Objective: Dexmedetomidine is an increasingly popular analgosedative in critically ill children receiving invasive mechanical ventilation (IMV). We conducted a systematic review to evaluate the efficacy of dexmedetomidine compared to other analgosedatives in this population. Data sources: Seven electronic databases and trial registries to July 2024, without language restrictions. Study selection: Randomized controlled trials comparing dexmedetomidine to other analgosedatives in critically ill children receiving IMV. Data extraction and synthesis: Independently and in duplicate, we conducted data extraction, risk of bias assessment, and certainty assessment using Grading of Recommendations, Assessment, Development, and Evaluation. We conducted random-effects meta-analyses, calculating pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals. Results: = 592 patients). Pooled analyses demonstrated dexmedetomidine has little to no effect on IMV duration (MD -2.2 h [-3.3, -1.1]; moderate certainty), clinically important bradycardia (RR 1.42 [0.45, 4.49]; moderate certainty), or clinically important hypotension (RR 1.35 [0.48, 3.82]; moderate certainty). Dexmedetomidine may reduce delirium risk (RR 0.83 [0.64, 1.07]; low certainty), but impact on withdrawal is uncertain (RR 0.93 [0.55, 1.59]; very low certainty). A narrative synthesis was used to evaluate dexmedetomidine sedation efficacy, demonstrating very low certainty in attaining sedation target. One trial reported on long-term outcomes. Conclusions: Twelve trials evaluating dexmedetomidine have been conducted to date, with low or very low certainty for its impact upon delirium, withdrawal, and long-term outcomes. Future analgosedation trials require attention to intervention design, outcome selection and reporting to improve certainty in critical outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-025-00091-4.
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