Singh Preet Mohinder, Borle Anuradha, Makkar Jeetinder Kaur, Trikha Anjan, Fish David, Sinha Ashish
Department of Anesthesia, All India Institute of Medical Sciences, New Delhi, India.
Department of Anesthesia, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
J Clin Pharmacol. 2018 Feb;58(2):131-143. doi: 10.1002/jcph.999. Epub 2017 Sep 15.
Haloperidol is an antipsychotic with well-known antiemetic potential. It is underutilized for postoperative nausea vomiting due to reported corrected QT interval (QTc) prolongation. This meta-analysis evaluates its safety and efficacy as an antiemetic in the perioperative period. Trials comparing haloperidol to 5-HT -receptor antagonists (5-HT -RA) for 24 postoperative vomiting incidences published up to May 2017 were searched in the medical database. Comparisons were made for antiemetic efficiency variables (vomiting incidence, rescue antiemetic need, and patients with complete response) during early (until 6 hours) and late postoperative phases. Eight randomized controlled double-blinded trials were included in the final analysis. Twenty-four-hour vomiting incidence was similar in groups (fixed effects, P = 0.52, I = 0%). Trial-sequential analysis confirmed noninferiority of haloperidol over 5-HT -RAs (α = 5%, β = 20%, δ = 10%), with "information size" being 859 (required > 812). Pooled results did not demonstrate superiority/inferiority of 5-HT -RAs over haloperidol in all other antiemetic efficacy variables (early and delayed). Negligible heterogeneity was found in all the comparisons made. Pooled Mantel Haenszel odds ratio for QTc prolongation was equivalent in both groups (fixed effects, P = 0.23, I = 0%). The mean dose of haloperidol used was 1.34 mg, and no trial reported extrapyramidal side effects. Trial-sequential analysis showed statistical equivalence (α = 5%, β = 20%, δ = 10%), with information size being 745 (required > 591). Publication bias was unlikely (Egger test, X-intercept = 2.07, P = 0.10). We conclude that haloperidol is equivalent to the well-established 5-HT -RAs in preventing vomiting during the first day after surgery. The incidence of QTc prolongation with haloperidol is statistically equivalent to 5-HT -RAs and thus should not be the factor that discourages its use for treatment/prophylaxis of postoperative nausea vomiting.
氟哌啶醇是一种具有众所周知的止吐潜力的抗精神病药物。由于有报道称其可导致校正QT间期（QTc）延长，它在术后恶心呕吐治疗中的应用未得到充分重视。本荟萃分析评估了其在围手术期作为止吐药的安全性和有效性。在医学数据库中检索了截至2017年5月发表的比较氟哌啶醇与5-羟色胺受体拮抗剂（5-HT-RA）治疗24例术后呕吐发生率的试验。对术后早期（至6小时）和晚期的止吐效率变量（呕吐发生率、急救止吐需求和完全缓解的患者）进行了比较。最终分析纳入了8项随机对照双盲试验。各组24小时呕吐发生率相似（固定效应，P = 0.52，I = 0%）。序贯分析证实氟哌啶醇不劣于5-HT-RA（α = 5%，β = 20%，δ = 10%），“信息大小”为859（要求>812）。汇总结果未显示5-HT-RA在所有其他止吐疗效变量（早期和延迟）方面优于或劣于氟哌啶醇。在所有进行的比较中发现异质性可忽略不计。两组中QTc延长的合并Mantel Haenszel优势比相当（固定效应，P = 0.23，I = 0%）。所用氟哌啶醇的平均剂量为1.34 mg，且无试验报告锥体外系副作用。序贯分析显示具有统计学等效性（α = 5%，β = 20%，δ = 10%），信息大小为745（要求>591）。不太可能存在发表偏倚（Egger检验，X截距 = 2.07，P = 0.10）。我们得出结论，氟哌啶醇在预防术后第一天呕吐方面与成熟的5-HT-RA等效。氟哌啶醇导致QTc延长的发生率与5-HT-RA在统计学上相当，因此不应成为阻碍其用于治疗/预防术后恶心呕吐的因素。
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