Cheng Shu-Li, Hsu Tien-Wei, Kao Yu-Chen, Yu Chia-Ling, Thompson Trevor, Carvalho Andre F, Stubbs Brendon, Tseng Ping-Tao, Hsu Chih-Wei, Yang Fu-Chi, Tu Yu-Kang, Liang Chih-Sung
Department of Nursing, Mackay Medical College, Taipei, Taiwan.
Department of Psychiatry, E-DA Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.
Crit Care. 2025 Mar 20;29(1):126. doi: 10.1186/s13054-025-05342-6.
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.
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.
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; I = 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.
Our study supported the use of haloperidol for delirium treatment in adult ICU patients, but not for delirium prevention.
尽管氟哌啶醇常用于治疗或预防重症监护病房（ICU）患者的谵妄，但证据仍不确凿。本研究旨在全面评估氟哌啶醇治疗和预防ICU患者谵妄的疗效和安全性。
我们检索了MEDLINE、Cochrane对照试验中心注册库、EMBASE、ClinicalTrial.gov和PubMed，检索时间从数据库建立至2024年6月27日，无语言限制。我们纳入了关于氟哌啶醇与安慰剂治疗和预防成年ICU患者谵妄的双盲随机对照试验（RCT）。除了频率分析外，还使用贝叶斯分析来计算任何益处/危害以及临床重要益处/危害（CIB/CIH）的后验概率。谵妄治疗的主要结局是全因死亡率和严重不良事件（SAE）。对于谵妄预防，主要结局包括新发谵妄、全因死亡率和SAE。疗效的次要结局是无谵妄或昏迷天数、无呼吸机天数、ICU住院时间、住院时间以及抢救用苯二氮䓬类药物的使用情况。安全性的次要结局是QTc延长和锥体外系综合征。
我们纳入了7项关于谵妄治疗的RCT（n = 1767）和5项关于谵妄预防的RCT（n = 2509）。贝叶斯分析显示，与安慰剂相比，在谵妄治疗中，氟哌啶醇降低全因死亡率实现CIB（定义为风险差[RD] < -0.02）的概率为68%，导致SAE实现CIH（RD > 0.02）的概率为2%，减少抢救用苯二氮䓬类药物使用实现CIB（RD < -0.02）的概率为78%。氟哌啶醇在所有其他安全性结局中导致CIH（RD > 0.02）的概率较低（均< 50%）。在谵妄治疗的频率分析中，与安慰剂相比，氟哌啶醇在抢救用苯二氮䓬类药物使用方面的合并估计RD为 -0.05（-0.09，-0.00；I² = 0%）。在谵妄预防的贝叶斯分析中，氟哌啶醇在全因死亡率方面实现CIB的概率为12%，在谵妄发生率方面实现CIB的概率为34%，在SAE方面实现CIB的概率为0%。重要的是，氟哌啶醇导致QTc延长的CIH（风险比> 1.1）的概率为65%，而在所有疗效结局中实现CIB的后验概率较低（均< 50%）。在谵妄预防的频率分析中，所有主要和次要结局在频率分析中均无统计学意义。
我们的研究支持在成年ICU患者中使用氟哌啶醇治疗谵妄，但不支持用于预防谵妄。
