Explanations
Supplemental Table 12. Evidence Summaries and Evidence-to-Decision Profiles for Sedation Group Actionable QuestionsQuestion: Light sedation compared to deep sedation in critically ill intubated adults Quality assessment№ of patientsEffectQualityImportance№ of studiesStudy designRisk of biasInconsistencyIndirectnessImprecisionOther considerationslight sedationdeep sedationRelative(95% CI)Absolute(95% CI)Mortality (90 days)2 randomised trials not serious not serious not serious serious anone b70/153 (45.8%) 79/171 (46.2%) RR 1.01(0.80 to 1.27) 5 more per 1,000(from 92 fewer to 125 more) ????MODERATE CRITICAL Self extubation4 randomised trials not serious not serious cnot serious very serious dnone b21/261 (8.0%) 18/285 (6.3%) RR 1.29(0.58 to 2.88) 18 more per 1,000(from 27 fewer to 119 more) ????LOW CRITICAL Time to extubation (days)3 randomised trials not serious serious enot serious serious fnone b218 235 - MD 0.77 days fewer(2.04 fewer to 0.5 more) ????LOW CRITICAL Shorter time to extubation (Observational studies)2 observational studies not serious not serious gnot serious not serious none HR 0.91(0.89 to 0.94) 8 fewer per 100(from 6 fewer to 11 fewer) h????LOW CRITICAL Delirium2 randomised trials serious inot serious not serious serious jnone 49/73 (67.1%) 48/67 (71.6%) RR 1.02(0.91 to 1.13) 14 more per 1,000(from 64 fewer to 93 more) ????LOW CRITICAL Depression 2 randomised trials not serious serious knot serious very serious lnone 5/65 (7.7%) 6/63 (9.5%) RR 0.76(0.10 to 5.58) 23 fewer per 1,000(from 86 fewer to 436 more) ????VERY LOW CRITICAL Post-traumatic stress disorder 2 randomised trials not serious not serious not serious very serious mnone 2/31 (6.5%) 3/31 (9.7%) RR 0.67(0.12 to 3.79) 32 fewer per 1,000(from 85 fewer to 270 more) ????LOW CRITICAL Tracheostomy2 observational studies not serious not serious not serious not serious none 49/275 (17.8%) 48/177 (27.1%) RR 0.57(0.41 to 0.80) 117 fewer per 1,000(from 54 fewer to 160 fewer) ????LOW CRITICAL CI: Confidence interval; RR: Risk ratio; MD: Mean difference; HR: Hazard Ratio Explanations: a. We downgraded the quality of evidence for imprecision by one level, the CI included significant benefit and harm b. We couldn't assess for publication bias because of small number of eligible studies c. Minimal inconsistency I2=15% d. We downgraded the quality of evidence by two levels for imprecision, the CI included substantial benefit and harm e. We downgraded the quality of evidence by one level for inconsistency, the I2=53% f. We downgraded the quality of evidence by one level for imprecision, the CI included small benefit and harm g. I2= 26%, we did not downgrade for inconsistency h. We manually estimated the absolute difference in percentage as this outcome is originally a continues outcome i. we downgraded the quality of evidence by one level for risk of bias, blinding was unclear in two RCTs j. We downgraded the quality of evidence for imprecision by one level, the number of events was small k. We downgraded the quality of evidence by one level for inconsistency, the I2= 57% l. We downgraded the quality of evidence by two levels for imprecision, the number of events is very low (11 events) and the CI included extreme benefit and extreme harm m. We downgraded the quality of evidence by two levels for imprecision, the number of events was very small (n=5), and the CI included extreme benefit and harm Should light sedation vs. deep sedation be used for critically ill intubated adults?Population:critically ill intubated adultsIntervention:light sedationComparison:deep sedationMain outcomes:Mortality (90 days); Self extubation; Time to extubation (days); Shorter time to extubation (Observational studies); Delirium; Depression ; Post-traumatic stress disorder ; Tracheostomy;AssessmentJudgementResearch evidenceAdditional considerationsProblemIs the problem a priority?○ No○ Probably no○ Probably yes● YesNo research evidence was identified.Desirable EffectsHow substantial are the desirable anticipated effects?● TrivialNo research evidence was identified.Undesirable EffectsHow substantial are the undesirable anticipated effects?● TrivialCertainty of evidenceWhat is the overall certainty of the evidence of effects?● LowNo research evidence was identified.ValuesIs there important uncertainty about or variability in how much people value the main outcomes?● Possibly important uncertainty or variabilityNo research evidence was identified.Balance of effectsDoes the balance between desirable and undesirable effects favor the intervention or the comparison?● Probably favors the interventionNo research evidence was identified.Resources requiredHow large are the resource requirements (costs)?○ Large costs○ Moderate costs● Negligible costs and savings○ Moderate savings○ Large savings○ Varies○ Don't knowNo research evidence was identified.Certainty of evidence of required resourcesWhat is the certainty of the evidence of resource requirements (costs)?○ Very low○ Low○ Moderate○ High○ No included studiesNo research evidence was identified.Cost effect- ivenessDoes the cost-effectiveness of the intervention favor the intervention or the comparison● No included studiesNo research evidence was identified.AcceptabilityIs the intervention acceptable to key stakeholders?● Probably yesNo research evidence was identified.FeasibilityIs the intervention feasible to implement● YesNo research evidence was identified.Summary of judgementsJudgementProblemNoProbably noProbably yesYesVariesDon't knowDesirable EffectsTrivialSmallModerateLargeVariesDon't knowUndesirable EffectsLargeModerateSmallTrivialVariesDon't knowCertainty of evidenceVery lowLowModerateHighNo included studiesValuesImportant uncertainty or variabilityPossibly important uncertainty or variabilityProbably no important uncertainty or variabilityNo important uncertainty or variabilityBalance of effectsFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesDon't knowResources requiredLarge costsModerate costsNegligible costs and savingsModerate savingsLarge savingsVariesDon't knowCertainty of evidence of required resourcesVery lowLowModerateHighNo included studiesCost effectivenessFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesNo included studiesEquityReducedProbably reducedProbably no impactProbably increasedIncreasedVariesDon't knowAcceptabilityNoProbably noProbably yesYesVariesDon't knowFeasibilityNoProbably noProbably yesYesVariesDon't knowShould light sedation vs. deep sedation be used in critically ill intubated adults?Type of recommendationStrong recommendation against the interventionConditional recommendation against the interventionConditional recommendation for either the intervention or the comparisonConditional recommendation for the interventionStrong recommendation for the intervention○ ○ ○ ● ○ RecommendationWe suggest using light sedation versus deep sedation in critically ill mechanically ventilated patients (conditional recommendation, low quality evidence). JustificationDefining light sedation: There are no universally accepted definitions of what constitutes light versus deep sedation in mechanically ventilated critically ill patients. For the purpose of the actionable questions pertaining to this topic, we evaluated studies in which the authors a priori included a definition of what constituted light versus deep sedation in their trial. For example in the studies by Shehabi et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaGVoYWJpPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48
