Surfactants in the management of RDS: a comparison

Respiratory distress syndrome (RDS) is primarily due to decreased production of pulmonary surfactant, and is associated with significant neonatal morbidity and mortality. The therapy of choice for RDS is exogenous pulmonary surfactant, which is able to decrease RDS-associated morbidity and mortality by reducing surface tension at the air-liquid interface in the lung and preventing collapse of the alveoli. Surfactants may be synthetic or derived from natural sources: this largely influence their composition.

Human pulmonary surfactant is a precise mixture of phospholipids (PL), neutral lipids, and proteins (SP-A, SP-B, SP-C, SP-D), with synergic functions. The currently available synthetic surfactants do not contain these specific surfactant-associated proteins. However, also natural surfactants may vary in composition with respects to lipid and protein contents. For instance, poractant alfa (Curosurf) presents an higher concentration of polyunsaturated PL and plasmalogen, which have been shown to enhance the fluidity of lipid layers and to protect cells from oxidative stress, with respect to other natural surfactant. It has also been suggested that the presence of these two components may reduce the risk of developing bronchopulmonary dysplasia (BD). Moreover, poractant alfa have a greater level of SP-B, which determines a lower viscosity. This may ease the administration of surfactant.

The efficacy of surfactants may be investigated with clinical trials. An early pivotal multicenter clinical trial of 146 infants with severe RDS, treated with a single dose of poractant alfa (200 mg/ kg) as rescue therapy, showed a reduction in 28-day mortality from 51% to 31% compared to controls. In addition, there were improvements in oxygenation and percentage of survivors without BD (55% vs 26%), and a decreased incidence of pulmonary interstitial emphysema (23% vs 39%) and pneumothorax (18% vs 35%).

Since then, many comparative trials have been conducted using the available surfactants. The efficacy of synthetic surfactants has been compared to that of natural surfactants in 14 clinical trials as of 2006. Overall, for infants with RDS, natural surfactants improved survival and had fewer associated comorbidities compared to synthetic products. Further benefits of the natural products included faster action and decreased dependence on supplemental oxygen and mechanical ventilation. The superior outcomes associated with natural surfactants were likely due to the presence of the surfactant-associated proteins. Different natural surfactants were directly compared in a few clinical trials. In one early trial, conducted on 73 preterm infants with RDS, poractant alfa was associated to less oxygen and ventilator requirements during the first 24 hours than beractant, as well as fewer complications and a low need for further doses. Similar results were obtained in two other studies, which showed also a lower mortality in infants born = 32 weeks gestation associated with poractant alfa (3% vs 11%). These findings were further confirmed by a recent metanalysis, in which poractant alfa (200 mg/kg) significantly decreased mortality if compared to beractant 100 mg/kg (RR 0.29). In one study, it was also suggested that poractant alfa may be associated with a lower incidence of patent ductus arteriosus. It is likely that the larger amounts of polar lipids and SP-B of poractant alfa may have accounted for the faster response observed with this surfactant. At present, poractant alfa is the only product available with the ability to deliver a 200 mg/kg dose in a smaller volume.

Taken together, these results support the superiority of natural surfactants in the reduction of morbidity and mortality associated with neonatal RDS with respect to syntetic ones and suggest that treatment with poractant alfa at 200 mg/kg was more effective than beractant at 100 mg/kg.

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