Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis

Hughes, Christopher; Mailloux, Patrick; Devlin, John W.; Swan, Joshua T.; Sanders, Robert D.; Anzueto, Antonio; Jackson, James C.; Hoskins, Aimee S.; Pun, Brenda T.; Orun, Onur M.; Raman, Rameela; Stollings, Joanna L.; Kiehl, Amy L.; Duprey, Matthew; Bui, Lan N.; O’Neal, Hollis R.; Snyder, Allison; Gropper, Michael A.; Guntupalli, Kalpalatha K.; Stashenko, Gregg J.; Patel, Mayur B.; Brummel, Nathan E.; Girard, Timothy D.; Dittus, Robert S.; Bernard, Gordon R.; Ely, E. Wesley; Pandharipande, Pratik

doi:10.1056/nejmoa2024922

Cited by 177 publications

(171 citation statements)

References 40 publications

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“…In addition, we reported VFDs as a co-primary outcome, which assumes that interventions may shorten ventilator duration, and improve mortality, thereby increasing efficiency as an outcome measure. In our trial, ketamine did not decrease the duration of MV and the median VFDs in our cohort is consistent with the one reported in the MENDS2 sedation trial; adjusted median, 23.7 days in dexmedetomidine vs. 24 days in propofol; OR, 0.96; 95% CI, 0.74 to 1.26) [25] . This neutral effect on VFDs could be because the majority of our population was from the medical ICU (48.2% of the entire cohort) and had moderate ARDS with a median baseline PaO2/FiO2 ratio of 152.…”

Section: Discussionsupporting

confidence: 91%

Adjunctive Ketamine for Sedation in Critically Ill Mechanically Ventilated Patients: An Active-Controlled, Pilot, Feasibility Clinical Trial

Amer

Bawazeer

Maghrabi

et al. 2021

Preprint

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Background: Ketamine showed to decrease sedative requirements in intensive care unit (ICU). Randomized trials are lacking on patient centered outcome. We aimed to compare the clinical characteristics and outcomes of mechanically ventilated adult ICU patients receiving ketamine as an adjunct analgosedative agent with those receiving standard of care (SOC) alone. We also described the feasibility during COVID-19 pandemic. Methods: In this randomized, open-label trial either ketamine or SOC, in a 1:1 ratio, was administered to patients who were intubated within 24 h (medical, surgical, or transplant/oncology ICUs), expected to require mechanical ventilation (MV) for the next calendar day, and had the institutional pain and sedation protocol initiated. Ketamine infusion was 2 μg/kg/min on day 1 and 1 μg/kg/min on day 2. The primary outcome was the 28-day MV duration and ventilator-free days as co-primary outcome. Cox-proportional regression analysis was used to assess factors associated with probability for weaning off MV. Results: A total of 83 patients (43 in SOC and 40 in ketamine) were included. Demographics were balanced between the groups. The median duration of MV was not significantly different between the groups [median (interquartile range): 7 (3;9.25) for ketamine and 5 (2;8) for SOC, p= 0.15]. The median ventilation-free days was 19 days (IQR 0;24.75) in the ketamine and 19 days (IQR 0;24) in the SOC (p=0.70). Surgical and transplant/oncology ICU patients had a higher probability of weaning off MV than those in medical ICU [hazard ratio (95% confidence interval) : 2.09 (1.06;4.14) for surgical ICU, 2.11 (1.02;4.35) for transplant/oncology ICU]. More patient was at goal RASS in ketamine compared to SOC. The sedatives and vasopressors cumulative doses were similar between the two arms at 48 h. We found no difference in 28-day mortality rate, ICU and hospital length of stay, and hemodynamic changes. The consent rate was adequate and the protocol adherence rate was 97.5%. Conclusions: Ketamine as an adjunct agent for sedation did not decrease the duration of MV and appeared to be safe, feasible, and effective in subgroups of ICU patients. No effect was noted in sedative and pressors requirements, or on hemodynamics. Trial registration: ClinicalTrials.gov: NCT04075006 and current-controlled trials: ISRCTN14730035

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Section: Discussionsupporting

confidence: 91%

Adjunctive Ketamine for Sedation in Critically Ill Mechanically Ventilated Patients: An Active-Controlled, Pilot, Feasibility Clinical Trial

Amer

Bawazeer

Maghrabi

et al. 2021

Preprint

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“…98 No lower mortality or delirium rates were seen with dexmedetomidine compared to propofol in a very recent study in mechanically ventilated patients with sepsis and mild sedation. 99 This study reported relevant cognitive dysfunction in about 25% of the surviving patients with a mean age of 60 years, which was not influenced by the selection of the sedative.…”