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ADDIN EN.CITE.DATA [1] a RASS of -2 to 1 was considered light sedation; Tregiarri ADDIN EN.CITE <EndNote><Cite><Author>Treggiari</Author><Year>2010</Year><RecNum>1931</RecNum><DisplayText>[2]</DisplayText><record><rec-number>1931</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232814">1931</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Treggiari, Miriam</author></authors></contributors><titles><title>Randomized trial of light versus deep sedation on mental health after critical illness</title><secondary-title>Crit. Care Med.</secondary-title></titles><periodical><full-title>Crit. Care Med.</full-title></periodical><pages>349-350</pages><volume>38</volume><number>1</number><dates><year>2010</year><pub-dates><date>2010/1</date></pub-dates></dates><isbn>0090-3493</isbn><urls><related-urls><url> Papers/T/Treggiari 2010 - Randomized trial of light versus deep sedation on mental health after critical illness.pdf</url></pdf-urls></urls><electronic-resource-num>10.1097/CCM.0b013e3181c546f8</electronic-resource-num></record></Cite></EndNote>[2] defined light sedation as Ramsay 1-2; and Tanaka PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYW5ha2E8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA [3] defined light sedation as a GCS>=9 which corresponds to a RASS -2 or lighter based on some earlier correlation studies. We did not use surrogates of light sedation such as reported plasma levels or ability to communicate versus not, unless accompanied by sedation scores that showed that patients met the defined criteria for light sedation in that study. Finally, the spirit of the definition was that patients would be targeted to be in the lighter vs deeper group for a substantial portion of the time; thus some studies that evaluated daily wake up trials were not included since they showed a lightening to a lower sedation score at a single time point in the day and not a sustained period. ?Low quality evidence?Small benefit (reduced DMV, reduced tracheostomy)?Uncertainty about other outcomes?Uncertainty about harm outcomes?Inconsistent V&P- different patients may have different preference with regards to light sedation?Uncertainty about cost-effectiveness?Intervention is likely acceptable and feasible to implementcomments during electronic Voting by Entire paneldiscussion should include rationale for "light" sedation& its facilitation of accurate pain& delirium assessments, physical activity, meaningful level of care discussions and MV liberation delirium is a critical outcome for the sedation group, not critical in the delirium groupThe EtoD body of the evidence proflie reports no evidence found - which conflicts with the data in the forest plots and GDT profile. Was the decision is based on the number of trachs? No other outcomes were significantly different.Author(s): Alhazzani W, Alshamsi F Question: Propofol compared to benzodiazepines in post cardiac surgery patients Setting: cardiovascular ICU Bibliography: Quality assessment№ of patientsEffectQualityImportance№ of studiesStudy designRisk of biasInconsistencyIndirectnessImprecisionOther considerationspropofolbenzodiazepinesRelative(95% CI)Absolute(95% CI)Time to Extubation-Hours7 randomised trials serious aserious bnot serious not serious none 207 202 - MD 1.41 lower(2.19 lower to 0.64 lower) ????LOW CRITICAL Time to light sedation2 randomised trials serious cnot serious not serious serious dnone e35 35 - MD 51.81 lower(77.42 lower to 26.19 lower) ????LOW IMPORTANT CI: Confidence interval; MD: Mean differenceExplanationsa. We downgraded the quality of evidence by one level for risk of bias, none of the studies were judged as low risk of bias, it is not clear if the observed treatment effect is influenced by study design b. We downgraded the quality of evidence for inconsistency by one level, the I2=93%, however, the variation between studies was not very large and all point estimates were in favour of propofol. c. We downgraded the quality of evidence by one level for risk of bias, the two trials were judged to be at high risk of bias, therefore, the observed treatment effect can't be confidently attributed to the intervention alone d. We downgraded the quality of evidence by one level for imprecision, the CI interval was wide and tot al number of patients was small e. We were not able t assess for publication bias, as only two studies were identified. However, we did not downgrade for publication bias Should propofol vs. benzodiazepines be used for post cardiac surgery patients?Intervention:propofolComparison:benzodiazepinesMain outcomes:Time to Extubation-Hours; Time to light sedation;Setting:cardiovascular ICUAssessmentJudgementResearch evidenceAdditional considerationsProblemIs the problem a priority?● YesDesirable EffectsHow substantial are the desirable anticipated effects?● ModerateIn the discussions, the expert group and patient representative agreed that in cardiac surgical patients a shortened time to light sedation of at least 30 minutes and time to extubation of at least 1 hour were clinically significant. Undesirable EffectsHow substantial are the undesirable anticipated effects?● TrivialCertainty of evidenceWhat is the overall certainty of the evidence of effects● LowOutcomesImportanceQuality of the evidence(GRADE)Time to Extubation-HoursCRITICAL????LOWa,b,cTime to Extubation-Hours Sens analysisCRITICAL????LOWa,dLongterm Cognitive DeclineCRITICAL????LOWe,f,gTime to light sedationIMPORTANT????LOWh,i,jWe downgraded the quality of evidence by one level for risk of bias, none of the studies were judged as low risk of bias, it is not clear if the observed treatment effect is influenced by study designWe downgraded the quality of evidence by one level for inconsistency, although I2 = 94% indicated significant statistical inconsistency, all point estimates were in favour of propofol and the variation in the magnitude was not large enough and subgroup analyses failed to explain this heterogeneity, Although the upper end of the CI represented trivial benefit, we did not downgrade the quality of evidence as we already downgraded for other categories We downgraded the quality of evidence for inconsistency by one level, the I2=93%, however, the variation between studies was not very large and all point estimates were in favour of propofol.We downgraded the quality of evidence by one level for risk of bias, this trial was assessed as unclear risk of bias, therefore, the impact of the trial design on the observed effect is uncertainThis category does not apply as this is a single trialWe downgraded the quality of evidence for imprecision by one level, the CI included very large and small benefit, and the number of events was small (48 events in total)We downgraded the quality of evidence by one level for risk of bias, the two trials were judged to be at high risk of bias, therefore, the observed treatment effect can't be confidently attributed to the intervention aloneWe downgraded the quality of evidence by one level for imprecision, the CI interval was wide and tot al number of patients was smallWe were not able t assess for publication bias, as only two studies were identified. However, we did not downgrade for publication biasValuesIs there important uncertainty about or variability in how much people value the main outcomes● Probably no important uncertainty or variabilityBalance of effectsDoes the balance between desirable and undesirable effects favor the intervention or the comparison?