Surfactant deficiency remains a significant cause of mortality and morbidity in preterm infants.1 The Less Invasive Surfactant Administration (LISA) procedure involves laryngoscopy and intratracheal surfactant administration via a thin catheter during spontaneous breathing supported by nasal CPAP or other types of non-invasive support or ventilation.2 In a recent study including 153 international LISA experts from 14 countries, 41% indicated no use of analgesic premedication for LISA, while 49% reported using fentanyl.3 On the contrary, non-pharmacological comfort care was used extensively for LISA but with no standardized approach.3

The NONA-LISA trial deals with the ethical imperative of providing adequate reduction in pain and discomfort for neonates while balancing potential adverse effects from premedication. Sufficient management of pain and discomfort is paramount, as pain and distress can result in adverse effects on the premature brain and other organs, which may ultimately affect neurodevelopment.4 Hence, there is a delicate balance between the desired effect of analgesia reducing discomfort and pain associated with laryngoscopy as opposed to the risk of over-sedation and apnoea, which can lead to LISA failure and the need for positive pressure ventilation, ultimately increasing the risk of BPD. The NONA-LISA trial (ClinicalTrials.gov, NCT05609877) compares LISA with saline to LISA with 0.5–1 mcg/kg fentanyl in infants born before 30 gestational weeks, assuming that adequate non-pharmacological support and attention may alleviate the pain and distress caused by the procedure without medication. All infants will receive standardized non-pharmacological comfort care. The primary outcome is the need for at least 30 min of mechanical ventilation within 24 h of the procedure.5 The NONA-LISA trial has obtained ethical approval from the regional ethics committee in Denmark, and an interdisciplinary and international Data Monitoring and Ethics Committee has been appointed to oversee the trial’s progression and results. This comment aims to discuss the NONA-LISA trial and its potential impacts following the comment by Ramanathan and Biniwale.6

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