sedation, analgesia, and neuromuscular blockade in the adult icu

Sedation, Analgesia, and Neuromuscular Blockade in the Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU Adult ICU

Giuditta Angelini, MDGiuditta Angelini, MDUniversity of Wisconsin

Madison, WI

Gil Fraser, PharmD, FCCMGil Fraser, PharmD, FCCMMaine Medical Center

Portland, ME

Doug Coursin, MD, FCCMDoug Coursin, MD, FCCMUniversity of Wisconsin

Madison, WI

What We Know About ICU Agitation/DiscomfortWhat We Know About ICU Agitation/Discomfort

Prevalence• 50% incidence in those with length of stay > 24 hours

Primary causes: unrelieved pain, delirium, anxiety, sleep deprivation, etc.

Immediate sequelae: • Patient-ventilator dyssynchrony

• Increased oxygen consumption

• Self (and health care provider) injury

• Family anxiety

Long-term sequelae: chronic anxiety disorders and post-traumatic stress disorder (PTSD)

Recall in the ICURecall in the ICU

Some degree of recall occurs in up to 70% of ICU patients.• Anxiety, fear, pain, panic, agony, or nightmares reported in 90% of

those who did have recall.

Potentially cruel:• Up to 36% recalled some aspect of paralysis.

Associated with PTSD in ARDS? • 41% risk of recall of two or more traumatic experiences.

Associated with PTSD in cardiac surgery

Need for Sedation

• Anxiety• Pain• Acute confusional status• Mechanical ventilation• Treatment or diagnostic procedures• Psychological response to stress

Goals of Sedation in ICU

• Patient comfort and • Control of pain• Anxiolysis and amnesia• Blunting adverse autonomic and hemodynamic

responses• Facilitate nursing management• Facilitate mechanical ventilation• Avoid self-extubation• Reduce oxygen consumption

• Lack of respiratory depression• Analgesia, especially for surgical patients• Rapid onset, titratable, with a short elimination

half-time• Sedation with ease of orientation and

arousability• Anxiolytic• Hemodynamic stability

Characteristics of an ideal sedation agents for the ICU

The Challenges of ICU Sedation

• Assessment of sedation• Altered pharmacology• Tolerance• Delayed emergence• Withdrawal• Drug interaction

Sedation

SedativesCauses for Agitation

Undersedation

Sedatives

Causes for AgitationAgitation & anxietyPain and discomfortCatheter displacementInadequate ventilationHypertensionTachycardiaArrhythmiasMyocardial ischemiaWound disruptionPatient injury

Oversedation

Sedatives

Causes for Agitation

Prolonged sedationDelayed emergenceRespiratory depressionHypotensionBradycardiaIncreased protein breakdownMuscle atrophyVenous stasisPressure injuryLoss of patient-staff interactionIncreased cost

• Full bladder• Uncomfortable bed position• Inadequate ventilator flow rates• Mental illness• Uremia• Drug side effects• Disorientation• Sleep deprivation• Noise• Inability to communicate

Correctable Causes of Agitation

Causes of Agitation Not to be Overlooked

• Hypoxia• Hypercarbia• Hypoglycemia• Endotracheal tube malposition• Pneumothorax• Myocardial ischemia• Abdominal pain• Drug and alcohol withdrawal

Sedation needs to be protocolized and titrated to goal:• Lighten sedation to appropriate wakefulness daily.

Effect of this strategy on outcomes:• One- to seven-day reduction in length of sedation and mechanical

ventilation needs

• 50% reduction in tracheostomies

• Three-fold reduction in the need for diagnostic evaluation of CNS

Daily Goal is Arousable, Comfortable SedationDaily Goal is Arousable, Comfortable Sedation

SCCM practice guidelines can be used as a template for institution-specific protocols.

Titration of sedatives and analgesics guided by assessment tools:• Validated sedation assessment tools (Ramsay Sedation Scale [RSS],

Sedation-Agitation Scale [SAS], Richmond Sedation-agitation Scale [RSAS], etc.)

- No evidence that one is preferred over another

• Pain assessment tools - none validated in ICU (numeric rating scale [NRS], visual analogue scale [VAS], etc.)

