Surfactant Treatment for Respiratory Distress Syndrome: A Review

The first use of an exogenous surfactant in the treatment of respiratory distress syndrome (RDS) was by Robillard et al. (1964) who used nebulized pure dipalmitoylphosphatidylcholine (DPPC) with very little effect. The real foundations of surfactant replacement therapy were laid by Enhorning and Robertson who showed that natural surfactant could be harvested from mature lungs by lavage, concentrated by centrifugation and then instilled into the pharynx or trachea of living premature rabbits (Enhorning & Robertson 1972, Robertson & Enhorning 1974, Enhorning et al. 1973a, b, 1975, Enhorning 1977). It improved the lung expansion, gas retention, compliance and survival. In ventilated rabbits it reduced the incidence of bronchiolar lesions (Nilsson et al. 1978). Similar experiments performed with ventilated premature rhesus monkeys showed improved oxygenation, reduced carbon dioxide tensions and better pressure/volume curves in the surfactant-treated group (Enhorning et al. 1978, Cutz et al. 1978). Studies with premature lambs confirmed these findings (Adams et al. 1978). With an unusual slant to the subject, Morley et al. (1978) pointed out that the natural surfactant was most effective in a dry,' crystalline state. This successful work encouraged the idea that this type of treatment might be useful in premature babies with RDS and set in motion a number of studies to find an effective surfactant which would be safe to use in babies: Chu et al. (1967) following Robillard's experience, tried nebulization of pure DPPC with minimal beneficial effect. Ikegami et al. (1979) studying a variety of phospholipid mixtures or natural surfactants in suspension, showed that no artificial mixture was as good at restoring the pressure/volume characteristics of surfactant-depleted lungs as natural surfactant, although a mixture of DPPC/unsaturated phosphatidylglycerol (UPG) was better than the other mixtures. Fujiwara and his colleagues (1979) showed that surfactant extracted from minced cow lung, and modified with DPPC and PG to the appropriate physicochemical properties, could improve the compliance of ventilated premature rabbit lungs and reduce the hyaline membrane formation and cell damage (Enhorning et al. 1973a). A completely synthetic surfactant consisting of pure DPPC and unsaturated PG in a ratio of 7: 3 was produced by Bangham et al. (1979) and shown to be at least partially effective in premature rabbits (Morley et al. 1980), although not as effective as natural surfactant (Robertson & Enhorning 1974). Artificial surfactant in the form of an emulsion (DPPC + unsaturated PG + palmitoleic acid + small amounts of lysolecithin dissolved in soyabean oil and emulsified in saline) was tried by Grossman & Larsson (1974); although partially effective it was clearly inferior to natural surfactant (Robertson 1980). Attempts at aerosolization of either synthetic surfactant or natural surfactants into lungs have failed to produce satisfactory results (Ohi et al. 1976, Shannon & Burnell 1976, Chu et al. 1967), whereas direct tracheal instillation seems to produce striking improvement in lung function.