Presentation on theme: "Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU"— Presentation transcript:
1Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU Giuditta Angelini, MDUniversity of WisconsinMadison, WIGil Fraser, PharmD, FCCMMaine Medical CenterPortland, MEDoug Coursin, MD, FCCM
2Objectives Participants should be able to: Describe the SCCM guidelines for sedation, analgesia, and chemical paralysisDescribe the benefits of daily awakening/lightening and sedation titration programsDevise a rational pharmacologic strategy based on treatment goals and comorbidities Participants should be able to:Devise a rational pharmacologic strategy based on treatment goals and comorbidities
3What We Know About ICU Agitation/Discomfort Prevalence50% incidence in those with length of stay > 24 hoursPrimary causes: unrelieved pain, delirium, anxiety, sleep deprivation, etc.Immediate sequelae:Patient-ventilator dyssynchronyIncreased oxygen consumptionSelf (and health care provider) injuryFamily anxietyLong-term sequelae: chronic anxiety disorders and post-traumatic stress disorder (PTSD)
4Recall in the ICUSome 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
5Appropriate Recall May be Important Factual memories (even unpleasant ones) help to put ICU experience into perspectiveDelusional memories risk panic attacks and PTSDThe optimal level of sedation for most patients is that which offers comfort while allowing for interaction with the environment.
6Need for SedationAnxietyPainAcute confusional statusMechanical ventilationTreatment or diagnostic proceduresPsychological response to stress
7Goals of Sedation in ICU Patient comfort andControl of painAnxiolysis and amnesiaBlunting adverse autonomic and hemodynamic responsesFacilitate nursing managementFacilitate mechanical ventilationAvoid self-extubationReduce oxygen consumptionThe specific individual goals of sedation are listed in this slide, taken from Dr Ramsay’s slide presentation on dexmedetomidine.com.
8Characteristics of an ideal sedation agents for the ICU Lack of respiratory depressionAnalgesia, especially for surgical patientsRapid onset, titratable, with a short elimination half-timeSedation with ease of orientation and arousabilityAnxiolyticHemodynamic stabilitySpeaker’s Notes:The characteristics of an ideal agent to be used for ICU sedation are listed. The lack of respiratory depression is particularly important because most of the available agents produce respiratory depression.
9The Challenges of ICU Sedation Assessment of sedationAltered pharmacologyToleranceDelayed emergenceWithdrawalDrug interaction
11Undersedation Sedatives Causes for Agitation Agitation & anxiety Pain and discomfortCatheter displacementInadequate ventilationHypertensionTachycardiaArrhythmiasMyocardial ischemiaWound disruptionPatient injury
12Oversedation Causes for Agitation Sedatives Prolonged sedation Delayed emergenceRespiratory depressionHypotensionBradycardiaIncreased protein breakdownMuscle atrophyVenous stasisPressure injuryLoss of patient-staff interactionIncreased cost
13Correctable Causes of Agitation Full bladderUncomfortable bed positionInadequate ventilator flow ratesMental illnessUremiaDrug side effectsDisorientationSleep deprivationNoiseInability to communicate
14Causes of Agitation Not to be Overlooked HypoxiaHypercarbiaHypoglycemiaEndotracheal tube malpositionPneumothoraxMyocardial ischemiaAbdominal painDrug and alcohol withdrawal
15Daily Goal is Arousable, Comfortable Sedation 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 needs50% reduction in tracheostomiesThree-fold reduction in the need for diagnostic evaluation of CNS
16Protocols and Assessment Tools 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 anotherPain assessment tools - none validated in ICU (numeric rating scale [NRS], visual analogue scale [VAS], etc.)
17Sedating/Analgesia Options Rule out reversible causes of discomfort/anxiety such as hypoxemia, hypercarbia, and toxic/drug side effect.Assess comorbidities and potential side effects of drugs chosen.Target irreversible etiologies of pain and agitation.
