Art of sedation in icu
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critically ill patients differs from other patients because of their altered Pk/Pd, hence sedation must be titrated to desired response
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Art of sedation in icu
- 2. Hypnosis ± Muscle Relaxation Analgesia •Latin word sedare = to calm or to allay fear = sedation
- 3. Conscioussedation • A minimally depressed level of consciousness induced by theadministration of pharmacologic agentsin which apatient 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
- 4. THE PATIENT IS HERE!
- 6. Complications from pain and anxiety Stimulation of theautonomic nervoussystem and releaseof humoral factors→ increased HR, BP, and myocardial oxygen consumption → myocardial ischemiaor infarction Altered humoral responsecan lead to hypercoagulability asaresult of increased level of factor VIII, fibrinogen, platelet activity, and inhibition of fibrinolysis
- 7. Cont…….. Stresshormonesalso produceinsulin resistance, increased metabolic rate, and protein catabolism Immunosuppression with reduction in number and function of lymphocytesand granulocytes Psychological disturbances- memoriesof vivid nightmares, hallucinations, and paranoid delusions
- 8. DeliriumDelirium 80% of ICU patients have delirium *may or may not be accompanied by agitation
- 9. Indications and Goals Facilitate mechanical ventilation Create anxiolysis, analgesia, amnesia Decrease oxygen consumption Reduce dyspnea Prevent patient self-injury “Rest” patient for weaning trials Induce sleep
- 10. Cont…… Create patient unawareness Improve long-term psychiatric outcomes (?) Permit delivery of efficient care Reduce nursing stress Ensure nursing safety Increase family acceptance of ICU care Weinert, et al. AJCC. 2001; 10:156
- 11. Sedation EvaluationSedation Evaluation Should be integral component of treatment algorithms precise dosing reduced sedative and analgesic drug use shorter duration of MV reduced need for vasopressor therapy reduced incidence of over sedation
- 13. scoring system should besimple, easily performed, noninvasive, and reproducible.
- 14. Richmond Agitation-Sedation Scale (RASS) Sedation Agitation Scale [SAS] Motor Activity Assessment Scale Ramsay Sedation Scale Adaptation to the Intensive Care Environment (ATICE) instrument Minnesota Sedation Assessment Tool (MSAT). Glasgow comascale(GCS) – assessment of level of consciousness
- 16. Richmond agitation sedation scale Score Term Description +4 Combative Violent; immediate danger to staff +3 Very agitated Pulls/ removes tubes, catheters; aggressive +2 Agitated Frequent non purposeful movement; patient ventilator asynchrony +1 Restless Anxious or apprehensive 0 Alert and calm -1 Drowsy Not fully alert but awakens for >10s, with eye contact, to voice -2 Light sedation Briefly awakens (<10s), with eye contact, to voice -3 Moderate sedation Any movement to voice but no eye contact -4 Deep sedation No response to voice but movement to physical stimulation -5 Unarousable No response to voice or physical stimulation
- 17. Ramsay sedation scale Awake 1 Anxiousand/or agitated 2 Cooperative, oriented, and tranquil 3 Respondsto commands Asleep 4 brisk responseto light glabellar tap or loud auditory stimulus 5 Sluggish responseto light glabellar tap or loud auditory stimulus 6 No response
- 18. Sedation agitation scale 1: Unarousable 2: Very sedated 3: Sedated 4: Calm and cooperative 5: Agitated 6: Very agitated 7: Dangerousagitation
- 19. What is “adequate sedation”? RAAS -0-3 SAS – 3-4 RAMSAY- 3
- 20. Measurement of Brain ActivityMeasurement of Brain Activity Bispectral index (BIS) Patient state index Cerebral state index Narcotrend index •Objective physiologicObjective physiologic parametersparameters •Numerical displayNumerical display •Near-continuous measurementNear-continuous measurement
- 21. Bispectral index A practical, processed EEG parameter that measuresthedirect effects of sedativeson the brain .
