5-HT3 receptor antagonists for the prevention of perioperative shivering undergoing spinal anaesthesia: a systematic review and meta-analysis of randomised controlled trials

Abstract

Objective: Perioperative shivering (POS) is a common complication in patients undergoing spinal anaesthesia. The present study investigated the efficacy of 5-HT₃ receptor antagonists in preventing POS following spinal anaesthesia.

Design: Systematic review and meta-analysis.

Data sources: Pubmed, Embase, the Web of Science and Cochrane Library were searched from database establishment on 31 July 2019.

Eligibility criteria: Randomised controlled trials that reported the effects of 5-HT₃ receptor antagonists in the prevention of POS in patients after spinal anaesthesia.

Data extraction and synthesis: Two reviewers independently extracted data. The primary outcome of the present study was the incidence of POS. The risk of bias for the included studies was assessed according to the Cochrane Handbook. The quality of primary outcome was evaluated by Grading of Recommendations Assessment, Development and Evaluation. Trial sequential analysis for the primary outcome was performed to reduce the type 1 error caused by repeated meta-analysis and the required information size was calculated.

Results: A total of 13 randomised controlled trials consisting of 1139 patients were included. The overall incidence of POS was significantly lower in the 5-HT₃ receptor antagonists group (risk ratio 0.31; 95% CI 0.26 to 0.38; p<0.01; I²=0%). Subgroup analysis for different types of 5-HT₃ receptor antagonists and timing of administration produced similar results. Also, patients had a lower incidence of postoperative nausea and vomiting after administrating 5-HT3 receptor antagonists. No statistically significant differences in drug-related adverse effects were observed. Grading of Recommendations Assessment, Development and Evaluation revealed a high level of evidence. The cumulative z-curve crossed the trial sequential monitoring boundary.

Conclusions: The present study revealed that prophylactic 5-HT₃ receptor antagonists were an effective measure for reducing the incidence of POS in patients after spinal anaesthesia. However, further studies investigating the different types of surgeries are required.

Prospero registration number: CRD42019148191.

Keywords: 5-HT3 receptor antagonists; meta-analysis; perioperative shivering; spinal anesthesia.

Figure 1

Diagram of the review process. RCT, randomised controlled trial.

Figure 2

The summary of risk of bias.

Figure 3

Forest plot of the meta-analysis of the incidence of perioperative shivering between 5-HT3 RAs and control groups. 1.2.1 Granisetron; 1.2.2 Ondansetron;1.2.3 Ramosetron. 5-HT3 RAs, 5-HT3 receptor antagonists; M-H, Mantel-Haenszel.

Figure 4

The subgroup analysis of perioperative shivering incidence with different medication timing. M-H, Mantel-Haenszel; SA, spinal anaesthesia.

Figure 5

Forest plot of the meta-analysis of the incidence of postoperative nausea and vomiting between 5-HT3 receptor antagonist and control groups. M-H, Mantel-Haenszel; PONV, postoperative nausea and vomiting.

Figure 6

Forest plot of the meta-analysis of the incidence of hypotension between 5-HT3 receptor antagonist and control groups. M-H, Mantel-Haenszel.

Figure 7

Forest plot of the meta-analysis of the incidence of bradycardia between 5-HT3 receptor antagonist and control groups. M-H, Mantel-Haenszel.

Figure 8

Trial sequential analysis of the preventive efficacy of 5-HT3RAs on POS. 5-HT3RAs, 5-HT₃ receptor antagonists; POS, perioperative shivering; RIS, required information size.