Presentation on theme: "Sedation and analgesia in ICU"— Presentation transcript:
1Sedation and analgesia in ICU Dr. B. UmaUniversity College of Medical Sciences & GTB Hospital, Delhi
2Sedation Sedation comes from the Latin word sedare. Sedare = to calm or to allay fearConscious sedation: A minimally depressed level of consciousness induced by the administration of pharmacologic agents in which a patient retains the ability to independently and continuously maintain an open airway and a regular breathing pattern, and to respond appropriately and rationally to physical stimulation and verbal commands
3Why is sedation necessary? To improve patient comfortFacilitate interventionsTo allay fear, anxiety and agitationAdequate sleepAvoid painFacilitation of mechanical ventilation/airway management/ weaningProtection against myocardial ischemiaAmnesia during neuromuscular blockade
4Goals for sedation and analgesia To minimize physical discomfort or pain during proceduresTo minimize psychological disturbanceTo maximize the potential for amnesiaTo guard patient safetyTo control behavior
5Complications from pain and anxiety Stimulation of the autonomic nervous system and release of humoral factors → increased heart rate, blood pressure, and myocardial oxygen consumption → myocardial ischemia or infarctionAltered humoral response can lead to hypercoagulability as a result of increased level of factor VIII, fibrinogen, platelet activity, and inhibition of fibrinolysis
6Complications (contd.) Stress hormones also produce insulin resistance, increased metabolic rate, and protein catabolismImmunosuppression with reduction in number and function of lymphocytes and granulocytesPsychological disturbances - memories of vivid nightmares, hallucinations, and paranoid delusions
7Assessment of pain and anxiety Any scoring system should be simple, easily performed, noninvasive, and reproducible. Six levels of sedation are used: 1. Anxious and agitated 2. Cooperative, orientated, and tranquil 3. Responds to verbal commands only 4. Asleep but brisk response to loud auditory stimulus/light glabellar tap 5. Asleep but sluggish response to loud auditory stimulus/light glabellar tap 6. Asleep, no response
8Commonly used sedation tools Glasgow coma scale (GCS) – assessment of level of consciousness6 point Ramsay scale – most commonly used sedation scaleSedation Agitation Scale (SAS)Motor Activity Assessment scale (MAAS)Richmond Agitation–Sedation Scale
11Richmond agitation sedation scale ScoreTermDescription+4CombativeViolent; immediate danger to staff+3Very agitatedPulls/ removes tubes, catheters; aggressive+2AgitatedFrequent non purposeful movement; patient ventilator asynchrony+1RestlessAnxious or apprehensiveAlert and calm-1DrowsyNot fully alert but awakens for >10s, with eye contact, to voice-2Light sedationBriefly awakens (<10s), with eye contact, to voice-3Moderate sedationAny movement to voice but no eye contact-4Deep sedationNo response to voice but movement to physical stimulation-5UnarousableNo response to voice or physical stimulation
12Ramsay sedation scaleAwake 1 Anxious and/or agitated 2 Cooperative, oriented, and tranquil 3 Responds to commands Asleep 4 Quiescent with brisk response to light glabellar tap or loud auditory stimulus 5 Sluggish response to light glabellar tap or loud auditory stimulus 6 No response
13Sedation agitation scale 1: Unarousable2: Very sedated3: Sedated4: Calm and cooperative5: Agitated6: Very agitated7: Dangerous agitation
14Bispectral indexA practical, processed EEG parameter that measures the direct effects of sedatives on the brainProvides objective information about a patient’s response to sedationNumerical scale correlates to sedation endpointsOptimizes sedation assessment and titration
17Objective sedation assessment Value of BIS in ICUObjective sedation assessmentMinimizeconsequencesof over- andunder-sedationOptimize clinicaland economicoutcomesImprove quality of sedation management
18Recommendation for Assessment of Sedation The use of a validated sedation assessment scale (SAS, MAAS, or Vancouver Interaction and Calmness Scale [VICS]) is recommended. (Grade of recommendation = B)The SCCM guidelines state: Objective measures of sedation, such as Bispectral Index, have not been completely evaluated and are not yet proven useful in the ICU. (Grade of recommendation = C)
