Dose- and endpoint-dependent effects of perioperative esketamine in children: evidence from a targeted review
- 1The First People’s Hospital of Huzhou, Huzhou, China
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.
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BibTeX
@article{yang2026dose,
title = {{Dose- and endpoint-dependent effects of perioperative esketamine in children: evidence from a targeted review}},
author = {Yun Yang and Tongyun He and Weiliang Mao and Xinqiang Wang},
journal = {Frontiers in Pediatrics},
year = {2026},
month = oct,
doi = {10.3389/fped.2026.1963881},
url = {https://doi.org/10.3389/fped.2026.1963881},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dose- and endpoint-dependent effects of perioperative esketamine in children: evidence from a targeted review
AU - Yun Yang
AU - Tongyun He
AU - Weiliang Mao
AU - Xinqiang Wang
PY - 2026
DA - 2026/10/21
JO - Frontiers in Pediatrics
DO - 10.3389/fped.2026.1963881
UR - https://doi.org/10.3389/fped.2026.1963881
AB - 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.
SN - 2296-2360
ER -