- 23. Value of BIS in ICU Minimize consequences of over- and under-sedation Improve quality of sedation management Objectivesedation assessment about apatient’sresponseto sedation Optimizeclinical and economic outcomes Numerical scale correlates to sedation endpoints
- 24. BIS Prone to artifacts ‘Electromyography‘ activity interferes with BIS measures of sedation Confounding factors that may influence BIS scores Hypoglycemia / Sleep / temperature / Age Drugs aminophylline, epinephrine, and ketamine. Increase variability of BIS in the critically ill pts Cannot be relied upon in circulatory arrest or
- 25. Daily interruption of sedation & analgesia [1B] Allows better assessment of a patient’s sedative needs Reduces drug bioaccumulation Reduced incidence of posttraumatic stress disorder Reduced complications of critical illness More ventilator-free days and earlier ICU and hospital discharge, at the expense of a higher incidence of self-extubation
- 26. Sedation therapy NON PHARMACOLOGICAL THERAPY: Good communicationwith regular reassurancefrom nursing staff Environmental control such ashumidity, lighting, temperature, and noise Explanationprior to procedures Management of thirst, hunger, constipation, and full bladder
- 27. Critically ill patients are different Pharmacokinetics of various drugs are altered including - drug bioavailability, volume of distribution, and clearance. Hepatic dysfunction Decreased hepatic blood flow Renal dysfunction Alteration in volume status Plasma protein binding
- 28. Pharmacologic therapy Thesedativeagent should possessthefollowing qualities: Both sedativeand analgesic properties Minimal cardiovascular sideeffects Controllablerespiratory sideeffects Rapid onset/offset of action No accumulation in renal/hepatic dysfunction Inactivemetabolites Inexpensive No interactionswith other ICU drugs
- 29. Pharmacologic therapy Benzodiazepines Propofol Etomidate Ketamine Barbiturate Short acting opioids Alpha2 agonists Inhalational agents
- 30. Benzodiazepines Anxiolytic, anticonvulsant, amnesic, hypnotic and providesomemusclerelaxation Effectsaremediated by depressing theexcitability of thelimbic system viareversiblebinding at GABA- benzodiazepinereceptor complex Minimal cardiorespiratory depressant effect Thecommon drugsin thisclassarediazepam, midazolam, and lorazepam
- 31. Pharmacodynamic response Patient-related factors can affect the BZD response age concurrent pathology prior alcohol use concurrent therapy with other sedative drugs Higher volume of distribution and slower clearance in elderly.
- 32. MIDAZOLM LORAZEPAM DIAZEPAM LOADING DOSE 0.01-0.05 mg/kg 0.02-0.04 mg/kg 0.05-0.2 mg/kg MAINTANENCE DOSE 0.02-0.1 mg/kg/hr 0.01-0.1 mg/kg/hr Rarely used ONSET 1-5 min 5-20 min 2-5 min DURATION 3-11 hrs 2-6 hrs 2-4 hrs CARDIAC EFFECTS Minimal Minimal Present RESPIRATORY EFFECTS Important depressant effect Important depressant effect Important depressant effect ANALGESIA None None None AMNESIA Potent None None ACTIVE METABOLITES Yes No Yes S/E Low BP Low BP, glycol/ nephrtoxicity Low BP, pleibitis
- 33. Propofol Themodeof action of propofol isviatheGABA receptor Rapid onset of action 1-2 min; metabolized rapidly hepatically and extrahepatically Recovery within 10 minutesof discontinuation, can accumulatewith prolonged use Ideally infused viaalargeor central vein Prolonged infusions–increasetriglycerideand cholesterol levels A theoretical maximum recommended doseis4 mg/kg/hour.
- 34. Propofol (contd.)Bolusdose– not recommended Infusions@25 to 100μg/kg/hr Theoretical maximum dose- 4mg/kg/hr Cautiousabout propofol infusion syndrome
- 35. Propofol: adverse effects Hypotension Reliable, dose-related Decreased SVR and contractility (CO) Respiratory depression Apneawith bolusdosing Synergistic CV and respiratory depression with opioids Vehicle(soybean emulsion): Hypertriglyceridemia Venoirritation Infection
- 36. Propofol infusion syndrome Propofol infusion syndromeisan adversedrug event associated with high doses(>4 mg/kg per hour or >67 µg/kg per minute) and long-term (>48 hours) useof propofol. Clinical features: - Cardiomyopathy with acutecardiac failure. - Myopathy. - Metabolic acidosis, K+ - Hepatomegaly. Inhibition of FFA entry into mitochondria failureof itsmetabolism.