19Sedation therapy NON PHARMACOLOGICAL THERAPY: Good communication with regular reassurance from nursing staffEnvironmental control such as humidity, lighting, temperature, and noiseExplanation prior to proceduresManagement of thirst, hunger, constipation, and full bladderVariety for the patient e.g. radio
20Pharmacologic therapy The sedative agent should possess the following qualities:Both sedative and analgesic propertiesMinimal cardiovascular side effectsControllable respiratory side effectsRapid onset/offset of actionNo accumulation in renal/hepatic dysfunctionInactive metabolitesInexpensiveNo interactions with other ICU drugs
22BenzodiazepinesAnxiolytic, anticonvulsant, amnesic, hypnotic and provide some muscle relaxationEffects are mediated by depressing the excitability of the limbic system via reversible binding at GABA-benzodiazepine receptor complexMinimal cardiorespiratory depressant effectThe common drugs in this class are diazepam, midazolam, and lorazepam
23Benzodiazepines: Midazolam Water-solubleShort elimination half life (1-4 hrs)No long acting metabolitesIn ICU patients, midazolam's elimination half-life may be greatly prolonged and clinically important accumulation may occurMinimal dose: 1 to 2 mg bolus0.5 to 10 mg/hr
24Benzodiazepines: Diazepam Elimination half-life of 21 to 37 hoursMajor active metabolite, desmethyldiazepam, has a half-life of 48 to 96 hoursIn terms of cost, diazepam has a clear advantage, being one-tenth the price of midazolam.Minimal dose: 5 to 10mg bolusInfusions not recommended
25Benzodiazepines : Lorazepam Lower lipid-solubility than midazolamLess hypotesnionMetabolised by liver to inactive metabolitesLower costLoading dose: mg/kgInfusion dose: mg/kg/hr
27Flumazenil Benzodiazepine antagonist Given in incremental doses of 0.2 to 0.5 mg upto 3 mgOnset – 2 minDuration- 30 to 60 min
28Propofol The mode of action of propofol is via the GABA receptor Rapid onset of action; metabolized rapidly hepatically and extrahepaticallyRecovery within 10 minutes of discontinuation, can accumulate with prolonged useIdeally infused via a large or central veinProlonged infusions –increase triglyceride and cholesterol levelsA theoretical maximum recommended dose is 4 mg/kg/hour.
29Propofol (contd.) Bolus dose – not recommended to 100μg/kg/hrTheoretical maximum dose- 4mg/kg/hrCautious about propofol infusion syndrome
30Propofol: adverse effects HypotensionReliable, dose-relatedDecreased SVR and contractility (CO)Respiratory depressionApnea with bolus dosingSynergistic CV and respiratory depression with opioidsVehicle (soybean emulsion):HypertriglyceridemiaVenoirritationInfection
31Propofol infusion syndrome Propofol infusion syndrome is an adverse drug event associated with high doses (>4 mg/kg per hour or >67 µg/kg per minute) and long-term (>48 hours) use of propofol.Clinical features:- Cardiomyopathy with acute cardiac failure.- Myopathy.- Metabolic acidosis, K+- Hepatomegaly.Inhibition of FFA entry into mitochondria failure of its metabolism.
32ManagementSupportive treatments addressing the clinical manifestationsThe propofol infusion should be discontinued immediatelyAlternative sedative should be startedIntravenous crystalloid and colloid replacement and vasopressor and/or inotropic supportCardiac pacing may be used for symptomatic bradycardiaHemodialysis or continuous renal replacement therapy to treat the acute renal failure
33Ketamine Ketamine acts at the N-methyl-D-aspartate (NMDA) receptor In subanesthetic doses, sedative and analgesicGenerally not used because of the increase in blood pressure, intracranial pressure (ICP), and pulse rateBronchodilatory properties, sometimes has a role in severe asthmaIn the ICU conjunction with a narcoticDose : 5 to 30 μg/kg/min
34OthersETOMIDATE :For maintenance of hypnosis, target concentration of 300 to 500 ng/mL may be achieved by administration of a two- or three-stage infusionBARBITURATES: Barbiturates such as Pentothal have been used in the ICU, especially in the management of patients with head injuries and seizure disorders. They cause significant cardiovascular depression and accumulate during infusions, leading to prolonged recovery times.