18Strategies for Patient Comfort Set treatment goalQuantitate sedation and painChoose the right medicationUse combined infusionReevaluate needTreat withdrawal
19Overview of SCCM Algorithm 1234Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:
22Hypertension Tachycardia Lacrimation Sweating Pupillary dilation Signs of PainHypertensionTachycardiaLacrimationSweatingPupillary dilation
23Principles of Pain Management Anticipate painRecognize painAsk the patientLook for signsFind the sourceQuantify painTreat:Quantify the patient’s perception of painCorrect the cause where possibleGive appropriate analgesics regularly as requiredRemember, most sedative agents do not provide analgesiaReassess
24Nonpharmacologic Interventions Proper position of the patientStabilization of fracturesElimination of irritating stimulationProper positioning of the ventilator tubing to avoid traction on endotracheal tube
26Opiates Benefits Risks Relieve pain or the sensibility to noxious stimuliSedation trending toward a change in sensorium, especially with more lipid soluble forms including morphine and hydromorphone.RisksRespiratory depressionNO amnesiaPruritusIleusUrinary retentionHistamine release causing venodilation predominantly from morphineMorphine 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.
33Sedation 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:Crit Care Med 1999;27:J Clin Psychopharmacol 1990;10:Crit Care Med 1999;27:
34The Ramsay Scale Scale Description 1 Anxious and agitated or restless, or both2Cooperative, oriented, and tranquil3Response to commands only4Brisk response to light glabellar tap or loud auditory stimulus5Sluggish response to light glabellar tap or loud auditory stimulus6No response to light glabellar tap or loud auditory stimulus
35The Riker Sedation-Agitation Scale ScoreDescriptionDefinition7Dangerous agitationPulling at endotracheal tube, trying to strike at staff, thrashing side to side6Very agitatedDoes not calm despite frequent verbal commands, biting ETT5AgitatedAnxious or mildly agitated, attempting to sit4Calm and cooperativeCalm, awakens easily, follows commands3SedatedDifficult to arouse, awakens to verbal stimuli, follows simple commands2Very sedatedArouse to physical stimuli, but does not communicate spontaneously1UnarousableMinimal or no response to noxious stimuli
36The Motor Activity Assessment Scale ScoreDescriptionDefinition6Dangerous agitationPulling at endotracheal tube, trying to strike at staff, thrashing side to side5AgitatedDoes not calm despite frequent verbal commands, biting ETT4Restless and cooperativeAnxious or mildly agitated, attempting to sit3Calm and cooperativeCalm, awakens easily, follows commands2Responsive to touch or nameOpens eyes or raises eyebrows or turns head when touched or name is loudly spoken1Responsive only to noxious stimuliOpens eyes or raises eyebrows or turns head with noxious stimuliUnresponsiveDoes not move with noxious stimuli
37What Sedation Scales Do Provide a semiquantitative “score”Standardize treatment endpointsAllow review of efficacy of sedationFacilitate sedation studiesHelp to avoid oversedation
38What Sedation Scales Don’t Do Assess anxietyAssess painAssess sedation in paralyzed patientsPredict outcomeAgree with each other
41BIS Range Guidelines BIS Awake 100 Responds to normal voice Axiolysis 80Responds to loud commandsor mild prodding/shakingModeratesedation60Low probability to explicit recallsUnresponsive to verbal stimuli40Burst suppressionDeep Sedation20Flat line EEG
43Choose the Right DrugBenzodiazepinesPropofol-2 agonists
44Sedation Options: Benzodiazepines (Midazolam and Lorazepam) Pharmacokinetics/dynamicsLorazepam: onset minutes, half-life 10 hours, glucuronidatedMidazolam: onset minutes, half-life 3 hours, metabolized by cytochrome P450, active metabolite (1-OH) accumulates in renal diseaseBenefitsAnxiolyticAmnesticSedatingRisksDeliriumNO analgesiaExcessive sedation: especially after long-term sustained usePropylene glycol toxicity (parenteral lorazepam): significance uncertain- Evaluate when a patient has unexplained acidosis- Particularly problematic in alcoholics (due to doses used) and renal failureRespiratory failure (especially with concurrent opiate use)Withdrawal
45Sedation Options: Propofol Pharmacology: GABA agonistPharmacokinetics/dynamics: onset minutes, terminal half-life 6 hours, duration 10 minutes, hepatic metabolismBenefitsRapid onset and offset and easily titratedHypnotic and antiemeticCan be used for intractable seizures and elevated intracranial pressureRisksNot reliably amnestic, especially at low dosesNO analgesia!HypotensionHypertriglyceridemia; lipid source (1.1 kcal/ml)Respiratory depressionPropofol 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
46Sample Sedation Protocol Sedation-agitation ScaleRiker RR et al. Crit Care Med. 1999;27:1325.
