Analgosedation in Neonatal Intensive Care: Current Strategies, Challenges, and Future Perspectives

Pain and stress are frequent and clinically relevant challenges in neonatal intensive care, particularly among preterm and critically ill newborns exposed to repeated invasive procedures, mechanical ventilation, surgery, and advanced life-support interventions. Effective analgosedation is essential to reduce discomfort, attenuate physiological instability, improve tolerance of intensive care procedures, and potentially limit adverse neurodevelopmental consequences. However, neonatal pain and analgosedation management remain complex because of developmental immaturity, pharmacokinetic and pharmacodynamic variability, and the need to balance adequate analgosedation against treatment-related complications. This narrative review summarizes current evidence on analgosedation in the Neonatal Intensive Care Unit, focusing on clinical indications, pharmacological agents, non-pharmacological strategies, monitoring tools, adverse effects, and future perspectives. Opioids, benzodiazepines, dexmedetomidine, and ketamine each have specific potential benefits and limitations, requiring individualized selection, careful titration, and continuous reassessment. Non-pharmacological interventions, including oral sucrose, non-nutritive sucking, facilitated tucking, breastfeeding, skin-to-skin care, and environmental modulation, should be integrated into multimodal pain-management protocols. Validated instruments such as COMFORTneo, N-PASS, and PIPP-R support standardized assessment and guide therapeutic decisions. Future advances may derive from objective monitoring technologies, artificial intelligence, developmental pharmacology, and precision-medicine approaches. A multidisciplinary, protocol-driven, and family-centered strategy is essential to optimize neonatal comfort while minimizing avoidable drug exposure.