35Others (contd.) BUTYROPHENONES AND PHENOTHIAZINES An aggressive dosing regimen of haloperidol may be useful in a patient with delirium to promote calm, 2 to 10 mg IV every 10 to 15 minutes until the desired response is achievedVOLATILE AGENTSIsoflurane has been used in concentrations of up to 0.6% for longterm sedation, with minimal cardiorespiratory side effects and rapid awakening.Desflurane has been shown to be effective in sedation, with rapid offset of effects.
382 Agonists Dexmedetomidine Clonidine Selectivity: 2:1 1620:1 Imidazole derivate 31:1t1/2 2 hrs94% protein boundEliminated by liver/kidneySedativeOnly available in IV formClonidineSelectivity: 2:1 250:1Imidazole derivate 16:1t1/2 10 hrsAntihypertensive
39Dexmedetomidine Pharmacology of dexmedetomidine alpha 2 agonist Molecular targets + neural substrateslocus ceruleusnatural sleep pathwaysClinical paradigms for use of dextomed in anesthesiasedation + analgesia w/o respiratory depressionattenuation of tachycardiasmooth emergence + weaning from mechanical ventilation
40Pharmacokinetics Rapid redistribution: 6 min Elimination half-life: 2 hVd steady state: 118 LClearance: 39 L/hProtein binding: 94%Metabolism: biotransformation in liver to inactive metabolites + excreted in urineNo accumulation after infusions hPharmacokinetics similar in young adults + elderly
41Sedation Typical doses (target plasma levels 0.3-1.2 ng/ml): 0.5 ug/kg load, 0.5 ug/kg/hr infusion1.0 ug/kg load, 0.7 ug/kg/hr infusionIncrease dose by bolus/infusionLoad only - short proceduresPatients with high sympathetic activity may need very high doses
42ClonidineClonidine is synergistic with opioids and acts at the spinal cord to inhibit nociceptive inputs, thus imparting analgesiaIt is contraindicated in hypovolemia and can cause hypotension, bradycardia, and dry mouth
43The Art of Sedation Under sedation: Fighting the ventilator. V/Q mismatch.Accidental extubation.Catheter displacement.CV stress ischemia.Anxiety, awareness.Post-traumatic stress disorder.Over sedation:Tolerance, tachyphylaxis.Withdrawal syndrome.Delirium.Prolonged ventilation.CV depression. neuro testing.Sleep disturbance.
45Analgesia in ICUPain is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. Thus, perception of sensory events is a requirement, but actual tissue damage is not. Although a majority of ICU patients receive parenteral analgesics routinely , 50% of patients discharged from the ICU remember pain as their worst experience while in the ICU. This emphasizes the need for effective pain control in the ICU.
46Indices of pain severity applicable in the critically ill SubjectiveVisual analogue scaleNumeric rating scaleVerbal descriptor scaleObjectiveVital signs measurementsBehavioural responses
47І─────────────────І Verbal rating scale None mild moderate severe Visual analog scaleІ─────────────────ІNo painWorst pain
48Recommendation for assessment of pain Use of the numeric rating scale(NRS) is recommended to assess pain. (Grade of recommendation = B)Patients who cannot communicate should be assessed through subjective observation of pain and physiological indicators and the change in these parameters following analgesic therapy. (Grade of recommendation =B)
49Analgesics used in ICUPain in the critically ill is best treated with a pure opioid agonistIn a recent clinical guideline, the recommended choices have been narrowed to morphine, fentanyl, and hydromorphone.Other drugs with analgesic properties and variable use in critically ill patients are :meperidine (pethidine)tramadolnonsteroidal anti-inflammatory drugs (NSAIDs)mixed opioid agonist-antagonist agentsketamine, a sedative drug with analgesic qualitiesα2 agonists.
