Dexmedetomidine and the Developing Brain: Current Evidence on Neuroprotection and Neurodevelopmental Safety in Neonatal and Pediatric Patients: A Structured Literature Review

Background: Dexmedetomidine is a highly selective α2-adrenergic receptor agonist increasingly used in neonatal and pediatric intensive care and anesthesia. Its central mechanism of action and experimental evidence suggesting anti-inflammatory, anti-apoptotic, antioxidant, and antiexcitotoxic effects have raised interest in its influence on the developing central nervous system. At the same time, uncertainty remains regarding its long-term neurodevelopmental consequences and the clinical relevance of reported neurological safety signals. Objective: This review aimed to critically evaluate the neurological and neurodevelopmental effects of dexmedetomidine in neonatal and pediatric populations, with particular emphasis on potential neuroprotective effects, acute neurological safety signals, and long-term neurodevelopmental outcomes. Methods: A structured literature review of publications from 1989 to 2026 was conducted. Evidence included primary clinical studies, prospective and retrospective cohorts, randomized controlled trials, follow-up studies, case reports, and secondary evidence syntheses, including systematic reviews and meta-analyses. Long-term neurodevelopmental and cognitive outcomes were analyzed separately from acute neurological effects and neurological safety signals. Secondary evidence was evaluated independently from primary studies to avoid double counting of participants. Preclinical and surrogate evidence of neuroprotection was distinguished from direct evidence of long-term human neurodevelopmental benefit. Results: Dexmedetomidine was associated with measurable effects on the developing central nervous system, although their clinical significance varied across populations and study designs. In neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia, secondary evidence suggested a lower pooled seizure risk with dexmedetomidine compared with conventional sedatives, although substantial heterogeneity and observational study designs limited causal interpretation. In pediatric anesthesia, dexmedetomidine reduced sevoflurane-related emergence agitation, but this short-term behavioral endpoint does not constitute evidence of long-term neuroprotection. Preclinical studies demonstrated attenuation of sevoflurane-associated neuronal migration delay, restoration of dendritic spine density, and improvement of transient somatosensory dysfunction, supporting a potential synaptic and developmental neuroprotective effect. However, clinical studies did not consistently demonstrate improvements in cognition, behavior, or long-term neurodevelopment. Reported neurological safety signals included altered cerebral activity, seizure-related events, abnormal movements, and posterior reversible encephalopathy syndrome following abrupt dexmedetomidine withdrawal with rebound hypertension. Conclusions: Dexmedetomidine exerts measurable effects on the developing central nervous system, but current evidence is insufficient to classify it as either a clinically proven neuroprotective agent or as directly neurotoxic to the developing human brain. Available data support short-term neurological effects and preclinical neuroprotective potential, whereas long-term human neurodevelopmental consequences remain uncertain. Further prospective studies using validated longitudinal neurodevelopmental outcomes are required to determine its long-term neurological safety and potential neuroprotective benefit. Anesthetic agents and method of discontinuation. Further prospective, adequately powered studies with standardized dosing and long-term neurodevelopmental follow-up are required.