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Sedation in the ICU

Doctor Chad


A 60 year old woman with a past medical history of IVDU and

poorly controlled COPD on home oxygen presents to the ED
after being found down by her husband. He reported she had 2
days of increasing cough and on arrival, she was noted to have
fevers to 103.4, was increasingly somnolent and hypotensive. In
the emergency room, she received several liters of normal
saline and was placed on a ventimask. Because of her increasing
oxygen requirement, she was transferred to the ICU.

In the intensive care unit, she became combative and an initial

ABG revealed hypercapnia with a pH of 7.25, pCO2 48, PaO2 of
69. She was tried on a BiPAP mask which she did not tolerate,
her hypercapnia worsened, and therefore she was intubated.


T 103.4, HR 132, RR 34, BP 85/56 oxygen saturation 100% on

the ventilator with a tidal volume of 400, respiratory rate 20,
FiO2 100% and a PEEP of 5.

Gen: White obese female on the ventilator, intubated and


HEENT: Pupils are equal, round, and reactive to light.

Conjunctivae pale. ET tube in place. Right IJ triple lumen
site clean.

CHEST: Very coarse breath sounds anterior and posterior

bilateral with occasional wheeze.

ABDOMEN: Obese, positive bowel sounds, soft, non-tender.

EXTREMITIES: Trace edema bilaterally and they are cool to

the touch.

What are the goals of sedation in this patient?

Goals of Sedation

Improving patient comfort

Blunting adverse autonomic and hemodynamic responses

Control of pain

Anxiolytics and amnesia

Facilitate nursing management

Facilitate mechanical ventilation

Avoid self-extubation and removal of invasive lines and

monitoring devices.

Reduce oxygen consumption

Case contd

She occasionally appears to be grimacing; she remains

tachycardia and her eyes are tearing.

What are some methods of evaluating pain in the

non-communicative adult patient?

Methods for assessing pain

Two of the most popular methods with well established validity and reliability
are the BPS and CPOT

The Behavior Pain Scale (BPS) is a scale based on a sum score of three items:

facial expression

movements of upper limbs

compliance with mechanical ventilation

Higher scores signify more pain.

Each pain indicator is scored from 1 (no response) to 4 (full response), with a
maximum score of 12.


Critical Care Pain Observational Tool is a similar tool

that scores on facial expression, body movement,
muscle tension, compliance with the ventilator OR
vocalizations in extubated patients.

Each of these behaviors is assigned a rating of 0 to 2.

Higher scores imply pain is under-treated.

What are some choices for analgesic agents in this



Opiates are the analgesics of choice in the ICU.

Morphine, Fentanyl and Dilaudid are the mainstays of this class.

Morphine is the recommended analgesic in critically ill

patients owing to its low cost, potency, euphoric effects and
analgesic efficacy.

SE: morphine is metabolized to active metabolites, including

morphine-6-glucuronide that accumulates in renal failure
potentially resulting in prolonged sedation and respiratory

Opiates contd

Fentanyl is the preferred analgesic for critically ill

patients with hemodynamic instability, for patients
with symptoms of histamine release with morphine
(e.g. hypotension, pruritus) or morphine allergy.

IV Fentanyl has a relatively short half-life (30 to 60


Due to its high lipophilicity, ongoing use leads to

accumulation in peripheral compartments increase
in half-life to 9 to 16 hrs.

Opiates contd

Hydromorphone (Dilaudid) can serve as an acceptable

alternative to morphine - more potent with less

All opioids produce a dose-dependent respiratory

depression; other common side effects include muscle
rigidity, hypotension, delayed GI transit, nausea,
pruritus, and urinary retention.

Analgesics to avoid in the ICU

Demerol and NSAIDS are not recommended in the

critically ill.

Demerol has an active metabolite, normeperidine

accumulates and produce central nervous system
excitation leading to seizures.

NSAIDs - potential risks of gastrointestinal bleeding,

renal insufficiency.

