• Nina Christine Andersen-Ranberg, Marija Barbateskovic, Anders Perner, Oxenbøll ColletMarieM0000-0002-8387-3960Collaboration for Research in Intensive Care (CRIC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.Department of Intensive Care, Copenhagen University Hospital - Rigshospitalet, Copenhagen, De, Musaeus PoulsenLoneL0000-0002-7030-3395Department of Anaesthesiology and Intensive Care, Zealand University Hospital, Lykkebækvej 1, 4600, Køge, Denmark.Collaboration for Research in Intensive Care (CRIC), Copenhagen University Hospital - Rigshospitalet, , Mathieu van der Jagt, Lisa Smit, Jørn Wetterslev, Ole Mathiesen, and Mathias Maagaard.
• Department of Anaesthesiology and Intensive Care, Zealand University Hospital, Lykkebækvej 1, 4600, Køge, Denmark. ncan@regionsjaelland.dk.
• Crit Care. 2023 Aug 26; 27 (1): 329329.

BackgroundHaloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we updated a systematic review assessing effects of haloperidol on mortality and serious adverse events in critically ill patients with delirium.MethodsThis is an updated systematic review with meta-analysis and trial sequential analysis of randomised clinical trials investigating haloperidol versus placebo or any comparator in critically ill patients with delirium. We adhered to the Cochrane handbook, the PRISMA guidelines and the grading of recommendations assessment, development and evaluation statements. The primary outcomes were all-cause mortality and proportion of patients with one or more serious adverse events or reactions (SAEs/SARs). Secondary outcomes were days alive without delirium or coma, delirium severity, cognitive function and health-related quality of life.ResultsWe included 11 RCTs with 15 comparisons (n = 2200); five were placebo-controlled. The relative risk for mortality with haloperidol versus placebo was 0.89; 96.7% CI 0.77 to 1.03; I2 = 0% (moderate-certainty evidence) and for proportion of patients experiencing SAEs/SARs 0.94; 96.7% CI 0.81 to 1.10; I2 = 18% (low-certainty evidence). We found no difference in days alive without delirium or coma (moderate-certainty evidence). We found sparse data for other secondary outcomes and other comparators than placebo.ConclusionsHaloperidol may reduce mortality and likely result in little to no change in the occurrence of SAEs/SARs compared with placebo in critically ill patients with delirium. However, the results were not statistically significant and more trial data are needed to provide higher certainty for the effects of haloperidol in these patients.Trial RegistrationCRD42017081133, date of registration 28 November 2017.© 2023. BioMed Central Ltd., part of Springer Nature.

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