Sedation

1,691 views

Published on

Published in: Health & Medicine, Business
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,691
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
124
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide

Sedation

  1. 1. Sedation of Patients inSedation of Patients in the Intensive Care Unitthe Intensive Care Unit Craig Weinert, MD, MPHCraig Weinert, MD, MPH PACCSPACCS Jan 2010Jan 2010
  2. 2. Indications and Goals forIndications and Goals for Sedative TherapySedative Therapy  Facilitate mechanical ventilationFacilitate mechanical ventilation  Create anxiolysis, analgesia,Create anxiolysis, analgesia, amnesiaamnesia  Decrease oxygen consumptionDecrease oxygen consumption  Reduce dyspneaReduce dyspnea
  3. 3. Indications and Goals forIndications and Goals for Sedative TherapySedative Therapy  Prevent patient self-injuryPrevent patient self-injury  ““Rest” patient for weaning trialsRest” patient for weaning trials  Induce sleepInduce sleep  Create patient unawarenessCreate patient unawareness  Improve long-term psychiatricImprove long-term psychiatric outcomes (?)outcomes (?)  Permit delivery of efficient carePermit delivery of efficient care  Reduce nursing stressReduce nursing stress  Ensure nursing safetyEnsure nursing safety  Increase family acceptance of ICU careIncrease family acceptance of ICU care Weinert, et al. AJCC. 2001; 10:156
  4. 4. THE PATIENT IS HERE!
  5. 5. BenzodiazepinesBenzodiazepines GABA receptor agonistsGABA receptor agonists  Midazolam:Midazolam: – Changes from water- to lipid-soluble inChanges from water- to lipid-soluble in bloodstream so rapid-actingbloodstream so rapid-acting – Liver metabolized to active metabolites thatLiver metabolized to active metabolites that accumulate in renal failureaccumulate in renal failure  Lorazepam:Lorazepam: – More water soluble so longer onset and longerMore water soluble so longer onset and longer effects (t1/2 = 12 hrs)effects (t1/2 = 12 hrs) – Propylene glycol carrierPropylene glycol carrier – Glucuronidated to inactive metabolitesGlucuronidated to inactive metabolites
  6. 6. PropofolPropofol  General anesthetic, lipid-solubleGeneral anesthetic, lipid-soluble delivered in lipid solutiondelivered in lipid solution  Elimination half-life is much longerElimination half-life is much longer than its clinical effect half-lifethan its clinical effect half-life  Hypotensive effects in volume-Hypotensive effects in volume- depleted patientsdepleted patients  Hypertriglyceridemia with high dosesHypertriglyceridemia with high doses  Propofol Infusion Syndrome (?)Propofol Infusion Syndrome (?)
  7. 7. OpiatesOpiates  Commonly used as adjunctiveCommonly used as adjunctive therapy with benzodiazepine ortherapy with benzodiazepine or propofolpropofol  Morphine: bolus or infusionsMorphine: bolus or infusions  Fentanyl: continuous infusionFentanyl: continuous infusion  Hydromorphone in organ failureHydromorphone in organ failure
  8. 8. DexmedetomidineDexmedetomidine (Precedex)(Precedex)  Alpha-2 adrenoreceptor agonistAlpha-2 adrenoreceptor agonist – Related to clonidineRelated to clonidine  Multiple effectsMultiple effects – Spinal cord and central nervous systemSpinal cord and central nervous system  Sedation (decreased responsiveness)Sedation (decreased responsiveness)  AmnesiaAmnesia  AnalgesiaAnalgesia  Minimal respiratory depressionMinimal respiratory depression
  9. 9. DexmedetomidineDexmedetomidine  Two clinical trials with intubatedTwo clinical trials with intubated post-operative patientspost-operative patients – Reduced need for propofolReduced need for propofol – Reduced need for midazolamReduced need for midazolam – Reduced need for morphineReduced need for morphine  Approved indication December 1999Approved indication December 1999 – Sedation of initially intubated andSedation of initially intubated and ventilated patients in an ICU not toventilated patients in an ICU not to exceed 24 hours.exceed 24 hours.
