Dose-response study of surfactant replacement in immature newborn rabbits

Physiological effects of: various doses and concentrations of exogenous sur f acta nt (Curosurf(R)) were tested in ventilated immature newborn rabbits. In one series of experiments, surfactant was administered at a standard do se volume (5 ml/kg) and at concentrations varying from 0 to 80 mg/ml. In an other series, the concentration of su rf acta nt was kept constant (80 mg/m l) a nd the dose ranged from 50 to 300 mg/kg. A third series of experiments evaluated the effect of a standard dose of surfactant (160 mg/kg) administ ered at concentrations varying between 40 and 80 mg/ml. Surfactant treatmen t improved survival during a 30-min period of mechanical ventilation in ani mals receiving doses greater than or equal to 50 mg/kg, and there was a cle arly dose-dependent improvement in lung-thorax compliance, reflected in bot h tidal volume and expiratory time constant measurements, end-expiratory lu ng gas volume, and alveolar volume density in histological sections. Seemin gly optimal effects were obtained with surfactant at a concentration of 80 mg/ml, administered at a dose of at least 200 mg/kg. These findings support currently recommended high-concentration, high-dose regimens for surfactan t treatment of neonatal respiratory failure due to lung immaturity.