● Probably favors the interventionintervention is propofolResources requiredHow large are the resource requirements (costs)?● Negligible costs and savingsThere are no recent CEA studies that compare propofol to BZDWhile older studies may have shown a reduction in cost using propofol over benzodiazepines, the group felt the cost savings now would be negligible given the effect size on outcomes was moderate and the medications per say are off patent nowCertainty of evidence of required resourcesWhat is the certainty of the evidence of resource requirements (costs)?● No included studiesCost effect-ivenessDoes the cost-effectiveness of the intervention favor the intervention or the comparison?● Does not favor either the intervention or the comparisonSee notes above on costAccept-abilityIs the intervention acceptable to key stakeholders?● YesFeasibilityIs the intervention feasible to implement?● YesSummary of judgementsJudgementProblemNoProbably noProbably yesYesVariesDon't knowDesirable EffectsTrivialSmallModerateLargeVariesDon't knowUndesirable EffectsLargeModerateSmallTrivialVariesDon't knowCertainty of evidenceVery lowLowModerateHighNo included studiesValuesImportant uncertainty or variabilityPossibly important uncertainty or variabilityProbably no important uncertainty or variabilityNo important uncertainty or variabilityNo known undesirable outcomesBalance of effectsFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesDon't knowResources requiredLarge costsModerate costsNegligible costs and savingsModerate savingsLarge savingsVariesDon't knowCertainty of evidence of required resourcesVery lowLowModerateHighNo included studiesCost effectivenessFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesNo included studiesEquityReducedProbably reducedProbably no impactProbably increasedIncreasedVariesDon't knowAcceptabilityNoProbably noProbably yesYesVariesDon't knowFeasibilityNoProbably noProbably yesYesVariesDon't knowConclusionsShould propofol vs. benzodiazepines be used in post cardiac surgery patients?Type of recommendationStrong recommendation against the interventionConditional recommendation against the interventionConditional recommendation for either the intervention or the comparisonConditional recommendation for the interventionStrong recommendation for the intervention○ ○ ○ ● ○ RecommendationWe suggest using propofol over BZD for sedation in post-cardiac surgery patients (Conditional recommendation, Low QoE)JustificationIn the discussions, the expert group and patient representative felt that elective cardiac surgical patients are different from critically ill medical and surgical patients who have been mechanically ventilated for a period of time; we therefore addressed the question separately for mechanically ventilated cardiac surgical patients and critically ill MV medical and surgical patients. For the purpose of this question “post-cardiac surgical patients” were those who were mechanically ventilated after elective cardiac surgery In cardiac surgical patients a shortened time to light sedation of at least 30 minutes and time to extubation of at least 1 hour were deemed clinically significant by the group. ?Low quality evidence ?Moderate benefit (reduced time to extubation, shorter wake up time- time to light sedation) ?Uncertainty about other outcomes ?Trivial harm ?V&P probably consistent ?Uncertainty about cost-effectiveness ?Intervention is likely acceptable and feasible to implement Question: Propofol compared to a benzodiazepine in critically ill ventilated adults (both intubated and non-intubated) Quality assessment№ of patientsEffectQualityImportance№ of studiesStudy designRisk of biasInconsistencyIndirectnessImprecisionOther considerationspropofol a benzodiazepineRelative(95% CI)Absolute(95% CI)Mortality 90 day10 randomised trials not serious not serious not serious serious anone 95/432 (22.0%) 94/426 (22.1%) RR 1.01(0.79 to 1.29) 2 more per 1,000(from 46 fewer to 64 more) ????MODERATE CRITICAL Time to Extubation-Hours (assessed with: hours)16 randomised trials serious bvery serious cnot serious not serious none 366 364 - MD 13.71 hours lower(20.01 lower to 7.4 lower) ????VERY LOW CRITICAL Time to Extubation-Hours Sens analysis10 randomised trials not serious dvery serious enot serious not serious none 211 212 - MD 11.6 lower(15.62 lower to 7.58 lower) ????LOW CRITICAL Time to light sedation7 randomised trials not serious serious fnot serious serious gnone 185 172 - MD 7.23 hours lower(8.91 lower to 5.54 lower) ????LOW CRITICAL Delirium1 randomised trials not serious not serious not serious very serious hnone 4/14 (28.6%) 5/14 (35.7%) RR 0.80(0.27 to 2.37) 71 fewer per 1,000(from 261 fewer to 489 more) ????LOW CRITICAL Self Extubations2 randomised trials not serious not serious not serious very serious inone j3/103 (2.9%) 1/101 (1.0%) RR 2.82(0.30 to 26.45) 18 more per 1,000(from 7 fewer to 252 more) ????LOW CRITICAL Neuropsychological Dysfunction2 randomised trials not serious very serious knot serious serious lnone 34/58 (58.6%) 41/56 (73.2%) RR 0.93(0.69 to 1.24) m51 fewer per 1,000(from 176 more to 227 fewer) ????VERY LOW CRITICAL CI: Confidence interval; RR: Risk ratio; MD: Mean differenceExplanationsa. We downgraded the quality of evidence by one level for imprecision, the CI included both significant benefit and harm b. We downgraded the quality of evidence by one level for risk of bias, majority of studies were judged to be at high risk of bias c. We downgraded the quality of evidence by two levels for inconsistency, the I2=100% d. Although non of the studies were at low risk of bias, we did not downgrade the quality of evidence as we downgraded by two levels for other categories e. We downgraded the quality of evidence by two levels for very serious inconsistency, the I2=99%, and subgroup analyses failed to explain the observed heterogeneity f. We downgraded the quality of evidence by two levels for serious inconsistency, the I2=98% g. We downgraded the quality of evidence for imprecision by one level, h. We downgraded the quality of evidence by two levels for serious imprecision, the number of events was very low and the CI was extremely wide i. We downgraded the quality of evidence by two levels for serious imprecision, the number of events is 4 in totoal j. We couldn't reliably assess for publication bias k. We downgraded the quality of evidence by two levels for serious imprecision, the I2=91% l. We downgraded the quality of evidence by one level for imprecision, the CI is wide including significant benefit and harm m. Fixed effect model used QuestionShould propofol vs. a benzodiazepine be used for critically ill ventilated adults (both intubated and non-intubated)?Population:critically ill ventilated adults (both intubated and non-intubated)Background:Intervention:propofol Comparison:a benzodiazepineMain outcomes:Mortality 90 day; Time to Extubation-Hours; Time to Extubation-Hours Sens analysis; Time to light sedation; Delirium; Self Extubations; Neuropsychological Dysfunction;AssessmentJudgementResearch evidenceAdditional considerationsProblemIs the problem a priority?