Paul E.

Marik, MD, FCP(SA), FRCPC, FCCM, FCCP

Version 2.00
Copyright, P Marik 2001
Table of Contents

Intro/Preface

Daily Management

Hyperglycemia

Blood Comp Rx

DVT Prophylaxis

Nutrition

Ventilator Pneumonia

Weaning

ARDS

Sedation

Neuromuscular Blockers
EBM ICU Protocols
By Paul Marik, MD
TOC
Note to reader:
The author has checked with sources believed to be reliable and up to date in an
effort to provide information that is complete and generally in accord with sta
ndards of practice at the time of publication. However, in view of the possibili
ty of human error or changes in medical science the author of this book cannot w

arrant that the information contained herein is in every respect accurate or com
plete. Readers are encouraged to confirm the information contained herein with o
ther sources.
Disclaimer:
Use at your own risk! Verify all information before initiating treatment.
Feedback:
Please e-mail comments, corrections or suggestions to pmarik@zbzoom.net
Evidence Based Critical Care Medicine:
Balancing the Evidence
Before medicine developed its scientific basis of pathophysiology, clinical prac
tice was learned empirically from the events of daily experience in diagnosing a
nd treating the maladies patients presented. Students learned as apprentices to
clinicians, observing the phenomena of disease, the skill of diagnosis and treat
ment, and the outcomes of different remedies. Sir William Osler's classic textbo
ok of medicine was based almost entirely on his personal experience correlated w
ith the general experience of others. With advances in our understanding of huma
n physiology and the pathophysiologic basis of disease these remedies fell by th
e wayside and treatment became based on modalities of treatment that were shown
to interrupt or otherwise modify the disease process. Until recently it was cons
idered sufficient to understand the disease process in order to prescribe a drug
or other form of treatment. However, when these treatment modalities were subje
cted to randomized controlled clinical trials (RCT's) examining clinical outcome
s and not physiological processes, the outcome was not always favorable. The RCT
has become the reference in medicine by which to judge the effect of an interve
ntion on patient outcome, because it provides the greatest justification for con
clusion of casualty, is subject to the least bias and provide the most valid dat
a on which to base all measures of the benefits and risk of particular therapies
. Numerous ineffective and harmful therapies have been abandoned as consequence
of RCT's, while others have become integral to the care of patients and become r
egarded as the standard of care.
Many RCT's are, however, inconclusive or provide conflicting results. In this si
tuation systematic reviews that are based on meta-analysis of RCT's are clearly
the best strategy for appraising the available evidence. While meta-analysis hav
e many limitations, they provide the best means of determining the significance
of the treatment effect from inconclusive or conflicting RCT's. Although over 25
0,000 RCT's have been performed, for many clinical problems there are no RCT's t
o which we can refer to answer our questions. In these circumstances we need to
base our clinical decisions on the best-evidence available from experimental stu
dies, cohort studies, case series and systematic reviews.
Intuition, anecdotes, common sense, personal experience and personal biases can
no longer be used to justify clinical decisions or therapeutic policies. Every d
ecision that the clinician makes must be based on sound scientific evidence (a c
ollection of anecdotes is not scientific evidence). Many clinicians justify thei
r c urrent practices by rationalizing that's the way I've been doing it for the
last 20 years. However, nothing in medicine stands still, and its likely that th
e physician has been repeating the same mistakes for the last 20 years.
Top
The Need for Evidence Based Protocols in the ICU
The practice of medicine is characterized by enormous variability, frequently wi
th opposing therapeutic strategies. Ambiguities in care may have disastrous impl
ications for ICU patients who are managed by a large team of health care profess
ionals. In order to achieve the best outcomes for these very complicated patient
s, it is essential that all members of the team have a common approach based on
the best available current evidence.
The role of the ICU is to provide temporary physiologic support for patients who
have suffered acute and often catastrophic insults. The care of these patients
requires the coordinated and integrated support of all the organ systems and the
prevention of the unique complications faced by these patients. As many of the
management issues are common to most ICU patients a standardized evidence based

approach to these issues will ensure a systematic and coordinated management str
ategy. Evidence based protocols prevent ambiguities in patient care, while allow
ing the individualization of the management of these exceedingly complex patient
s.
Contradictory therapeutic approaches have a negative impact on all the members o
f the team and compromise patient outcome. Changing the patients' therapy each t
ime different members of the team see the patient results in fragmented care and
undermines the team approach essential to achieving the best patient outcome. P
rotocols help avoid these ambiguities of care.
In order for this approach to succeed the protocols must be evidence based and h
ave the full support of all members of the team. If disagreements exist these ne
ed to be resolved (by reviewing the literature) prior to the implementation of a
protocol. Furthermore, protocols must evolve as clinical circumstances dictate
and as new evidence emerges.
Top
Daily ICU Management
TOC
Daily Exam
Neuro Exam
Labs & CXR
Presenting
Key Points
Intensive Care Units exemplify the miraculous advances of modern medicine. An IC
U provides an environment where high-quality, compassionate, physiologically ori
entated and evidence based medicine can be practiced. The ICU is an exciting and
challenging place to work and provides a remarkable learning environment. The k
eys to a successful rotation in the ICU are i) teamwork and ii) a systematic, di
sciplined and organized approach to patient care.
Admission History and Physical Examination
It is essential that a detailed and systematic history and physical examination
(H+P) be performed on all patients admitted to the ICU. It is essential that the
patients code status and the presence of advance directives be established on a
dmission to the ICU.
The Daily Examination
It is essential that a thorough physical examination be performed daily, the fol
lowing features should be documented:
General

Overall condition of patient

The presence of all invasive lines, tubes and devices

Vital signs:- temperature, including max. 24 hour temp, BP, pulse (rate+rhythm),
RR.

The presence of all pulses and the adequacy of peripheral perfusion

Limb symmetry and swelling (presence of venous thrombosis)

Presence of rashes and decubitus ulcers

Heart
Heart sounds and murmurs.
Chest
Symmetry of air entry and presence of rhonchi or crackles
Abdomen

The presence of distension and tenderness (esp. RUQ).

The type of enteral feeds should be recorded,evidence of reflux and the gastric
residual volumes.

Presence of diarrhoea should be noted.

