Ketamine for Analgosedation in Critically Ill Mechanically Ventilated Children: A Systematic Review and Meta-Analysis

OBJECTIVES: We conducted a systematic review and meta-analysis to compare continuous ketamine infusion to other analgosedatives in critically ill children receiving invasive mechanical ventilation (IMV). DATA SOURCES: We searched four electronic databases and trial registries to September 1, 2025. We searched published conference abstracts from two major critical care conferences (2022 to 2025). STUDY SELECTION: We preregistered the protocol on PROSPERO (CRD42025631768). Reviewers screened abstracts and full texts independently and in duplicate. We included randomized controlled trials (RCTs) and nonrandomized studies comparing ketamine to other analgosedatives in critically ill children receiving IMV. DATA EXTRACTION: Independently and in duplicate, we conducted data extraction. We assessed risk of bias using the Risk Of Bias instrument for Use in SysTematic reviews for RCTs or Risk Of Bias In Nonrandomized Studies of Interventions tool, and certainty of evidence using Grading of Recommendations, Assessment, Development, and Evaluation. We pooled data using random-effects models. DATA SYNTHESIS: We included three RCTs and five nonrandomized studies (n = 1436 participants). Pooled analysis demonstrated that ketamine may have no effect on IMV duration (mean difference, 0.00 d; 95% CI, 0.03 d fewer to 0.03 d more; low certainty) and may reduce opioid exposure (mean difference, -8.88 µg/kg cumulative fentanyl equivalents; 95% CI, -6.99 to -10.77; low certainty). We found an uncertain effect of ketamine on delirium, withdrawal, length of stay, clinically important hypotension, and mortality compared with other analgosedatives. Long-term outcomes were not measured in included studies. CONCLUSIONS: There is a paucity of studies examining ketamine analgosedation in children receiving IMV, yielding mostly very low certainty evidence for patient-important outcomes due to imprecision and issues related to serious risk of bias of included studies. Methodologically rigorous RCTs are needed to better understand the potential role of ketamine analgosedation in the PICU.