Pharmacological Management of Delirium in the Intensive Care Unit: A Randomized Pragmatic Clinical Trial

BACKGROUND/OBJECTIVE Delirium in the intensive care units (ICUs) is prevalent, with both delirium duration and delirium severity associated with adverse outcomes. We designed a pragmatic trial to test the efficacy of a pharmacological management of delirium (PMD) bundle in improving delirium/coma-free days and reducing delirium severity among ICU patients. DESIGN A randomized pragmatic clinical trial. SETTING Medical, surgical, and progressive ICUs of three tertiary care hospitals. PARTICIPANTS A total of 351 critically ill patients. INTERVENTION A multicomponent PMD bundle consisting of reducing the exposure to 20 definite anticholinergic medications and benzodiazepines and prescribing low-dose haloperidol. MEASUREMENTS The primary outcomes were delirium/coma-free days, measured through the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU), and delirium severity, measured through Delirium Rating Scale-Revised-98 and the CAM-ICU-7. Secondary outcomes were in-hospital and posthospital discharge 30-day mortality, ICU and hospital lengths of stay, and delirium-related hospital complications. RESULTS We randomized 351 critically ill delirious patients (mean age = 59.3 years [SD = 16.9 years]; 52% female, 42% African Americans) to receive the PMD bundle or usual care. There were no significant differences in median delirium/coma-free days at day 8 (PMD vs usual care = 4 [interquartile range {IQR} = 2-7] days vs 5 [IQR = 1-7] days; P = .888) or at day 30 (PMD vs usual care = 26 [IQR 19-29] days vs 26 [IQR, 14-29] days; P = .991). There were no significant differences for decrease in delirium severity at day 8, but at hospital discharge, the intervention group showed a greater reduction in delirium severity (mean decrease in CAM-ICU-7 score for PMD vs usual care = 3.2 [SD = 3.3] vs 2.5 [SD = 3.2]; P = .046). No differences were observed between groups for ICU and hospital lengths of stay, mortality, and delirium-related hospital complications. Similar results were observed when analyses were limited to patients 65 years or older and 75 years or older. CONCLUSION AND RELEVANCE Implementing the PMD bundle in the ICU did not reduce delirium duration or severity among critically ill patients. TRIAL REGISTRATION Identifier: NCT00842608. J Am Geriatr Soc 67:1057-1065, 2019.