Oxygen Toxicity in the Premature Baboon with Hyaline Membrane Disease

Abstract

Immaturity, pulmonary barotrauma, and oxygen toxicity have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). Although the physiologic and biochemical consequences of oxygen toxicity have been described in newborn and adult animals, there have been no controlled observations in prematures. We compared the physiologic and morphologic effects of prolonged hyperoxia with those of clinically appropriate oxygen in premature baboons with hyaline membrane disease (HMD) supported with conventional positive pressure ventilation and continuous distending airway pressure (PPV/PEEP). Twenty-one premature baboons were delivered at 140 days gestation, intubated and resuscitated, and supported with PPV/PEEP and standard NICU techniques for 11 days. The FIO2, PaO2, PaCO2, pHa, ventilator and airway pressures, and blood pressure were intermittently measured and recorded. The physiologic observations could be divided into 3 distinct phases. During Phase 1 (0 to 42 h) there were no significant intergroup differences, and (a/A)PO2 and IO2 (oxygenation index; (a/A)PO2/.hivin.Paw) remained stable. In Phase 2 (43 to 96 h) there was a rapid improvement in (a/A)PO2 and IO2 in both groups, but the response in the hyperoxic animals were significantly dampened. During Phase 3 (97 to 264 h) there was continued improvement in the "prn" animals, which contrasted with progressive deterioration in those exposed to FIO2 1.0. Five of 11 "prn" and 3 of 10 FIO2 1.0 baboons developed air leaks during Phase 1 or early Phase 2. Four of 10 of the hyperoxic animals died after the late onset of air leak. Pathologic changes of BPD were found in all FIO2 1.0 animals surviving more than 6 days but in none of the "prn" long-term survivors. These data suggest that oxygen toxicity in the premature with HMD results in additive parenchymal injury, which prolongs the period of high risk for barotrauma. Both barotrauma and oxygen injury contribute to BPD in the premature baboon with HMD.