Network meta-analysis of ketamine regimens for pediatric ED procedural sedation safety and efficacy

The purpose of this study is to compare the safety and efficacy of different ketamine-based regimens for emergence pediatric procedural sedation. We searched PubMed, Scopus, and Web of Science for RCTs enrolling pediatric patients undergoing painful procedures in the emergency department. Studies comparing ketamine alone with ketamine combined with other sedatives or alternative agents were included. A frequentist random effects NMA was conducted using R (netmeta package). Results were expressed as mean differences (MD) or risk ratios (RR) with 95% confidence intervals, and treatments were ranked according to relative efficacy and safety. A total of 24 RCTs were included in this NMA. Using IV ketamine as the reference, IM ketamine was associated with longer sedation (MD + 19.6 min, 95% CI 17.5-21.6) and longer recovery times (MD + 37.7 min, 95% CI 1.6-73.8). Recovery time was extended even further when atropine was added to IM ketamine (MD + 73.5 min, 95% CI 10.9-136.1). IM ketamine was associated with less emergence reactions (RR = 0.38, 95% CI 0.20-0.69). Regarding the adverse events, IV ketamine and midazolam significantly raised the risk of hypoxia (RR = 4.71, 95% CI 1.05-21.08), whereas the combination of IV ketamine with propofol led to less nausea (RR = 0.34, 95% CI 0.17-0.68). In conclusion, across ketamine-based sedation regimens, IM administration achieved deeper and longer sedation but was accompanied by prolonged recovery. IV combinations offered faster recovery and fewer emetic events. Among these, ketamine combined with propofol provided the most balanced profile, maintaining sedation efficacy while minimizing nausea and hypoxia.