- 37. Management Supportivetreatmentsaddressing theclinical manifestations Thepropofol infusion should bediscontinued immediately Alternativesedativeshould bestarted Intravenouscrystalloid and colloid replacement and vasopressor and/or inotropic support Cardiac pacing may beused for symptomatic bradycardia Hemodialysisor continuousrenal replacement therapy to treat theacuterenal failure
- 38. Ketamine Ketamineactsat theN-methyl-D-aspartate(NMDA) receptor In subanesthetic doses, sedativeand analgesic Generally not used becauseof theincreasein blood pressure, intracranial pressure(ICP), and pulserate Bronchodilatory properties, sometimeshasarolein severeasthma In theICU conjunction with anarcotic Dose: 5 to 30 μg/kg/min
- 39. Others ETOMIDATE :For maintenanceof hypnosis, target concentration of 300 to 500 ng/mL may beachieved by administration of atwo- or three-stageinfusion BARBITURATES: Barbituratessuch asPentothal havebeen used in theICU, especially in the management of patientswith head injuriesand seizure disorders. They causesignificant cardiovascular depression and accumulateduring infusions, leading to prolonged recovery times.
- 40. Others (contd.) BUTYROPHENONESAND PHENOTHIAZINES An aggressivedosing regimen of haloperidol may be useful in apatient with delirium to promotecalm, 2 to 10 mg IV every 10 to 15 minutesuntil thedesired responseisachieved VOLATILE AGENTS Isofluranehasbeen used in concentrationsof up to 0.6% for longterm sedation, with minimal cardiorespiratory sideeffectsand rapid awakening. Desfluranehasbeen shown to beeffectivein sedation, with rapid offset of effects.
- 41. Others (contd.) Shorter acting opioids Fentanyl, alfentanyl, remifentanyl α2 agonists Clonidine dexmedetomidine Musclerelaxants Fentanyl 50-100μg 1-2 min 30-60 min 50-350μg/hr No No Loading dose Onset Duration Infusion rate Active metabolites Histamine release
- 42. α2 Agonists Clonidine Selectivity: α2:α1 250:1 Imidazolederivate16:1 t1/2 β 10 hrs Antihypertensive Dexmedetomidine Selectivity: α2:α1 1620:1 Imidazolederivate31:1 t1/2 β 2 hrs 94% protein bound Eliminated by liver/kidney Sedative Only availablein IV form
- 43. Dexmed.Dexmed. Clinical paradigms Sedation without respiratory deppressio n Sympat holytic smooth emergence+ weaning from mechanical ventilation Molecular targets+ neural substrates 1.locusceruleus 2.natural sleep pathways
- 44. Pharmacokinetics Rapid redistribution: 6 min No accumulation after infusions12-24 h Typical doses(target plasmalevels0.3-1.2 ng/ml): Onset 5-10 min Et1/2 1.8-3.1 hr 1 ug/kg loading doseover 10 min f/b 0.2-0.7 ug/kg/hr infusion Load only - short procedures Patientswith high sympathetic activity may need very high doses
- 45. Clonidine Clonidine issynergistic with opioidsand actsat the spinal cord to inhibit nociceptiveinputs, thus imparting analgesia It iscontraindicated in hypovolemiaand can cause hypotension, bradycardia, and dry mouth
- 46. The Art of Sedation Under sedation: Fighting theventilator. 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.
- 47. Titration of Sedative Medications Large variation in dose requirements Altered PK/PD in critically ill Acute and chronic tolerance Differences in severity of symptom or behavior Most drugs are titrated to effect Similar to hypertensive medications
- 48. How to titrate sedative medications Identify the target symptom or behavior “Measure” the intensity or severity Agree on the appropriate symptom level for that patient at that time Realize that changes will occur
- 52. Hooper. Critical Care Clinics - 25 (July 2009) Before Assesing daily awakening exclude Raised ICT NMB Very high PEEPn FiO2 CABG- immediate postop
- 53. Results: ABC Trial SAT + SBT = more Ventilator-free days 15 v 12 (p =0.02) Less days in ICU: 9 v 13 Less coma but more self-extubations Decreased risk of dying up to 1 yr Girard Lancet 371:126 2008