Abstract
BackgroundWhile porcine seems to be superior to bovine surfactants in terms of respiratory outcomes, it is unclear if a surfactant can improve extra-pulmonary outcomes in preterm neonates with respiratory distress syndrome and if there is any physiopathological/biological mechanism linking surfactant therapy to these outcomes. We aim to fill these knowledge gaps.MethodsSystematic and pragmatic review coupled with meta-analysis of randomized controlled trials of bovine or porcine surfactants administered to treat RDS in preterm neonates; common extra-pulmonary neonatal intensive care outcomes were considered. As additional analysis, animal or human translational studies about mechanisms linking surfactant replacement to extra-pulmonary neonatal outcomes were also systematically reviewed.ResultsPorcine surfactant is associated with lower incidence of patent ductus arteriosus (OR:0.655; 95%CI:0.460–0.931); p = 0.018; 12 trials; 1472 patients); prenatal steroids (coeff.:-0.009, 95%CI:-0.03–0.009, p = 0.323) and gestational age (coeff.:0.079, 95%CI:-0.18–0.34, p = 0.554) did not influence this effect size. No significant differences were found between porcine and bovine surfactants on neonatal intensive care unit length of stay (mean difference (days):-2.977; 95%CI:-6.659–0.705; p = 0.113; 8 trials; 855 patients), intra-ventricular hemorrhage of any grade (OR:0.860; 95%CI:0.648–1.139); p = 0.293; 15 trials; 1703 patients), severe intra-ventricular hemorrhage (OR:0.852; 95%CI:0.624–1.163); p = 0.313; 15 trials; 1672 patients), necrotizing entero-colitis (OR:1.190; 95%CI:0.785–1.803); p = 0.412; 9 trials; 1097 patients) and retinopathy of prematurity (OR:0.801; 95%CI:0.480–1.337); p = 0.396; 10 trials; 962 patients).ConclusionsPhysiopathological mechanisms explaining the effect of surfactant have been found for patent ductus arteriosus only, while they are lacking for all other endpoints. Porcine surfactant is associated with lower incidence of PDA than bovine surfactants. As there are no differences in terms of other extra-pulmonary outcomes and no physiopathological plausibility, these endpoints should not be used in future trials.RegistrationPROSPERO n.CRD42018100906.
Highlights
Respiratory distress syndrome (RDS) represents the main cause of respiratory failure in preterm neonates and is associated with an increasing burden of care [1]
Since RDS is caused by primary surfactant deficiency, the availability of exogenous surfactants allows an effective replacement therapy, which is recommended by current international guidelines, in neonates failing continuous positive airway pressure (CPAP) [2, 3]
The beneficial effect of surfactant replacement on Broncho-pulmonary dysplasia (BPD) and other respiratory outcomes is physiopathologically sound, as surfactant increases compliance and alveolar recruitment reducing the need for distending pressure and invasive mechanical ventilation, which is a main pro-inflammatory trigger involved in BPD development [11]
Summary
Respiratory distress syndrome (RDS) represents the main cause of respiratory failure in preterm neonates and is associated with an increasing burden of care [1]. Our recent meta-analysis demonstrated the superiority of high dose poractant-α over bovine surfactants at their licensed dose in terms of respiratory outcomes, using a pragmatic design [7]. This has been possible because earlier metaanalysis showed clinical equivalence between bovine surfactants [8] and this has a strong biological plausibility given their similar biochemical composition and pharmacological features [7, 9, 10]. While porcine seems to be superior to bovine surfactants in terms of respiratory outcomes, it is unclear if a surfactant can improve extra-pulmonary outcomes in preterm neonates with respiratory distress syndrome and if there is any physiopathological/biological mechanism linking surfactant therapy to these outcomes.
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