Protocols and Assessment ToolsProtocols and Assessment Tools

Strategies for Patient Comfort

• Set treatment goal

• Quantitate sedation and pain

• Choose the right medication

• Use combined infusion

• Reevaluate need

• Treat withdrawal

Overview of SCCM AlgorithmOverview of SCCM Algorithm

Yes

Reassess goal daily,Titrate and taper therapy to maintain goal,Consider daily wake-up,Taper if > 1 week high-dose therapy & monitorfor withdrawal

No

Set Goalfor

Analgesia

Hemodynamically UnstableFentanyl 25 - 100 mcg IVP Q 5-15 min, orHydromorphone 0.25 - 0.75 mg IVP Q 5 - 15 min

Hemodynamically stableMorphine 2 - 5 mg IVP Q 5 - 15 min

Repeat until pain controlled, then scheduled doses + prn

Set Goalfor

Sedation

Acute Agitation #

Midazolam 2 - 5 mg IVP Q 5 - 15 min untilacute event controlled

Ongoing Sedation #

Lorazepam 1 - 4 mg IVP Q 10-20 min untilat goal then Q 2 - 6 hr scheduled + prn , orPropofol start 5 mcg/kg/min, titrate Q 5 minuntil at goal

Set Goalfor Controlof Delirium

Haloperidol 2 - 10 mg IVP Q 20 - 30 min,then 25% of loading dose Q 6hr x 2-3 days,then taper

IVP Dosesmore often than Q

2hr?

Consider continuousinfusion opiate or

sedative

> 3 Days Propofol?(except neuro pt.)

Convert toLorazepam

Yes

Benzodiazepine or Opioid:Taper Infusion Rate by

10-25% Per Day

Yes

Dosesapproximate for

70kg adult

Rule out and Correct Reversible Causes

Use Non-pharmacologic Treament,Optimize the Environment

ALGORITHM FOR SEDATION AND ANALGESIA OF MECHANICALLY VENTILATED PATIENTS

Use Pain Scale * toAssess for Pain

Use Sedation Scale **

to Assess forAgitation/Anxiety

Use Delirium Scale *** toAssess for Delirium

Is the Patient Comfortable & at Goal?

Lorazepam viainfusion?

Use a low rate and IVPloading doses

1

2

3

4

Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:119-141.

Pain

Assess Pain Separately

Visual Pain Scales

0 1 2 3 4 5 6 7 8 9 10

No pain Worst possible pain

Signs of Pain

• Hypertension

• Tachycardia

• Lacrimation

• Sweating

• Pupillary dilation

Principles of Pain Management

• Anticipate pain• Recognize pain

– Ask the patient– Look for signs– Find the source

• Quantify pain • Treat:

– Quantify the patient’s perception of pain– Correct the cause where possible– Give appropriate analgesics regularly as required

• Remember, most sedative agents do not provide analgesia• Reassess

Nonpharmacologic Interventions

• Proper position of the patient

• Stabilization of fractures

• Elimination of irritating stimulation

• Proper positioning of the ventilator tubing to avoid traction on endotracheal tube

Address PainAddress Pain

Set G oalfor

Analgesia

Hem odynam ically UnstableFentanyl 25 - 100 m cg IVP Q 5-15 m in, orHydromorphone 0.25 - 0.75 m g IVP Q 5 - 15 m in

Hem odynam ically stableMorphine 2 - 5 m g IVP Q 5 - 15 m in

Repeat until pain controlled, then scheduled doses + prn

Use Pain Scale * toAssess for Pain

Reassess goal daily,T itrate and taper therapy to m aintain goal,Consider daily wake-up,Taper if > 1 week high-dose therapy & m onitorfor withdrawal

Is the Patient Com fortable & at Goal?

OpiatesOpiates

Benefits• Relieve pain or the sensibility to noxious stimuli

• Sedation trending toward a change in sensorium, especially with more lipid soluble forms including morphine and hydromorphone.

Risks• Respiratory depression

• NO amnesia

• Pruritus

• Ileus

• Urinary retention

• Histamine release causing venodilation predominantly from morphine

• Morphine metabolites which accumulate in renal failure can be analgesic and anti-analgesic.

• Meperidine should be avoided due to neurotoxic metabolites which accumulate, especially in renal failure, but also produces more sensorium changes and less analgesia than other opioids.

