Comparison of sedation with dexmedetomidine versus lorazepam in septic ICU patients

Abstract

Introduction New strategies for sedation in mechanically ventilated (MV) patients have yielded improvements in patient outcomes, including acute brain dysfunction, but the differential effect of sedation regimens across patient diagnosis categories is not known. In this pilot project, we evaluated the impact of sedation using dexmedetomidine versus lorazepam, in an a priori determined subgroup of septic patients enrolled in the MENDS trial 1. Methods The MENDS study enrolled 103 adult medical/surgical MV patients and excluded those with neurological disease, severe liver failure, active coronary ischemia, and seizures. Patients were randomized in a double-blind fashion to receive dexmedetomidine (DEX)-based (maximum 1.5 g/kg/hour) or lorazepam (LZ)-based (maximum 10 mg/hour) sedation for up to 5 days, titrated to a target Richmond Agitation-Sedation Scale score. Patients were monitored for delirium daily with the Confusion Assessment Method for the ICU. Results Thirty-nine patients in the MENDS study were admitted with sepsis, with 19 in the DEX group and 20 in the LZ group. Baseline demographics, ICU type and admission diagnoses of this septic subgroup were balanced between DEX and LZ, with the median (interquartile range) age being 57 (49, 66) vs 55 (44, 65) years, P = 0.66 and APACHE II scores of 30 (24, 32) vs 28.5 (25, 32), P = 0.86, respectively. The median DEX dose was 0.9 g/kg/hour and the median LZ dose was 3 mg/hour. DEX patients had greater delirium and coma-free days (8 (4, 10) vs 1.5 (0.7, 5) days, P = 0.002), delirium-free days (10 (7.5, 11) vs 7.4 (4, 8.2) days, P = 0.007), MV-free days (9.5 (0, 11.6) vs 2 (0, 8.5) days, P = 0.037) and a reduction in the risk of dying at 28 days (hazard ratio 0.3 (0.1, 0.9), P = 0.036) as compared with the LZ patients. Conclusion In this subgroup analysis of severe sepsis patients from the MENDS trial, sedation incorporating dexmedetomidine reduced the duration of delirium and coma and the length of time on the ventilator, and decreased the risk of dying as compared with lorazepam. This serves as a hypothesis-generating analysis to help direct further prospective study in such patients.