CNS - A focused neurological examination is essential, particularly in patients
receiving hypnotic/sedative agents, and should include the following:

Level of consciousness and response to commands

Pupillary size and response

Eye movements

Limb movements; spontaneous and in response to noxious stimuli (pain)

Presence of deep tendon reflexes

The Ventilator: The ventilator is an extension of the patient and it is therefor
e essential that the following features be recorded:

Mode of ventilation (AC, SIMV, PCV etc)

Set rate & patient rate

Tidal volume

FiO2

PEEP

Peak airway pressure and plateau airway pressure

Top
The importance of the daily neurological examination
Critically ill patients in the ICU are at risk of developing serious neurologica
l complication including, ICU psychosis, septic encephalopathy, critical illness
polyneuropathy, entrapment neuropathies, compartment syndromes, cerebral edema,
intracerebral hemorrhages (related to coagulopathies), cerebral ischemia (relat
ed to hemodynamic instability) and cerebral embolism. These conditions can only
be detected and diagnosed by physical examination. Furthermore, these conditions
may frequently be masked in patients who are being sedated. It is therefore ess
ential that the motor and eye response to a noxious stimulus (pain) as well as t
he deep tendon reflexes be recorded in all sedated patients. If the patient does
not respond to a noxious stimuli the sedation must immediately be stopped, in o
rder to facilitate further neurological evaluation.
The Glasgow Coma Scale (GCS) was developed to assess the level of consciousness
of trauma patients. The GCS is a measure of pathologic obtundation. This scale i
s difficult to apply to intubated and sedated ICU patients. A description of the
patients' level of consciousness (or arousal) and response to a noxious stimuli
is more useful than documentation of the GCS. This description should include t
he type and power of the motor response.
Top
Laboratory tests and chest-radiographs

All ICU patients require a daily CBC, and urea and electrolytes

Oxygenation - by pulse oximetry & blood gasses when appropriate

All other laboratory tests should be ordered on merit

All intubated patients require a daily chest radiograph. In all other patients c
hest radiographs should be ordered when indicated.
Top
Presenting on Daily Rounds
The presentation must be logical, sytematic, clear and succinct. The following a
pproach is suggested:
1.
Begin your presentation with the patient's name, sex and age.
2.
List the primary medical problems responsible for ICU admission then, the list s
ignificant secondary medical problems and chronic health problems
3.
Outline the events of the past 24 hours

4.
24 hour urine output and fluid balance
5.
Current Physical findings

BP, HR, RR, Temp & T.max

General

Chest

Heart

Abdomen

CNS

Extremeties
6.
Ventilator settings and most recent blood gas [pH/pCO2/PO2/HCO3/Sat] or oxygen s
aturation
7.
Relevant Labs
8.
Review of medications
9.
Assessment and plan.
Top
KEY POINTS:
1.
ICU patients are at a high risk for DVT and therefore all ICU patients require D
VT prophylaxis (i.e SQ heparin, s/q LMWH, compression stockings alone or in comb
ination).
2.
All ICU patients should be evaluated for risk factors for stress ulceration and
high risk patients should receive stress ulcer prophylaxis.
3.

All intubated patients require a gastric tube. The orogastric route is preferred
. Gastric tubes provide access to the GI tract for feeding, allow measurement of
the residual volumes and allow decompressions of the stomach to minimize the ri
sk of aspiration. Small bore tubes have no advantages over standard NG tube unle
ss feeding is being given into the small intestine.
4.
Determine the adequacy of venous access.
5.
Don't forget to feed the patient; absent bowel sounds do not preclude enteral fe
eding.
6.
Communicate with the patients' nurse and respiratory therapist.
7.
If you don't understand something, ASK!
Top
Stress-induced hyperglycemia
TOC
Introduction
Sliding Scale
Infusion
Introduction
Stress-induced hyperglycemia is common in ICU patients. Hyperglycemia is associa
ted with an increase risk of infections complications; recent evidenece suggests
that the maintenance of euglycemia can reduce infectious complications and redu
ce the mortality of ICU patients.
Long-acting insulin has no role in the management of hyperglycemia in acutely il
l ICU patients. In patients with mild stress induced hyperglycemia a s/c insulin
sliding scale maybe appropriate. However, in many patients s/c insulin prevents
large fluctuations in glucose level but rarely controls blood glucose in the 12
5-200 mg/dl range. For this reason a continuous insulin infusion is suggested. T
he target blood glucose is 125 to 200 mg/dl
6 Hourly Sliding Scale
BG ......... U s/c insulin
< 150 ............. 0
150-200 ........ 2 (or 4)
201-250 ........ 4 (or 6)
> 250 ............. insulin infusion
Top
Insulin Infusion Protocol
1.
Mix 200 units regular insulin in 200 cc NS (= 1 U/cc)
2.
Flush tubing with 50 cc of insulin saline infusion
3.
Begin IV insulin infusion at a rate of 2 U/hr
4.
Check capillary blood 1 to 2 hourly until stable then 4 to 6 hourly
5.
Adjust infusion rate as follows:

i. If BG 80-124 mg/dl or if BG falls by > 50 mg/dl/hr

Rate(U/hr) ... DECR. by U/hr
<2 ............................. 0.5
2-10 .......................... 1
10-20 ........................ 2
> 20 .......................... 4
ii. If BG 125 to 200 mg/dl,continue current drip rate
iii. If BG > 200 mg/dl
Rate (U/hr) ... INCR. by U/hr
< 2........................... 0.5
2-10 ........................ 1
10-20 ...................... 2
> 20 ........................ 4
iv. For hypoglycemia
BG < 80 mg/dl
STOP infusion, give amp D50
BG < 60 mg/dl
STOP infusion, give 1 amp D50

Repeat finger stick in 15 minutes and repeat D50 until BG > 100

When BG > 100, resume insulin infusion at 50% of prior rate

Top
BLOOD COMPONENT THERAPY
TOC
RBC
Platelet
FFP
Cryoprecipitate
Dosing
DIC
EPO
Notes
Indications for red blood cell transfusion (See note 1)

Hb < 9 in patients with evidence of cardiac decompensation, unstable CAD, or Hx

of CAD and preop

Acute GI tract bleed with Hct < 30

Hb < 7.5 in all other ICU patients

Indications for platelet transfusion (See note 2)

Chronic thrombocytopenia (< 5000) and patient bleeding

Acute or chronic thrombocytopenia (< 10,000) and patient on chemotherapy

Acute or chronic thrombocytopenia (< 50,000) and patient bleeding

Acute or chronic thrombocytopenia (< 100,000) and operative bleeding

Acute or chronic thrombocytopenia (< 50 -100,000 depending on procedure) undergo

ing invasive or operative procedure

CONTRAINDICATED IN TTP
Indications for fresh frozen plasma (See note 3)

Replacement of clotting factors when PT and or PTT 1.5 X control or greater and
patient bleeding or facing hemostatic challenge

Treatment of thrombocytopenic purpura (TTP)

Treatment of ATIII deficiency

Rapid reversal of warfarin effect

C1 esterase inhibitor deficiency

Indications for cryoprecipitate (See note 4)