Agent Dose (iv)

Half-life Metabolic pathway

Active metabolites

Fentanyl 200 g 1.5-6 hr Oxidation None

Hydromorphone 1.5 mg 2-3 hr Glucuronidation None

Morphine 10 mg 3-7 hr Glucuronidation Yes (Sedation in RF)

Meperidine 75-100 mg

3-4 hr Demethylation & hydroxylation

Yes (neuroexcitation in RF)

Codeine 120 mg 3 hr Demethylation & Glucuronidation

Yes ( analgesia, sedation)

Remifentanil 3-10 min Plasma esterase

None

Keterolac 2.4-8.6 hr

Renal None

Pharmacology of Selected Analgesics

Opioids

Lipid Solubility

Histamine Release

Potency

Morphine +/- +++ 1

Hydromorphone + + 5

Fentanyl +++ - 50

Opioids

Onset Peaks Duration

Morphine 2 min 20 min 2-7 hr

Fentanyl 30 sec 5-15 min 30-60 min

Opiate Analgesic Options: Fentanyl, Morphine, HydromorphoneOpiate Analgesic Options: Fentanyl, Morphine, Hydromorphone

Fentanyl Hydromorphone Morphine

Rapid onset X

Rapid offset X*

Avoid in renal disease X**

Preload reduction X

Avoid in hemodynamic instability

X

Equivalent doses 100 mcg 1.5 mg 10 mg

* Offset prolonged after long-term use

** Active metabolite accumulation causes excessive narcosis

Sample Analgesia ProtocolSample Analgesia Protocol

Numeric Rating Scale

Sedation Scoring Scales

• Ramsay Sedation Scale (RSS)• Sedation-agitation Scale (SAS)• Observers Assessment of Alertness/Sedation Scale

(OAASS)• Motor Activity Assessment Scale (MAAS)

BMJ 1974;2:656-659Crit Care Med 1999;27:1325-1329J Clin Psychopharmacol 1990;10:244-251Crit Care Med 1999;27:1271-1275

Scale Description

1 Anxious and agitated or restless, or both

2 Cooperative, oriented, and tranquil

3 Response to commands only

4 Brisk response to light glabellar tap or loud auditory stimulus

5 Sluggish response to light glabellar tap or loud auditory stimulus

6 No response to light glabellar tap or loud auditory stimulus

The Ramsay Scale

Score Description Definition

7 Dangerous agitation

Pulling at endotracheal tube, trying to strike at staff, thrashing side to side

6 Very agitated Does not calm despite frequent verbal commands, biting ETT

5 Agitated Anxious or mildly agitated, attempting to sit

4 Calm and cooperative

Calm, awakens easily, follows commands

3 Sedated Difficult to arouse, awakens to verbal stimuli, follows simple commands

2 Very sedated Arouse to physical stimuli, but does not communicate spontaneously

1 Unarousable Minimal or no response to noxious stimuli

The Riker Sedation-Agitation Scale

The Motor Activity Assessment Scale

Score Description Definition

6 Dangerous agitation

Pulling at endotracheal tube, trying to strike at staff, thrashing side to side

5 Agitated Does not calm despite frequent verbal commands, biting ETT

4 Restless and cooperative

Anxious or mildly agitated, attempting to sit

3 Calm and cooperative

Calm, awakens easily, follows commands

2 Responsive to touch or name

Opens eyes or raises eyebrows or turns head when touched or name is loudly spoken

1 Responsive only to noxious stimuli

Opens eyes or raises eyebrows or turns head with noxious stimuli

0 Unresponsive Does not move with noxious stimuli

What Sedation Scales Do

• Provide a semiquantitative “score”• Standardize treatment endpoints• Allow review of efficacy of sedation• Facilitate sedation studies• Help to avoid oversedation

What Sedation Scales Don’t Do

• Assess anxiety

• Assess pain

• Assess sedation in paralyzed patients

• Predict outcome

• Agree with each other

BIS Monitoring

BIS Range Guidelines

Awake

Responds to loud commands or mild prodding/shaking

Low probability to explicit recallsUnresponsive to verbal stimuli

Burst suppression

Flat line EEG

Responds to normal voice Axiolysis

Moderatesedation

Deep Sedation

100

80

60

40

20

0

BIS

Set G oalfor

Sedation

Acute Agitation #

Midazolam 2 - 5 m g IVP Q 5 - 15 m in untilacute event controlled

Ongoing Sedation #

Lorazepam 1 - 4 m g IVP Q 10-20 m in untilat goal then Q 2 - 6 hr scheduled + prn, orPropofol start 5 m cg/kg/m in, titrate Q 5 m inuntil at goal

IVP Dosesm ore often than Q

2hr?

