Sedation, Analgesia, and Sedation, Analgesia, and Neuromuscular Blockade in Neuromuscular Blockade in

the Adult ICU the Adult ICU

Division of Critical Care Division of Critical Care MedicineMedicine

University of AlbertaUniversity of Alberta

ObjectivesObjectives

SCCM guidelines for sedation, analgesia, and chemical paralysisSCCM guidelines for sedation, analgesia, and chemical paralysis

Benefits of daily awakening/lightening and sedation titration Benefits of daily awakening/lightening and sedation titration programsprograms

Devise a rational pharmacologic strategy based on treatment Devise a rational pharmacologic strategy based on treatment goals and comorbiditiesgoals and comorbidities

Agitation/Discomfort : The ProblemAgitation/Discomfort : The Problem

PrevalencePrevalence• 50% incidence in those with length of stay > 24 hours50% incidence in those with length of stay > 24 hours

Causes: uncontrolled pain, delirium, anxiety, Causes: uncontrolled pain, delirium, anxiety, sleep deprivation, etc.sleep deprivation, etc.

Immediate Sequelae: Immediate Sequelae: • Patient-ventilator dys-synchrony > respiratory failurePatient-ventilator dys-synchrony > respiratory failure• Increased oxygen consumption Increased oxygen consumption • Self (and health care provider) injurySelf (and health care provider) injury• Family anxietyFamily anxiety

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

Recall in the ICURecall in the ICU

Some degree of recall occurs in up to 70% of ICU Some degree of recall occurs in up to 70% of ICU patients.patients.

• Anxiety, fear, pain, panic, agony, or nightmares reported in Anxiety, fear, pain, panic, agony, or nightmares reported in 90% of those who did have recall.90% of those who did have recall.

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

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

Associated with PTSD in cardiac surgeryAssociated with PTSD in cardiac surgery

Appropriate Recall May be ImportantAppropriate Recall May be Important

Factual memories (even unpleasant ones) help to put Factual memories (even unpleasant ones) help to put ICU experience into perspective ICU experience into perspective

Delusional memories risk panic attacks and PTSDDelusional memories risk panic attacks and PTSD

The optimal level of sedation for most patients is that The optimal level of sedation for most patients is that which offers comfort while allowing for interaction with which offers comfort while allowing for interaction with the environment. This the environment. This IS NOT THE SAME AS COMAIS NOT THE SAME AS COMA..

Daily Goal is Arousable, Daily Goal is Arousable, Comfortable SedationComfortable Sedation

Sedation needs to be titrated to goal:Sedation needs to be titrated to goal:• Lighten sedation to appropriate wakefulness dailyLighten sedation to appropriate wakefulness daily

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

mechanical ventilation needsmechanical ventilation needs• 50% reduction in tracheostomies50% reduction in tracheostomies• Three-fold reduction in the need for diagnostic evaluation of CNSThree-fold reduction in the need for diagnostic evaluation of CNS

Protocols and Assessment ToolsProtocols and Assessment Tools

Titration of sedatives and analgesics guided by Titration of sedatives and analgesics guided by assessment tools:assessment tools:

• Ramsay Sedation Scale [RSS], Sedation-Agitation Scale [SAS], Ramsay Sedation Scale [RSS], Sedation-Agitation Scale [SAS], Richmond Sedation-agitation Scale [RSAS], etc.Richmond Sedation-agitation Scale [RSAS], etc.

-- No evidence that one is preferred over anotherNo evidence that one is preferred over another• Pain assessment tools - none validated in ICU (numeric rating Pain assessment tools - none validated in ICU (numeric rating

scale [NRS], visual analogue scale [VAS], etc.)scale [NRS], visual analogue scale [VAS], etc.)

Sedating/Analgesia OptionsSedating/Analgesia Options

Rule out reversible causes of discomfort/anxiety such Rule out reversible causes of discomfort/anxiety such as hypoxemia, hypercarbia, and toxic/drug side effect.as hypoxemia, hypercarbia, and toxic/drug side effect.

Assess comorbidities and potential side effects of Assess comorbidities and potential side effects of drugs chosen.drugs chosen.