● YesNo research evidence was identified.textDesirable EffectsHow substantial are the desirable anticipated effects?● ModerateNo research evidence was identified.For the general medical and surgical ICU patients who have been on sedation for a while (excluding the fast track surgical and cardiac surgical patients discussed earlier), the group, including the patient representative, felt that shortened time to light sedation of at least 4 hours and time to extubation of approximately 8-12 hours (a shift or so) were clinically significantOne study looked at functional decline but had a large effect size and was a small study reducing the confidence in that study. While those outcomes would be a large effect, there was a tempered enthusiasm due to the quality of the studyUndesirable EffectsHow substantial are the undesirable anticipated effects?● TrivialUndesirable effects includes S/E, extubation .. etc. While there was a numerical increase in the self extubations in the propofol arm, the Ci were wide precluding any firm conclusion. Addiitonally it was not clear if the self extubations actually caused any harm (this was important for the physician group), though the patient representative did feel from a family perpective, a self extubation would be viewed as a undesirable effect. In the end thought to be a trivial undesirable anticipated effect given small numbersDelirium and neuropsychological outcomes were not addressed in many of these earlier studies making it difficult to comment on those undesirable effects.Certainty of evidenceWhat is the overall certainty of the evidence of effects?● LowNo research evidence was identified.ValuesIs there important uncertainty about or variability in how much people value the main outcomes?● Probably no important uncertainty or variabilityNo research evidence was identified.Balance of effectsDoes the balance between desirable and undesirable effects favor the intervention or the comparison?● Probably favors the interventionNo research evidence was identified.Resources requiredHow large are the resource requirements (costs)?● Negligible costs and savingsolder studies showed that propofol was more costly, but these data do not apply now, and The moderate effect on outcomes precludes any major effects on costs especially now that propofol is off patent.Certainty of evidence of required resourcesWhat is the certainty of the evidence of resource requirements (costs)?● No included studiesNo research evidence was identified.Cost effectivenessDoes the cost-effectiveness of the intervention favor the intervention or the comparison?● Does not favor either the intervention or the comparisonNo research evidence was identified.AcceptabilityIs the intervention acceptable to key stakeholders?● YesNo research evidence was identified.FeasibilityIs the intervention feasible to implement?● YesNo research evidence was identified.Summary of judgementsJudgementProblemNoProbably noProbably yesYesVariesDon't knowDesirable EffectsTrivialSmallModerateLargeVariesDon't knowUndesirable EffectsLargeModerateSmallTrivialVariesDon't knowCertainty of evidenceVery lowLowModerateHighNo included studiesValuesImportant uncertainty or variabilityPossibly important uncertainty or variabilityProbably no important uncertainty or variabilityNo important uncertainty or variabilityBalance of effectsFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesDon't knowResources requiredLarge costsModerate costsNegligible costs and savingsModerate savingsLarge savingsVariesDon't knowCertainty of evidence of required resourcesVery lowLowModerateHighNo included studiesCost effectivenessFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesNo included studiesEquityReducedProbably reducedProbably no impactProbably increasedIncreasedVariesDon't knowAcceptabilityNoProbably noProbably yesYesVariesDon't knowFeasibilityNoProbably noProbably yesYesVariesDon't knowConclusionsShould propofol vs. a benzodiazepine be used in critically ill ventilated adults (both intubated and non-intubated)?Type of recommendationStrong recommendation against the interventionConditional recommendation against the interventionConditional recommendation for either the intervention or the comparisonConditional recommendation for the interventionStrong recommendation for the intervention○ ○ ○ ● ○ RecommendationWe suggest using propofol over BZD for sedation in critically ill ventilated patients (conditional reccomendation, low quality of evidence)JustificationFor the general medical and surgical ICU patients who have been on sedation for a while (excluding the fast track surgical and cardiac surgical patients discussed earlier), the group, including the patient representative, felt that shortened time to light sedation of at least 4 hours and time to extubation of approximately 8-12 hours (a shift or so) were clinically significant. While there was a numerical increase in the self extubations in the propofol arm, the CI were wide precluding any firm conclusion. Additionally it was not clear if the self extubations actually caused any harm (this was important for the physician group), though the patient representative did feel from a family perspective, a self extubation would be viewed as an undesirable effect. In the end thought to be a trivial undesirable anticipated effect given small numbers Delirium and neuropsychological outcomes were not addressed in many of these earlier studies making it difficult to comment on those undesirable effects. ?Low quality evidence?Moderate benefit (reduced time to extubation, shorter wake up time)?Uncertainty about other outcomes?Trivial harm?V&P probably will not largely vary between patients?Uncertainty about cost-effectiveness?Intervention is likely acceptable and feasible to implementcomments during electronic Voting by Entire panelIn some circumstances benzos are fine... deep sedation, gaba agonist withdrawal.administration of drugs...propofol (continuous infusion) vs benzo (whatever way, not just infusion?) wording of the question should be related to recommendation outcomesspecify which benzos were in studies; was delirium diagnosis made by a clinician (gold standard) or screened with a scale confounded (or not) by sedation?little evaluation of propofol infusion syndrome with potential risk of a large-scale change to much greater propofol use. Given modest benefits of propofol in meta-analysis and their questionable clinical significance, a small increase in PRIS would reverse potential propofol benefit. Will more propofol infusion result in less bolus dosing of sedation