Consider continuousinfusion opiate or

sedative

> 3 Days Propofol?(except neuro pt.)

Convert toLorazepam

Benzodiazepine or Opioid:Taper Infusion Rate by

10-25% Per Day

Use Sedation Scale **

to Assess forAgitation/Anxiety

Lorazepam viainfusion?

Use a low rate and IVPloading doses

Yes

Reassess goal daily,T itrate and taper therapy to m aintain goal,Consider daily wake-up,Taper if > 1 week high-dose therapy & m onitorfor withdrawal

Is the Patient Com fortable & at Goal?

Address SedationAddress Sedation

Choose the Right Drug

• Benzodiazepines

• Propofol-2 agonists

Pharmacokinetics/dynamics• Lorazepam: onset 5 - 10 minutes, half-life 10 hours, glucuronidated• Midazolam: onset 1 - 2 minutes, half-life 3 hours, metabolized by cytochrome P450,

active metabolite (1-OH) accumulates in renal disease

Benefits• Anxiolytic• Amnestic• Sedating

Risks• Delirium• NO analgesia• Excessive sedation: especially after long-term sustained use• Propylene glycol toxicity (parenteral lorazepam): significance uncertain

- Evaluate when a patient has unexplained acidosis

- Particularly problematic in alcoholics (due to doses used) and renal failure

• Respiratory failure (especially with concurrent opiate use)

• Withdrawal

Sedation Options: Benzodiazepines (Midazolam and Lorazepam)Sedation Options: Benzodiazepines (Midazolam and Lorazepam)

Pharmacology: GABA agonist

Pharmacokinetics/dynamics: onset 1 - 2 minutes, terminal half-life 6 hours, duration 10 minutes, hepatic metabolism

Benefits• Rapid onset and offset and easily titrated• Hypnotic and antiemetic• Can be used for intractable seizures and elevated intracranial pressure

Risks• Not reliably amnestic, especially at low doses• NO analgesia!• Hypotension• Hypertriglyceridemia; lipid source (1.1 kcal/ml)• Respiratory depression• Propofol Infusion Syndrome

- Cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure

- Caution should be exercised at doses > 80 mcg/kg/min for more than 48 hours

- Particularly problematic when used simultaneously in patient receiving catecholamines and/or steroids

Sedation Options: PropofolSedation Options: Propofol

Sedation-agitation Scale

Riker RR et al. Crit Care Med. 1999;27:1325.

Sample Sedation ProtocolSample Sedation Protocol

Sedation Options: DexmedetomidineSedation Options: Dexmedetomidine

Alpha-2-adrenergic agonist like clonidine but with much less imidazole activity

Has been shown to decrease the need for other sedation in postoperative ICU patients

Potentially useful while decreasing other sedatives to prevent withdrawal

Benefits• Does not cause respiratory depression• Short-acting• Produces sympatholysis which may be advantageous in certain patients such as

postop cardiac surgery

Risks• No amnesia• Small number of patients reported distress upon recollection of ICU period despite

good sedation scores due to excessive awareness• Bradycardia and hypotension can be excessive, necessitating drug cessation and

other intervention

Benzodiazepines


Diazepam 2-5 min 5-30 min >20 hr

Midazolam 2-3 min 5-10 min 30-120 min

Lorazepam 5-20 min 30 min 10-20 hr

Propofol


Propofol 30-60 sec

2-5 min short

Propofol Dosing

• 3-5 g/kg/min antiemetic

• 5-20 g/kg/min anxiolytic

• 20-50 g/kg/min sedative hypnotic

• >100 g/kg/min anesthetic

Midazolam Propofol Opioids

Prolonged weaning X - X

Respiratory depression X - X

Severe hypotension X X -

Tolerance X - X

Hyperlipidemia - X -

Increased infection - X -

Constipation - - X

Lack of orientation and cooperation

X X X

Problems with Current Sedative Agents

Use Continuous and Combined Infusion

Plasma Level

Load

Maintenance

Repeated Bolus

Plasma levels

Choose the Right Drug

Sedation Analgesia

Amnesia AnxiolysisHypnosis

Propofol

Patient ComfortBenzodiazepines

-2 agonists

Opioids

Altered PharmacologyMidazolam and Age

00.5

11.5

22.5

33.5

44.5

5

10 20 30 40 50 60 70 80

Age (y)