Target irreversible etiologies of pain and agitationTarget irreversible etiologies of pain and agitation

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.

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

BenefitsBenefits• Relieve pain or the sensibility to noxious stimuliRelieve pain or the sensibility to noxious stimuli• Sedation trending toward a change in sensorium, especially with Sedation trending toward a change in sensorium, especially with

more lipid soluble forms including morphine and hydromorphone.more lipid soluble forms including morphine and hydromorphone.

RisksRisks• Respiratory depressionRespiratory depression• NO amnesiaNO amnesia• PruritusPruritus• IleusIleus• Urinary retentionUrinary retention• Histamine release causing venodilation predominantly from morphineHistamine release causing venodilation predominantly from morphine• Morphine metabolites which accumulate in renal failure can be Morphine metabolites which accumulate in renal failure can be

analgesic and anti-analgesic.analgesic and anti-analgesic.• Meperidine should be avoided due to neurotoxic metabolites which Meperidine should be avoided due to neurotoxic metabolites which

accumulate, especially in renal failure, but also produces more accumulate, especially in renal failure, but also produces more sensorium changes and less analgesia than other opioids.sensorium changes and less analgesia than other opioids.

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

FentanylFentanyl HydromorphonHydromorphonee

MorphineMorphine

Rapid onsetRapid onset XX

Rapid offsetRapid offset X*X*

Avoid in renal Avoid in renal diseasedisease

X**X**

Preload reductionPreload reduction XX

Avoid in Avoid in hemodynamic hemodynamic instabilityinstability

XX

Equivalent dosesEquivalent doses 100 mcg100 mcg 1.5 mg1.5 mg 10 mg10 mg* Offset prolonged after long-term use

** Active metabolite accumulation causes excessive narcosis

Sample Analgesia ProtocolSample Analgesia Protocol

Numeric Rating Scale

Address SedationAddress Sedation

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?

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

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

cytochrome P450, active metabolite (1-OH) accumulates in renal diseasecytochrome P450, active metabolite (1-OH) accumulates in renal disease

BenefitsBenefits• AnxiolyticAnxiolytic• AmnesticAmnestic• SedatingSedating

RisksRisks• DeliriumDelirium• NO analgesiaNO analgesia• Excessive sedation: especially after long-term sustained useExcessive sedation: especially after long-term sustained use• Propylene glycol toxicity (parenteral lorazepam): significance uncertain Propylene glycol toxicity (parenteral lorazepam): significance uncertain

-- Evaluate when a patient has unexplained acidosisEvaluate when a patient has unexplained acidosis

-- Particularly problematic in alcoholics (due to doses used) and renal failureParticularly problematic in alcoholics (due to doses used) and renal failure• Respiratory failure (especially with concurrent opiate use)Respiratory failure (especially with concurrent opiate use)• WithdrawalWithdrawal

Sedation Options: PropofolSedation Options: PropofolPharmacology: GABA agonistPharmacology: GABA agonist

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

BenefitsBenefits• Rapid onset and offset and easily titratedRapid onset and offset and easily titrated• Hypnotic and antiemeticHypnotic and antiemetic• Can be used for intractable seizures and elevated intracranial pressureCan be used for intractable seizures and elevated intracranial pressure

RisksRisks• Not reliably amnestic, especially at low dosesNot reliably amnestic, especially at low doses• NO analgesia!NO analgesia!• HypotensionHypotension• Hypertriglyceridemia; lipid source (1.1 kcal/ml)Hypertriglyceridemia; lipid source (1.1 kcal/ml)• Respiratory depressionRespiratory depression• Propofol Infusion SyndromePropofol Infusion Syndrome

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

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

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

Sample Sedation ProtocolSample Sedation Protocol

Sedation-agitation Scale

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

Opiate and Benzodiazepine Opiate and Benzodiazepine WithdrawalWithdrawal

Frequency related to dose and durationFrequency related to dose and duration• 32% if receiving high doses for longer than a week32% if receiving high doses for longer than a week