before starting any infusion? With unintended consequences when the field is moving to minimize infusions.wording of recommendation should clarify if the benzo comparison group is benzo infusion, rather than influsion and/or bolus dosing. A bolus-only benzo approach (if present in any study) should not be grouped with a benzo infusion control group. most of the studies are old and likely had different sedation practices than current practice and the associated sensitivity analysis showed weaker evidence benefit when only the more modern studies were included? validity of these data - and of recommendation - to current practice.Also,the only 2 outcomes that had benefit not patient-centered; the size of the difference was larger than the expert group's impression of the MID for these 2 outcomes, but those MID are, I believe, only based on expert opinion. Ppfol infusion syndrome could be a real issue if there is much larger scale use as a result of this SCCM recommendation with more liberal use, higher doses and longer durations, and less careful selection/screening of patients for use of this drugQuestion: Should dexmedetomidine compared to a benzodiazepine in critically ill ventilated adults (both intubated and non-intubated) Quality assessment№ of patientsEffectQualityImportance№ of studiesStudy designRisk of biasInconsistencyIndirectnessImprecisionOther considerationsan alpha-2 agonist (e.g. dexmedetomidine) a benzodiazepineRelative(95% CI)Absolute(95% CI)28 Day Mortality3 randomised trials not serious not serious anot serious serious bnone c127/543 (23.4%) 95/424 (22.4%) RR 0.98(0.68 to 1.41) 4 fewer per 1,000(from 72 fewer to 92 more) ????MODERATE CRITICAL Duration of Mechanical Ventilation (days)5 randomised trials not serious dserious enot serious serious fnone c586 466 - MD 0.71 lower(1.87 lower to 0.45 higher) ????LOW CRITICAL ICU length of stay in days3 randomised trials not serious serious gnot serious serious hnone c545 424 - MD 0.23 lower(0.57 lower to 0.11 higher) ????LOW CRITICAL Delirium4 randomised trials not serious serious inot serious serious jnone c193/563 (34.3%) 164/444 (36.9%) RR 0.81(0.60 to 1.08) 70 fewer per 1,000(from 30 more to 148 fewer) ????LOW CRITICAL Bradycardia6 randomised trials not serious not serious not serious serious knone c151/583 (25.9%) 39/464 (8.4%) RR 2.44(1.77 to 3.36) 121 more per 1,000(from 65 more to 198 more) ????MODERATE IMPORTANT Hypotension4 randomised trials not serious serious lnot serious serious mnone c192/531 (36.2%) 98/413 (23.7%) RR 1.38(0.79 to 2.41) 90 more per 1,000(from 50 fewer to 335 more) ????LOW IMPORTANT CI: Confidence interval; RR: Risk ratio; MD: Mean differenceExplanationsa. We did not downgraded the quality of evidence for inconsistency, the I2=49% b. We downgraded the quality of evidence by one level for imprecision, the CI included both significant benefit and harm c. We were not able to reliably assess for publication bias d. Although none of the included studies were at low risk of bias, we did not downgrade for risk of bias as its unlikely that the study design biased the results to no difference e. We downgraded the quality of evidence by one level for inconsistency, the I2=91% and not explained by excluding studies with shorter DMV f. We downgraded the quality of evidence for imprecision by one level, the CI included both benefit and harm g. We downgraded the quality of evidence for inconsistency by one level, the I2=52% h. We downgraded the quality of evidence by two levels for imprecision, the number of patients was small and the CI included significant benefit and harm i. We downgraded the quality of evidence by one level for inconsistency, the I2=70% not explained by risk of bias j. We downgraded the quality of evidence by one level for imprecision, the CI included significant benefit and small harm k. We downgraded the quality of evidence for imprecision by one level, the CI included both extreme and large harm and l. We downgraded the quality of evidence by one level for inconsistency, the I2=73% m. We downgraded the quality of evidence by one level for imprecision, the CI included both large benefit and harm QuestionShould an alpha-2 agonist (e.g. dexmedetomidine) vs. a benzodiazepine be used for critically ill ventilated adults (both intubated and non-intubated)?Population:critically ill ventilated adults (both intubated and non-intubated)Intervention:an alpha-2 agonist (e.g. dexmedetomidine) Comparison:a benzodiazepineMain outcomes:28 Day Mortality; Duration of Mechanical Ventilation (days); ICU length of stay in days; Delirium; Bradycardia; Hypotension;AssessmentJudgementResearch evidenceAdditional considerationsProblemIs the problem a priority?● YesDesirable EffectsHow substantial are the desirable anticipated effects?● ModerateWhile there was no difference in outcomes with regards to morality, there were important trends with regards to delirium, duration of MV and ICU LOS. There was discussion of whether the Jacob study really evaluated delirium like all other studies since they did it once 48 hours after stopping sedation. Importantly the study with the lowest risk of bias (Riker 2009) had the greatest impact on Mv and delirium and therefore should guide reccs and the previous guideline reccs should also inform our decision. The way we will show these is all studies first and then sensitivity excluding Jacob. A note was also made that the Jacob MIDEX study had some non invasive ventilation. Doing a subgroup analysis of the low risk of bias studies may be consideredUndesirable EffectsHow substantial are the undesirable anticipated effects?● SmallWhile bradycardia were greater in dex group, it is not clear if these are undesirable. In both Pandharipande and Riker the bradycardia did not require intervention to a greater extent than the benzo group. In some patients bradycardia may be helpful when they are running tachycardic. This guided the recc to say the undesirable impact was smallCertainty of evidenceWhat is the overall certainty of the evidence of effects?● LowOutcomesImportanceQuality of the evidence(GRADE)28 Day MortalityCRITICAL????MODERATEa,b,cDuration of Mechanical Ventilation (days)CRITICAL????LOWc,d,e,fICU length of stay in daysCRITICAL????LOWc,g,hDelirium incidenceCRITICAL????LOWc,i,jBradycardiaIMPORTANT????MODERATEc,kHypotensionIMPORTANT????LOWc,l,mWe did not downgraded the quality of evidence for inconsistency, the I2=49%We downgraded the quality of evidence by one level for imprecision, the CI included both significant benefit and harmWe were not able to reliably assess for publication biasAlthough none of the included studies were at low risk of bias, we did not downgrade for risk of bias as its unlikely that the study design biased the results to no differenceWe downgraded the quality of evidence by one level for inconsistency, the I2=91% and not explained by excluding studies with shorter DMVWe downgraded the quality of evidence for imprecision by one level, the CI included both benefit and harmWe downgraded the quality of evidence by two levels for imprecision, the number of patients was small and the CI included significant benefit and harmWe downgraded the quality of evidence for inconsistency by one level, the I2=52%We downgraded the quality of evidence by one level for inconsistency, the I2=70% not explained by risk of biasWe downgraded the quality of evidence by one level for imprecision, the CI included significant benefit and small harmWe downgraded the quality of evidence for imprecision by one level, the CI included both extreme and large harm and We downgraded the quality of evidence by one level for inconsistency, the I2=73%We downgraded the quality of evidence by one level for imprecision, the CI included both large benefit and harmValuesIs there important uncertainty about or variability in how much people value the main outcomes?