Adjunctive Ketamine for Sedation in Critically Ill Mechanically Ventilated Patients: An Active-Controlled, Pilot, Feasibility Clinical Trial
Edward De Vol,
Posted 29 Apr 2021
medRxiv DOI: 10.1101/2021.04.26.21256072
Posted 29 Apr 2021
BackgroundKetamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are lacking on patient-centered outcomes. We aimed to compare the clinical characteristics and outcomes of mechanically ventilated adult ICU patients receiving ketamine as an adjunct analgosedative with those receiving standard of care (SOC) alone. We also described the feasibility during COVID-19 pandemic. MethodsIn this randomized, open-label trial either ketamine or SOC, in a 1:1 ratio, was administered to patients who were intubated within 24 hours (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 g/kg/min on day 1 and 1 g/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. ResultsA 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 hours. 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%. ConclusionsKetamine 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 registrationClinicalTrials.gov: NCT04075006 and current-controlled trials: ISRCTN14730035
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