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

Clinical signs and symptoms are common among agentsClinical signs and symptoms are common among agents• CNS activation: seizures, hallucinations, CNS activation: seizures, hallucinations, • GI disturbances: nausea, vomiting, diarrheaGI disturbances: nausea, vomiting, diarrhea• Sympathetic hyperactivity: tachycardia, hypertension, tachypnea, Sympathetic hyperactivity: tachycardia, hypertension, tachypnea,

sweating, feversweating, fever

No prospectively evaluated weaning protocols availableNo prospectively evaluated weaning protocols available• 10 - 20% daily decrease in dose10 - 20% daily decrease in dose• 20 - 40% initial decrease in dose with additional daily reductions of 20 - 40% initial decrease in dose with additional daily reductions of

10 - 20%10 - 20%

Consider conversion to longer acting agent or Consider conversion to longer acting agent or transdermal delivery formtransdermal delivery form

Significance of ICU DeliriumSignificance of ICU Delirium

Seen in > 50% of ICU patients Seen in > 50% of ICU patients

Three times higher risk of death by six monthsThree times higher risk of death by six months

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

Four times greater frequency of medical device removalFour times greater frequency of medical device removal

Nine times higher incidence of cognitive impairment at Nine times higher incidence of cognitive impairment at hospital dischargehospital 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 DxPrimary CNS Dx

InfectionInfection

Metabolic derangementMetabolic derangement

PainPain

Sleep deprivationSleep deprivation

AgeAge

Substances including tobacco (withdrawal as well Substances including tobacco (withdrawal as well as direct effect)as direct effect)

Diagnostic Tools: ICUDiagnostic Tools: ICU

Routine monitoring Routine monitoring recommended by recommended by SCCMSCCM

• Only 6% of ICUs use Only 6% of ICUs use Confusion Assessment Confusion Assessment Method (CAM-ICU) or Method (CAM-ICU) or Delirium Screening Delirium Screening Checklist (DSC)Checklist (DSC)

Requires Patient Requires Patient ParticipationParticipation

• Cognitive Test for Cognitive Test for DeliriumDelirium

• Abbreviated Cognitive Abbreviated Cognitive Test for DeliriumTest for Delirium

• CAM-ICUCAM-ICU

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

Delirium Screening ChecklistDelirium Screening Checklist

No Patient ParticipationNo Patient Participation• Delirium Screening ChecklistDelirium Screening Checklist

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

Treatment of DeliriumTreatment of Delirium

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

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

severity of symptomsseverity of symptoms• Typical and atypical antipsychotic agentsTypical and atypical antipsychotic agents• Sedatives?Sedatives?

- Particularly in combination with antipsychotic and for drug/alcohol Particularly in combination with antipsychotic and for drug/alcohol withdrawal deliriumwithdrawal delirium

HaloperidolHaloperidol

No prospective randomized controlled trials in ICU No prospective randomized controlled trials in ICU delirium delirium

> 700 published reports involving > 2,000 > 700 published reports involving > 2,000 patientspatients

The good:The good:• Hemodynamic neutralityHemodynamic neutrality• No effect on respiratory driveNo effect on respiratory drive

The bad:The bad:• QTc prolongation and QTc prolongation and torsades de pointestorsades de pointes• Neuoroleptic malignant syndromeNeuoroleptic malignant syndrome - only three cases with - only three cases with

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

haloperidolhaloperidol

Atypical Antipsychotics: Quetiapine, Atypical Antipsychotics: Quetiapine, Olanzapine, Risperidone, Olanzapine, Risperidone,

ZiprasidoneZiprasidoneMechanism of action unknownMechanism of action unknown

Less movement disorders than haloperidolLess movement disorders than haloperidol

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

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

olanzapine to haldol with less EPSolanzapine to haldol with less EPS

IssuesIssues• Lack of available IV formulationLack of available IV formulation• Troublesome reports of CVAs, hyperglycemia, NMSTroublesome reports of CVAs, hyperglycemia, NMS• Titratability hamperedTitratability hampered

-- QTc prolongation with ziprasidone IMQTc prolongation with ziprasidone IM

-- Hypotension with olanzapine IMHypotension with olanzapine IM

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

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

IssuesIssues• NO ANALGESICNO ANALGESIC or or SEDATIVESEDATIVE properties properties• Concurrent sedation with amnestic effect is paramount Concurrent sedation with amnestic effect is paramount