● Probably no important uncertainty or variabilityIn discussion with patient representative it was felt that patients would value shorter time on MV, and delirium than the concern for bradycardia given the HR was not determined to greater than a small undesirable effectBalance of effectsDoes the balance between desirable and undesirable effects favor the intervention or the comparison?● Probably favors the interventionAs above- patient rep felt this still favors intervention since bradycardia impact is smallResources requiredHow large are the resource requirements (costs)?○ Large costs○ Moderate costs○ Negligible costs and savings○ Moderate savings○ Large savings○ Varies○ Don't know1. Can J Hosp Pharm 2012;65(2):103–110. ADDIN EN.CITE <EndNote><Cite><Author>Lachaine</Author><Year>2012</Year><RecNum>2477</RecNum><DisplayText>[4]</DisplayText><record><rec-number>2477</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507736427">2477</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lachaine, J.</author><author>Beauchemin, C.</author></authors></contributors><auth-address>, PhD, is Associate Professor in the Faculty of Pharmacy, Universite de Montreal, Montreal, Quebec.</auth-address><titles><title>Economic evaluation of dexmedetomidine relative to midazolam for sedation in the intensive care unit</title><secondary-title>Can J Hosp Pharm</secondary-title><alt-title>The Canadian journal of hospital pharmacy</alt-title></titles><periodical><full-title>Can J Hosp Pharm</full-title><abbr-1>The Canadian journal of hospital pharmacy</abbr-1></periodical><alt-periodical><full-title>Can J Hosp Pharm</full-title><abbr-1>The Canadian journal of hospital pharmacy</abbr-1></alt-periodical><pages>103-10</pages><volume>65</volume><number>2</number><edition>2012/04/25</edition><keywords><keyword>dexmedetomidine</keyword><keyword>economic evaluation</keyword><keyword>intensive care unit</keyword><keyword>sedation</keyword></keywords><dates><year>2012</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0008-4123</isbn><accession-num>22529402</accession-num><urls></urls><custom2>PMC3329902</custom2><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[4]The average cost of the medication DEX Vs. midazolam ($1929.57 Vs. $180.10 per patient).Average costs associated with mechanical ventilation ($2939 Vs. $4448) and management of delirium ($2127 Vs. $3012). The overall cost per patient was ($7022 V. $7680). Cost effectiveness favors alpha2 agonists (dex) but costs are varied since off patent but still many countries have different costs for dex which makes this challengingCertainty of evidence of required resourcesWhat is the certainty of the evidence of resource requirements (costs)?x LowCost effectivenessDoes the cost-effectiveness of the intervention favor the intervention or the comparison?● Probably favors the interventionAcceptabilityIs the intervention acceptable to key stakeholders?● Probably yesFeasibilityIs the intervention feasible to implement?● YesSummary of judgementsJudgementProblemNoProbably noProbably yesYesVariesDon't knowDesirable EffectsTrivialSmallModerateLargeVariesDon't knowUndesirable EffectsLargeModerateSmallTrivialVariesDon't knowCertainty of evidenceVery lowLowModerateHighNo included studiesValuesImportant uncertainty or variabilityPossibly important uncertainty or variabilityProbably no important uncertainty or variabilityNo important uncertainty or variabilityNo known undesirable outcomesBalance of effectsFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesDon't knowResources requiredLarge costsModerate costsNegligible costs and savingsModerate savingsLarge savingsVariesDon't knowCertainty of evidence of required resourcesVery lowLowModerateHighNo included studiesCost effectivenessFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesNo included studiesEquityReducedProbably reducedProbably no impactProbably increasedIncreasedVariesDon't knowAcceptabilityNoProbably noProbably yesYesVariesDon't knowFeasibilityNoProbably noProbably yesYesVariesDon't knowConclusions: Should an alpha-2 agonist (e.g. dexmedetomidine) vs. a benzodiazepine be used in critically ill ventilated adults (both intubated and non-intubated)?Type of recommendationStrong recommendation against the interventionConditional recommendation against the interventionConditional recommendation for either the intervention or the comparisonConditional recommendation for the interventionStrong recommendation for the intervention○ ○ ○ ● ○ RecommendationWe suggest using an alpha-2 agonist (e.g. dexmedetomidine) over BZD for sedation in critically ill ventilated patients (conditional recommendation, low QOE)JustificationWhile there was no difference in outcomes with regards to morality, there were important trends with regards to delirium, duration of MV and ICU LOS. For the general medical and surgical ICU patients who have been on sedation for a while (excluding the fast track surgical and cardiac surgical patients discussed earlier), the group, including the patient representative, felt that shortened time to light sedation of at least 4 hours and time to extubation of approximately 8-12 hours (a shift or so) were clinically significant. Important to note that the Jacob study evaluated delirium differently than the other studies since they did it once 48 hours after stopping sedation. The study with the lowest risk of bias (Riker 2009) ADDIN EN.CITE <EndNote><Cite><Author>Riker</Author><Year>2009</Year><RecNum>1952</RecNum><DisplayText>[5]</DisplayText><record><rec-number>1952</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232815">1952</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Riker, Richard R.</author><author>Shehabi, Yahya</author><author>Bokesch, Paula M.</author><author>Ceraso, Daniel</author><author>Wisemandle, Wayne</author><author>Koura, Firas</author><author>Whitten, Patrick</author><author>Margolis, Benjamin D.</author><author>Byrne, Daniel W.</author><author>Ely, E. Wesley</author><author>Rocha, Marcelo G.