Penehyclidine combined with antiemetics for preventing postoperative nausea and vomiting: A meta-analysis of randomized control trials and trial sequential analysis

Abstract

Background: Postoperative nausea and vomiting (PONV) is one of the most common adverse complications associated with anesthesia and after surgical procedures. PONV is related to patient dissatisfaction and can lead to several postoperative complications. This study aimed to examine the efficacy and safety of penehyclidine combined with antiemetics in preventing PONV.

Methods: We searched English databases (including PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library), Chinese electronic databases (including China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical Literature) and trial registry databases to find randomized controlled trials researching the clinical validity of penehyclidine combined with antiemetics for PONV. The retrieval time was up to January 2025, without publication date restrictions. Articles published in the English and Chinese languages were considered. The primary outcome was the incidence of PONV within and over 24 hours postoperatively. The secondary outcomes were the incidence of different severities of PONV, incidence of postoperative rescue antiemetic therapy and postoperative complications. Quality assessment was conducted with the Cochrane Collaboration's risk of bias tool and grading of recommendations assessment, development and evaluation method. Subgroup analyses were performed according to the postoperative observation period. Trial sequential analysis was performed to validate the reliability of the primary outcome. Publication bias was assessed by funnel plots and Egger's regression test.

Results: Sixteen randomized controlled trials comprising 1561 participants were included. Compared with the control group, penehyclidine combined with antiemetics provided a lower incidence of PONV (risk ratio [RR]: 0.65; 95% CI: 0.57-0.74; P < .00001; I2 = 11%; low quality), lower incidence of severe PONV over 24 hours postoperatively (RR: 0.29; 95% CI: 0.15-0.56; P = .0003; I2 = 0%; low quality), and a lower incidence of postoperative rescue antiemetic therapy (RR = 0.42, 95% CI: 0.26-0.69; P = .0006; I2 = 58%; low quality). However, it was associated with a higher incidence of dry mouth (RR: 3.10, 95% CI: 2.28-4.20; P < .00001; I2 = 19%; low quality), but did not increase the incidence of other anticholinergic-related complications (RR: 1.08; 95% CI: 0.91-1.28; P = .38; I2 = 2%; low quality).

Conclusion: Compared with antiemetics, penehyclidine combined with antiemetics could provide better prevention efficiency for PONV, with lower incidence of PONV, lower incidence of severe PONV over 24 hours postoperatively and lower incidence of postoperative rescue antiemetic therapy.

Keywords: PONV; meta-analysis; penehyclidine; postoperative nausea and vomiting.

Figure 1.

PRISMA flow diagram. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Source from Page et al.^[36] For more information, visit: https://www.prisma-statement.org/prisma-2020.

Figure 2.

(A) Risk of bias assessment results for individual studies. (B) Summary plot for risk of bias assessment for individual studies.

Figure 3.

Forest plots and trial sequential analysis (TSA) of the incidence of postoperative nausea and vomiting (PONV). (A) Forest plot for the incidence of PONV. (B) TSA of the incidence of PONV within 24 h postoperatively: α = 2.5%; β = 90%; RR = 30%. The cumulative Z-curve crossed the trial sequential monitoring boundary, establishing sufficient and conclusive evidence. (C) TSA of the incidence of PONV over 24 h postoperatively: α = 2.5%; β = 90%; RR = 30%. The cumulative Z-curve did not cross the trial sequential monitoring boundary, establishing insufficient and uncertain evidence. The continuous blue full line filled with a Black square represents the cumulative Z-curve, the red full line with a blank circle represents the trial sequential monitoring boundaries, and the RIS. The gray dashed lines represent the conventional CIs. CI = confidence interval, PONV = postoperative nausea and vomiting, RIS = required information size, TSA = trial sequential analysis.

Figure 4.

Forest plots for severity of PONV. (A) Forest plot for the incidence of PONV within 24 h postoperatively. (B) Forest plot for the incidence of PONV over 24 h postoperatively. PONV = postoperative nausea and vomiting.

Figure 5.

Forest plots for the incidence of postoperative rescue antiemetic therapy.

Figure 6.

Forest plots for the incidence of postoperative complications. (A) Forest plot for the incidence of postoperative dry mouth. (B) Forest plot for the incidence of other postoperative complications.

Figure 7.

Forest plots for the incidence of postoperative nausea (PON). PON = postoperative nausea.

Figure 8.

Forest plots for the incidence of postoperative vomiting (POV). POV = postoperative vomiting.

Figure 9.

Funnel plot for publication bias of the studies included in the incidence of PONV. (A) Distribution of studies included in the incidence of PONV within 24 h postoperatively. (B) Distribution of studies included in the incidence of PONV over 24 h postoperatively. (C) Funnel plots of the incidence of PONV within 24 h postoperatively after applying the trim-and-fill method. The closed dots indicate the observed studies, and the white dots indicate the missing studies imputed by the trim-and-fill method. (D) Funnel plots of the incidence of PONV over 24 h postoperatively after applying the trim-and-fill method. The closed dots indicate the observed studies, and the white dots indicate the missing studies imputed by the trim-and-fill method. PONV = postoperative nausea and vomiting.