• Zhen Chen, Rui Chen, Donghua Zheng, Yongpeng Su, Shuchao Wen, Huocheng Guo, Zhigang Ye, Yingxin Deng, Genglong Liu, Liuer Zuo, Xuxia Wei, and Yunqi Hou.
• Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong Province, PR China.
• J Clin Anesth. 2020 May 1; 61: 109623.

Study ObjectiveTo identify the efficacy and safety of haloperidol prophylaxis in adult patients with a high risk for delirium.DesignA meta-analysis with trial sequential analysis of randomized controlled trials.InterventionA comprehensive search was performed in PubMed, the ISI Web of Knowledge, the Cochrane Library, and Embase databases from inception through to March 2019.Citation screening, data abstraction and quality assessment were performed in duplicate. Meta-analysis with trial sequential analysis (TSA) were used to assess the primary and secondary outcomes. In addition, we used the Grading of Recommendations Assessment Development and Evaluation (GRADE) to evaluate the certainty of the body of evidence.Main ResultsWe appraised 8 RCTs involving 3034 patients that that were in compliance with inclusion and exclusion criterion. Pooled analyses indicated patients receiving haloperidol prophylaxis and placebo or normal saline did not significantly differ in incidence of delirium (relative risk [RR] = 0.90, 95% confidence interval [CI] = 0.70 to 1.15), with TSA inconclusive. Notably, compared with the control group, use of haloperidol significantly decreased the duration of delirium (Mean difference [MD] -0.94; 95% CI -1.82 to -0.06 days), with a marked heterogeneity. Additionally, haloperidol prophylaxis does not significantly affect duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay and mortality. In terms of safety profiles, haloperidol was not associated with increased risk for QTc prolongation, extrapyramidal symptoms, or adverse events. GRADE indicated the level of evidence was very low for a benefit from haloperidol prophylaxis.ConclusionsThe results of our meta-analysis suggested the use of prophylactic haloperidol compared with placebo had no beneficial impacts on incidence of delirium, duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay and mortality in adult patients. It appeared to have a positive effect on duration of delirium, while with a significant heterogeneity. These findings do not support the routine usage of haloperidol for delirium prevention.Trial RegistrationPROSPERO registration number: CRD42018100511. Registered on 17 July 2018.Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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