</author><author>Sedcom Study Group</author></authors></contributors><auth-address>University of Vermont College of Medicine, USA. rikerr@</auth-address><titles><title>Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial</title><secondary-title>JAMA</secondary-title></titles><periodical><full-title>JAMA</full-title></periodical><pages>489-499</pages><volume>301</volume><number>5</number><dates><year>2009</year><pub-dates><date>2009/2/4</date></pub-dates></dates><isbn>0098-7484</isbn><urls><related-urls><url> Papers/R/Riker et al. 2009 - Dexmedetomidine vs midazolam for sedation of critically ill patients - a randomized trial.pdf</url></pdf-urls></urls><electronic-resource-num>10.1001/jama.2009.56</electronic-resource-num></record></Cite></EndNote>[5] had the greatest impact on MV and delirium and therefore guided recommendations. ?Low quality evidence ?Moderate benefit with regards to DMV, delirium and ICU LOS, uncertainty about other outcomes ?Small harm possibly with bradycardia. Important to note that bradycardia may be considered beneficial in some circumstances in the ICU, therefore cannot always be considered as a harmful effect. The Riker and Pandharipande studies both demonstrated higher bradycardia in the dex group but there were no differences in the patients that were deemed to require treatment for the bradycardia ?Values and preferences probably will not vary between patients ?DEX is cost-effectiveness ?Intervention is likely acceptable and feasible to implement Low risk of bias study has outcomes favoring intervention supporting recommendations comments during electronic Voting by Entire panelsuitability of benzos under certain circumstances? Knowledge gap how to sedate hemodynamically unstable patients very helpful to have the risk of bias chart on the forest plot as it is shown here.A reader of this recommendation will not know if we are recommending Dexmed infusion rather than attempting prn bolus dosing of benzo, or Dexmed vs. benzo infusion. no statistically significant differences in the meta-analyses to support this recommendation. subgroup analysis of the RCT(s) with low risk of bias first. Similar to last set of guidelines and we may not want to contradict, but I no current strength of evidence supporting a conditional recommendation without further analyses to discount the higher ROB; No significant out-come difference across RCTsQuestion: An alpha-2 agonist (e.g., dexmedetomidine) compared to propofol in critially ill ventilated adults (both intubated and non-intubated) Quality assessment№ of patientsEffectQualityImportance№ of studiesStudy designRisk of biasInconsistencyIndirectnessImprecisionOther considerationsan alpha-2 agonist (e.g., dexmedetomidine)propofolRelative(95% CI)Absolute(95% CI)28 Day Mortality1 randomised trials not serious not serious not serious serious anone b37/246 (15.0%) 46/249 (18.5%) RR 0.81(0.55 to 1.21) 35 fewer per 1,000(from 39 more to 83 fewer) ????MODERATE CRITICAL Delirium1 randomised trials serious cnot serious not serious serious dnone b7/246 (2.8%) 19/249 (7.6%) RR 0.37(0.16 to 0.87) 48 fewer per 1,000(from 10 fewer to 64 fewer) ????LOW CRITICAL Duration of Mechanical Ventilation in hours3 randomised trials serious enot serious not serious serious fnone b427 423 - MD 0.04 hours lower(0.08 lower to 0.01 lower) ????LOW CRITICAL ICU Length of stay in days1 randomised trials not serious not serious not serious very serious gnone b251 247 - MD 2.83 days fewer(8.13 fewer to 2.47 more) ????LOW CRITICAL Bradycardia1 randomised trials not serious not serious not serious serious hnone b32/246 (13.0%) 27/249 (10.8%) RR 1.20(0.74 to 1.94) 22 more per 1,000(from 28 fewer to 102 more) ????MODERATE IMPORTANT Hypotension1 randomised trials not serious not serious not serious serious inone b32/246 (13.0%) 33/249 (13.3%) RR 0.98(0.62 to 1.54) 3 fewer per 1,000(from 50 fewer to 72 more) ????MODERATE IMPORTANT CI: Confidence interval; RR: Risk ratio; MD: Mean differenceExplanationsa. We downgraded the quality of evidence for imprecision by one level, the CI included both benefit and harm b. We were not able to reliably assess for publication bias c. We downgraded the quality of evidence by one level for risk of bias, the trial was judged to be at high risk of bias d. We downgraded the quality of evidence by one level for imprecision, the CI is very wide and the total number of events is low (26 events in total) e. We downgraded the quality of evidence by one level for risk of bias, the studies were all at high risk of bias, and we can't exclude the possibility of bias f. We downgraded the quality of evidence by one level for imprecision, the CI included both trivial and significant benefit g. We downgraded the quality of evidence by two levels for serious imprecision, the CI included very large benefit and harm h. We downgraded the quality of evidence by one level for imprecision, the CI included large harm and benefit i. We downgraded the quality of evidence for imprecision by one level, the CI included both significant benefit and harm QuestionShould an alpha-2 agonist (e.g., dexmedetomidine) vs. propofol be used for critially ill ventilated adults (both intubated and non-intubated)?Population:critially ill ventilated adults (both intubated and non-intubated)Background:Intervention:an alpha-2 agonist (e.g., dexmedetomidine)Comparison:propofolMain outcomes:28 Day Mortality; Delirium; Duration of Mechanical Ventilation in hours; ICU Length of stay in days; Bradycardia; Hypotension;AssessmentJudgementResearch evidenceAdditional considerationsProblemIs the problem a priority?● YesDesirable EffectsHow substantial are the desirable anticipated effects?● SmallThere was a consistent message with about a day shorter on mechanical ventilation but no difference in most other outcomes. Similar to the alpha2 vs benzo comparisons the Jakob PRODEX ADDIN EN.CITE <EndNote><Cite><Author>Jakob</Author><Year>2012</Year><RecNum>1950</RecNum><DisplayText>[6]</DisplayText><record><rec-number>1950</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232815">1950</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jakob, Stephan M.</author><author>Ruokonen, Esko</author><author>Grounds, R. Michael</author><author>Sarapohja, Toni</author><author>Garratt, Chris</author><author>Pocock, Stuart J.</author><author>Bratty, J. Raymond</author><author>Takala, Jukka</author><author>Dexmedetomidine for Long-Term Sedation, Investigators</author></authors></contributors><auth-address>Department of Intensive Care Medicine, Bern University Hospital and University of Bern, Bern, Switzerland.</auth-address><titles><title>Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials</title><secondary-title>JAMA</secondary-title></titles><periodical><full-title>JAMA</full-title></periodical><pages>1151-1160</pages><volume>307</volume><number>11</number><dates><year>2012</year><pub-dates><date>2012/3/21</date></pub-dates></dates><isbn>0098-7484</isbn><urls><related-urls><url> Papers/J/Jakob et al. 2012 - Dexmedetomidine vs midazolam or propofol for sedati ... ng prolonged mechanical ventilation - two randomized controlled trials.pdf</url></pdf-urls></urls><electronic-resource-num>10.1001/jama.2012.304</electronic-resource-num></record></Cite></EndNote>[6] study's eval of delirium was considered difficult to interpret because of its distant measurement. With regards to ICU LOS wide CI. So really only difference was small diff in MVUndesirable EffectsHow substantial are the undesirable anticipated effects?● TrivialBradycardia was not different and the hypotension was not diffferent so no real undersirable effect differencesCertainty of evidenceWhat is the overall certainty of the evidence of effects?