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Surfactant inactivation has been shown to be a significant factor in animal models of lung injury and may also be important in some forms of respiratory failure in full-term newborns. Fourteen full-term newborns with respiratory failure associated with pneumonia (7 patients) and meconium aspiration syndrome (7 patients) were treated with 90 mg/kg of a calf lung surfactant extract, given intratracheally up to every 6 hours for a maximum of four doses. The group mean fraction of inspired oxygen (Fi02) before treatment was 0.99 ± 0.01 SEM, and the mean airway pressure (MAP) was 14.6 ± 1.0 cm H2O. Patients showed significant improvement in oxygenation after initial surfactant treatment, with the arterial-alveolar oxygenation ratio (a/A ratio) rising from 0.09 ± 0.01 before surfactant treatment to 0.22 ± 0.05 by 15 minutes (P = .03) and remaining improved for 6 hours. The oxygenation index, incorporating MAP as well as oxygen variables, also improved significantly from 26.2 ± 3.1 to 11.2 ± 1.7 at 15 minutes (P < .001), with improvement sustained for more than 6 hours. Chest radiographs were blindly scored from 0 (normal) to 5 (severe opacification), and these improved with marginal significance after initial surfactant treatment (from 2.9 ± 0.2 to 2.5 ± 0.2, P = .05). Eight patients subsequently met retreatment criteria (Fi02 ≥ 0.5 and MAP ≥ 7 cm H2O) and received a second surfactant dose, with a/A ratio rising from 0.124 ± 0.02 before treatment to 0.26 ± 0.07 after 45 minutes (P = .03) and remaining improved for more than 4 hours; the oxygenation index was also significantly improved over similar times by the second surfactant dose. Six patients received a third surfactant dose, with no increase in a/A ratio and a less prominent improvement in oxygenation index. There were no significant improvements in oxygenation in the three patients who received a fourth surfactant dose. Of the 14 patients treated, none died, required extracorporeal membrane oxygenation, had tension pneumothorax after study entry, required oxygen supplementation for more than 14 days, or required oxygen supplementation at discharge. These findings suggest that surfactant supplementation may provide therapeutic benefits for newborns with respiratory failure due to pneumonia or meconium aspiration and that expanded controlled trials of this therapy are indicated.

In this paper current knowledge of the palmonary surfactant system with particular emphasis on aspects that relate to exogenous surfactant replacement therapy for the neonatal respiratory distress syndrome (RDS) is considered. The work provides an overview, but concentrates on several facets of lung surfactant research that help to elucidate and evaluate past and present attempts toward such therapy. Subjects addressed include the functional need for specific lung surfactant components to obtain optimal surface activity and some of the required surface property measurements to characterize such activity. Also discussed is current knowledge of lung surfactant synthesis and secretion and the potential effect of exogenous surfactant on the endogenous pulmonary surfactant sytem. A primary theme throughout is that an analysis of previous clinical trials involving surfactant replacement shows the necessity for strong interactions with related basic science investigations. It is suggested that future human infant surfactant replacement trials proceed deliberately, and include maximal correlations with basic in vitro research on lung surfactant biophysics and biochemistry and with experiments in animal models.

A prospective, double-blind, controlled trial was conducted to determine whether instillation of an exogenous surfactant into the lungs before the first breath could prevent hyaline membrane disease. The surfactant is calf lung lipid extracted from saline lung lavage. Entry was limited to infants who were 24 to 28 weeks' gestation, who were born at Children's Hospital of Buffalo, and whose mothers had not received betamethasone for more than 24 hours before birth. Treated infants received 3 mL (90 mg) of calf lung surfactant extract instilled into their trachea before the first breath; control infants received 3 mL of normal saline. A prospective scoring system and respiratory support variables were used to compare the groups. At 48 hours of age, only two of 14 calf lung surfactant extract-treated infants (14%) had hyaline membrane disease compared with seven of 13 control infants (54%) (P = .033). Inspired oxygen, mean airway pressure, ventilator rate and ventilator efficiency index were also lower in the treated group during the first 48 hours of life (P < .01 to P < .001). Calf lung surfactant extract instillation at birth appears to be an effective material and method of preventing hyaline membrane disease in extremely premature infants.

Organic solvent extraction of surfactant obtained by lavage of calf lungs yields a highly surfaceactive material. A double blind, randomized clinical trial to determine the effect of this material on respiratory distress syndrome in premature infants was initiated in the Neonatal Intensive Care Unit at the University of Rochester in December 1983. Infants 25 to 29 weeks gestational age were eligible for entry into the trial. At the time of this interim analysis 32 patients had been randomly selected and entered into the trial, 16 surfactant-treated patients and 16 in a control group who received only saline. At birth, intrapulmonary instillation of the calf lung surfactant extract dispersed in saline or saline alone occurred in the delivery room immediately after intubation and prior to ventilation; infants were then ventilated and treated as usual. At 6, 12, 24, 48, and 72 hours after birth, the severity of respiratory distress was categorized as either minimal, intermediate, or severe based on oxygen and mean airway pressure requirements. Differences observed at six hours after birth were of marginal significance, but at 12 and 24 hours the surfactant-treated group had significantly (P < .01) less severe respiratory distress compared with the control group. Differences between treated and control infants were not statistically significant at 48 and 72 hours after birth. In four surfactant-treated infants the severity of respiratory distress worsened between 24 and 48 hours after birth, suggesting that one dose of surfactant at birth may not be sufficient for some infants.