Fibrinogen < 100 mg/dl and patient bleeding

Hemophilia A or von Willebrand's disease

Dosing Guidelines for Blood Components

Fresh frozen plasma: 2 - 4 units (400-1000 ml) over 1 hour

Platelets:Use whatever dose is necessary to increase platelet count above 50 000

; 6 units is usually sufficient; or 1 unit or random platelets per 10 kg over 30
minutes

Cryoprecipitate:desired increase in g/L= (0.2 X number bags)/plasma volume in L;

or use 1 bag/5kg, IV push or 1000u/10 min

Packed red blood cells; 1 unit increases hemoglobin by 1.0-1.5 g/dL; give over 2
-3 hours
Top
Rx of DIC
DIC is characterized by bleeding and widespread microvascular thrombosis. While
the bleeding manifestations usually receive the most attention, the microvascula
r thrombosis are pathologically more important and strongly implicated in the de
velopment of organ failure.
Blood component therapy is a potentially hazardous in patients with DIC as it ad
ds fuel (thrombin & fibrinogen) to the fire. The administration of FFP and plate
lets should be restricted to patients with active hemorrhage and severe decrease
s in PT and platelet count AND should be coadministered with activated Protein C
. Fibrinogen concentrates should be avoided.
Erythropoeitin (EPO) & ICU anemia
Anemia is common in ICU pateints. The casues are multifactorial, including low e
rythropoietin, blunted response to EPO, and venesection. rhEPO has been demonstr
ated to decrease the transfusion requirements of ICU patients.
Indications

Pts expected to be in ICU > 3 days

Hct < 36
Regimen

On 2nd ICU day or when Hct < 36

40 000u s/c weekly

PO iron daily (150 mg of elemental iron)

IV iron should be considered if ferritin < 100 ng/ml despite PO iron

Monioring

Baseline: Retic's, Fe, TIBC,ferritin

Twice weely: Retics's, ferritin

Top
Notes:
1.
There is a lack of reliable data to define "the ideal" hemoglobin concentration
in critically ill patients. However, blood transfusion is associated with signif
incat compliations, the most important being immunosupression. recent data sugge
sts that the number of units of transfused blood may be an independent predictor
of MSOF and death. Currently a transfusion "trigger" of 7-8 g/dl is reccommende
d. However, patients with unstbale coronary artery disease or "cardiac decompens
ation" maybe at risk of silent ischemia at this level, and a transfusion trigger
of 9-10 g/dl may be more appropriate in this group of patients.(Back to text)
2.
Platelets should generally be reserved for thrombocytopenic patients who are BLE
EDING and thrombocytopenic patients undergoing invasive or operative procedures.
(Back to text)
3.
Fresh frozen plasma contains all the stable and labile plasma constituents. One
unit of FFP contains approximately 400 mg of fibrinogen and 1 U clotting activit
y per milliliter.(Back to text)
4.
Cryoprecipitate is prepared from a cold insoluble precipitate of plasma. It cont
ains high levels of factor VIII (both procoagulant activity and von Willebrand f
actor) and fibrinogen. Insufficient amounts of the other clotting factors are pr
esent to be of therapeutic value.(Back to text)
Top
DVT Prophylaxis
TOC
Introduction
Risk 1
Risk 2
Risk 3
Risk 4
N/S
Introduction
ICU patients have many of the risk factors for DVT. ICU patients who do not rece
ive DVT prophylaxis have a high incidence of thromboembolic disease. Consequentl
y routine DVT prophylaxis is recommended in all ICU patients. Within the ICU pop
ulation a number of risk factors significancantly increase the risk of DVT, incl
uding obesity, trauma, neurosurgery and hip and knee surgery. The prophylactic s
trategy therefore depends upon the patients risk profile. While the optimal prop
hylactic approach for certain groups has yet to be determined, the results of re
cent RCT's form the basis for the current recommendations in specific risk group
s. The recommendations in those risk groups which have not been subject to well
conducted RCT's are based on the recommendations of "expert panels."
Top
Risk Group 1

ICU patient NOT represented below

5000 U heparin s/c q 8 hourly
.. Or
External pneumatic compression
Risk Group 2

Obesity (BMI > 30)

Deep sedation/paralysis

GBS/M.gravis/Stroke

Spinal cord injury

Urological surgery

Femoral catheters
External pneumatic compression and 5000 heparin s/c q 8 hourly
.. Or
Lovenox 40 mg s/c daily
Top
Risk Group 3

Total hip replacement

Total knee replacement

Fracture hip/femur

Trauma (excluding TBI)

Lovenox 30mg s/c q 12 hourly
.. Or
Lovenox 30mg s/c q 12 hourly and external pneumatic compression (if feasible)
Risk Group 4

Intracerebral hemorrhage

TBI

Coagulopathy (PT or PTT > 1.5 x control)

Active bleeding
External pneumatic compression
Neurosurgery

Lovenox 40 mg s/c daily (started post-op) and external pneumatic compression/com

pression stockings
Top
Nutrition in the ICU
TOC
Principles
Protocol
Notes
Liver failure
Pancreatitis
Renal failure
"If The Bowel Works, Use It" ....
"There is no disease process that benefits from starvation"
Principle of nutritional support in the ICU
1.
Nutritional support is an essential component in the management of critically il
l patients.
2.
There is no data that TPN is of any benefit in critically ill patients. The avai
lable evidence suggests that TPN increases complications and mortality rates (se
e note 1). TPN should therefore be limited to patients, who after 5-7 days of st
arvation, are unable to tolerate even small volumes of enteral nutrition (EN). T
he addition of "trickle feeds" reduce the complications associated with TPN. Des
pite this data, patients with a functional gut continue to receive TPN!
3.
Early EN (within 24 hours of admission to the ICU) has been shown to reduce comp
lications and improve the outcome of critically ill patients when compared to de
layed EN.No studies demonstrate an advantage to delaying nutritional support in
seriously ill patients.
4.
Over 20 RCT's have demonstrated that "immune enhancing diets" (IED) decrease ind
ices of inflammation, improve cell mediated immunity, decrease organ failure and
ICU complications, and reduce LOS. Immune enhancing diets should therefore be g
iven to all patients with ALI/ARDS, sepsis, poly-trauma and other "high risk" pa
tients with an anticipated ICU stay in excess of 5 days.
5.
Overfeeding patients is associated with significant complications including hype
rglycemia, hepatic steatosis with hepatic dysfunction, elevated BUN and excessiv
e CO2 production.
6.
There is no data to suggest that accurately measuring energy expenditure and nut
ritional requirements improves outcome.
Summary: "Do It early, Do It slowly and Do It with an IED"
Top

Nutrition Protocol

EN should be initiated within 12 hours of admission to the ICU.