T 1/

2 ho

urs

Harper et al. Br J Anesth, 1985;57:866-871

Delayed Emergence

• Overdose (prolonged infusion)– pK derived from healthy patients– Drug interaction– Individual variation

• Delayed elimination– Liver (Cp450)– Kidney dysfunction– Active metabolites

Opiate and Benzodiazepine WithdrawalOpiate and Benzodiazepine Withdrawal

Frequency related to dose and duration• 32% if receiving high doses for longer than a week

Onset depends on the half-lives of the parent drug and its active metabolites

Clinical signs and symptoms are common among agents• CNS activation: seizures, hallucinations,

• GI disturbances: nausea, vomiting, diarrhea

• Sympathetic hyperactivity: tachycardia, hypertension, tachypnea, sweating, fever

No prospectively evaluated weaning protocols available• 10 - 20% daily decrease in dose

• 20 - 40% initial decrease in dose with additional daily reductions of 10 - 20%

Consider conversion to longer acting agent or transdermal delivery form

Significance of ICU DeliriumSignificance of ICU Delirium

Seen in > 50% of ICU patients

Three times higher risk of death by six months

Five fewer ventilator free days (days alive and off vent.), adjusted P = 0.03

Four times greater frequency of medical device removal

Nine times higher incidence of cognitive impairment at hospital discharge

DeliriumDelirium

1. Acute onset of mental status changes or a fluctuating course

&2. Inattention

&

or

Courtesy of W Ely, MD

3. Disorganized Thinking

4. Altered level of consciousness

Risk Factors for DeliriumRisk Factors for Delirium

Primary CNS Dx

Infection

Metabolic derangement

Pain

Sleep deprivation

Age

Substances including tobacco (withdrawal as well as direct effect)

Diagnostic Tools: ICUDiagnostic Tools: ICU

Routine monitoring recommended by SCCM• Only 6% of ICUs use

Confusion Assessment Method (CAM-ICU) or Delirium Screening Checklist (DSC)

Requires Patient Participation• Cognitive Test for Delirium• Abbreviated Cognitive Test

for Delirium• CAM-ICU

Ely. JAMA. 2001;286: 2703-2710.

Delirium Screening ChecklistDelirium Screening Checklist

No Patient Participation• Delirium Screening Checklist

Bergeron. Intensive Care Med. 2001;27:859.

Treatment of DeliriumTreatment of Delirium

Correct inciting factor, but as for pain…relief need not be delayed while identifying causative factor

Control symptoms?• No evidence that treatment reduces duration and severity of

symptoms

• Typical and atypical antipsychotic agents

• Sedatives?- Particularly in combination with antipsychotic and for drug/alcohol withdrawal

delirium

No treatment FDA approved

HaloperidolHaloperidol

No prospective randomized controlled trials in ICU delirium

> 700 published reports involving > 2,000 patients

The good:• Hemodynamic neutrality

• No effect on respiratory drive

The bad:• QTc prolongation and torsades de pointes

• Neuoroleptic malignant syndrome - only three cases with IV haloperidol

• Extrapyramidal side effects - less common with IV than oral haloperidol

Atypical Antipsychotics: Quetiapine, Olanzapine, Risperidone, ZiprasidoneAtypical Antipsychotics: Quetiapine, Olanzapine, Risperidone, Ziprasidone

Mechanism of action unknown

Less movement disorders than haloperidol

Enhanced effects on both positive (agitation) and negative (quiet) symptoms

Efficacy = haloperidol?• One prospective randomized study showing equal efficacy of olanzapine

to haldol with less EPS

Issues• Lack of available IV formulation

• Troublesome reports of CVAs, hyperglycemia, NMS

• Titratability hampered- QTc prolongation with ziprasidone IM

- Hypotension with olanzapine IM

Neuromuscular Blockade (NMB) (Paralytics) in the Adult ICUNeuromuscular Blockade (NMB) (Paralytics) in the Adult ICU

Used most often acutely (single dose) to facilitate intubation or selected procedures

Issues• NO ANALGESIC or SEDATIVE properties

• Concurrent sedation with amnestic effect is paramount analgesic as needed

• Never use without the ability to establish and/or maintain a definitive airway with ventilation

• If administering for prolonged period (> 6 - 12 hours), use an objective monitor to assess degree of paralysis.

