Association of haloperidol use with mortality in critically ill patients with delirium: a retrospective propensity...

Delirium is a prevalent and serious neuropsychiatric syndrome in the intensive care unit (ICU), associated with increased mortality, prolonged hospitalization, and long-term cognitive impairment. Haloperidol, a first-generation antipsychotic, is commonly used for its management, yet its efficacy and impact on mortality remain controversial due to inconsistent findings from recent large-scale randomized controlled trials.

This study was performed to evaluate the effect of haloperidol on mortality and clinical outcomes in patients with delirium in the intensive care unit (ICU) and to explore its potential clinical value and limitations.

Using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (2008-2022), we included 9109 ICU patients diagnosed with delirium on their first ICU admission, of whom 1359 (14.92%) received haloperidol treatment. Propensity score matching (PSM) at a 1:1 ratio with a calliper width of 0.05 was used to balance baseline characteristics, including age, sex, race, comorbidities, laboratory indicators, treatments and severity scores. This resulted in 1323 matched cases in each group (total n = 2646). The association between haloperidol use and 28-day as well as in-hospital mortality was analysed using Cox proportional hazards models. Kaplan-Meier survival curves and subgroup analyses were conducted to verify the robustness of the results.

Before matching, the haloperidol group had significantly lower 28-day mortality (15.08% vs. 26.79%, P < 0.001) and in-hospital mortality (13.76% vs. 23.38%, P < 0.001) than the non-haloperidol group but experienced longer hospital stays (16.61 vs. 13.38 days, P < 0.001) and ICU stays (8.10 vs. 5.81 days, P < 0.001). After PSM, the haloperidol group continued to show a significant survival advantage (28-day mortality hazard ratio = 0.65 (95% confidence interval: 0.54-0.78); in-hospital mortality hazard ratio = 0.69 (95% confidence interval: 0.57-0.83); both P < 0.001), with consistent findings among subgroups.

Haloperidol use is associated with a significant reduction in short-term mortality in ICU patients with delirium (risk reduction of approximately 31%-35%), although it may be linked to longer ICU and hospital stays.