Combined effects of surfactant substitution and prolongation of inspiration phase in artificially ventilated premature newborn rabbits

Premature newborn rabbits, delivered by hysterotomy on day 27 of gestation, were tracheotomized at birth, kept in body plethys- mographs, and subjected to pressure-generated ventilation at a working pressure of 25 cm H₂O, 100% O₂, and frequency 40/min. Thirty-seven animals received 50 µl of heterologous surfactant (phospholipid content 40 mg/ml) via the tracheal cannula before onset of artificial ventilation, eight were ventilated with a positive end-expiratory pressure (PEEP) of 6 cm H₂O, and 44 served as controls. All animals were ventilated in a randomized sequence of 2-min periods with 20, 40, 60, or 80% inspiration time. After the experiment the trachea was clamped at end-inspiration and the lungs fixed by immersion in formalin. Plethysmograph recordings of tidal volume revealed that lung-thorax compliance was low in control animals, even at inspiration time 80% (mean ± S.E. = 0.17 ± 0.03 ml/cm H₂O • kg). In animals treated with surfactant or PEEP, compliance was significantly improved at all ventilator settings. The highest mean compliance values, obtained at 60% inspiration time were 0.91 ± 0.07 and 0.73 ± 0.14 ml/cm H₂O • kg in surfactant- and PEEP-treated animals, respectively. Compliance of surfactant-treated animals was significantly higher than that of PEEP-treated animals at inspiration time 40% (0.85 ± 0.07 versus 0.52 ± 0.13 ml/cm H₂O • kg; P < 0.05). The relative volume of the alveolar compartment, determined morphometrically in histologic sections and expressed as the alveolar expansion index (I_a), was significantly higher in surfactant-treated animals than in controls (1.60 ± 0.12 versus 0.74 ± 0.06; P < 0.005), but not improved in animals ventilated with PEEP. In animals receiving surfactant, Ia increased with the duration of the inspiration phase, from 0.99 ± 0.10 at 20% to 1.95 ± 0.22 at 80% inspiration time. There was also histologic evidence of enhanced recruitment of aerated alveoli in surfactant-treated animals ventilated with prolonged inspiration time. Speculation: The air expansion of the premature neonatal lung can be enhanced to a significant degree by treatment with surfactant in combination with appropriate prolongation of the inspiration phase. Such a therapeutic regimen might be useful in the management of newborn infants with severe respiratory distress syndrome, requiring artificial ventilation; however, because excessive prolongation of the inspiration phase could have adverse effects on pulmonary hemodynamics and lead to hypoventilation with respiratory acidosis, the setting of the ventilator should be carefully adjusted with respect to the therapeutic response in patients with respiratory distress syndrome who are treated with supplementary surfactant.