  10. 10. Titration of SedativeTitration of Sedative MedicationsMedications  Large variation in dose requirementsLarge variation in dose requirements – Altered PK/PD in critically illAltered PK/PD in critically ill – Acute and chronic toleranceAcute and chronic tolerance – Differences in severity of symptom orDifferences in severity of symptom or behaviorbehavior  Most drugs are titrated to effectMost drugs are titrated to effect – Similar to hypertensive medicationsSimilar to hypertensive medications
  11. 11. How to titrate sedativeHow to titrate sedative medicationsmedications  Identify the target symptom orIdentify the target symptom or behaviorbehavior  ““Measure” the intensity or severityMeasure” the intensity or severity  Agree on the appropriate symptomAgree on the appropriate symptom level for that patient at that timelevel for that patient at that time  Realize that changes will occurRealize that changes will occur
  12. 12. What is “adequate sedation”?What is “adequate sedation”?  274 MICU/SICU patients intubated > 36 hrs274 MICU/SICU patients intubated > 36 hrs  4-hour data intervals4-hour data intervals – MSATMSAT – 8 sedative drugs8 sedative drugs  18,050 intervals during MV18,050 intervals during MV  85% had sedatives given85% had sedatives given  12,050 had MSAT assessments12,050 had MSAT assessments – 83% adequately sedated83% adequately sedated – 14% undersedated14% undersedated – 3% rated as “oversedated” although 32% of the time3% rated as “oversedated” although 32% of the time patients did not respond to stimulation and 21% had nopatients did not respond to stimulation and 21% had no spontaneous movementspontaneous movement Weinert CCM 2007
  13. 13. 0 5 10 15 20 25 30 35 40 Dexmedetomidine Haloperidol Midazolam Fentanyl Hydromorphone Lorazepam Morphine Propofol Percent of four-hour intervals in which sedative was given Single sedative 46% Two sedatives 31% Three: 6% Co-Sedation is common…
  14. 14. Ramsay ScaleRamsay Scale AwakeAwake 1.1. Anxious and agitated and restless orAnxious and agitated and restless or bothboth 2.2. Cooperative, oriented or tranquilCooperative, oriented or tranquil 3.3. Responds to commands onlyResponds to commands only AsleepAsleep 4.4. Brisk response to glabellar tap orBrisk response to glabellar tap or loud voiceloud voice 5.5. Sluggish response to glabellar tap orSluggish response to glabellar tap or loud voiceloud voice 6.6. No response to glabellar tap or loudNo response to glabellar tap or loud voicevoice Ramsay, BMJ 1974
  15. 15. Richmond Agitation-SedationRichmond Agitation-Sedation ScaleScale 44 CombativeCombative 33 Very agitatedVery agitated 22 AgitatedAgitated 11 Restless, anxious, apprehensiveRestless, anxious, apprehensive 00 Alert and calmAlert and calm -1-1 Eye contact > 10 secEye contact > 10 sec -2-2 Eye contact < 10 secEye contact < 10 sec -3-3 Movement but no eye contactMovement but no eye contact -4-4 Movement to physical stimuliMovement to physical stimuli -5-5 No movementNo movement Sessler, 1992
  16. 16. Clinical Trials of SedativeClinical Trials of Sedative Delivery ProtocolsDelivery Protocols  Bedside assessment by RNsBedside assessment by RNs – FrequentFrequent – StandardizedStandardized – Targeted goalsTargeted goals  Minimize use of continuous infusionsMinimize use of continuous infusions – Risk factor for prolonging ventilationRisk factor for prolonging ventilation  Decrease infusion ratesDecrease infusion rates  Limited medication choicesLimited medication choices  Caution: trials performed in academicCaution: trials performed in academic ICUsICUs
  17. 17. ““Effect of a nursing-implemented sedation protocolEffect of a nursing-implemented sedation protocol on the duration of mechanical ventilation”on the duration of mechanical ventilation” 321 ventilated pts randomized at321 ventilated pts randomized at intubationintubation 1.1. Traditional M.D. sedation managementTraditional M.D. sedation management 2.2. Nurse-directed written protocolNurse-directed written protocol Ramsay target = 3Ramsay target = 3 Fentanyl and midazolam boluses for acuteFentanyl and midazolam boluses for acute controlcontrol Lorazepam and morphine drip if frequentLorazepam and morphine drip if frequent boluses req.boluses req. Decrease drip rateDecrease drip rate q 4 hr if at target goal.q 4 hr if at target goal. Brook, et al. CCM 1999; 27:2609
  18. 18. ResultsResults  Decreased time on vent: 89 vs 124Decreased time on vent: 89 vs 124 hrshrs  Decreased ICU LOS: 5.7 vs 7.5 daysDecreased ICU LOS: 5.7 vs 7.5 days  Decreased hospital LOS: 14 vs 19.9Decreased hospital LOS: 14 vs 19.9 daysdays  Decreased tracheotomy rate: 6% vsDecreased tracheotomy rate: 6% vs 13%13%  No difference in mortality or organNo difference in mortality or organ failuresfailures Brook, et al. CCM 1999; 27:2609