Neuromuscular Blockade in the ICUNeuromuscular Blockade in the ICU

Current use in ICU limited because of risk of prolonged weakness and other complications• Maximize sedative/analgesic infusions as much as possible prior to

adding neuromuscular blockade

Indications• Facilitate mechanical ventilation, especially with abdominal

compartment syndrome, high airway pressures, and dyssynchrony

• Assist in control of elevated intracranial pressures

• Reduce oxygen consumption

• Prevent muscle spasm in neuroleptic malignant syndrome, tetanus, etc.

• Protect surgical wounds or medical device placement

Neuromuscular Blocking AgentsNeuromuscular Blocking Agents

Two classes of NMBS:• Depolarizers

- Succhinylcholine is the only drug in this class

- Prolonged binding to acetylcholine receptor to produce depolarization (fasciculations) and subsequent desensitization so that the motor endplate cannot respond to further stimulation right away

• Nondepolarizers- Blocks acetylcholine from postsynaptic receptor competitively

- Benzylisoquinoliniums• Curare, atracurium, cisatracurium, mivacurium, doxacuronium

- Aminosteroids• Pancuronium, vecuronium, rococuronium

Quick Onset Muscle Relaxants for IntubationQuick Onset Muscle Relaxants for Intubation

Patients with aspiration risk need rapid onset paralysis for intubation.

Not usually used for continuous maintenance infusions

Rocuronium• Nondepolarizer with about an hour duration and 10% renal elimination

• Dose is 1.2 mg/kg to have intubating conditions in 45 seconds

Succinylcholine• Depolarizer with a usual duration of 10 minutes

• All or none train of four after administration due to desensitization (can be prolonged in patients with abnormal plasma cholinesterase)

• Dose is 1 - 2 mg/kg to have intubating conditions in 30 seconds

Potential Contraindications of SuccinylcholinePotential Contraindications of Succinylcholine

Increases serum potassium by 0.5 to 1 meq/liter in all patients

Can cause bradycardia, anaphylaxis, and muscle pain

Potentially increases intragastric, intraocular, and intracranial pressure

Severely elevates potassium due to proliferation of extrajunctional receptors in patients with denervation injury, stroke, trauma, or burns of more than 24 hours


Nondepolarizing muscle relaxants• Pancuronium, vecuronium, cisatracurium

• All rapid onset (2 - 3 minutes)

• Differ in duration (pancuronium 1 - 2 hours, vecuronium 0.5 hours, cisatracurium 0.5 hours)

• Differ in route of elimination (pancuronium = renal/liver, vecuronium = renal/bile, cisatracurium = Hoffman degradation)


Infusion doses• Pancuronium 0.05 - 0.1 mg/kg/h

• Vecuronium 0.05 - 0.1 mg/kg/h

• Cisatracurium 0.03 - 0.6 mg/kg/h

Other distinguishing features• Pancuronium causes tachycardia

• Vecuronium has neutral effects on hemodynamics but has several renally excreted active metabolites

• Elimination of cisatracurium is not affected by organ dysfunction, but it is expensive

Monitoring NMBAsMonitoring NMBAs

Goal - To prevent prolonged weakness associated with excessive NMBA administration

Methods:• Perform NMBA dose reduction or cessation once daily if possible

• Clinical evaluation: Assess skeletal muscle movement and respiratory effort

• Peripheral nerve stimulation - Train of four response consists of four stimulae of 2 Hz, 0.2 msec in

duration, and 500 msec apart.

- Comparison of T4 (4th twitch) and T1 with a fade in strength means that 75% of receptors are blocked.

- Only T1 or T1 and 2 is used for goal in ICU and indicates up to 90% of receptors are blocked.

