PRINCIPLES OF SURFACTANT REPLACEMENT

Surfactant therapy is an established part of routine clinical manageme nt of babies with respiratory distress syndrome. An initial dose of ab out 100 mg/kg is usually needed to compensate for the well documented deficiency of alveolar surfactant in these babies, and repeated treatm ent is required in many cases. Recent experimental and clinical data i ndicate that large doses of exogenous surfactant may be beneficial als o in conditions characterized by inactivation of surfactant, caused by , for example, aspiration of meconium, infection, or disturbed alveola r permeability with leakage of plasma proteins into the airspaces. The acute response to surfactant therapy depends on the quality of the ex ogenous material (modified natural surfactants are generally more effe ctive than protein-free synthetic surfactants), timing of treatment in relation to the clinical course (treatment at an early stage of the d isease is better than late treatment, and may reduce the subsequent ne ed for mechanical ventilation), and mode of delivery (rapid instillati on via a tracheal tube leads to more uniform distribution and is more effective than slow airway infusion). Treatment with aerosolized surfa ctant improves lung function in animal models of surfactant deficiency or depletion, but is usually associated with large losses of the nebu lized material in the delivery system. Furthermore, data from experime nts on immature newborn lambs indicate that treatment response may dep end on the mode of resuscitation at birth, and that manual ventilation with just a few large breaths may compromise the effect of subsequent surfactant therapy. The widespread clinical use of surfactant has red uced neonatal mortality and lowered costs for intensive care in develo ped countries. The hydrophobic surfactant proteins SP-B and SP-C are p robably essential for optimal biophysical and physiological activity o f exogenous surfactants isolated from mammalian lungs, and the dose-ef fectiveness (in part reflecting resistance to inactivation) can be fur ther improved by enrichment with SP-A. The development of new artifici al surfactant substitutes, based on synthetic analogues of the native surfactant proteins, is an important challenge for future research. (C ) 1998 Elsevier Science B.V. All rights reserved.