<b><i>Background:</i></b> Surfactant therapy is the cornerstone of respiratory distress syndrome management. “Less-invasive surfactant administration (LISA)” is now recommended for spontaneously breathing preterm infants. Analgosedation remains controversial as 52% of European neonatologists do not use any. This systematic review aims to describe the efficacy and safety of different drugs for analgosedation during LISA. <b><i>Methods:</i></b> MEDLINE via Ovid, Embase, Scopus, and Cochrane Library of Trials were searched independently by 2 reviewers for studies on sedation or analgesia for LISA, without filters or limits. <b><i>Results:</i></b> Eight studies (1 randomized controlled trial) recruiting 945 infants were included. Infant pain was significantly reduced, with more infants evaluated as comfortable. Failure, defined as need for intubation or for a second dose of surfactant, was not different between sedated and unsedated groups. Analgosedation was associated with a higher occurrence of desaturation and need for positive pressure ventilation during procedure, but the need for mechanical ventilation within 24 or 72 h of life was not significantly different. There does not seem to be any difference in clinical tolerance and complications (e.g., hypotension, mortality, air leaks, etc.). Procedural conditions were evaluated as good or excellent in 83% after sedation. <b><i>Discussion and Conclusion:</i></b> Analgesia or sedative drugs increase infant comfort and allow good procedural conditions, with a limited impact on the clinical evolution. Questions remain about the best choice of drugs and dosages, with the constraint to maintain spontaneous breathing and have a rapid offset. Further good quality studies are needed to provide additional evidence to supplement those limited existing data.

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<b><i>Aim:</i></b> Pain management is important for newborns’ immediate and long-term well-being. While intranasal analgesia and sedation have been well studied in children, their use could be extended to term and preterm infants. This systematic review aims to assess the use of intranasal medications for procedural analgesia or sedation in the neonatal intensive care unit. <b><i>Methods:</i></b> MEDLINE via Ovid, Scopus, Embase, and Cochrane Library were searched independently by two reviewers for clinical studies on sedation or analgesia given intranasally. <b><i>Results:</i></b> Seven studies, with 401 patients, were included. The studies described various molecules (midazolam, fentanyl, ketamine, or dexmedetomidine) for different procedures such as intubation in the delivery room, screening for retinopathy, or magnetic resonance imaging. All studies reported significant reduction in pain and sedation markers (based on clinical scales, skin conductance, and clinical variables such as heart rate and crying time). Adverse effects were uncommon and mostly consisted in desaturation, apnoea, hypotension, or paradoxical reactions. <b><i>Discussion and Conclusion:</i></b> The intranasal route seems a potential alternative for procedural pain management and sedation in neonates, especially when intravenous access is not available. However, data about safety remain limited. Reported sides effects could be attributed to molecules used rather than the intranasal route. Optimal drugs and doses still need to be characterized. Further studies are needed to ensure safety before promoting a widespread use of intranasal medications in neonatology.

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