  19. 19. Benefits of using sedationBenefits of using sedation algorithmsalgorithms  Numerous other studies show thatNumerous other studies show that sedation algorithms or guidelinessedation algorithms or guidelines (often pharmacist-derived)…(often pharmacist-derived)… – Decrease drug costsDecrease drug costs – Less hypotension and VAPLess hypotension and VAP – Decrease aggregate dosingDecrease aggregate dosing – Often decrease MV durationOften decrease MV duration
  20. 20. ““Daily interruption of Sedative Infusions in CriticallyDaily interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation”Ill Patients Undergoing Mechanical Ventilation”  150 MICU ventilated pts “requiring150 MICU ventilated pts “requiring continuous infusion of sedatives”continuous infusion of sedatives” 1.1. Usual care for tapering of infusionsUsual care for tapering of infusions 2.2. Daily interruption (at 48 hours) ofDaily interruption (at 48 hours) of sedative (DIS) until awake or agitatedsedative (DIS) until awake or agitated with resumption at half the ratewith resumption at half the rate  Ramsay target of 3 or 4Ramsay target of 3 or 4  Second randomization to propofol orSecond randomization to propofol or midazolammidazolam  All received morphineAll received morphine Kress, et al. NEJM 2000; 342:1471
  21. 21. ResultsResults  Decreased time on ventilation: 4.9 vsDecreased time on ventilation: 4.9 vs 7.3d7.3d  Decreased ICU LOS: 6.4 vs 9.9 dDecreased ICU LOS: 6.4 vs 9.9 d  Increased % of days briefly awake:Increased % of days briefly awake: 86% vs 9%86% vs 9%  Decreased use of diagnostic tests toDecreased use of diagnostic tests to assess decreased mental statusassess decreased mental status  No difference in main outcomes withNo difference in main outcomes with propofol vs midazolampropofol vs midazolam
  22. 22. Additional resultsAdditional results  No increase in ICU adverse eventsNo increase in ICU adverse events  Little recall of ICU in both groupsLittle recall of ICU in both groups  Better long-term psychologicalBetter long-term psychological adjustment during recovery in dailyadjustment during recovery in daily interruption groupinterruption group  Subsequent study showed noSubsequent study showed no increase in cardiac ischemia duringincrease in cardiac ischemia during sedation reductionsedation reduction Kress AJRCCM 2004 and CCM 2007
  23. 23. New Drug Trial in the DIS Era:New Drug Trial in the DIS Era: Lorazepam vs PropofolLorazepam vs Propofol  132 MICU patients expected intubation > 48 hrs132 MICU patients expected intubation > 48 hrs and requiring sedationand requiring sedation  Open-label lorazepam by bolus or propofol dripOpen-label lorazepam by bolus or propofol drip  Goal Ramsay score of 2-3 (awake or responds toGoal Ramsay score of 2-3 (awake or responds to voice)voice) – Daily interruptionDaily interruption – Continuous infusion morphine for allContinuous infusion morphine for all  Results: Decreased ventilator days for propofolResults: Decreased ventilator days for propofol (5.6 vs 8.4) mostly because of decreased days(5.6 vs 8.4) mostly because of decreased days for survivorsfor survivors – ICU LOS 2 days less for survivorsICU LOS 2 days less for survivors – No difference in hospital LOS or mortalityNo difference in hospital LOS or mortality – Interestingly, at Ramsay goal only 45% of timeInterestingly, at Ramsay goal only 45% of time Carson CCM 2006
  24. 24. Comparing DIS and PSComparing DIS and PS A randomized trial of daily awakening in critically ill patients managedA randomized trial of daily awakening in critically ill patients managed with a sedation protocol:with a sedation protocol:  Randomized to PS alone, or PS + DI.Randomized to PS alone, or PS + DI. – sedatives/analgesics were titrated to achieve Sedationsedatives/analgesics were titrated to achieve Sedation Agitation Score 3-4.Agitation Score 3-4. – PS + DI group had infusions interrupted daily until thePS + DI group had infusions interrupted daily until the patients awoke.patients awoke.  Results: Median duration of MV in the PS = 8 andResults: Median duration of MV in the PS = 8 and PS + DI = 10.5 daysPS + DI = 10.5 days  SAS within target range (3-4) in 59% of 9,611SAS within target range (3-4) in 59% of 9,611 measurementsmeasurements  Nursing and respiratory therapist workload wasNursing and respiratory therapist workload was lowlow  Adverse events were similar in both groups.Adverse events were similar in both groups. Mehta Critical Care 36:2092-9 2008