● LowValuesIs there important uncertainty about or variability in how much people value the main outcomes?● Probably no important uncertainty or With a small difference in MV and no difference in undersiable effects effects the patient rep felt most would not have any uncertainty on what they would prefer Balance of effectsDoes the balance between desirable and undesirable effects favor the intervention or the comparison?● Probably favors the interventionResources requiredHow large are the resource requirements (costs)?● Don't knowno cost data comparing propofol and dexCertainty of evidence of required resourcesWhat is the certainty of the evidence of resource requirements (costs)?● No included studiesCost effecti-venessDoes the cost-effectiveness of the intervention favor the intervention or the comparison?● No included studiesAccept-abilityIs the intervention acceptable to key stakeholders?● Probably yesFeasibilityIs the intervention feasible to implement?● YesSummary of judgementsJudgementProblemNoProbably noProbably yesYesVariesDon't knowDesirable EffectsTrivialSmallModerateLargeVariesDon't knowUndesirable EffectsLargeModerateSmallTrivialVariesDon't knowCertainty of evidenceVery lowLowModerateHighNo included studiesValuesImportant uncertainty or variabilityPossibly important uncertainty or variabilityProbably no important uncertainty or variabilityNo important uncertainty or variabilityNo known undesirable outcomesBalance of effectsFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesDon't knowResources requiredLarge costsModerate costsNegligible costs and savingsModerate savingsLarge savingsVariesDon't knowCertainty of evidence of required resourcesVery lowLowModerateHighNo included studiesCost effectivenessFavors the comparisonProbably favors the comparisonDoes not favor either the intervention or the comparisonProbably favors the interventionFavors the interventionVariesNo included studiesEquityReducedProbably reducedProbably no impactProbably increasedIncreasedVariesDon't knowAcceptabilityNoProbably noProbably yesYesVariesDon't knowFeasibilityNoProbably noProbably yesYesVariesDon't knowConclusionsShould an alpha-2 agonist (e.g., dexmedetomidine) vs. propofol be used in critially ill ventilated adults (both intubated and non-intubated)?Type of recommendationStrong recommendation against the interventionConditional recommendation against the interventionConditional recommendation for either the intervention or the comparisonConditional recommendation for the interventionStrong recommendation for the intervention○ ○ ● ○ ○ RecommendationWe suggest using either dexmedetomidine or propofol for sedation in critically ill patients (conditional reccomendation, low QOE)JustificationFor the general medical and surgical ICU patients who have been on sedation for a while (excluding the fast track surgical and cardiac surgical patients discussed earlier), the group, including the patient representative, felt that shortened time to light sedation of at least 4 hours and time to extubation of approximately 8-12 hours (a shift or so) were clinically significant. There was a consistent message with about shorter time on mechanical ventilation with dexmedetomidine but no difference in most other outcomes. Similar to the alpha2 vs benzo comparisons the Jakob PRODEX ADDIN EN.CITE <EndNote><Cite><Author>Jakob</Author><Year>2012</Year><RecNum>1950</RecNum><DisplayText>[6]</DisplayText><record><rec-number>1950</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232815">1950</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jakob, Stephan M.</author><author>Ruokonen, Esko</author><author>Grounds, R. Michael</author><author>Sarapohja, Toni</author><author>Garratt, Chris</author><author>Pocock, Stuart J.</author><author>Bratty, J. Raymond</author><author>Takala, Jukka</author><author>Dexmedetomidine for Long-Term Sedation, Investigators</author></authors></contributors><auth-address>Department of Intensive Care Medicine, Bern University Hospital and University of Bern, Bern, Switzerland.</auth-address><titles><title>Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials</title><secondary-title>JAMA</secondary-title></titles><periodical><full-title>JAMA</full-title></periodical><pages>1151-1160</pages><volume>307</volume><number>11</number><dates><year>2012</year><pub-dates><date>2012/3/21</date></pub-dates></dates><isbn>0098-7484</isbn><urls><related-urls><url> Papers/J/Jakob et al. 2012 - Dexmedetomidine vs midazolam or propofol for sedati ... ng prolonged mechanical ventilation - two randomized controlled trials.pdf</url></pdf-urls></urls><electronic-resource-num>10.1001/jama.2012.304</electronic-resource-num></record></Cite></EndNote>[6] study's evaluation of delirium was considered difficult to interpret because of its distant measurement. With regards to ICU LOS there were wide CI, hence the only difference was small diff in MV There was furthermore, no new evidence since the 2013 guidelines which would warrant a change in the interpretation of the data and thus the recommendations ?Low quality evidence?Small benefit?Uncertainty about other outcomes?Trivial harm?V&P probably will not vary between patients?Uncertain effect on cost?Intervention is likely acceptable and feasible to implementcomments during electronic Voting by Entire panelIs dex preferable in patients at highest risk of delirium or peri-extubation? These are not equivalent.Recommendation wording not specific enough when compared to the question. Challenged by text vs. the meta-analysis. In the meta-analysis, the difference in MV duration was very small, but the text suggests a 1 day difference. In a recommendation stating "we suggest using either dexmed or ppfol..." the comparator is not clear. The recommendation infers it compares other sedative agents (i.e. benzos), when this was really a comparison of only these 2 drugs. Can we give a more direct recommendation based on the question as originally posed?References ADDIN EN.REFLIST 1.Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Murray L, Seppelt IM, Webb S et al: Early goal-directed sedation versus standard sedation in mechanically ventilated critically III patients: A pilot study. Crit Care Med 2013, 41(8):1983-1991.2.Treggiari M: Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med 2010, 38(1):349-350.3.Tanaka LMS, Azevedo LCP, Park M, Schettino G, Nassar AP, Re?a-Neto A, Tannous L, de Souza-Dantas VC, Torelly A, Lisboa T et al: Early sedation and clinical outcomes of mechanically ventilated patients: A prospective multicenter cohort study. Crit Care 2014, 18(4).4.Lachaine J, Beauchemin C: Economic evaluation of dexmedetomidine relative to midazolam for sedation in the intensive care unit. The Canadian journal of hospital pharmacy 2012, 65(2):103-110.5.Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW et al: Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009, 301(5):489-499.6.Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J, Dexmedetomidine for Long-Term Sedation I: Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012, 307(11):1151-1160. ................
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