Efficacy of intravenous nalbuphine for managing post-anaesthesia shivering: A systematic review and meta-analysis of randomised controlled trials with trial sequential analysis

Abstract

Background and aims: Post-anaesthesia shivering is distressing and is observed after spinal and general anaesthesia. Nalbuphine, a partial mu-opioid receptor antagonist with kappa-opioid receptor agonist properties, has been successfully used to manage post-anaesthesia shivering.

Methods: After registering the review with the International Prospective Register of Systematic Reviews (PROSPERO), we searched PubMed/Medline, Scopus, Ovid, Cochrane Library and clinicaltrials.gov with keywords for randomised controlled trials. The risk of bias-2 (RoB-2) scale was used to assess the quality of evidence. We also used Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines to evaluate the strength of evidence and trial sequential analysis to validate the conclusions.

Results: Of the 240 articles, 10 were considered eligible for review (700 patients, 350- nalbuphine, 350- control or placebo). When compared to placebo, the success rate of nalbuphine controlling shivering was significantly better (risk ratio [RR]: 2.37, 95% confidence interval [CI]:1.91, 2.94; P = 0.04, I² = 94%), but comparable to the control group drugs (opioids, dexmedetomidine, ondansetron, pethidine). Compared to placebo, shivering recurrence was significantly less with nalbuphine than with placebo (RR: 0.47, 95% CI: 0.26, 0.83; P = 0.01, I² = 61%), but comparable with the control group. The incidence of postoperative nausea/vomiting (PONV) was significantly less with nalbuphine when compared to the control group (RR: 0.67, 95% CI: 0.47, 0.95; P = 0.02, I² = 37%), but PONV in the nalbuphine group was comparable to placebo (RR: 1.20, 95% CI: 0.68, 2.12; P = 0.54, I² = 0%). Other outcomes, like the grade of shivering and hypotension, were comparable between the nalbuphine and control groups.

Conclusion: Nalbuphine successfully controls post-anaesthesia shivering and reduces the recurrence of shivering.

Keywords: Anaesthesia; dexmedetomidine; meta-analysis; nalbuphine; ondansetron; opioid; shivering; systematic review.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart

Figure 2

Bias assessment. (a) Traffic light plot. (b) Summary plot

Figure 3

(a) Forest plot comparing the success of treating shivering between nalbuphine and the control group. (b) Forest plot comparing the success of treating shivering between nalbuphine and placebo. (c) Forest plot comparing the grades of shivering between nalbuphine and tramadol. (d) Forest plot comparing the grades of shivering between nalbuphine and dexmedetomidine. (e) Forest plot comparing the grades of shivering between nalbuphine and placebo

Figure 4

Trial sequential analysis for the effect of nalbuphine in controlling post-anaesthesia shivering. The lower half favours nalbuphine, and the upper half favours placebo. The horizontal brown line: conventional threshold for statistical significance at an Z-value of 1.96 (corresponds to P = 0.05). The curved red line: trial sequential boundaries. Blue line: cumulative Z-curve (each square is a trial). The blue line (cumulative Z-score line) crosses the brown lines, that is, conventional boundaries, suggesting nalbuphine's superiority over placebo. The curved red lines (above and below) have crossed the red vertical line, which indicates that the required information size (RIS) has reached

Figure 5

(a) Forest plot comparing recurrence of shivering between nalbuphine and control group. (b) Forest plot comparing recurrence of shivering between nalbuphine and placebo. (c) Forest plot comparing the timing of shivering between nalbuphine and the control group

Figure 6

(a) Forest plot comparing postoperative nausea and vomiting (PONV) between nalbuphine and the control group. (b) Forest plot comparing PONV between nalbuphine and the placebo group. (c) Forest plot comparing the incidence of hypotension between nalbuphine and the control group