Use IED in high risk patients

Place NG tube. If a patient is at high risk for poor gastric emptying then a sma
ll bowel tube should be placed.

The head of the bed should be elevated to 30o to decrease the risk of aspiration
.

Feeding may be administered by boluses of 100-250 ml every two to four hours or

by continuous infusion started at 25 to 30 ml/hr and increased by 10 to 25ml/hr
every six hours as tolerated (i.e gastric residual volumes < 150 ml) until calor
ic goal is achieved (25 to 30 kcal/day).

Gastric residuals should be measured every 6 hours with continuous feeding or pr

ior to each bolus. If the gastric residual is > 150 ml and/or should the patient
reflux, the stomach should be emptied, feedings held for 2 hours, and then rest
ated at one-half the volume. Erythromycin (250 mg IV q 8 hourly) improves gastri
c emptying and should be started.

Should the residual volumes remain high and/or the patient tolerate tube feeding
poorly, post pyloric access should be obtained.

In patients with discontinuity of the bowel TPN maybe indiated.TPN should be ini
tiated slowly; 50% of goal first day, 75% second day, 100% 3-4th day. In additio
n TPN should not be suddenly stopped (may cause profound hypoglycemia). Standard
TPN orders include:

Non protein calories:25-30 kcals/kg/day

CHO: MAX 4mg/kg/day ( 1600 cals)

Lipid: 4-12 kcals/kg/day

Protein ~1.5 g/kg/day

Vitamins and trace elements

Top
Notes:
1.
TPN is associated with significant complications, including an increased inciden
ce of infections, metabolic disturbances such as hyperglycemia, hypophosphatemia
, hypokalemia and trace element deficiency; atrophy of the GIT mucosa and lympho
id system predisposing to bacterial translocation; immune suppression and hepati
c dysfunction.(back to text)
2.
Propofol emulsion contains 0.1g of fat (1.1 Kcal) for every milliliter. An infus
ion of propofol may therefore provide a significant caloric load. In patients re
ceiving high dose propofol infusions, the enteral feeds need to be adjusted to t
ake into account the added caloric load. A low-fat enteral formulation, such as
Vivonex (10g fat/L) may be used.
3.
The refeeding syndrome: Feeding malnourished patients, particularly after a peri
od of starvation may result in severe metabolic disturbances, most notably hypop
hosphatemia. Hypophosphatemia developing after initiating parenteral or enteral
nutrition has been termed the refeeding syndrome. In addition to hypophosphatemi
a, changes in potassium, magnesium and glucose metabolism occur during refeeding
. Although classically described in cachectic patients after prolonged starvatio
n, this syndrome has been reported to occur commonly in poorly nourished ICU pat
ients who have been starved for as short as 48 hours.
Top
Nutrition in specific disease states
Liver Failure
The use of protein restriction in hepatic encephalopathy/liver failure is contro
versial. Intolerance of dietary protein should be balanced against the increasin
g evidence that adequate nutrition, including fair amounts of protein, can impro
ve clinical outcome in patients with hepatic encephalopathy. Therefore, in patie
nts with liver cirrhosis and hepatic encephalopathy, one should initially restri
ct daily protein intake to 0.5 g/kg/day and slowly increasing the intake to 1.0
g/kg per day. Zinc deficiency is common in patients with cirrhosis; supplement w
ith 600mg zinc sulphate daily.
Pancreatitis
Despite the lack of prospective data, "conventional wisdom" dictates that gut re
st with or without the provision of parenteral nutrition remains the treatment o
f choice in acute pancreatis. However, the results of a number of RCT's has disp
roved this standard dogma. These studies have clearly demonstrated that oral fee
ds in mild/moderate pancreatitis and enteral feeding via a nasoenteric tube plac
ed distal to the ligament of Treitz in patients with severe pancreatitis reduces
indices of pancreatic and systemic inflammation and reduces the incidence of in
tra-abdominal sepsis, multiple organ failure, need for operative intervention, a
nd mortality when compared with the parenterally fed patients. TPN consequently
appears to have little (NO) role in the management of patients with acute pancre
atitis. Oral refeeding is only recommended once pain has subsided and the serum
amylase has approached normal levels.
Renal Failure
Most patients with ARF are hypercatabolic and require increased quantities of nu
trients. Patients with ARF should receive a minimum of 1g protein/kg/day and opt

imal non-protein calories. Protein intake in critically patients should not be l

imited in an attempt to avoid initiation of dialysis.
Top
Approach to Suspected VAP
TOC
Introduction
PSB sampling
Bacteriology
Empiric Rx
PSB Results
Introduction: Clinical criteria alone are notoriously unreliable in the diagnosi
s of VAP; consequently many patients without pneumonia are needlessly treated wi
th antibiotics. Sputum culture (tracheal aspirate-T/A) should not be used to dia
gnose VAP as this test is plagued by both high false-positive and false-negative
results; the specificity of sputum culture is only 50% (no better than flipping
a coin).
Consequently, lower respiratory tract sampling together with quantitative cultur
e is recommended to diagnose VAP. This can be performed bronchoscopically or bli
ndly; the blind technique (B-PSB) has operating characteristics similar to the b
ronchoscopic technique; however, it is quicker, safer, more cost effective and e
asier to perform.
Patients with suspected PCP, immunocompromised and/or neutropenic patients shoul
d undergo formal bronchoscopy with PSB and BAL. T/A are suitable specimens in pa
tients with suspected tuberculosis. Post-intubation T/A's may be useful for the
diagnosis of community acquired pneumonia.
Top
Indications for PSB sampling:
1.
Patient intubated for greater than 24 hours
2.
New or progressive pulmonary infiltrate on the chest radiograph (NO infiltrate,
NO VAP)
3.
At least two of the following clinical criteria:

Fever > 38.3C (101F)

Leukocytosis (> 10 x 109/L)

Purulent tracheal secretions

Contraindications to Blind PSB:
1.
Non intubated patients
2.
Patients with uncontrolled bleeding
3.
Ptients with PT/PTT greater than twice normal or a platelet count < 60 000

4.
Ptients with known or suspected intrabronchial lesions
5.
Patients who have recently undergone a pneumonectomy or lobectomy
Top
Blind PSB Procedure:
1.
Administer 80 to 100% oxygen throughout the procedure and monitor O2 sats.
2.
Midazolam/propofol should be administered to non-sedated patients to limit cough
ing during the procedure.
3.
A standard microbiology specimen brush is inserted through the ET tube until app
roximately 35cm or until resistance is met.
4.
A specimen is obtained by advancing the inner canula (expressing the wax plug),
advancing the brush, twisting the brush then retracting the brush into the inner
canula.
5.
The entire catheter is then removed from the ET tube.
6.
The brush is then cut and placed in 1 ml of ringers lactate and processed by the
microbiology laboratory within 30 minutes.
7.
Quantitative culture should be performed using standardized techniques.
Bacteriology of VAP
A consistent pattern of pathogens has been reported in patients with VAP. The co
mmonest pathogens are:

S. aureus

P. aeruginosa

Enterobacter spp.

