Artificial versus natural surfactant — Can we base clinical practice on a firm scientific footing?

Abstract

Now that surfactant is in widespread use, clinical trials are beginning to address the critical question of whether the choice of surfactant really matters in terms of major morbidity and mortality. The trials reported so far focus on the effects of artificial and natural surfactant on acute gas exchange and duration of oxygen or ventilation therapy. Although the number of infants recruited to comparative trials of different surfactants is increasing, we are still a long way from being able reliably to answer the question ‘Which type of surfactant should we use and under what circumstances?’ In understanding the uncertainty in this field it is pertinent to consider the interrelationships between three levels of research for any new therapy in clinical science. At the first level animal studies or case reports suggest potential clinical benefits. At the second, more focused physiological studies and trials address questions of mechanism. At the third, definitive randomised trials compare major adverse clinical outcomes in human patients. Only studies conducted at this third level can finally establish clinical practice on a firm scientific footing. In this review, a preliminary meta-analysis of 801 patients recruited in three trials of artificial (Exosurf) versus natural (Survanta) surfactant shows no clear advantage for either surfactant but does not rule out moderate differences in major adverse outcomes. To establish reliably whether such differences exist will require large multicentre clinical trials. Since neonatal respiratory distress syndrome remains a common and life threatening disease, any moderate reductions in mortality and major morbidity which might be gained from using one type of surfactant rather than another would be important and well worth knowing about. Such clinical trials could answer more than one question by investigating the safety, efficacy and cost-effectiveness of each surfactant in pre-specified groups of patients stratified by initial clinical risk and illness severity and by simultaneously addressing other therapeutic issues using factorial designs. Despite their organisational problems, until such definitive “third level” comparative clinical trials of different surfactants are performed key questions for clinicians, patients and policy-makers will remain unanswered.