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Background  Nasal continuous‐positive airway pressure (nCPAP) with the INSURE (INtubation‐SURfactant‐Extubation) or LISA (Less‐Invasive Surfactant Administration) procedures are increasingly being chosen as the initial treatment for neonates with surfactant deficiency. Our objective was to compare the effects on cerebral oxygenation of different methods for surfactant administration: INSURE and LISA, using a nasogastric tube (NT) or a LISAcath® catheter, in spontaneously breathing SF‐deficient newborn piglets.    Methods  Eighteen newborn piglets with SF‐deficient lung injury produced by repetitive bronchoalveolar lavages were randomly assigned to INSURE, LISA‐NT, or LISAcath® groups. We assessed pulmonary (gas exchange, lung mechanics, lung histology) and hemodynamic (mean arterial blood pressure, heart rate) changes, cerebral oxygenation (cTOI) and cerebral fractional tissue extraction (cFTOE), with near‐infrared spectroscopy, carotid blood flow and brain histology.    Results  SF‐deficient piglets developed respiratory distress (F iO2  = 1, pH <7.2, P aCO2  >70 mmHg, P aO2  <70 mmHg, C dyn  <0.5 mL/cmH 2 O/kg). Rapid improvements in pulmonary status were observed in all surfactant‐treated groups without hemodynamic alterations. In the INSURE group, a transient decrease in cTOI occurred during and immediately after surfactant administration, while cTOI only decreased during surfactant administration in the LISA‐NT group and did not change significantly in the LISAcath® group. Brain injury scores were low in all surfactant‐treated groups.    Conclusion  In spontaneously breathing SF‐deficient newborn piglets, short‐lasting decreases in cerebral oxygenation are associated with surfactant administration by the INSURE method or LISA using an NT, while no cerebral oxygenation changes occurred with LISA using a LISAcath®. Notably, none of treatments studied seems to have a negative impact on the neonatal brain.

Cerebral oxygenation associated with INSURE versus LISA procedures in surfactant‐deficient newborn piglet RDS model