Section: Nutritionmentioning

confidence: 60%

Updated Perspectives on the Management of Sleep Disorders in the Intensive Care Unit

Nilius¹,

Richter²,

Schroeder³

2021

NSS

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Sleep disorders and circadian dysrhythmias are extremely prevalent in critically ill patients. Impaired sleep has a variety of etiologies, exhibits a wide range of negative effects and, moreover, might deteriorate the patient's prognosis. Despite a number of scientific findings and increased awareness, the importance of sleep optimization is still lower on the list of priories in the intensive care unit (ICU). The techniques of measuring and the evaluation of sleep quantity and quality are a great challenge in the ICU setting. The subjective and objective tools of sleep validation continue to suffer from deficiencies. Treatment approaches to improve the critically ill patient's sleep have focused on nonpharmacologic and pharmacologic strategies with some promising results. But pharmacological interventions alone could not provide sufficient patient benefit. Being aware and knowing of sleep problems and the beneficial effect of the necessary therapies in ICU patients requires greater acceptance. The application of available methods and the development of new methods to prevent sleep disorders in the ICU offer the potential to improve the critically ill patient's outcome.

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“…Nine interventions studied in 26 trials ( N = 11,385) [ 34 – 36 , 40 , 44 , 49 – 51 , 55 , 56 , 59 , 62 , 67 , 69 , 73 , 74 , 76 , 81 , 82 , 85 , 97 – 99 , 102 , 107 , 113 ] connected to the evidence network for mortality (Table 1 , Fig. 2 E, eTable 5); 25% (9/36) of the pairwise comparisons were direct evidence.…”

Section: Resultsmentioning

confidence: 99%

Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis

et al. 2021

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Purpose To compare the effects of prevention interventions on delirium occurrence in critically ill adults. Methods MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clinical trial registry were searched from inception to April 8, 2021. Randomized controlled trials of pharmacological, sedation, non-pharmacological, and multi-component interventions enrolling adult critically ill patients were included. We performed conventional pairwise meta-analyses, NMA within Bayesian random effects modeling, and determined surface under the cumulative ranking curve values and mean rank. Reviewer pairs independently extracted data, assessed bias using Cochrane Risk of Bias tool and evidence certainty with GRADE. The primary outcome was delirium occurrence; secondary outcomes were durations of delirium and mechanical ventilation, length of stay, mortality, and adverse effects. Results Eighty trials met eligibility criteria: 67.5% pharmacological, 31.3% non-pharmacological and 1.2% mixed pharmacological and non-pharmacological interventions. For delirium occurrence, 11 pharmacological interventions (38 trials, N = 11,993) connected to the evidence network. Compared to placebo, only dexmedetomidine (21/22 alpha 2 agonist trials were dexmedetomidine) probably reduces delirium occurrence (odds ratio (OR) 0.43, 95% Credible Interval (CrI) 0.21–0.85; moderate certainty). Compared to benzodiazepines, dexmedetomidine (OR 0.21, 95% CrI 0.08–0.51; low certainty), sedation interruption (OR 0.21, 95% CrI 0.06–0.69; very low certainty), opioid plus benzodiazepine (OR 0.27, 95% CrI 0.10–0.76; very low certainty), and protocolized sedation (OR 0.27, 95% CrI 0.09–0.80; very low certainty) may reduce delirium occurrence but the evidence is very uncertain. Dexmedetomidine probably reduces ICU length of stay compared to placebo (Ratio of Means (RoM) 0.78, CrI 0.64–0.95; moderate certainty) and compared to antipsychotics (RoM 0.76, CrI 0.61–0.98; low certainty). Sedative interruption, protocolized sedation and opioids may reduce hospital length of stay compared to placebo, but the evidence is very uncertain. No intervention influenced mechanical ventilation duration, mortality, or arrhythmia. Single and multi-component non-pharmacological interventions did not connect to any evidence networks to allow for ranking and comparisons as planned; pairwise comparisons did not detect differences compared to standard care. Conclusion Compared to placebo and benzodiazepines, we found dexmedetomidine likely reduced the occurrence of delirium in critically ill adults. Compared to benzodiazepines, sedation-minimization strategies may also reduce delirium occurrence, but the evidence is uncertain. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06490-3.

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Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis

Cited by 177 publications

References 40 publications

Adjunctive Ketamine for Sedation in Critically Ill Mechanically Ventilated Patients: An Active-Controlled, Pilot, Feasibility Clinical Trial

Adjunctive Ketamine for Sedation in Critically Ill Mechanically Ventilated Patients: An Active-Controlled, Pilot, Feasibility Clinical Trial

Updated Perspectives on the Management of Sleep Disorders in the Intensive Care Unit

Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis

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