Cheng, Shu-Li, Hsu, Tien-Wei, Kao, Yu-Chen, Yu, Chia-Ling, Thompson, Trevor ORCID: https://orcid.org/0000-0001-9880-782X, Carvalho, Andre F., Stubbs, Brendon, Tseng, Ping-Tao, Hsu, Chih-Wei, Yang, Fu-Chi, Tu, Yu-Kang ORCID: https://orcid.org/0000-0002-2461-474X and Liang, Chih-Sung ORCID: https://orcid.org/0000-0003-1138-5586 (2025) Haloperidol in treating delirium, reducing mortality, and preventing delirium occurrence: Bayesian and frequentist meta-analyses. Critical Care, 29:126. ISSN 1364-8535 (Print), 1466-609X (Online) (doi:10.1186/s13054-025-05342-6)

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Abstract

Background
Although haloperidol is commonly used to treat or prevent delirium in intensive care unit (ICU) patients, the evidence remains inconclusive. This study aimed to comprehensively evaluate the efficacy and safety of haloperidol for delirium treatment and prevention in ICU patients.
Methods
We searched MEDLINE, the cochrane central register of controlled trials, EMBASE, ClinicalTrial.gov, and PubMed without language restrictions from database inception to June 27, 2024. We included double-blind randomized controlled trials (RCTs) on haloperidol versus placebo for treating and preventing delirium in adult ICU patients. In addition to frequentist analyses, Bayesian analysis was used to calculate the posterior probabilities of any benefit/harm and clinically important benefit/harm (CIB/CIH). The primary outcomes for delirium treatment were all-cause mortality and serious adverse events (SAEs). For delirium prevention, the primary outcomes included incident delirium, all-cause mortality, and SAEs. The secondary outcomes for efficacy were delirium-or coma-free days, ventilator-free days, length of stay in ICU, length of stay in hospital, and rescue benzodiazepine use. The secondary outcomes for safety were QTc prolongation and extrapyramidal syndrome.
Results
We included seven RCTs on delirium treatment (n = 1767) and five on delirium prevention (n = 2509). The Bayesian analysis showed that, compared to placebo for delirium treatment, haloperidol had a 68% probability of achieving CIB (defined as risk difference [RD] < −0.02) in reducing all-cause mortality, a 2% probability of achieving CIH (RD > 0.02) in causing SAEs, and a 78% probability of achieving CIB (RD < −0.02) in reducing the need for rescue benzodiazepine use. The probabilities of haloperidol causing CIH (RD > 0.02) across all other safety outcomes were low (all < 50%). In frequentist analysis on delirium treatment, the pooled estimated RD for haloperidol compared to placebo was -0.05 (−0.09, −0.00; I2 = 0%) for rescue benzodiazepine use. In Bayesian analysis on delirium prevention, haloperidol had a 12% probability of achieving CIB in all-cause mortality, a 34% probability of achieving CIB in delirium incidence, and a 0% probability of achieving CIB in SAEs. Importantly, haloperidol had a 65% probability of causing CIH (risk ratio > 1.1) for QTc prolongation, while the posterior probabilities of achieving CIB across all efficacy outcomes were low (all < 50%). In frequentist analysis on delirium prevention, all primary and secondary outcomes were not statistically significant in frequentist analysis.
Conclusion
Our study supported the use of haloperidol for delirium treatment in adult ICU patients, but not for delirium prevention.

Item Type:	Article
Uncontrolled Keywords:	Haloperidol, delirium, intensive care unit patients, Bayesian meta-analysis, mortality
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Faculty / School / Research Centre / Research Group:	Faculty of Education, Health & Human Sciences Faculty of Education, Health & Human Sciences > Institute for Lifecourse Development Faculty of Education, Health & Human Sciences > Institute for Lifecourse Development > Centre for Chronic Illness and Ageing Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Last Modified:	07 Apr 2025 11:14
URI:	http://gala.gre.ac.uk/id/eprint/50175

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