Dosing of poractant alfa: effect on kinetics and gas-exchange in RDS

Exogenous surfactant therapy is considered as a cornerstone of modern neonatology. However, information on the effect of different exogenous surfactant dosing is still limited. Some studies compared beractant 100 mg/kg and poractant alfa, administered at either 100 or 200 mg/kg to infants with moderate/severe nRDS. Results showed that poractant alfa has a faster onset of action and is associated with lower neonatal mortality rates. The most significant effects on mortality were seen with poractant alfa 200 mg/kg; this dose-effect relationship was confirmed in other studies. A recent meta-analysis comparing single versus multiple surfactant doses showed greater improvements in oxygenation and ventilatory requirements, a decreased risk of pneumothorax and a trend toward improved survival rates in infants receiving multiple surfactant doses. However, the optimal timing for the administration of retreatment is still unclear. It is likely that better knowledge of the pharmacokinetic features of exogenous surfactant in RDS could help optimizing the treatment.
An Italian group has investigated the kinetics of exogenous surfactant by analyzing the isotopic enrichment of disaturated phosphatidylcholine (DSPC) isolated from tracheal aspirates in nRDS infants. Within 24 hours after birth, patients received poractant alfa 100 mg/kg (N=40) or 200 mg/kg (N=21) mixed with [U^-13C] DSPC. Clinical and respiratory parameters were recorded and DSPC pharmacokinetics parameters were calculated.
Clinical characteristics and incidence of mechanical ventilation, mortality or bronchopulmonary dysplasia were not different between groups. In the 100 mg/kg group, 28 infants (70%) received a second surfactant dose and 9 (22.5%) a third dose; in the 200 mg/kg group, only 6 infants (28.6%) received a second dose (p<0.01) and 1 a third dose. The DSPC half-life was significantly longer in the 200 mg/kg group (first dose: 32±19 vs 15±15 hours; second dose: 43±32 vs 21±13 hours). DSPC synthesis rate and pool size before the first and second dose did not differ between groups. Of note, the 200 mg/kg group showed a statistically significant improvement in the oxygenation index after the first and second dose compared to the 100 mg/kg group. The main clinical findings of this study were that a larger dose of poractant alfa is associated with a longer half-life, a lower requirement for additional doses and better oxygenation index values. Further studies will verify if the higher dose might also lead to earlier extubations and/or fewer reintubations.

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