Haloperidol Versus 5‐HT₃ Receptor Antagonists for Postoperative Vomiting and QTc Prolongation: A Noninferiority Meta‐Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Abstract

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.

Management strategies for the treatment and prevention of postoperative/postdischarge nausea and vomiting: an updated review

“…Nevertheless, Bourdaud et al 207 compared the efficacy of a combination of ondansetron (100 µg/kg, IV), dexamethasone (125 µg/kg, IV), and droperidol (50 µg/kg, IV) in pediatric patients at high risk of POV and concluded that adding droperidol to a prophylactic combination of ondansetron and dexamethasone did not decrease the incidence of POV below that obtained with the two drugs alone, though the addition of droperidol increased the risk of drowsiness. Singh et al 208 reported that haloperidol was equivalent to the popular 5-HT 3 receptor antagonists in preventing vomiting on the first day after surgery. The incidence of QTc prolongation with haloperidol is statistically equivalent to the 5-HT 3 antagonists.…”

“…Singh et al . 208 reported that haloperidol was equivalent to the popular 5-HT 3 receptor antagonists in preventing vomiting on the first day after surgery. The incidence of QTc prolongation with haloperidol is statistically equivalent to the 5-HT 3 antagonists.…”

Long QT Syndrome and Perioperative Torsades de Pointes: What the Anesthesiologist Should Know

“…Droperidol is contraindicated in patients with known or suspected QT prolongation and should be administered with extreme caution in patients at risk of QT prolongation 190 . Low-dose haloperidol (mean dose 1.34mg) administered for post-operative vomiting has a similar odd ratio of QTc prolongation as 5-HT3 receptor antagonists 191 .…”

PONV management in patients with QTc prolongation on the EKG

“…Various drugs have been successfully used to prevent and treat PONV (Table 1). Many of these drugs share the potential to prolong the QTc on EKG, something that increases the risk for development of ventricular arrhythmias, specifically, Torsade de Pointes (TdP): a phenomenon first described in 1966 by Dessertenne (Charbit et al, 2005;Curigliano et al, 2009;Drew et al, 2010;Singh et al, 2018;Berul, 2020) Indeed, most of the episodes of QTc prolongation seen with the use of antiemetic drugs remain clinically silent, self-limited, and rarely require active intervention. Nevertheless, there is a group of patients with hereditary or acquired risk factors for development of long QTc and TdP, and these patients require special attention during the perioperative period.…”