumption respectively
 Percutaneous transluminal coronary angiography is
recommended for patients with cardiogenic shock, ST elevation,
left bundle branch block and less than 75 years old
 Coronary artery bypass grafting seems to be more appropriate
for patients with multiple vessel diseases or left main coronary
artery diseases
E. OBSTRUCTIVE SHOCK
 Most commonly due to presence of tension pneumothorax
 Cardiac tamponade occurs when sufficient fluid has
accumulated in the pericardial sac to obstruct blood flow to
the ventricles
 Hemodynamic abnormalities are due to elevation of
intracardiac pressures with limitation of ventricular filling in
diastole with resultant decreases in cardiac output
 The pericardium does not extend, hence small blood volume
may produce cardiac tamponade
 If the effusion accumulates slowly, the quantity of fluid may
reach 2000 mL
 Pericardial pressure is the major determinant of degree of
hypotension
 Cardiac tamponade or tension pneumothorax reduces filling
on the right side of the heart by:
 Increased intrapleural pressure secondary to air
accumulation (tension pneumothorax)
 Increased interpericardial pressure precluding atrial
filling secondary to blood accumulation (cardiac
tamponade)
 Resulting in decreased cardiac output associated with
increased central venous pressure
Diagnosis and Treatment:
 Diagnosis of tension pneumothorax should be made on clinical
examination
 Findings include:
 Respiratory distress
 Hypotension
 Diminished breath sounds over one hemithorax
 Hyper-resonance to percussion
 Jugular venous distension
 Shift of mediastinal structures to the unaffected side with
tracheal deviation
 Pleural space can be decompressed with a large calibre needle
 Definitive treatment for tension pneumothorax is immediate tube
thoracotomy placed at the fourth intercostal space at the anterior
axillary line
Page 13 of 15
 Cardiac tamponade results from accumulation of blood in the
pericardial sac or chronic medical conditions such as heart failure
or uremia
 Manifestations of cardiac tamponade may be catastrophic or
subtle and may be associated with dyspnea, orthopnea, cough,
peripheral edema, chest pain, tachycardia, muffled heart tones,
jugular venous distension and elevated central venous pressure
 Beck’s triad: hypotension, muffled heart tones and neck vein
distension
 Invasive hemodynamic monitoring may support the diagnosis of
cardiac tamponade if elevated central venous pressure, pulsus
paradoxus or elevated right atrial and right ventricular pressure by
pulmonary artery catheter is present
 Echocardiography has become the preferred test for the
diagnosis of cardiac tamponade
 Standard two dimensional and trans-esophageal
echocardioradiography are sensitive techniques to evaluate the
pericardium
 Pericardiocentesis to diagnose pericardial blood and potentially
relieve tamponade may be used
 Diagnostic pericardial window represents the most direct
method to determine the presence of blood within the
pericardium, performed through either subxiphoid or
transdiaphragmatic approach
 Exposure of the heart can be achieved by extending the incision to
a median sternotomy, performing a left anterior thoracotomy or
performing bilateral anterior thoracotomies (clamshell)
F. NEUROGENIC SHOCK
 Diminished tissue perfusion as a result of loss of vasomotor
tone to peripheral arterial beds
 Loss of vasoconstrictor impulses results in increased vascular
capacitance, decreased venous return and decreased cardiac
output
 Usually secondary to spinal cold injuries from vertebral
fractures of the cervical or high thoracic region that disrupt
sympathetic regulation of peripheral vascular tone
 Acute spinal cord injury results in activation of multiple
secondary injury mechanisms:
 Vascular compromise to the spinal cord with loss of
autoregulation, vasospasm and thrombosis
 Loss of cellular membrane integrity and impaired
energy metabolism
 Neurotransmitter accumulation and release of free
radicals
 Hypotension contributes to worsening of acute spinal cord
injury as the result of further reduction in blood flow to the
spinal cord
Diagnosis:
 Acute spinal cord injury may result in:
 Bradycardia
 Hypotension
 Cardiac dysrhytmias
  Reduced cardiac output
 Decreased peripheral vascular resistance
 Severity of the spinal cold injury correlates with the magnitude of
cardiovascular dysfunction
 Classic description of neurogenic shock:
 Decreased blood pressure associated with bradycardia
 Warm extremities
 Motor and sensory deficits indicative of a spinal cord injury
 Radiographic evidence of a vertebral column fracture
Treatment:
 Most patients with neurogenic shock will respond to restoration
of intravascular volume alone, with satisfactory improvement in
perfusion and resolution of hypotension
 Administration of vasoconstrictors will improve vascular tone,
decrease vascular capacitance and increases venous return but
should only be considered once hypovolemia is excluded as the
cause of the hypotension
 Dopamine is used if patient’s blood pressure has not responded
to what is felt to be adequate volume resuscitation
 Pure α agonist is used in patients who are not responsive to
dopamine
ENDPOINTS OF RESUSCITATION
 Resuscitation is complete when O2 debt is repaid, tissue acidosis
is corrected and aerobic metabolism is restored
 Resuscitation requires simultaneous evaluation and treatment
 Hemorrhagic shock, septic shock and traumatic shock are the
most common types encountered on surgical services
 Early control of the hemorrhage and adequate volume
resuscitation (RBC and crystalloid solutions) are necessary
 Attempts to stabilize an actively bleeding patient anywhere but in
the operating room are inappropriate
 Compensated shock exists when inadequate tissue perfusion
persists despite normalization of blood pressure and heart rate
 Patients failing to reverse their lactic acidosis within 12 hours of
admission develop an infection three times as often as those who
normalize their lactate levels within 12 hours
 Endpoints in resuscitation can be divided into:
 Systemic or global parameters
 Tissue-specific parameters
 Cellular parameters
 Global endpoints include:
 Vital signs
 Cardiac output
 Pulmonary artery wedge pressure
 O2 delivery and consumption
 Lactate
 Base deficit
Page 14 of 15
Assessment of Endpoints of Resuscitation
 Inability to repay O2 dept is a predictor of mortality and organ
failure
 Easily obtainable parameters of arterial blood pressure, heart
rate, urine output, central venous pressure and pulmonary artery
occlusion pressure are poor indicators of the adequacy of tissue
perfusion
 Serum lactate and base deficit have been shown to correlate with
O2 debt
Lactate
 Generated by conversion of pyruvate to lactate by lactate
dehydrogenase in the setting of insufficient O2
 Released into the circulation and is predominantly taken up by the
liver (50%) and the kidneys (30%)
 Elevated serum lactate is an indirect measure of the O2 debt and
therefore an approximation of the magnitude and duration of the
severity of shock
 Admission lactate level, highest lactate level and time interval to
normalize the serum lactate are important prognostic indicators
for survival
 Base deficit and volume of blood transfusion required in the first
24 hours of resuscitation may be better predictors of mortality
than plasma lactate alone
Base Deficit
 Amount of base in millimoles that is required to titrate 1L of
whole blood to a pH of 7.40 with the sample fully saturated with
O2 at 37°C (98.6°F) and a partial pressure of CO2 at 40mmHg
 Usually measured by ABG analysis in clinical practice
 Mortality of trauma patients can be stratified according to
magnitude of base deficit measured in the first 24 hours after
admission
 Categories of stratification of Base Deficits:
 Mild: 3-5mmol/L
 Moderate: 6-14mmol/L
 Severe: 15mmol/L
 When elevated base deficits persists (or lactic acidosis), ongoing
bleeding is often the etiology
 Trauma patients with a base deficit greater than 15mmol/L
require twice the volume of fluid infusion and six times more
 blood transfusion in the first 24 hours compared to patients with  It has been described that left ventricular power output as an
mild acidosis endpoint (LVP >320mmHg  L/min per square meter), which is
 Frequency of organ failure and mortality increases as base deficit associated with improved clearance of base deficit and a lower
increases rate of organ dysfunction following injury
 Factors that may compromise the utility of base deficit estimating
O2 debt are:
 Administration of Bicarbonate
 Hypothermia
 Hypocapnia (overventiliation)
 Heparin
 Ethanol
 Ketoacidosis