  25. 25. A randomized trial of protocol-directed sedationA randomized trial of protocol-directed sedation management for mechanical ventilation in anmanagement for mechanical ventilation in an Australian intensive care unitAustralian intensive care unit  Randomized to sedation directed by formalRandomized to sedation directed by formal guidelines (n = 153) or usual local clinicalguidelines (n = 153) or usual local clinical practice (n = 159)practice (n = 159)  Results: median MV hrs were 79 hrs forResults: median MV hrs were 79 hrs for patients in the protocol group comparedpatients in the protocol group compared with 58 hrs for patients who receivedwith 58 hrs for patients who received control care (p = .20).control care (p = .20).  In a proportional hazards model, protocolIn a proportional hazards model, protocol sedation management was associated withsedation management was associated with a 22% decrease in the occurrence ofa 22% decrease in the occurrence of successful weaning from mechanicalsuccessful weaning from mechanical ventilation.ventilation. Bucknall Critical Care Medicine. 36 2008
  26. 26. Dexmedetomidine versusDexmedetomidine versus midazolammidazolam  Dex up to 1.4 mcg/kg/hr vs continuousDex up to 1.4 mcg/kg/hr vs continuous infusion midazolam…infusion midazolam…  In 375 MV patients (>24 hrs expected)In 375 MV patients (>24 hrs expected)  No difference at achieving RASS targetNo difference at achieving RASS target (77% at - 2 to +1)(77% at - 2 to +1)  Less delirium (54% v 76%)Less delirium (54% v 76%)  Decreased MV (3.7 vs 5.6 days) butDecreased MV (3.7 vs 5.6 days) but similar ICU LOSsimilar ICU LOS  More bradycardia (42.% vs 18% )More bradycardia (42.% vs 18% ) Riker JAMA 2009
  27. 27. Copyright restrictions may apply. Riker, R. R. et al. JAMA 2009;301:489-499. Time to Extubation and Intensive Care Unit (ICU) Length of Stay Among Patients Treated With Dexmedetomidine vs Midazolam
  28. 28. Copyright restrictions may apply. Riker, R. R. et al. JAMA 2009;301:489-499. Daily Prevalence of Delirium Among Intubated Intensive Care Unit Patients Treated With Dexmedetomidine vs Midazolam
  29. 29. Copyright restrictions may apply. Riker, R. R. et al. JAMA 2009;301:489-499. Efficacy Outcomes in Patients Treated With Dexmedetomidine vs Midazolam
  30. 30. Copyright restrictions may apply. Riker, R. R. et al. JAMA 2009;301:489-499. Safety Outcomes During Treatment With Dexmedetomidine vs Midazolam
  31. 31. Cost minimizationCost minimization  Median cost savings of $9700 (95%Median cost savings of $9700 (95% CI $2300-$17000)CI $2300-$17000)  2/3 from decreased ICU LOS and 1/32/3 from decreased ICU LOS and 1/3 from decreased MV)from decreased MV)  Dex: $50 for 200 mcg vialDex: $50 for 200 mcg vial  Midazolam $1.56 for 5 mg vialMidazolam $1.56 for 5 mg vial Dasta CCM Feb 2010
  32. 32. Combining sedationCombining sedation andand ventilatorventilator weaning protocolsweaning protocols  336 MV patients in 4 hospitals336 MV patients in 4 hospitals  Sedation awakening trial (SAT) +Sedation awakening trial (SAT) + SBT vs usual sedation + SBTSBT vs usual sedation + SBT  Non-protocolized sedation practiceNon-protocolized sedation practice  Main outcome: days alive and free ofMain outcome: days alive and free of MV up to 28MV up to 28thth dayday Girard Lancet 371:126 2008
  33. 33. Hooper. Critical Care Clinics - 25 (July 2009)
  34. 34. Results: ABC TrialResults: ABC Trial  SAT + SBT = more Ventilator-freeSAT + SBT = more Ventilator-free daysdays – 15 v 12 (p =0.02)15 v 12 (p =0.02)  Less days in ICU: 9 v 13Less days in ICU: 9 v 13  Less coma but more self-extubationsLess coma but more self-extubations  Decreased risk of dying up to 1 yrDecreased risk of dying up to 1 yr – Hazard ratio 0.68Hazard ratio 0.68 – NNT = 7NNT = 7 Girard Lancet 371:126 2008
  35. 35. Non-traditional therapies toNon-traditional therapies to manage symptoms of MV patientsmanage symptoms of MV patients  Patient-controlled sedationPatient-controlled sedation – Dexmedetomidine in standard PCADexmedetomidine in standard PCA pumppump – Initiate at 0.2 mcg/kg/hrInitiate at 0.2 mcg/kg/hr – Patients can self-administer 0.25Patients can self-administer 0.25 mcg/kg boluses up to 3 times/hrmcg/kg boluses up to 3 times/hr – Adjust basal infusion hourly based onAdjust basal infusion hourly based on amount of bolus dosesamount of bolus doses  Music therapy RCT in MV patientsMusic therapy RCT in MV patients Chlan, RN, PhD; Tracy RN, PhD; Skaar, PharmD; Weinert, MD, MPH

×