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Introduction: This study evaluates the efficacy and safety of various anesthetic and sedative regimens for Endoscopic Retrograde Cholangiopancreatography (ERCP) procedures. Methods: A systematic search was conducted across PubMed, Web of Science, Scopus, and Embase to identify randomized controlled trials (RCTs) published until March 2024. Primary outcomes included procedure time, patient satisfaction, oxygen saturation (SpO2), incidence of SpO2 below 90%, and adverse events. The analysis was performed using R software, analyzing continuous outcomes with mean differences and dichotomous outcomes with risk ratios. Results: 42 RCTs were included. Combination therapies such as remifentanil plus tramadol and propofol plus midazolam plus pethidine demonstrated significantly shorter procedure times. Propofol plus oxycodone yielded higher patient satisfaction. Oxygenation results indicated that propofol plus fentanyl, oxycodone, and ketamine improved SpO2. Propofol plus oxycodone (RR<0.01), dexmedetomidine plus fentanyl (RR<0.01), propofol plus nalbuphine (RR=0.01), Mg sulfate plus propofol (RR=0.01), and propofol plus fentanyl (RR=0.02), showed a significant lower rate of patients with SpO2 below 90% compared to propofol. Midazolam plus pethidine plus dexmedetomidine (RR=0.01), propofol plus oxycodone (RR=0.09), and dexmedetomidine plus fentanyl (RR=0.2) exhibited lower rates of adverse events compared to propofol. Conclusion: This study provides comprehensive evidence to guide clinical decision-making and optimize anesthetic management for ERCP procedures.

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