Gastric Tonometry:
 Used to assess perfusion of the GI Tract
 Concentration of CO2 accumulating in the gastric mucosa can be
sampled with a specially designed nasogastric tube
 Assuming that gastric bicarbonate is equal to serum levels, gastric
intramucosal pH (pHi) is calculated by applying the Henderson-
Hasselbalch equation
 pHi should be greater than 7.3, it is lowered in cases of decreased
O2 delivery to the tissues
 pHi is a good prognostic indicator, patients with normal pHi has
greater outcome than patients with lower pHi

Near Infrared Spectroscopy (NIR):

 Can measure tissue oxygenation and state of cytochrome a,a3 on a
continues, noninvasive basis
 The NIR probe permits multiple wavelength of light in the NIR
spectrum (650 to 1100nm)
 Photons are absorbed by the tissue or reflected back to the probe
 Reduction in cytochrome a,a3 correlates with tissue lactate
elevation
 NIR spectroscopy can be used to compare tissue oxyhemoglobin
level thus demonstrating flow-independent mitochondrial
oxidative dysfunction and need for further resuscitation
 Trauma patients with decoupled deoxyhemoglobin and
cytochrome a,a3 have redox dysfunction and shown to have a
higher incidence of organ failure

Tissue pH, Oxygen and Carbon Dioxide Concentration:

 Tissue probes with optical sensors have been used to measure
tissue pH and partial pressure O2 and CO2 in subcutaneous sites,
muscle and bladder
 Use transcutaneous methodology with Clark electrodes or direct
percutaneous probes “Shock is the manifestation of the rude unhinging of the machinery
 Percutaneous probes can be inserted through an 18-gauge of life.”
catheter and hold promise as continous monitors if tissue perfusion - Samuel V. Gross, 1872

Right Ventricular End-Diastolic Volume Index (RVEDVI):
 More accurately predict preload for cardiac index than
pulmonary artery wedge pressure
 A parameter that correlate with pre-load related increases in
cardiac output
Eyel varthasoe she ilekaan rikhoya arrekaan vekha vosi yeroon
vosma tolorro!
“The rain will fall on your rotting skin until nothing is left of you but
bones”

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