Ketamine Procedural Sedation in 38,910 Children: Frequency and Predictors of Critical and High-Risk Events

Objectives: Ketamine is a commonly administered sedative to facilitate painful procedures in children, and recommendations for its optimal practice require accurate estimates of the frequency and nature of adverse events. Our objective was to assess the frequency of critical and high-risk adverse events associated with ketamine as the primary sedative, and to identify clinical predictors of such adverse events. Design: Retrospective analysis of a prospective registry of 38,910 children receiving ketamine for procedural sedation from July 1, 2004, to July 1, 2024. Setting: Critical care units, sedation units, emergency departments, radiology suites, and other locations providing ketamine sedation in 84 participating institutions. Patients: Children receiving ketamine used as their primary sedative, defined as ketamine as a single agent or with adjunctive benzodiazepines or dexmedetomidine, but excluding co-administered primary sedative agents such as propofol. Interventions: None. Measurements and Main Results: Of 38,910 unique sedation encounters of ketamine as a primary sedative, there were 15 critical adverse events (0.04% or 1 per 2,594 sedations): cardiac arrest (1), aspiration (3), intubation (8), anaphylaxis (1), and laryngeal mask airway (2). There were no reported deaths or descriptions of any permanent adverse outcomes. The strongest independent risk factor was upper respiratory infection, but only in those also receiving benzodiazepines or dexmedetomidine. Other predictors were opioids, and, to a lesser degree, age younger than 6 months or older than 10 years. We found no patterns of association with severe underlying illness, obstructive sleep apnea, preemptive supplemental oxygen, ketamine route (intramuscular vs. IV), or ketamine dose. Conclusions: In this largest study of ketamine as a primary procedural sedative, we found that critical and high-risk adverse events were rare. The strongest risk factors were presence of an upper respiratory infection in association with added benzodiazepines or dexmedetomidine, and when opioids were also administered.