S. pneumonia

H. influenzae

E. coli

Klebsiella spp

A. baumannii.
P. aeruginosa and A. baumannii are more common in patients intubated > 4 days wh
ile S. pneumonia and H. influenzae are more common in patients intubated for < 4
days. Anaerobes have been shown to be unimportant in most patients with VAP.
Top
Empiric antibiotics until culture data available
The choice of empiric antibiotics is extremely important in determining the outc
ome of patients with VAP and should be based on local epidemiological data. The
empiric regimen must be broad to cover the most likely pathogens; the appropriat
eness of the initial regimen determines outcome. This regimen is then tailed onc
e culture data are available. A number of studies have demonstrated that the sch
eduled change (every 4-6 months) of antibiotic class can reduce both the inciden
ce of VAP and the incidence of VAP attributed to antibiotic-resistant bacteria.
The following antibiotic(s) are reccommended. These reccommendations require mod
ification depending on the importance of MRSA and pseudomonas in individual ICU'
s. Rotating antibiotics is reccommended.

Piperacillin/Tazobactam vancomycin gentamycin

Imipenem vancomycin gentamycin

Ciprofloxacin vancomycin gentamycin

The use of 3rd generation cephalosporins should be limited due to the induction
of ESBL and VRE.
Top
Interpretation of PSB results
The results of the b-PSB should be recorded and interpreted as follows:
1.
no growth
2.
<500 cfu/ml (contaminant)
3.
500-1000 cfu/ml (borderline +ve)
4.
> 1000 cfu/ml (positive)

Patients with borderline +ve or +ve culture should be considered to have VAP.

Candida or coagulase negative staphylococci should be ignored.

In patients with +ve and borderline +ve cultures the antibiotic regimen MUST be
tailored/narrowed according to the sensitivities of the pathogen(s) isolated.

In patients with negative cultures, the decision to continue or stop the antibio
tics should be made by the patients' attending physicians based on his/her asses
sment of the risk of stopping antibiotics. However, it is recommended that unles
s VAP is strongly suspected, antibiotics be stopped and the patient re-cultured
if a strong index of suspicion for VAP still exists.
Top
ARDS
TOC
Definitions
Low TV
PCV
Hemo support
Sedation
Other Rx
Chronic
Lung Protection
Definitions
ARDS/ALI is a condition characterized by:

An oxygenation defect with bilateral alveolar infiltrates

A patient who has suffered an acute catastrophic event

A patient with a PCWP < 18 mmHg and/or no clinical evidence of an elevated left
atrial pressure
ALI:- PO2/FiO2 < 300
ARDS:- PO2/FiO2 < 200
Rx of acute phase
The management of ARDS is essentially supportive and includes:

Cardio-respiratory and nutritional support

The prevention of further lung injury

The prevention of complications

Top
Ventilation
See Lung Protective Strategy
Initiating a Lung Protective Strategy
Patients with bilateral pulmonary infiltrates and any of the following ventilato

r parameters on standard assist-controlled ventilation should be be switched to

PCV/low TV vent.:

Plateau pressure > 35 cmH2O

PEEP > 10 cmH2O

FiO2 > 60%

Top
Low TV ventilation
Initial settings:

Adequate sedation must be achieved

Mode: AC

Tidal volume: 8ml/kg reduced by 1ml/kg to 4-6 ml/kg

Rate: Set to match initial MV (max 30/min)

FiO2: Original setting titrate Sats > 88%

PEEP: Best determine by static PV curve, else by FiO2

FiO2 40 -- 8

FiO2 50 -- 10

FiO2 60 -- 12

FiO2 > 60 -- 15

Flow rate (I:E): Flow rate adjusted to achieve I:E of 1:1 - 1:1.3
Goals:

Plateau Press < 35 cmH2O

Sat > 88%

pH > 7.15
Top
Pressure Controlled Vent.
Required equip:

Ventilator that supports PCV

Ventilator with wave-form capabilities

Ventilator that can measure auto-PEEP

Continuous pulse oximetry

End-tidal CO2 monitoring

Initial PCV settings:

Adequate sedation must be achieved

An inspiratory pressure of 20 cmH2O

PEEP 15 cmH2O (if possible obtain a static pressure/volume curve and set PEEP ab
ove the lower inflection point)

Same FiO2 as on A/C ventilation

Rate 14/minute

Set inspiratory time such that the initial I:E is 1:1.5

Top
Refining the initial settings:

The inspiratory and expiratory times ( I:E ratio) and respiratory rate are best
adjusted by analyzing the Flow vs. Time Waveform. It is essential that adequate
inspiratory time be given so that all the airways, both healthy and diseased, ha
ve time to reach the preset pressure level. If expiration begins before flow has
reached zero the inspiritary time needs to be increased. This will therefore in
crease mean alveolar pressure and improve oxygenation. The inspiratory time can
be lengthened in 2 ways;

Increase the inspiratory time until the inspiratory flow reaches zero (recommend
ed method)

Reducing the "E" part of the I/E ratio will increase "I".

If flow reaches zero and there is a long inspiratory pause, this is an indicatio
n that inspiratory time is too long. Setting inspiratory time longer than that w
hich is required to open recruitable airways increases the likelihood of signifi
cant auto-peep.

To evaluate the adequacy of the expiratory time, the Flow vs. Time Waveform need
s to be studied again. This waveform shows whether the patient has enough time t
o exhale to the pre-set PEEP level before the ventilator gives the next breath.
Should inspiration begin before flow reaches zero air trapping will occur with t
he development of auto-PEEP. There is no data that intrinsic PEEP has any advant
age over extrinsic (ie applied) PEEP. However, the unrecognized development of a
uto-PEEP may result in hemodynamic compromise leading to the inappropriate use o
f fluid and vasopressor therapy. Air trapping is corrected by either reducing th
e respiratory rate or inspiratory time. Each should both be independently and se
quentially reduced, in order to determine which maneuver affects ventilation the
least.
Top
Monitoring PCV

It is essential that the e TV be monitored and the ventilator alarms set at the
appropriate level

Continuous end-tidal CO2 monitoring is essential.These measures are important as

changes in airway/lung compliance will result in a fall in tidal volume and inc
rease in PaCO2 without this being clinically obvious.

