Abstract
Objectives: This study reviewed the efficacy of midazolam, ketamine, and their combination for sedation of uncooperative pediatric dental patients. Materials and Methods: Medline, PubMed, Cochrane Central Register of Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform were searched up to August 31, 2023 for randomized controlled trials (RCTs) comparing midazolam, ketamine, and midazolam-ketamine in pediatric patients. Methodological assessment was conducted using the revised Cochrane ROB-2 tool. A dose-response meta-analysis was performed to analyze the effect of oral midazolam dosage on treatment duration (in minutes). Results: Initially, 2,345 records were identified through database searching. After removing the duplicates, 1,230 records remained. Of which, 941 were excluded after title and abstract screening. Subsequently, 289 full-text articles were reviewed; of which, 269 were excluded for various reasons. The remaining 20 publications underwent detailed screening for qualitative synthesis. Risk of bias assessment categorized eight studies as low risk, six with some concerns, and six as having high risk of bias. The meta-analysis, involving three RCTs with 215 children, indicated an increasing trend in treatment duration up to 0.8 mg/kg dosage of oral midazolam. The combination of midazolam-ketamine was highly successful in providing rapid and effective pain relief and sedation for challenging pediatric patients, outperforming either drug alone, irrespective of the administration method. Conclusion: The findings of this systematic review suggest that when it comes to ease of treatment and clinical efficacy, using a combination of midazolam and ketamine is superior to midazolam or ketamine alone.