Could Exogenous Surfactant Administration Be Neuroprotective? A NIRS Study of the Efficacy and Short- and Long-Term Cerebrovascular Effects of Fractionated Surfactant Administration in Preterm Infants

Background: Thirty years ago, Saliba and colleagues first attempted to mitigate the negative effects (hypercarbia) of exogenous surfactant (ES) by slowing its administration. Sixteen years later, Kribs and colleagues introduced the first less invasive surfactant administration (LISA) technique. Since then, numerous studies have aimed to reduce the invasiveness of ES and subsequent cerebral blood flow perturbations using near-infrared spectroscopy (NIRS). This study addresses this medical challenge by exploring a less problematic ES administration method, delivering multiple aliquots instead of a single dose. The aim was to test the hypothesis that administering ES in multiple aliquots could be a safe alternative, warranting further investigation. Methods: Patients between 23 + 0 and 34 + 0 weeks of gestational age (GA) requiring ES administration were enrolled (January 2023-July 2024). Differently fractioned doses (2 to 6 aliquots) were administered as determined by the attending neonatologist, with continuous NIRS and transcutaneous CO2 (tCO2) monitoring. The effectiveness of ES was assessed by the reduction in the Oxygen Saturation Index (OSI) post-administration. Adverse effects, including persistent desaturation, bradycardia, and airway obstruction, were monitored to evaluate safety, alongside variability in NIRS-rSO2 values and tCO2. All infants underwent brain ultrasound before and within six hours after treatment. Infants with a birth weight <1500 g also underwent brain MRI at term-corrected age, with the TMS score calculated for each. Results: Fifty-eight infants were enrolled, with a median GA of 29.5 weeks and a birth weight of 1230 g. The population was divided into two groups based on the number of surfactant aliquots: more than 3 aliquots versus 3 or fewer. No differences were observed between the groups in gestational age at birth, birth weight, or common complications of prematurity. Monitoring began before the procedure and continued for 60 minutes after the last ES aliquot. The group receiving 3 or fewer aliquots showed significantly higher variability in NIRS-SpO2 values (p = 0.03), increased NIRS-rSO2 values (p < 0.01), and elevated tCO2 levels (p < 0.01). TMS scores did not show significant statistical differences Conclusion: Our data support the hypothesis that administering surfactant in multiple smaller aliquots is safer and results in less variability in cerebral oxygen extraction and carbon dioxide levels compared to fewer, larger aliquots. The combination of reduced NIRS variability and lower tCO2 maximum levels indicates more stable cerebral blood flow during the challenging period of ES administration. This lays the foundation for more comprehensive studies, involving a greater number of patients and multiple centers.