INTRODUCTION: Ketamine is the most common medication for procedural sedation and analgesia (PSA) of pediatric patients in the emergency department (ED). Since ketamine injection is painful, some studies have assessed the routes other than intravenous and intramuscular. Therefore, this systematic review aims to evaluate the details of noninjectable ketamine (NIK) administration.

METHODS: The review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis for Systematic Review (PRISMA) guidelines. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science Core Collection (SCIE and ESCI), and Scopus were searched for relevant studies from inception to 3 July 2025. All English original clinical research on PSA with NIK administration in pediatric populations in the ED was included. Risk of bias and certainty of evidence (COE) were also assessed.

RESULTS: From 5617 identified records, 12 studies (7 interventional and 5 observational) with a total number of 1484 patients were included. Most of the studies evaluated laceration repair among children 2-12 years of age. Seven single-center double-blinded randomized controlled trials showed that oral ketamine (5-10 mg/kg) alone or in combination with other medications (mainly midazolam) provided the desirable level of sedation (COE: very low) relative to the oral comparators. It also resulted in faster onset of action (OA) (15-35 min) and shorter duration of action (DA) (60-265 min) (COE: low). Oral and nasal ketamine studies did not report any serious adverse event (SAE) associated with invasive interventions (COE: moderate to low).

CONCLUSION: Sedation with oral ketamine might have a desirable depth, faster OA, and shorter DA relative to the oral comparators. Furthermore, NIK probably showed no SAE during PSA. Nevertheless, the limited number of heterogeneous studies leaves uncertainty, highlighting the need for further research.

Pediatric Emergency Medicine rater

Ketamine is widely used for procedural sedation in the pediatric emergency department because of its well-documented safety, predictable onset, and ability to preserve airway reflexes. Recently, there has been increasing interest in non-injectable ketamine (NIK) formulations, especially for children for whom needle-based procedures can be stressful or difficult. Although emerging evidence suggests that non-injectable routes offer effective and less invasive options for analgesia and sedation, the existing literature is limited by small sample sizes, diverse study designs, and varying outcome measures. These gaps lead to uncertainty about optimal dosing, onset, and duration, and comparative safety in different clinical scenarios. This review highlights the need for well-designed, multicenter trials to develop standardized protocols and define the role of NIK in pediatric procedural sedation.