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Comparative Outcomes of Ketamine Versus Dexmedetomidine Sedation in Mechanically Ventilated ICU Patients
Abstract   Peer reviewed

Comparative Outcomes of Ketamine Versus Dexmedetomidine Sedation in Mechanically Ventilated ICU Patients

K K Das, Z Li and P Tiberio
American journal of respiratory and critical care medicine, v 212(Supplement_1), A55-45
01 May 2026
DOI: https://doi.org/10.1093/ajrccm/aamag162.4636

Abstract

Rationale Sedation is a key component of care for mechanically ventilated ICU patients, with current guidelines favoring dexmedetomidine or propofol for light sedation. Ketamine is increasingly utilized in ICU patients with shock due to its favorable hemodynamics, yet supporting evidence remains limited. Comparative outcome data between ketamine and dexmedetomidine infusions are underexplored. This study evaluates 28-day and 3-month outcomes in ICU patients with acute respiratory failure receiving ketamine or dexmedetomidine. Methods A retrospective cohort study was conducted using the TriNetX US Collaborative Network, aggregating de-identified electronic health records from 71 healthcare organizations. Adults (≥18 years) receiving mechanical ventilation with ketamine or dexmedetomidine were identified using International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes. The index date was defined as the first concurrent administration of the sedative and mechanical ventilation. Propensity score matching (1:1) was performed across demographics, comorbidities, and concurrent medications. Outcomes assessed at 28 days and 3 months included mortality, vasopressor use, dialysis, emergent re-intubation, acute brain dysfunction (defined as delirium, disorientation, or coma), use of adjunctive sedatives (propofol and fentanyl), major adverse cardiac events (acute myocardial infarction, cardiac arrest, or heart failure), and utilization of critical care services. Risk differences, risk ratios (RR), and hazard ratios (HR) were calculated using the TriNetX statistical engine. Results From 2005 to the present, a total of 26,595 patients received ketamine and 48,168 received dexmedetomidine during mechanical ventilation. After matching, 25,961 patients per group (51,922 total) were analyzed. At 28 days, mortality was similar between groups (HR = 1.02, 95% CI 0.98-1.05). Compared with dexmedetomidine, ketamine was associated with higher risk of emergent intubation (RR = 1.04, 95% CI 1.02-1.06), vasopressor exposure (RR = 1.04, 95% CI 1.03-1.05), acute brain dysfunction (RR = 1.12, 95% CI 1.07-1.16), as well as greater adjunctive sedative exposure to propofol (RR = 1.01, 95% CI 1.00-1.02) and fentanyl (RR = 1.03, 95% CI 1.02-1.03). In contrast, major adverse cardiac events (RR = 0.86, 95% CI 0.82-0.89), critical care service utilization (RR = 0.93, 95% CI 0.92-0.94), and dialysis rates (RR = 0.89, 95% CI 0.85-0.93) were lower in patients who received ketamine. Outcomes were similar at 3 months. Conclusion In mechanically ventilated patients, sedation with ketamine was associated with worse outcomes at 28 days and 3 months compared with those receiving dexmedetomidine, highlighting the need for prospective studies to define its optimal role in critical care.

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