Dexmedetomidine Mitigates Sevoflurane-Induced Neurodevelopmental Effects in Paediatric Anaesthesia: A Meta-Analysis and Preclinical Study

TL;DR

Dexmedetomidine reduces the harmful effects of sevoflurane on developing brains in children, both in clinical trials and animal studies.

Contribution

This study combines clinical meta-analysis and preclinical experiments to show that Dex mitigates Sevo-induced neurodevelopmental damage.

Findings

Dex significantly reduces emergence agitation in children when combined with Sevo.

Neonatal Sevo exposure reduces dendritic spine density and impairs somatosensory function.

Dex pretreatment ameliorates Sevo-induced neuronal migration delays and functional deficits.

Abstract

Sevoflurane (Sevo) anaesthesia in children is linked to an increased incidence of postoperative emergence agitation (EA) and potential neurotoxicity in developing brains. However, the specific risks of subanaesthetic foetal or neonatal exposure to Sevo remain unclear. This study evaluates the safety and efficacy of combining dexmedetomidine (Dex) with Sevo to manage EA in paediatric anaesthesia. A systematic review and meta-analysis of randomized controlled clinical trials involving children under 8 years old revealed that Dex significantly reduces EA incidence when administered via intravenous, perineural, and intranasal routes. Using in utero electroporation, we found that pregnant mice exposed to 2.5% Sevo at embryonic days 14.5 and 15.5 exhibited transient neuronal migration deficits, with 25% of neurons delayed in deeper cortical layers. However, these neurons migrated to the cortex by postnatal day 8. Neonatal mice exposed to 2.5% Sevo experienced a 10% reduction in dendritic spine density in adolescence, associated with impaired somatosensory function, as assessed by the Von Frey test. Remarkably, Dex pretreatment ameliorated these pathological and functional changes. Thus, foetal or neonatal Sevo exposure can delay neuronal migration and reduce dendritic spine density. Dex co-administration effectively mitigates these adverse outcomes, supporting its potential use in paediatric anaesthesia to protect developing brains.

The online version contains supplementary material available at 10.1007/s11481-025-10273-8.

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