Patent ductus arteriosus hemodynamics in very premature infants treated with poractant alfa or beractant for respiratory distress syndrome

Abstract

Objective: Respiratory distress syndrome (RDS), requiring mechanical ventilation and exogenous surfactant treatment, and patent ductus arteriosus (PDA), are common co-morbidities in very premature infants. The effects of intra-tracheal surfactant administration on the cardiovascular and pulmonary systems in very premature infants with RDS and PDAs are not well characterized. We evaluated the effects of poractant alfa and beractant, surfactants with different rapidity of onset and duration of action, in very premature infants with RDS. To assess whether there were differences in PDA hemodynamics in very premature infants with RDS treated with poractant alfa and beractant during the first week of life and to assess whether poractant alfa or beractant had a direct effect on PDAs and PDA hemodynamics following the second dose of surfactant.Study Design: We studied 50 in-born, very premature infants with RDS, 24 0 of 7 to 29 6 of 7 weeks gestation, treated with poractant alfa or beractant, in an open label, 1:1, randomized clinical trial. A subgroup of 16 patients with severe RDS, treated with a second dose of surfactant, had echocardiographical assessments before and 20 to 30 min after the second dose of surfactant.Result: There were 25 infants treated with poractant alfa (27.1 ± 1.6 weeks, birth weight 930±231 g) and 25 treated with beractant (26.7 ± 1.7 weeks, P ¼ 0.407 and birth weight 898 ± 282 g, P ¼ 0.666). Clinically significant PDAs were diagnosed and treated in 8 of 25 (32%) of the poractant alfa and 19 of 25 (76%) of the beractant group (P ¼ 0.002). Indomethacin treatment was slightly earlier (3.4 ± 2.5 days) in the poractant alfa than in the beractant group (5.1±4.9 days, P ¼ 0.038). Right ventricle pressure (RVP)/systolic arterial pressure (SAP) ratio in the first week was slightly lower in the poractant alfa (64±20%) than in the beractant (78 ± 26%, P ¼ 0.048) group. Following a second dose of surfactant, neither poractant alfa nor beractant changed PDA flow. These hemodynamic observations were associated with less respiratory support in the poractant alfa group, allowing earlier extubation (13 of 25 at 48 h and 15 of 25 at 72 h), than in the beractant group (6 of 25 at 48 h, P ¼ 0.044, and 8 of 25 at 72 h, P ¼ 0.049). Conclusion:The more rapid improvement in pulmonary function in the poractant alfa-treated infants was associated with a lower RVP/SAP ratio and a corresponding earlier treatment with indomethacin. Neither surfactant had a significant direct effect on PDA hemodynamics. The lower frequency of clinically significant PDAs in the poractant alfa compared with the beractant group may represent an indirect effect of the differences in the pulmonary improvement induced by the two surfactants.

Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome

“…The early improvement in respiratory support in infants who received poractant alfa, compared with beractant, was associated with a higher rate of early extubation at 48 and 72 h. This is the first prospective randomized control trial to report a prolonged early difference between poractant alfa and beractant, associated with a difference in the frequency of hemodynamically significant PDA, 10 making this a unique comparison of these two commonly used surfactant preparations.…”

“…Differences in PDA were addressed in a separate paper, as assessment of the hemodynamic effects of poractant alfa and beractant was one of the primary aims of the original proposal. 10 …”

“…This report is part of a comprehensive evaluation of the acute and longer-term hemodynamic effects of poractant alfa and beractant in very premature infants with RDS. 10 …”

Is there really a clinical difference in surfactant preparations?

“…6 In addition, our preliminary data suggest that improved pulmonary function in the poractant-treated very premature infants with respiratory distress syndrome may reduce the number with clinically significant patent ductus arteriosus. 2 We agree with Dr Lutchman that the surfactant story is far from complete and that ideally a comprehensive series of definitive, randomized control trials of available surfactants, with appropriate power for subgroup analysis, be funded and conducted to assess relative efficacy of surfactant preparations and dosing on preterm infant morbidity and mortality. 7 Unfortunately, these studies are challenging to design, expensive to conduct and the question of how to fund them persists.…”

Controversies in Management of Patent Ductus Arterious in the Preterm Infant

“…Although surfactant itself has no direct effect on ductal hemodynamics [25], it may alter the pulmonary vascular resistance and lead to an earlier clinical presentation of the left-to-right shunt through the PDA [26].…”