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Efficacy and safety of ketamine and esketamine for preventing opioid-induced cough: a systematic review and meta-analysis of randomized controlled trials

Kuo-Chuan Hung, Ting-Sian Yu, Chih-Wei Hsu, Wei-Cheng Liu, Jheng-Yan Wu, Shu-Wei Liao, Chien-Ming Lin, I-Wen Chen

Systematic Reviews, 2025

4 citations

Abstract

Opioid-induced cough (OIC) is a common side effect during anesthetic induction. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of ketamine/esketamine in preventing OIC during anesthetic induction. We systematically searched Medline, Embase, Cochrane Library, and Google Scholar from inception through December 2024 for randomized controlled trials that examined the efficacy of ketamine/esketamine in preventing OIC (Registration: INPLASY2024120102). Studies were included if they: (1) evaluated surgical patients receiving short-acting opioids (e.g., fentanyl) during anesthetic induction; (2) compared ketamine or esketamine against placebo/no treatment; and (3) reported OIC incidence. Studies were assessed using the Cochrane Risk of Bias 2.0 tool. Random-effects meta-analysis was performed using risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). The primary outcome was the overall incidence of OIC within 3 min after opioids administration. Twelve trials involving ketamine (nine trials) and esketamine (three trials) were analyzed. Notably, both agents significantly reduced the overall incidence of OIC compared to placebo (RR: 0.30; 95% CI: 0.22–0.41; p < 0.00001, I2 = 61%, moderate certainty). All studies demonstrated low risk of bias across all domains for primary outcome. These agents also demonstrated efficacy against mild cough (RR: 0.41, 95% CI: 0.28–0.59, high…

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