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Dexmedetomidine (DEX) is increasingly used for neonatal sedation, but safety data remain limited. We conducted a single-center retrospective study including neonates receiving continuous DEX infusion. Cardiorespiratory events were extracted from bedside monitoring during the 8 h before and the 24 h after initiation. Hemodynamic and clinical parameters were analyzed, and autonomic activity was assessed using Newborn Infant Parasympathetic Evaluation (NIPE) monitoring in a subgroup. Thirty-seven infants (18 preterm, 19 term) were included; 86% received concomitant morphine. Bradycardia episodes increased after DEX initiation, particularly in preterm infants (p < 0.05). In contrast, hypotension, lactate levels remained unchanged, while urine output varied over time without a clinically meaningful reduction. Hypoxemic events decreased, while oxygen requirements remained stable. In the NIPE subgroup, heart rate decreased, with a trend toward increased NIPE values. DEX was associated with increased bradycardia without clear evidence of impaired hemodynamic or respiratory tolerance. These findings suggest an overall reassuring short-term safety profile and suggest a physiologically mediated sedative effect. What is Known: • Dexmedetomidine is increasingly used for sedation in preterm and term neonates, but cardiorespiratory safety data remain limited. • Bradycardia is the most frequently reported adverse effect. What is New: • Continuous monitor-derived data show increased bradycardia after dexmedetomidine initiation, without hypotension or impaired perfusion, while hypoxemic events decreased. • Autonomic monitoring (NIPE) suggests a trend toward increased parasympathetic activity, which may reflect modulation of autonomic balance under dexmedetomidine.