Dose- and endpoint-dependent effects of perioperative esketamine in children: evidence from a targeted review
Year: 2026
Type: article
Abstract: Esketamine is being evaluated for several paediatric perioperative indications, including analgesia, procedural sedation, attenuation of propofol injection pain, and prevention of emergence delirium (ED) or emergence agitation (EA). This mini review examines whether evidence identified in a targeted search supports a clinically useful therapeutic window and how dose, timing, route, developmental stage, anaesthetic technique, procedure, co-medication, and outcome definition modify treatment effects. Randomised trials and meta-analyses generally report fewer ED or EA events after low intravenous doses, particularly during sevoflurane anaesthesia for adenotonsillectomy. Direct dose-comparison evidence shows increasing benefit up to 0.5 mg·kg −1 intravenously in that setting, without identifying an upper efficacy or safety boundary. An observational association between esketamine exposure and more ED cannot establish a threshold because treatment selection and perioperative context were not controlled. Effective doses are endpoint-specific: propofol injection pain, procedural sedation, analgesia, and emergence outcomes require different exposure profiles. Intranasal regimens cannot be converted into intravenous equivalents from bioavailability alone, and preclinical neurotoxicity findings do not define a ceiling for a single perioperative dose in children. Among the studies identified, 0.2–0.5 mg·kg −1 was the best-studied intravenous range in selected emergence-prevention settings, not a universal recommendation or validated therapeutic window. Future trials should compare dose and timing directly, incorporate paediatric pharmacokinetic–pharmacodynamic sampling, use endpoint-specific assessment, and extend safety follow-up.
Source: Frontiers in Pediatrics
Authors: Yun Yang, Tongyun He, Weiliang Mao, Xinqiang Wang
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223128205