Ketamine for Analgosedation in Mechanically Ventilated Adults: A Double-Blind Randomized Trial

Abstract

OBJECTIVES: The role of ketamine for analgosedation in the ICU remains unclear. This study aimed to assess the efficacy of low-dose ketamine infusion for adjunct analgosedation in adults receiving mechanical ventilation. DESIGN: A prospective, double blind, randomized, placebo-controlled trial. SETTING: The study was conducted at two university-affiliated ICUs in Melbourne, Australia, between September 2022 and December 2024. PATIENTS: Adult patients receiving mechanical ventilation in the ICU who were also receiving opioid infusion for analgosedation (excluding cardiac surgical patients). INTERVENTIONS: Patients were randomized to receive low-dose ketamine infusion (0.15 mg/kg/hr) or placebo during the period of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the hourly dose of opioids. Secondary outcomes included, among others, delirium, as well as ventilator, ICU, and hospital-free days to day 28. A total of 538 patients were screened for inclusion. Of these, 413 patients were ineligible based on exclusion criteria. A further five patients had consent withdrawn, leaving 120 patients (59 ketamine and 61 placebo) included for primary analysis. The median (interquartile range) hourly dose of opioids in fentanyl equivalents was 64 µg/hr (36-89 µg/hr) in the ketamine group and 77 µg/hr (47-100 µg/hr) in the placebo group (median difference, -13.0 [95% credible interval, -26.6 to 2.4]; probability of benefit, 95.1%). There were no differences between groups for most of the secondary outcomes, including delirium and significant adverse events. CONCLUSIONS: Low-dose ketamine infusion appeared safe and was associated with a reduction in hourly opioid requirements in ICU patients receiving mechanical ventilation. Larger randomized controlled trials are required to assess effects on other patient-centered outcomes.