47Sedation Options: Dexmedetomidine Alpha-2-adrenergic agonist like clonidine but with much less imidazole activityHas been shown to decrease the need for other sedation in postoperative ICU patientsPotentially useful while decreasing other sedatives to prevent withdrawalBenefitsDoes not cause respiratory depressionShort-actingProduces sympatholysis which may be advantageous in certain patients such as postop cardiac surgeryRisksNo amnesiaSmall number of patients reported distress upon recollection of ICU period despite good sedation scores due to excessive awarenessBradycardia and hypotension can be excessive, necessitating drug cessation and other intervention
51Problems with Current Sedative Agents MidazolamPropofolOpioidsProlonged weaningX-Respiratory depressionSevere hypotensionToleranceHyperlipidemiaIncreased infectionConstipationLack of orientation and cooperation
61Opiate and Benzodiazepine Withdrawal Frequency related to dose and duration32% if receiving high doses for longer than a weekOnset depends on the half-lives of the parent drug and its active metabolitesClinical signs and symptoms are common among agentsCNS activation: seizures, hallucinations,GI disturbances: nausea, vomiting, diarrheaSympathetic hyperactivity: tachycardia, hypertension, tachypnea, sweating, feverNo prospectively evaluated weaning protocols available% daily decrease in dose% initial decrease in dose with additional daily reductions of %Consider conversion to longer acting agent or transdermal delivery form
62Significance of ICU Delirium Seen in > 50% of ICU patientsThree times higher risk of death by six monthsFive fewer ventilator free days (days alive and off vent.), adjusted P = 0.03Four times greater frequency of medical device removalNine times higher incidence of cognitive impairment at hospital discharge
63Acute onset of mental status changes or a fluctuating course DeliriumAcute onset of mental status changes or a fluctuating course&2. Inattention3. DisorganizedThinkingor4. Altered level ofconsciousnessCourtesy of W Ely, MD
64Risk Factors for Delirium Primary CNS DxInfectionMetabolic derangementPainSleep deprivationAgeSubstances including tobacco (withdrawal as well as direct effect)
65Diagnostic Tools: ICU Routine monitoring recommended by SCCM Only 6% of ICUs use Confusion Assessment Method (CAM-ICU) or Delirium Screening Checklist (DSC)Requires Patient ParticipationCognitive Test for DeliriumAbbreviated Cognitive Test for DeliriumCAM-ICUEly. JAMA. 2001;286:
66Delirium Screening Checklist No Patient ParticipationDelirium Screening ChecklistBergeron. Intensive Care Med. 2001;27:859.
67Treatment of DeliriumCorrect inciting factor, but as for pain…relief need not be delayed while identifying causative factorControl symptoms?No evidence that treatment reduces duration and severity of symptomsTypical and atypical antipsychotic agentsSedatives?Particularly in combination with antipsychotic and for drug/alcohol withdrawal deliriumNo treatment FDA approved
68HaloperidolNo prospective randomized controlled trials in ICU delirium> 700 published reports involving > 2,000 patientsThe good:Hemodynamic neutralityNo effect on respiratory driveThe bad:QTc prolongation and torsades de pointesNeuoroleptic malignant syndrome - only three cases with IV haloperidolExtrapyramidal side effects - less common with IV than oral haloperidol
69Mechanism of action unknown Less movement disorders than haloperidol Atypical Antipsychotics: Quetiapine, Olanzapine, Risperidone, ZiprasidoneMechanism of action unknownLess movement disorders than haloperidolEnhanced effects on both positive (agitation) and negative (quiet) symptomsEfficacy = haloperidol?One prospective randomized study showing equal efficacy of olanzapine to haldol with less EPSIssuesLack of available IV formulationTroublesome reports of CVAs, hyperglycemia, NMSTitratability hampered- QTc prolongation with ziprasidone IM- Hypotension with olanzapine IM
70Neuromuscular Blockade (NMB) (Paralytics) in the Adult ICU Used most often acutely (single dose) to facilitate intubation or selected proceduresIssuesNO ANALGESIC or SEDATIVE propertiesConcurrent sedation with amnestic effect is paramount analgesic as neededNever use without the ability to establish and/or maintain a definitive airway with ventilationIf administering for prolonged period (> hours), use an objective monitor to assess degree of paralysis.