Case contd

An hour after intubation, she opens her eyes and

begins to buck and fight against the ventilator. She
unable to follow commands, lashes out trying to hit her
nurse and appears to be trying to self extubate.

What are some methods you could use to assess

her level of sedation and agitation?

Assessing agitation

There are several scales developed to assess the level of sedation of

the critically ill adult. These include the:

Richmond Agitation-Sedation Scale (RASS)

Ramsay Sedation Scale (RSS)

Sedation Agitation Scale (SAS)

Motor Activity Assessment Scale

Vancouver Interactive and Calmness Scale (VICS)

Adaptation to Intensive Care Environment (ATICE) instrument

Minnesota Sedation Assessment Tool (MSAT)

Ramsay Sedation Scale

Ramsay sedation scale



Anxious or restless or both

Cooperative, orientated and tranquil

Responding to commands

Brisk response to stimulus

Sluggish response to stimulus

No response to stimulus

+Richmond Agitation Sedation Scale (RASS) *

Score Term Description

+4 Combative Overtly combative, violent, immediate danger to staff

+3 Very agitated Pulls or removes tube(s) or catheter(s); aggressive

+2 Agitated Frequent non-purposeful movement, fights ventilator

+1 Restless Anxious but movements not aggressive vigorous

0 Alert and calm

-1 Drowsy Not fully alert, but has sustained awakening

(eye-opening/eye contact) to voice (>10 seconds)

-2 Light sedation Briefly awakens with eye contact to voice (<10 seconds)

-3 Moderate sedation Movement or eye opening to voice (but no eye contact)

-4 Deep sedation No response to voice, but movement or eye opening

to physical stimulation

-5 Unarousable No response to voice or physical stimulation

What are some choices for sedative agents in this



Propofol and benzodiazepines such as Midazolam (Versed) are the

mainstay for sedation in the ICU.

Propofol has the fastest onset and shortest duration. It should be

used for short term sedation (24-36 hours).

Boluses should be avoided as this increased the risk of hypotension.

Triglycerides should be monitored during infusion

SE: Dose related hypotension, hypertriglyceridemia and Propofol infusion

syndrome (PRIS), a rare clinical syndrome of rhabdomyolysis, metabolic
acidosis, renal failure, and cardiac failure after high doses of Propofol


Benzos as a class associated with increased delirium

and ICU stays

Versed (Midazolam) is the preferred agent for shortterm (< 48 h) sedation.

Fast onset and is good for acute agitation and anxiety.

However its active metabolite -hydroxymidazolam

accumulates in renal dysfunction and can lead to
delayed emergence.

SE: Increased risk of delirium esp in elderly


Ativan (Lorazepam) is the preferred agent for

prolonged sedation in critically ill adults.

Slower onset than Propofol or Versed but has a longer


SE: High-dose administration of Lorazepam can result in

accumulation of the vehicle, propylene glycol, resulting in
worsening renal function, metabolic acidosis, and altered
mental status.

What are some choices for neuromuscular

blockade agents in ICU patients?

When would you recommend the use of one?


Most common indications for long-term administration of Neuromuscular

Blockade agents (NMBA) include:

Facilitation of mechanical ventilation

Control of intracranial pressure

Decreasing oxygen consumption

Ablate muscular activity in patients with elevated ICP or seizures

Shivering, including therapeutic hypothermia

Treatment of muscle spasms related to drug overdose ortetanus

Status epilepticus

Preservation of delicate reconstructive surgery

Facilitation of diagnostic or therapeutic procedures eg ECMO

**All patients who are undergoing neuromuscular blockade must receive a

continuous infusion sedative medication.**

Non-depolarizing NMBA

Competitively blocking the binding of acetylcholine to its receptors.

Pancuronium - the most common agent used. However in patients with

cardiovascular disease, careful as pancuronium causes vagolysis
leading to tachycardia.

accumulates in renal failure leading to prolonged blockade.

Vecuronium and rocuronium are good alternatives known for their

hemodynamic stability with little change in heart rate or arterial
blood pressure.

