The efficacy and safety of haloperidol for the treatment of delirium in critically ill patients: a systematic review and meta-analysis of randomized controlled trials

PURPOSE: Delirium is common during critical illness and is associated with poor outcomes. Therefore, we conducted this meta-analysis to investigate the efficacy and safety of haloperidol for the treatment of delirium in critically ill patients. METHODS: Randomized controlled trials enrolling critically ill adult patients to compare haloperidol with placebo were searched from inception through to February 20th, 2023. The primary outcome were delirium-free days and overall mortality, secondary outcomes were length of intensive care unit stay, length of hospital stay, and adverse events. RESULTS: Nine trials were included in our meta-analysis, with a total of 3,916 critically ill patients. Overall, the pooled analyses showed no significant difference between critically ill patients treated with haloperidol and placebo for the delirium-free days (MD −0.01, 95%CI −0.36 to 0.34, p = 0.95, I(2) = 30%), overall mortality (OR 0.89, 95%CI 0.76 to 1.04, p = 0.14, I(2) = 0%), length of intensive care unit stay (MD −0.06, 95%CI −0.16 to 0.03, p = 0.19, I(2) = 0%), length of hospital stay (MD −0.06, 95%CI −0.61 to 0.49, p = 0.83, I(2) = 0%), and adverse events (OR 0.90, 95%CI 0.60 to 1.37, p = 0.63, I(2) = 0%). CONCLUSION: Among critically ill patients, the use of haloperidol as compared to placebo has no significant effect on delirium-free days, overall mortality, length of intensive care unit and/or hospital stay. Moreover, the use of haloperidol did not increase the risk of adverse events.