50Opioids :Morphine Plasma levels do not correlate with clinical effect. Low lipid solubility causes slow equilibration across BBB.Metabolized in the liver by conjugation. Morphine-6-glucuronide active metabolite with sedative action.The analgesic dose is highly variable, and may be delivered as an intermittent boluses or as a continuous infusion.Minimal cardiovascular side effectsRelatively contraindicated in asthma and renal failure
51Morphine CNS effects mediated via μ1 and μ2 receptors Analgesia: pain componentsAffective- greater effectSensoryEuphoriaSedationMood changeMental cloudiness
52FentanylFentanyl : synthetic opioid derived from meperidine (pethidine)Short-acting opioid with rapid onsetAfter prolonged infusion the duration of action approaches that of morphineDoes not accumulate in renal failureIt does not cause histamine release and is suitable for analgesia in the hemodynamically unstable patient
53Alfentanyl Alfentanil is a synthetic opioid Onset of action about five times faster than fentanyl, due to the small volume of distributionLess lipid solubleThe duration of action is about one-third that of fentanylAlfentanil has minimal cardiovascular effects
54RemifentanilRemifentanil, an ultra-short-acting opioid metabolized by nonspecific tissue esterasesRapid onset of actionDoes not accumulate after infusions even in organ dysfunction.Selective mu-receptor agonist.Potency similar to fentanyl.Terminal half-life < 10 min.Rapid blood-brain equilibrium.Can cause significant bradycardia
56Epidural analgesiaOpioidsConcentrationMorphineμg/mlFentanyl2- 5 μg/mlAdverse effects of epidural analgesia are more common with morphine than fentanyl. Epidural morphine can produce respiratory depression, and the onset can be delayed up to 12 hours . The incidence of respiratory depression is equivalent with epidural and intravenous morphine. More frequent side effects of epidural analgesia include pruritis, nausea, and urinary retention.
57Unwanted side-effects of opioids VasodilationConfusionRespiratory depressionGut motility depression
58Other opioid agonists Tramadol Synthetic 4-phenyl-piperidine analog of codeineStimulates the µ-receptor1/5th to 1/10th as potent as morphineAnalgesic doses of tramadol may produce less respiratory depression and have minimal effects on gastrointestinal motor function
59Naloxone Opioid antagonist Used to restore spontaneous ventilation in patients who breathe inadequately after opioid overdoseOnset of action is 1 -2 minDuration of effect is minDosage – 0.4 to 0.8mgSide effects: tachycardia, hypertension, pulmonary edema
60Non steroidal anti inflammatory drugs There is only one NSAID approved for use in the United States: ketorolac.Nonspecific inhibitor of cyclooxygenase with strong analgesic activity and moderate anti inflammatory activityMetabolized in the liver and excreted by the kidneysDose: 30 mg IV or 60 mg IM, f/b 30 mg IM or IV every 6 hours (maximum of 120 mg/day) for up to 5 days
61iv paracetamolThe time course of action is quick with iv paracetamol as it reaches peak concentration as soon as infusion is complete (about 15 minutes).According to the product information, the analgesic effect starts within 5 minutes, peaks at 1 hour and lasts 4 to 6 hours.
62Clinical practice guidelines for sedation and analgesia from the Society of Critical Care Medicine and American College of Critical Care Medicine Pain
63PainAn assessment of pain and the response to therapy should be regularly assessed using an appropriate pain scale.Therapeutic plans and goals should be developed for all patients.Recommended intravenous opioids are fentanyl for acute distress, fentanyl or hydromorphone for patients with hemodynamic instability or renal insufficiency, and morphine and hydromorphone for longer-term therapy.Scheduled doses or continuous infusions are preferred over intermittent boluses.Nonsteroidal anti-inflammatory drugs and acetaminophen can be useful adjuncts, but beware of renal insufficiency or gastrointestinal bleeding.
64SedationTreatment of pain and other reversible causes should be conducted before sedating an agitated patient.A treatment plan/goal should be established for each patient; therapy should be assessed with a sedation scale.Midazolam or diazepam is useful for the acutely agitated patient.Propofol is preferred when rapid awakening is crucial; triglyceride levels should be monitored for >2 d of continuous infusions.Lorazepam is recommended for longer infusions.Doses should be tapered daily to assess underlying mental status, and sedation protocols can be helpful and beneficial.
67ReferencesGabrielli A, Layon A, Joseph, et al. Anesthesia in the ICU. Civetta, Taylor, & Kirby's: Critical Care, 4th Edition; Lippincott Williams & Wilkins:2009Marino, PL. Analgesia and Sedation. ICU Book, 3rd Edition; Lippincott Williams & Wilkins:2007Miller RD. Critical care protocols. Miller’s Anaesthesia. 7th edition:2010