Cisatricurium (Nimbex) and atracurium tends to be the agent of choice

because there is a lower incidence of nephrotoxicity and hepatotoxicity.

Rapid sequence intubation

Succinylcholine - act by depolarizing the plasmatic membrane

of the muscle.

Rapid onset of action and short duration (~3 mins).

SE: causes depolarization with muscle twitching, it may be

associated with hyperkalemia and arrythmias. It is contraindicated
in pts with renal failure, neuromuscular disease, paraplegia
and in those with muscular atrophy due to long-term ICU or hospital
length of stay

Rocuronium is an alternative to succinylcholine that can be

used in RSI. Like vecuronium, it has marked cardiovascular

rapid onset of action which makes it useful for patients in whom RSI
is needed but in whom succinylcholine is contraindicated

NMBA adverse effects

NMBA prolonged recovery with myopathy and acute

quadriplegic myopathy syndrome (AQMS)

AQMS clinical triad of

acute paresis

myonecrosis with increased creatine phosphokinase (CPK)

abnormal electromyography (EMG)

Do NMBA improve first attempt

successful intubations in the MICU?

One study to evaluate the effect of NMBA on first attempt

success (FAS) tracheal intubation of 709 MICU patients

Well matched except median total difficult airway characteristics

(DACs) were higher in the non-NMDA group (2 vs. 1, p<0.001)

More NMBA pts received etomidate (83% vs. 35%) and more
non-NMBA patients received ketamine (39% vs. 9%) (p<0.001).

First attempt success for NMBA group was 80.9% vs. 69.6% for
non-NMBA p=0.003.

In video laryngoscope subgroup, adjusted odds of first attempt

success with NMBA was 2.50 (1.43-4.37, p<0.001).

No differences in complications between groups

Neuromuscular Blockade Improves First Attempt Success for Intubation in the Intensive Care Unit: A
Propensity Matched Analysis Dr. Jarrod M Mosier, Annals of the American Thoracic Society


A French Multicenter, double blind, RCT (n=340) to identify if 48 hour therapy

with the cisatracurium early in ARDS reduces adjusted 90-day in-hospital
mortality rate

Primary outcome - proportion of patients who died either before hospital

discharge or within 90 days after study enrollment

Adjusted* Hazard ratio for death at 90 days in cisatracurium group vs.

placebo group 0.68, p=0.04.

Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and
33.3% (95% CI, 26.5 to 40.9) with placebo (P = 0.05).

Rate of ICU-acquired paresis did not differ significantly between the two

Conclude: In patients with severe ARDS, early, short (<48hrs) administration

of a NMBAs improves the adjusted 90-day survival and increased the time off
the ventilator without increasing muscle weakness.

Crit Care. 2011; 15(5): 311.

What about sedation
A randomized control trial of 128 patients by Kress et al:

In mechanical ventilated patients, daily interruption of

sedative-drug infusions decreased the duration of mechanical
ventilation by more than 2 days and the length of stay in the
intensive care unit by 3.5 days.

More opportunity to assess the patients neurological status

in the lightly sedated patient and detect early neurological

Reducing the duration of mechanical ventilation, lowering

cost both monetary costs and those related to
complications of mechanical ventilation, such as ventilatorassociated
JP, Pohlman AS, O'Connor
MF, et al. and
Daily Interruption
of Sedative Infusions in Critically Ill Patients Undergoing

Mechanical Ventilation. N Engl J Med 2000; 342:1471-1477


Care Pain Observational Tool & Behavour

pain scale are ways of assessing pain in nonverbal sedated patients


are first line for analgesia and sedation in

the ICU

a second agent is needed, then propofol or

benzos can be considered


can be used as an adjunct induction agent

when intubating and to facilitate mechanical
ventilation in some situations eg Severe ARDS.


of NMBA associated with acute quadriplegic

myopathy syndrome (AQMS)


vacation should be routinely practiced

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