71Neuromuscular Blockade in the ICU Current use in ICU limited because of risk of prolonged weakness and other complicationsMaximize sedative/analgesic infusions as much as possible prior to adding neuromuscular blockadeIndicationsFacilitate mechanical ventilation, especially with abdominal compartment syndrome, high airway pressures, and dyssynchronyAssist in control of elevated intracranial pressuresReduce oxygen consumptionPrevent muscle spasm in neuroleptic malignant syndrome, tetanus, etc.Protect surgical wounds or medical device placement
72Neuromuscular 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 awayNondepolarizers- Blocks acetylcholine from postsynaptic receptor competitively- BenzylisoquinoliniumsCurare, atracurium, cisatracurium, mivacurium, doxacuronium- AminosteroidsPancuronium, vecuronium, rococuronium
73Quick Onset Muscle Relaxants for Intubation Patients with aspiration risk need rapid onset paralysis for intubation.Not usually used for continuous maintenance infusionsRocuroniumNondepolarizer with about an hour duration and 10% renal eliminationDose is 1.2 mg/kg to have intubating conditions in 45 secondsSuccinylcholineDepolarizer with a usual duration of 10 minutesAll or none train of four after administration due to desensitization (can be prolonged in patients with abnormal plasma cholinesterase)Dose is mg/kg to have intubating conditions in 30 seconds
74Potential Contraindications of Succinylcholine Increases serum potassium by 0.5 to 1 meq/liter in all patientsCan cause bradycardia, anaphylaxis, and muscle painPotentially increases intragastric, intraocular, and intracranial pressureSeverely elevates potassium due to proliferation of extrajunctional receptors in patients with denervation injury, stroke, trauma, or burns of more than 24 hours
76Neuromuscular Blocking Agents Infusion dosesPancuronium mg/kg/hVecuronium mg/kg/hCisatracurium mg/kg/hOther distinguishing featuresPancuronium causes tachycardiaVecuronium has neutral effects on hemodynamics but has several renally excreted active metabolitesElimination of cisatracurium is not affected by organ dysfunction, but it is expensive
77Monitoring NMBAsGoal - To prevent prolonged weakness associated with excessive NMBA administrationMethods:Perform NMBA dose reduction or cessation once daily if possibleClinical evaluation: Assess skeletal muscle movement and respiratory effortPeripheral 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.
78Monitoring 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 patientsNo 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.
79Complications of Neuromuscular Blocking Agents Associated with inactivity:Muscle wasting, deconditioning, decubitus ulcers, corneal dryingAssociated with inability to assess patient:Recall, unrelieved pain, acute neurologic event, anxietyAssociated with loss of respiratory function:Asphyxiation from ventilator malfunction or accidental extubation, atelectasis, pneumoniaOther: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.
81References Jacobi J, et al. Crit Care Med. 2002;30:119-141. Jones, et al. Crit Care Med. 2001;29:Cammarano, et al. Crit Care Med. 1998;26:676.Ely, et al. JAMA. 2004;292:168.
82Case Scenario #122-year-old male with isolated closed head injury who was intubated for GCS of 7He 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?
83Case 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 examCan treat seizures and elevated ICP which may be present in a head trauma with GCS of eight or lessMinimizing dose and duration will avoid side effects.
84Case Scenario #254-year-old alcoholic who has been admitted for Staph sepsisIntubated in the ICU for seven days and is currently on midazolam at 10 mg/hourHis 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?
85Case Scenario #2 - Answer 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.
86Case Scenario #362-year-old, 65-kg woman with ARDS from aspiration pneumoniaHer 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?
87Case Scenario #3 - Answer 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.
88Withdrawal from preoperative drugs Sudden cessation of sedation Return of underlying agitationHyperadrenergic syndromeHypertension, tachycardia,sweatingOpioid withdrawalSalivation, yawning, diarrhea
89Barr, Donner. Crit Care Clin. 1995;11827 Reassess NeedUse sedation score as endpointInitiate sedation incrementally to desired levelPeriodically (q day) titrate infusion rate down until the patient begins to emergeGradually increase infusion rate again to desired level of sedationBarr, Donner. Crit Care Clin. 1995;11827