(analgesic as needed)(analgesic as needed)• Never use without the ability to establish and/or maintain a Never use without the ability to establish and/or maintain a

definitive airway with ventilationdefinitive airway with ventilation• If administering for prolonged period (> 6 - 12 hours), use an If administering for prolonged period (> 6 - 12 hours), use an

objective monitor to assess degree of paralysis.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 Current use in ICU limited because of risk of prolonged weakness and other complicationsprolonged weakness and other complications

• Maximize sedative/analgesic infusions as much as possible Maximize sedative/analgesic infusions as much as possible prior to adding neuromuscular blockadeprior to adding neuromuscular blockade

IndicationsIndications• Facilitate mechanical ventilation, especially with abdominal Facilitate mechanical ventilation, especially with abdominal

compartment syndrome, high airway pressures, and compartment syndrome, high airway pressures, and dyssynchronydyssynchrony

• Assist in control of elevated intracranial pressuresAssist in control of elevated intracranial pressures• Reduce oxygen consumptionReduce oxygen consumption• Prevent muscle spasm in neuroleptic malignant syndrome, Prevent muscle spasm in neuroleptic malignant syndrome,

tetanus, etc.tetanus, etc.• Protect surgical wounds or medical device placementProtect surgical wounds or medical device placement

Neuromuscular Blocking AgentsNeuromuscular Blocking Agents

Two classes of NMBS:Two classes of NMBS:• DepolarizersDepolarizers

-- Succhinylcholine is the only drug in this classSucchinylcholine is the only drug in this class

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

• NondepolarizersNondepolarizers-- Blocks acetylcholine from postsynaptic receptor competitively Blocks acetylcholine from postsynaptic receptor competitively

-- BenzylisoquinoliniumsBenzylisoquinoliniums• Curare, atracurium, cisatracurium, mivacurium, doxacuroniumCurare, atracurium, cisatracurium, mivacurium, doxacuronium

-- AminosteroidsAminosteroids• Pancuronium, vecuronium, rococuroniumPancuronium, vecuronium, rococuronium

Quick Onset Muscle Relaxants for Quick Onset Muscle Relaxants for IntubationIntubation

Patients with aspiration risk need rapid onset Patients with aspiration risk need rapid onset paralysis for intubation.paralysis for intubation.

Not usually used for continuous maintenance Not usually used for continuous maintenance infusionsinfusions

RocuroniumRocuronium• Nondepolarizer with about an hour duration and 10% renal Nondepolarizer with about an hour duration and 10% renal

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

SuccinylcholineSuccinylcholine• Depolarizer with a usual duration of 10 minutes Depolarizer with a usual duration of 10 minutes • All or none train of four after administration due to desensitization All or none train of four after administration due to desensitization

(can be prolonged in patients with abnormal plasma cholinesterase)(can be prolonged in patients with abnormal plasma cholinesterase)• Dose is 1 - 2 mg/kg to have intubating conditions in 30 secondsDose is 1 - 2 mg/kg to have intubating conditions in 30 seconds

Potential Contraindications of Potential Contraindications of SuccinylcholineSuccinylcholine

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

Can cause bradycardia, anaphylaxis, and muscle painCan cause bradycardia, anaphylaxis, and muscle pain

Potentially increases intragastric, intraocular, and Potentially increases intragastric, intraocular, and intracranial pressureintracranial pressure

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

Neuromuscular Blocking AgentsNeuromuscular Blocking Agents

Nondepolarizing muscle relaxantsNondepolarizing muscle relaxants• Pancuronium, vecuronium, rocuronium, cisatracurium Pancuronium, vecuronium, rocuronium, cisatracurium • All rapid onset (2 - 3 minutes)All rapid onset (2 - 3 minutes)• Differ in duration (pancuronium 1 - 2 hours, rocuronium 0.5 Differ in duration (pancuronium 1 - 2 hours, rocuronium 0.5

hours, cisatracurium 0.5 hours)hours, cisatracurium 0.5 hours)• Differ in route of elimination (pancuronium = renal/liver, Differ in route of elimination (pancuronium = renal/liver,

vecuronium = renal/bile, cisatracurium = Hoffman vecuronium = renal/bile, cisatracurium = Hoffman degradation)degradation)