It is essential that the level of auto-PEEP be measured.

Continuous pulse oximetry is essential with the arterial saturation kept above 8
8%.

The Flow vs Time waveform should be monitored regularly. As the patients pulmona
ry mechanics change the inspiratory time and respiratory rate may need to be alt
ered.

Arterial blood gas analysis should be performed at least once daily.

Top
Hemodynamic support
The optimal fluid strategy in patients with ARDS is a hotly debated subject with
a "wet lung" and a "dry lung" camp. These two approaches have as yet to been co
mpared in an adequately powered RCT. In the absence of such data, "experts in th
e field" suggest a strategy that maintains the lowest intravascular volume (or P
CWP) that sustains an adequate cardiac output (and renal perfusion). Inotropic a
gents may be required to maintain an adequate cardiac output and perfusion press
ure (MAP > 75-80 mmHg). If hemodynamics allow the patient should be kept in a ne
gative fluid balance. Once hemodynamic stability is achieved the patient should
be actively diuresed (until the BUN climbs to approximately 30 mg/dl).
Sedation
All patients receiving low-volume/high PEEP ventilation require deep sedation to
achieve ventilator synchrony. Sedation is best achieved with a continuous infus
ion of propofol and lorazepam supplemented with fentanyl as required.
Neuromuscular blocking agents are associated with signifincat complications are
their use is strongly discouraged.
Top
Other supportive measures:

GI prophylaxis

DVT prophylaxis

Early initiation of enteral nutrition with an immune enhancing formula

Screen for nosocomial infection esp VAP

Top
Rx of Chronic Phase
Patients who after 10-14 days of aggressive supportive therapy require high leve
ls of ventilatory support (FiO2 50%) are candidates for corticosteroid therapy.

Corticosteroids should only be considered if lower respiratory tract sampling ca

n be performed to diagnose and treat pulmonary sepsis. Prior to embarking on cor
ticosteroid therapy sepsis should be excluded. Once corticosteroids are commence
d surveillance cultures and protected lower respiratory tract sampling performed
every 4th day.
Corticosteroid Protocol (methylprednisolone):
Days 1-14:
Loading dose of 2mg/kg then 0.5 mg/kg q 6 hourly
Days 15 -21
1 mg/kg/day
Days 22-28
0.5 mg/kg/day
If patient extubated prior to day 14, treatment is tapered after day 15.
Top
Lung Protective Strategy
Because a significant portion of the lung is consolidated and not recruitable, o
nly a small amount of aerated lung receives the total tidal volume - ARDS leads
to "baby lungs". The use of traditional tidal volumes (12 to 15 ml/kg) in these
patients will result in high inspiratory pressures with overdistension of the no
rmally aerated lung units. An impressive body of experimental and clinical evide
nce has clearly demonstrated that mechanical ventilation that results in high tr
ans-pulmonary pressure gradients and overdistension of lung units will cause acu
te lung injury. Animal studies have demonstrated that a trans-pulmonary pressure
in excess of 35 cmH2O will lead to alveolar damage. Furthermore the cyclic open
ing and closing of lung units (recruitment and derecruitment) in patients with A
RDS who are ventilated with insufficient PEEP will further potentiate this iatro
genic lung injury. It has clearly demonstrated that ventilatory strategies that
avoid overdistension of lung units and also avoids end-expiratory alveolar colla
pse limits the degree of lung injury in ARDS, reduces complications and improves
survival.
A relative form of "lung rest" using low tidal volume mechanical ventilation is
therefore recommended. This may be achieved with low-volume, volume-cycled venti
lation with a decelerating inspiratory flow or pressure controlled ventilation (
PCV).
Permissive hypercapnia.The strategy to reduce volume induced lung injury by usin
g small tidal volumes may lead to CO2 retention. The term "permissive hypercapni
a" has been used to the describe this ventilatory strategy. Hypercapnic acidosis
is generally well tolerated by the patients, especially when it develops gradua
lly over 1 to 2 days. Aministration of bicarbonate to correct the acidosis is no
t reccommended. Permissive hypercapnia should not be used in patients with acute
intracranial pathology.
Top
Protocol for Liberation/Weaning From Mechanical Ventilation
TOC
Step 1
Step 2
Step 3
Failure to wean
Notes
Introduction
A number of different approaches to ventilator liberation have been reported (Se
e note 1). The most popular and efficient method is described. According to this
approach:
1.
All ICU patients are screened daily by the RT (See note 2)
2.
Suitable patients undergo a 3 minute spontaneous breathing trial

3.
This is followed by a 30 minute to 2 hour spontaneous breathing trial in those w
ho pass the 3 minute test
Step 1. Screening of patients
Candidates for the 3 minute spontaneous breathing trial: (See note 3)

Adequate gas exchange

Non COPD: a PaO2 > 60mmHg with a FiO2 of 0.4 or less (PaO2/FiO2> 150)

COPD: pH > 7.30, PaO2 > 50mmHg with a FiO2 of 0.35 or less

PEEP < 6 cmH2O

Alert and cooperative patient.

Patient not on a continuous infusion of sedatives/narcotics

Temperature < 38C and > 36.5C

No requirement for vasopressor agents

dopamine > 10 ug/kg/min

norepinephrine

Minute ventilation < 15 L/min and RR < 30

Adequate cough during suctioning

Heart rate less 100 beats/min

Systolic blood pressure > 90 and < 180 mmHg

Top

Step 2. Three minute spontaneous breathing trial

Patients who meet all the above criteria then undergo a 3 minute spontaneous bre
athing trial.
The patient will be placed on one of the following trial modes:

CPAP with auto-flow

CPAP with pressure support of 5cm/H20 (See note 4)

The FiO2 is set at the same level as that used during mechanical ventilation. Tr
ial must be monitored by pulse oximetry and electrocardiography. The trial must
be stopped immediately when the patient meets any of the following criteria:

Resp Rate/Tidal Volume (Liters) > 105

Respiratory rate < 8 or > 35

Spontaneous tidal volume < 4cc/kg

Arterial saturation < 90%

Heart rate > 140 or heart rate change (either direction ) > 20%; no arrhythmia
Top
Step 3. Trial of Liberation
Patients continue to breath through the CPAP circuit. The FiO2 may be increased
up to 50%.
Back-up apnea parameters must be set on the ventilator to activate at a 20 secon
d apneic interval.
Trial terminated when:

