Effect of Various Inspired Oxygen Concentrations During Resuscitation of a Surfactant Deficient Asphyxiated Preterm Ovine Model

Background: Current guidelines for resuscitating preterm infants recommend beginning with 21-30% oxygen (O2). A recent meta-analysis showed that preterm neonates, who do not achieve a heart rate (HR) of ≥100 bpm & peripheral oxygen saturation (SpO2) of ≥ 80% by 5 min, are at an increased risk of mortality and morbidity. In an asphyxiated preterm neonate with surfactant deficiency, it remains unknown if starting resuscitation with 30% is sufficient to achieve HR ≥100 bpm & peripheral oxygen saturation (SpO2) of ≥ 80% by 5 min.

Methods: Preterm lambs (126-128d, equivalent to < 28-week human neonate) with respiratory distress syndrome (surfactant deficiency) were asphyxiated by umbilical cord occlusion to achieve HR < 100bpm. Once target HR was achieved, the cord was clamped, and positive pressure ventilation (PPV) was initiated with 100% O2 (OX100), 60% O2 (OX60), and 30% O2 (OX30) for 2 min and then titrated based on ILCOR/NRP recommended predutal SpO2. The primary composite outcome is to achieve a combined target of HR ≥100 bpm & peripheral SpO2 of ≥ 80% by 5 min. Time taken to achieve the primary outcome was recorded. The effect of this intervention on gas exchange, pulmonary/systemic hemodynamics, and oxidative injury was evaluated. Data were analyzed for the first 10 min (before surfactant administration).

Results: Characteristics of the lambs are shown in figure 1a. Two lambs in OX100 & OX60 achieved primary outcome by 5 min, while none achieved in OX30. Time taken to achieve the primary outcome in OX100 (6±2 min) was significantly lower (p-0.042), compared to OX30 (10±3 min). With OX60 it took 8±3 min to achieve the target. The preductal SpO2 was significantly higher with OX100 compared to OX30 (fig 1). Oxygen concentration used during the first 10 min of PPV with OX100 was significantly lower than OX30 and higher than OX60 (fig 1). The arterial oxygenation (PaO2) and the peak pulmonary blood flow (PBF) were lowest in the OX30 group (fig 1 & 2). There was no difference in the left carotid blood flow between the groups (fig 2). The oxidized to reduced glutathione ratio was significantly higher at 5 min in the OX100 group compared to OX30.

Conclusion: In asphyxiated preterm lambs, an initial oxygen concentration of 100%, decreased the duration to achieve HR of ≥ 100 bpm & SpO2 ≥80% compared to 60% & 30%. The arterial oxygenation and peak pulmonary blood flow were lowest with OX30. Higher oxidative stress was noted at 5 min with 100% compared to 30%, with no difference between the groups noted at 10 min. Although 100% O2 reduced the time to achieve the primary outcome, more translational studies are required to understand the pulmonary and cerebral toxicity secondary to higher oxygen exposure in the background of asphyxia.