Monitoring Sedation During ParalysisMonitoring Sedation During Paralysis

Bispectral index is based on cumulative observation of a large number of clinical cases correlating clinical signs with EEG signals.

While used to titrate appropriate sedation (and amnesia) in anesthetized patients to the least amount required, not proven to achieve this goal.

Increased potential for baseline neurologic deficit and EEG interference in ICU patients

No randomized controlled studies to support reliable use in ICU.

Other neuromonitoring (awareness) modalities are likely to be developed.

Cessation of NMB as soon as safe in conjunction with other patient parameters should be a daily consideration.

Complications of Neuromuscular Blocking AgentsComplications of Neuromuscular Blocking Agents

Associated with inactivity:• Muscle wasting, deconditioning, decubitus ulcers, corneal drying

Associated with inability to assess patient:• Recall, unrelieved pain, acute neurologic event, anxiety

Associated with loss of respiratory function:• Asphyxiation from ventilator malfunction or accidental extubation,

atelectasis, pneumonia

Other:• Prolonged paralysis or acute NMBA related myopathy

- Related to decreased membrane excitability or even muscle necrosis

- Risk can be compounded by concurrent use of steroids.

Sample NMBA ProtocolSample NMBA Protocol

ReferencesReferences

Jacobi J, et al. Crit Care Med. 2002;30:119-141.

Jones, et al. Crit Care Med. 2001;29:573-580.

Cammarano, et al. Crit Care Med. 1998;26:676.

Ely, et al. JAMA. 2004;292:168.

Case Scenario #1Case Scenario #1

22-year-old male with isolated closed head injury who was intubated for GCS of 7

He received 5 mg of morphine, 40 mg of etomidate, and 100 mg of succinylcholine for his intubation.

He is covered in blood spurting from an arterial catheter that was just removed, and he appears to be reaching for his endotracheal tube.

What sedative would you use and why?

What are the particular advantages in this situation?

How could you avoid the disadvantages of this drug?

Case Scenario #1 - AnswerCase Scenario #1 - Answer

Propofol will rapidly calm a patient who is displaying dangerous behavior without need for paralysis.

Titratable and can be weaned quickly to allow for neurologic exam

Can treat seizures and elevated ICP which may be present in a head trauma with GCS of eight or less

Minimizing dose and duration will avoid side effects.


54-year-old alcoholic who has been admitted for Staph sepsis

Intubated in the ICU for seven days and is currently on midazolam at 10 mg/hour

His nurse was told in report that he was a “madman” on the evening shift.

Currently, he opens his eyes occasionally to voice but does not follow commands nor does he move his extremities to deep painful stimulation.

Is this appropriate sedation?

What would you like to do?

How would you institute your plan of action?


This patient is oversedated. Not only can a neurologic exam not be performed, but it would be unlikely to be able to perform a wakeup test within one 24-hour period.

Given the need to examine the patient, midazolam should be stopped immediately.

Rescue sedatives including midazolam should be available if agitation develops.

Flumazenil should be avoided.


62-year-old, 65-kg woman with ARDS from aspiration pneumonia

Her ventilator settings are PRVC 400, RR 18, PEEP 8, and FIO2 100%. She is dyssynchronous with the ventilator and her plateau pressure is 37 mm Hg.

She is on propofol at 50 mcg/kg/min, which has been ongoing since admit four days ago.

She is also on norepinephrine 0.1 mcg/kg/min and she was just started on steroids.

What do you want to do next?

Do you want to continue the propofol?

Why or why not?

What two iatrogenic problems is she likely at risk for?


This patient needs optimization of her sedatives, and potentially chemical paralysis to avoid complications of ventilator dyssynchrony and high airway pressures.

If you continue to use propofol, higher doses are required and the patient is already on norepinephrine. In addition, if paralysis is used, you do not have reliable amnesia.

She is at risk for propofol infusion syndrome and critical illness polyneuropathy.

Withdrawal

• Withdrawal from preoperative drugs

• Sudden cessation of sedation– Return of underlying agitation

• Hyperadrenergic syndrome– Hypertension, tachycardia,sweating

• Opioid withdrawal– Salivation, yawning, diarrhea

sedation, analgesia, and neuromuscular blockade in the adult icu

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