Respiratory rate > 35/min

Arterial saturation < 90

Heart rate > 140 or heart rate change (either direction ) > 20% or arrhythmias

SBP > 180 and < 90

Increased anxiety and diaphoresis

Should the patient tolerate the CPAP trial for 2 hours (some studies have used 3
0 minutes) then the patient may be extubated.
The trial is repeated daily in those patients who fail to tolerate this spontane
ous breathing trial.
The time to liberation is not shortened by repeating the spontaneous breathing t
rial multiple times per day.
The ICU team must be notified should the patient pass this phase of the liberati
on process and an order obtained to extubate the patient.
Orogastric tubes, if present should be removed to reduce the risk of aspiration.
If gastric access is required a naso-gastric tube should be placed. The tube fe
eds should be stopped at this point in time. Intravenous glucose must be given t
o prevent hypoglycemia.
Top
Treatable causes of "failure to wean"

Hypophosphatemia

Hypokalemia

Hypomagnesemia

Hypocalcemia (ionized)

Pulmonary edema

Angina

Anemia

Malnutrition

Overfeeding with excessive carbohydrate (increased CO2 production)

Notes:
1.
Weaning/liberation is the process by which a patient is removed from the ventila
tor. In many patients ventilatory assistance need not be decreased gradually, me
chanical ventilation and artificial airways can simply be removed (liberated). A
ccording to this thesis patients can simply be removed from the ventilator once

the disease process which led to intubation and mechanical ventilation has impro
ved or resolved; a prolonged "weaning process"is therefore not required."
Several studies have been performed comparing the efficacy of SIMV, T-piece/CPAP
, and PSV weaning. No technique has proven superior to T-piece/CPAP weaning.
Cinical judgement alone does not accurately predict whether mechanical ventilati
on can be discontinued successfully.It has recently been demonstrated that scree
ning patients daily to identify those who can breathe spontaneously will promote
earlier weaning from mechanical ventilation.(Return to text)
2.
These are screening criteria; some patients who fail to meet these criteria may
be candidates for the "three minute trial" if approved by the ICU medical team.(
Return to text)
3.
Patient evaluations should begin early in the morning (around 5:00 am) and the p
atients who meet the inclusion criteria will then immediately begin this protoco
l. Attending physicians will be notified during morning rounds with an update of
all evaluated patients.(Return to text)
4.
Patients with cardiac disease are best weaned with CPAP and pressure support; th
is includes patients with cardiac failure and patients with significant coronary
artery disease. The level of pressure support should initially be set at betwee
n 10-12 cmH20 and reduced by 2 cmH20 until the patient is able to tolerate a PSV
of 5 cm H20 for 2 or more hours. An electrocardiogram should be obtained prior
to extubation in patients with a history of coronary artery disease.(Return to t
ext)
Top
Sedation in the ICU
TOC
Introduction
Assessment
SAS Scale
Agents
Protocol
Introduction
Anxiety is an almost universal feature of ICU patients. Consequently, sedation i
s an integral component of the management of the ICU patient. The primary object
ives of sedation is too allay anxiety, enhance patient comfort, promote sleep, r
educe O2 consumption, reduce the stress response, and facilitate mechanical vent
ilation. The desirable level of sedation/hypnosis will depend in large part upon
the patient's acute disease process as well as the need for mechanical ventilat
ion.
In anxious patients it is important to exclude treatable causes of anxiety and n
ot just increase the amount of sedative drugs being used. Treatable causes of an
xiety include:

Uncontrolled pain (NB)

Ventilator settings inappropriate (esp inadequate flow rate) - respiratory incoo

rdination

Drug or alcohol withdrawal syndrome

Increased work breathing, e.g. pneumothorax, kinked/blocked tube

Pulmonary edema

Loud ventilator alarms and monitors

Poor communication with patient as regards diagnosis, therapy etc.

Top Assessing the degree of sedation and titrating the drug regimen to predeterm
ined end-points is essential as both over sedation and inadequate sedation are a
ssociated with significant complications.
Complications of under-sedation include:
Severe anxiety with delusional behavior
nterference with medical and nursing care
Sympathetic over-activity with increased myocardial oxygen consumption
Self-injury
Self-extubation
Complications of over-sedation include:
Prolonged intubation with an increased risk of pulmonary complications
Disorientation and "ICU-psychosis" following emergence
Masking of significant neurological and neuromuscular complications
Top
Assessing the level of sedation
Ongoing clinical evaluation is the most effective method of assessing sedation.
In order to provide a more consistent and objective means of assessing the degre
e of sedation a number of "sedation scales" have been used. The Glasgow Coma Sca
le (GCS) was developed to assess the level of consciousness of trauma patients.
This scale is commonly used to monitor the level of sedation in ICU patients. Th
e GCS is, however, essentially a measure of pathologic obtundation and cannot be
recommended for monitoring sedation. The Sedation-Agitation Scale (SAS) was dev
eloped and tested on ICU patients and designed specifically for evaluating the l
evel of sedation in the ICU. This is the preferred assessment scale.
Top
The Sedation-Agitation Scale (SAS)
1.
Unarousable - deep hypnosis, non-rousable, no spontaneous movement, no coughing
2.
Very sedated - rousable with strong tactile stimulus, occasional spontaneous and
non-purposeful movements, does not respond to commands
3.
Sedated - Asleep/sedated but rousable with tactile stimulus and displays purpose
ful movements and follows simple commands
4.
Calm cooperative - Calm, awakens easily, follows commands -----------------5.
Agitated - Anxious or mildly agitated, attempting to sit up, calms down to verba
l instructions

6.
Very agitated - Does not calm despite frequent verbal remind; requires physical
restraints, biting ET tube
7.
Dangerous agitation - Severe anxiety, diaphoresis, frequent vigorous movements,
pulling on ET tube , trying to remove catheters, climbing over bed rails, striki
ng at staff, thrashing side to side
Goals of Sedation
Non-ventilated patients
SAS 3-4
Ventilated pts: AC, SIMV, PS
SAS 2-4
Ventilated pts: PCV, low TV AC
SAS 1-2
Top
Sedative/Hypnotic agents of choice
The following drugs have been selected based on cost, efficacy, tolerance, pharm
acokinetics and pharmacodynamics and side-effects.
1.
Long term sedation
Lorazepam is the drug of choice for non-intubated patients and patients who will
require long term sedation/hypnosis in the ICU (> 48 hours). Benzodiazepines sh
ould be avoided in patients with liver disease. Lorazepam and propofol act syner
gistically; the addition of propofol should be considered to prevent oversedatio
n and long waking time.
2.
Short term sedation, neurological/neurosurgical patients
Propofol is the drug of choice due to the rapid emergence once discontinued
3.
Deep hypnosis to facilitate "lung protective ventilation"
This may be achieved with propofol alone. However, propofol and lorazepam have s
ynergistic effects and the combination may achieve the desired level of hypnosis
at a lower cost.
4.
Treatment of Delirium or sedation without respiratory depression
Haloperidol
5.
Sedation for invasive procedures
Midazolam alone or in combination with fentanyl
The daily interruption of sedative-drug infusions is recommended in patients rec
eiving mechanical ventilation. This approach allows daily assessment of neurolog
ical function that would otherwise not be possible and prevents oversedation and
reduction of total sedative dosages.
Top
Sedation Protocol
1.
To treat SAS 7, sedation for PCV, neurosurgical/neurology patients , patients wi
th hepatic dysfunction and short term sedation (< 24 hours)