Neuromuscular Blocking AgentsNeuromuscular Blocking Agents

Infusion dosesInfusion doses• Pancuronium 0.05 - 0.1 mg/kg/hPancuronium 0.05 - 0.1 mg/kg/h• Rocuronium 0.05 - 0.1 mg/kg/hRocuronium 0.05 - 0.1 mg/kg/h• Cisatracurium 0.03 - 0.6 mg/kg/hCisatracurium 0.03 - 0.6 mg/kg/h

Other distinguishing featuresOther distinguishing features• Pancuronium causes tachycardiaPancuronium causes tachycardia• Rocuronium is neutral Rocuronium is neutral • Elimination of cisatracurium is not affected by organ Elimination of cisatracurium is not affected by organ

dysfunction, but it is expensivedysfunction, but it is expensive

Monitoring NMBAsMonitoring NMBAs

Goal - To prevent prolonged weakness associated Goal - To prevent prolonged weakness associated with excessive NMBA administrationwith excessive NMBA administration

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

possiblepossible• Clinical evaluation: Assess skeletal muscle movement and Clinical evaluation: Assess skeletal muscle movement and

respiratory effortrespiratory effort• Peripheral nerve stimulation Peripheral nerve stimulation

-- Train of four response consists of four stimulae of 2 Hz, 0.2 msec in Train of four response consists of four stimulae of 2 Hz, 0.2 msec in duration, and 500 msec apart.duration, and 500 msec apart.

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

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

Monitoring Sedation During Monitoring Sedation During ParalysisParalysis

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

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

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

No randomized controlled studies to support reliable use in No randomized controlled studies to support reliable use in ICU.ICU.

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

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

Complications of Neuromuscular Complications of Neuromuscular Blocking AgentsBlocking Agents

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

dryingdrying

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

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

extubation, atelectasis, pneumoniaextubation, atelectasis, pneumonia

Other:Other:• Prolonged paralysis or acute NMBA related myopathyProlonged paralysis or acute NMBA related myopathy

-- Related to decreased membrane excitability or even muscle Related to decreased membrane excitability or even muscle necrosisnecrosis

-- Risk can be compounded by concurrent use of steroids.Risk can be compounded by concurrent use of steroids.

Sample NMBA ProtocolSample NMBA Protocol

ReferencesReferences

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

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

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

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

Case Scenario #1Case Scenario #1

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

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

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

What sedative would you use and why?What sedative would you use and why?

What are the particular advantages in this situation?What are the particular advantages in this situation?

How could you avoid the disadvantages of this drug?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 Propofol will rapidly calm a patient who is displaying dangerous behavior without need for paralysis.dangerous behavior without need for paralysis.

Titratable and can be weaned quickly to allow for Titratable and can be weaned quickly to allow for neurologic examneurologic exam

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

Minimizing dose and duration will avoid side effects.Minimizing dose and duration will avoid side effects.

Case Scenario #2Case Scenario #2

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

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

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

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

Is this appropriate sedation?Is this appropriate sedation?

What would you like to do?What would you like to do?

How would you institute your plan of action?How would you institute your plan of action?

Case Scenario #2 - AnswerCase Scenario #2 - Answer

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

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

Rescue sedatives including midazolam should be Rescue sedatives including midazolam should be available if agitation develops.available if agitation develops.

Flumazenil should be avoided.Flumazenil should be avoided.

Case Scenario #3Case Scenario #3

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

Her ventilator settings are PRVC 400, RR 18, PEEP 8, and Her ventilator settings are PRVC 400, RR 18, PEEP 8, and FIOFIO22 100%. She is dyssynchronous with the ventilator and 100%. She is dyssynchronous with the ventilator and her plateau pressure is 37 mm Hg.her plateau pressure is 37 mm Hg.

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

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

What do you want to do next?What do you want to do next?

Do you want to continue the propofol?Do you want to continue the propofol?

Why or why not?Why or why not?

What two iatrogenic problems is she likely at risk for?What two iatrogenic problems is she likely at risk for?

Case Scenario #3 - AnswerCase Scenario #3 - Answer

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

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

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