Controversies: synthetic or natural surfactant. The case for natural surfactant.

Abstract

Surfactant replacement therapy for respiratory distress syndrome (RDS) is not new, the first trials having been performed over 30 years ago. These early trials used synthetic protein-free surfactants administered as aerosols and were unsuccessful. Since 1980 a variety of natural and synthetic surfactant preparations have been used to treat or prevent RDS, and both demonstrate clinical effects. I have used evidence derived from 3 areas to demonstrate the superiority of natural surfactants: in vitro physical properties, in vivo physiological effects and the results of comparative clinical trials. using the pulsating bubble surfactometer, the surface tension at maximum and minimum bubble size are significantly lower for natural compared to synthetic surfactants (31 and 0 mN/m versus 53 and 29 mN/m respectively). Physiological effects of surfactants have been compared in immature rabbits and lambs and both models demonstrate the superiority of natural surfactants. For example in immature rabbits lung compliance values after 60 minutes of ventilation are 0.60 ml/cmH2O in natural surfactant treated animals, 0.44 ml/cmH2O in synthetic surfactant treated animals and 0.34 ml/cmH2O in controls (p < 0.01). The technique of meta-analysis was used to analyse the outcome of 6 comparative clinical trials of natural and synthetic surfactants. These 6 studies included 3536 babies and 5 of them compared Survanta (a bovine natural surfactant) and Exosurf (a synthetic protein-free surfactant). One study compared Infasurf (another bovine natural surfactant with Exosurf). Meta-analysis shows a 19% reduction in the odds of neonatal death for natural compared to synthetic surfactant treated babies (OR, 0.81; 95% CI 0.66-0.98). For bronchopulmonary dysplasia there was a non-significant reduction in risk for Survanta-treated babies (OR, 0.93; 95% CO 0.78-1.10). In summary, there is now clear evidence of physiological and clinical superiority of natural compared to synthetic surfactants. Surfactant proteins B and C are needed to facilitate rapid adsorption and spreading of phospholipids. They also account for the more rapid clinical action allowing oxygen and ventilator pressures to be lowered soon after administration. The odds of neonatal mortality are reduced by about 20% if natural surfactants are preferred to their synthetic protein-free counterparts. Long-term follow-up studies of babies treated with both types of surfactant should be a top priority.