POSITIVE END-EXPIRATORY PRESSURE DURING KL(4) SURFACTANT INSTILLATION ENHANCES INTRAPULMONARY DISTRIBUTION IN A SIMIAN MODEL OF RESPIRATORY-DISTRESS SYNDROME

Intrapulmonary distribution of a peptide-phospholipid (KL(4)) surfactant administered through an adapter permitting maintenance of positive end-expiratory pressure was compared with distribution by instillation with disconnection from mechanical ventilation in 10 surfactant-deficient Macaca mullata preterm infants. Animals received KL(4) surfactant (200 mg/kg) when the arterial to alveolar (oxygen ratio) (a/Ao(2)) was less than or equal to 0.22 (approximately 50 min after birth) on mechanical ventilation. Six rhesus infants received bolus instillation of two half doses of KL(4) surfactant through an endotracheal tube adapter over 10-15 s while maintaining positive end-expiratory pressure (0.4 kPa) accompanied by turning to the right and left lateral positions for 60 s. In four rhesus premature infants KL(4) surfactant was injected as two half-dose boluses through the endotracheal tube with disconnection from mechanical ventilation while positioning the infant rhesus monkey in the right and left lateral positions for 30 s of mechanical ventilation between instillation. Acute effects on oxygen saturation were monitored, and physiologic measures of a/Ao(2), mean airway pressure, and the ventilatory efficiency index were monitored over the 12-h study. Intrapulmonary distribution of KL(4) surfactant was determined using dye-labeled microspheres or [H-3]dipalmitoylphosphatidylcholine-labeled KL(4) surfactant, measured by colorimetry or by scintillation counting. Lungs of each monkey were processed into 50 +/- 5 pieces to determine distribution of radiolabel or microspheres and for scanning electron microscopy. The drop in oxygen saturation was greater among monkey infants disconnected from the ventilator for surfactant instillation. Surfactant distribution in lung pieces inside a distribution interval 0.6-1.4 of the mean was greater among infants having instillation accompanied by positive end-expiratory pressure (p < 0.04), whereas the proportion of lung pieces receiving less than or equal to 10% of the normalized mean number of microspheres/mg of lung tissue was significantly greater in the group removed from the ventilator for surfactant instillation. The a/Ao(2), lung compliance, and mean airway pressures improved in both treatment groups; however, the ventilatory efficiency index increased more above pretreatment values among infants treated using the endotracheal adapter with positive end-expiratory pressure (p < 0.04). More homogeneous distribution of KL(4) surfactant results when this surfactant is administered while maintaining positive end-expiratory pressures during surfactant instillation.