Remifentanil and Neonatal Intubation: Balancing Efficacy and Safety

Background: Endotracheal intubation is a painful and stressful procedure for neonates, and premedication is recommended for non-emergent settings. However, there is no consensus on the optimal pharmacological regimen. In recent years, several drugs have emerged as treatment options to improve comfort and safety of neonates undergoing endotracheal intubation. Worldwide, a range of agents are used. Remifentanil is a short-acting opioid with rapid onset and recovery characteristics that may be useful for neonatal intubation. Methods: A structured search of PubMed/MEDLINE, Embase, and Cochrane Library databases (1990–December 2024) identified publications evaluating remifentanil for neonatal intubation. Clinical studies, pharmacokinetic investigations, reviews and guidelines were qualitatively synthesized with an emphasis on dosing, efficacy, safety, dosing, administration technique, and clinical context. Results: The literature search retrieved 45 publications, but only a small subset were randomized clinical studies. Findings generally support feasibility and short-term efficacy, while results vary across studies, particularly for intubation conditions and respiratory adverse events. Chest wall rigidity, apnea, and desaturation appear to be influenced by dose, administration rate, patient characteristics, and co-medication, although the available studies are too small and heterogeneous to define an optimal regimen. Conclusions: Remifentanil can be considered for selected non-emergent neonatal intubation and INSURE procedures when administered by experienced teams under appropriate monitoring conditions. Particular caution is warranted in clinically unstable infants, during LISA procedures where preservation of spontaneous breathing is desirable, and in settings where immediate airway rescue capabilities are unavailable. The study did not demonstrate clear superiority of remifentanil. Current evidence is limited and heterogeneous, and larger comparative studies with standardized dosing, administration, and outcome definitions are needed.