Title: Ketamine versus Dexmedetomidine for ICU Sedation
Authors: Rebecca Olisa, Anh Nguyen, Jana Mills, Nikulkumar Chaudhari, MD
Background/Purpose:
Critically ill, mechanically ventilated patients often require sedation to manage pain and agitation. Traditional agents like benzodiazepines and propofol can prolong ventilation and increase intensive care unit (ICU) delirium. Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, offers potent analgesia and hemodynamic support but carries a risk of psychomimetic effects. Conversely, dexmedetomidine, an alpha-2 agonist, provides cooperative sedation and reduced delirium without respiratory depression, though its use is often limited by bradycardia and hypotension. Evidence suggests that using these agents, individually or combined, can improve sedation quality, stabilize hemodynamics, and reduce time to extubation when compared to traditional sedatives.
This retrospective chart review evaluated the impact of ketamine or dexmedetomidine on clinical outcomes in mechanically ventilated patients with the primary endpoint being time from initiation of continuous sedation, with ketamine or dexmedetomidine, to successful extubation.
Methods:
This single-center retrospective cohort study was conducted between October 31, 2022, and July 31, 2025. Adult patients were eligible for inclusion if they required mechanical ventilation and received continuous infusions of either ketamine or dexmedetomidine, whether administered alone or were begun as adjuncts to wean traditional sedatives.
Patients were excluded from the analysis if they failed to receive either dexmedetomidine or ketamine, or if they received both agents concurrently or sequentially during a single ICU stay. Further clinical exclusions included patients receiving ketamine at a fixed rate or a dose exceeding 2 mg/kg/hour, those with an overlap of more than 24 hours between primary and adjunctive sedatives, individuals with an ICU stay of less than 24 hours or mortality prior to extubation, and patients who were transitioned to comfort measures, diagnosed with anoxic brain injury, or pregnant.
The primary endpoint was the time from initiation of continuous sedation with ketamine or dexmedetomidine to successful extubation. Secondary assessments included ICU length of stay, total ventilator duration, and the incidences of ICU mortality, hemodynamic instability, and delirium.
Results:
A total of 20 patients met inclusion criteria, 7 in the ketamine group, and 13 in the dexmedetomidine group. The two groups were similar in age (mean 55.6 ± 14.7 vs. 60.8 ± 14.6 years, p = 0.751) and sex distribution (57.1% vs. 53.8% female). Median pre-initiation ventilation times for ketamine and dexmedetomidine were 7.82 vs. 12.30 hours (p=0.699). These comparable durations, alongside similar Richmond Agitation-Sedation Scale scores (RASS), indicate equivalent sedation depth and suggest that pre-sedation ventilation did not confound the primary outcome. For the primary endpoint, ketamine was associated with a shorter median time from sedation initiation to extubation compared to dexmedetomidine (15.5 vs. 23.2 hours), though this difference did not reach statistical significance (p = 0.157). Among secondary endpoints, ketamine patients had numerically shorter total ventilator duration (median 24.3 vs. 39.9 hours, p = 0.097) and ICU length of stay (median 2.0 vs. 3.0 days, p = 0.057). Rates of ICU delirium were lower in the ketamine group (28.6% vs. 46.2%, p = 0.642), as were rates of hemodynamic instability (0% vs. 15.4%, p = 0.521). No deaths occurred in either group during the ICU stay.
Conclusion:
This retrospective pilot study compared ketamine and dexmedetomidine as primary weaning agents for mechanically ventilated patients at two sites within a single healthcare system. Although underpowered for statistical significance, ketamine was associated with shorter times to extubation, reduced ventilator duration, and shorter ICU stays. Furthermore, the ketamine group experienced lower rates of delirium and hemodynamic instability, with no deaths in either cohort. These findings suggest a consistent trend favoring ketamine and support the rationale for a larger, randomized study to definitively evaluate its utility as a weaning sedative in this population. Future research should incorporate illness severity scoring and standardized weaning protocols to build on these promising preliminary trends.
