AUTHOR=Qi Jiazheng , Luo Mengqiang , Zong Wenru , Zhang Lingjing , Chen Baoxuan , Yang Xiaoyu , Xu Bo , Zhao Xu TITLE=Adjunctive esketamine in propofol-based sedation for gastrointestinal endoscopy: a systematic review and meta-analysis of randomized trials JOURNAL=Frontiers in Pharmacology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1662057 DOI=10.3389/fphar.2025.1662057 ISSN=1663-9812 ABSTRACT=BackgroundWhile propofol is widely used for gastrointestinal endoscopic sedation, its cardiovascular and respiratory side effects and lack of analgesia can compromise safety and comfort. Esketamine provides both sedation and analgesia with minimal hemodynamic or respiratory impact. Combining esketamine with propofol may miti-gate propofol’s adverse effects while enhancing sedation quality. However, the com-bination’s overall safety and efficacy remain inconclusive.MethodsThis systematic review and meta-analysis compared propofol-based sedation with versus without intravenous esketamine in gastrointestinal endoscopy, synthesizing evidence from randomized controlled trials. The primary outcome was the incidence of hypotension. Secondary outcomes included intraoperative adverse respiratory events, propofol consumption, involuntary movement, hypertension, arrhythmias, PONV recovery times, and dizziness.ResultsEighteen trials were included in the analysis. Additional esketamine significantly reduced the incidence of hypotension (risk ratio [RR]: 0.32; 95% confidence interval [CI]: 0.24 to 0.43; P < 0.01; I2 = 44.4%; moderate quality). The addition of esketamine to propofol can reduce the incidence of adverse respiratory events (RR: 0.57, 95% CI: 0.38 to 0.86; P < 0.01; I2 = 67.8%; moderate quality). Esketamine added to propofol decreased involuntary movement (RR: 0.61, 95% CI: 0.42 to 0.92; P = 0.02; I2 = 77.2%; low quality) and reduced the propofol consumption (mean difference [MD]: −0.94, 95% CI: −1.53 to −0.35 mg/kg; P < 0.01; I2 = 96.2%; low quality). No significant differences were found for hypertension, arrhythmias, PONV, recovery time or dizziness.ConclusionSupplementing propofol-based sedation with esketamine reduced the risk of hypotension and adverse respiratory events, without increasing cardiovascular complications, or extending recovery-time.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251030940.