Propofol: Start IV drip at 10ug/kg/min, titrate dose by increments of 5-10 mcg/k

g/min at 10 minute intervals

Lorazepam 2-4 mg IV Q4 hour; hold if patient requiring < 50 mcg/kg/min propofol

Hold propofol drip Q AM to assess neuro status, restart drip at previous level

Check triglyceride Monday and Thursday: if > 400 mg/dl halve propofol dose and s
tart lorazepam infusion at XX mg/hr (if > 600 mg/dl stop propfol)
2.
To treat SAS 5 or 6 or for any patient for whom sedation is required
Non Intubated patient

Lorazepam 2-4 mg IV Q 6 hours. Hold for SAS < 3

Intubated Patient

SAS 6. Lorazepam infusion - start at 2mg/hr and then titrate to SAS level XX inc
reasing by 2mg/hr no more frequently than every 15 minutes.

SAS < 6. Lorazepam 2-4 mg Q 4 hourly IV. If poor response change to an infusion
of lorazepam at 2mg/hr and then titrate to SAS level XX increasing by 1mg/hr no
more frequently than every 15 minutes.

Hold lorazepam drip Q AM to assess neuro status, restart drip at previous level.
3.
Delerium

Haloperidol 5-25 mg IV Q 10 minutes PRN for SAS 6 or 7. DO not exceed 80 mg over

2 hours

Haloperidol 5-25 mg IV Q 4 hours. Hold for SAS < 3

Note: Propofol should only be used in intubated patients
Weaning propofol
Decrease propofol by 10ug/kg/min q 2 hour
IF SAS > 4 choose from:

Lorazepam 2-4 mg IV Q 4 hours. Hold for SAS < 3

Haloperidol 10 mg IV Q 10 minutes PRN for SAS 6 or 7. DO not exceed 80 mg over 2

hours

Haloperidol 5 mg IV Q 4 hours. Hold for SAS < 3

Top
Neuro-muscular blockers in the ICU
TOC
Introduction
NMBA's
TOF
Introduction
NMBA have historically been used in the OR where they have been found to be rema
rkably safe. The safety of these drugs in the ICU has been questioned, due to th
e increasing number of case reports of prolonged paralysis following their use.
In particular, the concomitant use of NMBA and corticosteroids has been linked t
o a syndrome known as "acute quadriplegic myopathy". This syndrome may occur aft
er use for as short as 8 hours and without the concomitant use of corticosteroid
s. Acute quadriplegic myopathy has been associated with the use of both steroid
and non-steroid based NMBA. NMBA's should, therefore, be used only when absolute
ly indicated (and only when high dose propofol has failed) and then only for the
shortest possible period of time. Neuromuscular blockade should NEVER be used f
or the treatment of anxiety or restlessness.
The major indication for NMBA in the ICU is to facilitate ventilation in the fol
lowing circumstances:

High PEEP

When peak airway pressures are high

PCV

Low tidal volume ventilation

To prevent excessive and prolonged neuromuscular blockade all patients receiving
NMBA should be monitored using a nerve stimulator. For practical purposes the T
rain-Of-Four (TOF) should be used to access the degree of neuromuscular blockade
. The goal is to achieve one to two twitches.
Top
Choice of NMBA

Long term paralysis

Vecuronium - duration 60-75 minutes
Intubation: 0.07-0.1 mg/kg
Maintenance: 4-10 mg/hr

Renal failure
Atracurium - duration 45-60 minutes
Intubation: 0.4-0.5 mg/kg
Maintenance: 20-50 mg/hr

Intubation
Rocuronium - acts 1 min, duration minutes
0.6-1.2 mg/kg
Succinylcholine - acts 30s, duration 5-15 minutes.
1mg/kg
CONTRAINDICATIONS to the use of Succinylcholine include:

Renal failure

Burns

Severe trauma with muscle injury

Severe sepsis

Ocular injuries

severe acidosis
Top
Train of Four (TOF) Monitoring
The train of four (4 stimuli 0.5s apart) is a convenient way of monitoring the d
egree of neuromuscular blockade and roughly correlates with the degree of neuromuscular junction receptor occupation:

4 twitches ... 0-70% receptors occupied

3 twitches ... 70-80% receptors occupied

2 twitches ... 80-90% receptors occupied

1 twitch ... > 95% receptors occupied

0 twitches ... 100% receptors occupied

In principle, any superficially located peripheral motor nerve can be stimulated
. The ulnar nerve is however the most popular site. The electrodes are best appl
ied on the volar side of the wrist.
From a practical point of view 1 to 2 twitches (of TOF) of the adductor pollicis
muscle will result in sufficient diaphragmatic paralysis to prevent the patient
from coughing, hiccoughing and breathing during mechanical ventilation.
Prior to paralysis the supramaximal stimulation (SMS) must be determined. The SM
S is defined as the level at which additional stimulation current does not incre
ase the twitch response. It is important to note that each nerve may have a diff
erent SMS and inadequate stimulation may lead the clinician to overestimate the
degree of neuromuscular blockade present. The SMS is usually in the range of 2060 mA.
Starting at 10 mA, increase the TOF current by 10mA until four equal responses a
re obtained. Continue to increase the current until the intensity of the respons
e does not increase any further. When this occurs the prior setting will be the
SMS for that nerve. Once the patient is paralyzed the TOF is then performed usin
g the SMS.
Top
The TOF test should be performed hourly until the goal is achieved (1-2 twitches
) and then 6 hourly. The rate of the infusion should be adjusted as follows:
0 twitches
Stop infusion, restart when 2 twitches are present. Restart infusion rate at:

80% if takes 1 hour for 2 twitches

75% if takes 2 hour for 2 twitches

50% if takes 3 hour for 2 twitches

25% if takes 4 hour for 2 twitches

1 twitch
Reduce to 80% of present infusion rate
2 twitches
Maintain present infusion rate
3 twitches
Reload with 25% of loading dose
Increase infusion rate by 25%
4 twitches
Reload with 50% of loading dose
Increase infusion rate by 50%
Top