Abrupt Weaning To Room Air Limits Cerebral Oxygen Delivery And Oxidative Stress Following Recovery From Ovine Neonatal Asphyxial Arrest

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ESPR451
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Background: The neonatal resuscitation program (NRP) recommends using 100% oxygen (O2) during chest compressions (CC). There are no guidelines on weaning inspired O2 after return of spontaneous circulation (ROSC).

Objective: Abrupt weaning of inspired to 21% Oafter ROSC will limit cerebral O2 delivery and oxidative stress compared to gradual weaning from 100% O2

Methods: Twenty-five near-term lambs asphyxiated by umbilical cord occlusion were resuscitated per NRP guidelines. Following ROSC, lambs were randomized to 100% O2-wean down or abrupt wean to 21% O2 followed by titrating up to achieve NRP O2 saturation targets. Hemodynamics and blood gases were monitored, and blood samples were obtained for measurement of glutathione (GSH) metabolites.

Results: Characteristics at fetal baseline were similar between the study groups (table 1). Partial arterial oxygen tension (PaO2) at 3 min after ROSC was 229 ±110 mmHg in 100% O2-wean down compared to 57 ±41 in 21% O2-titrate up (p <0.001) and remained significantly higher at 10 min after ROSC (110 ±33 vs. 67 ±37, p <0.01) despite similar FiO2 at 10 min (figures 1 and 2). Cerebral O2 delivery (C-DO2) was similar during CC (0.03± 0.06 vs. 0.07± 0.10 ml/kg/min, in 100% O2-wean down and 21% O2- titrate up respectively). Following ROSC, C-DO2 was higher and above physiological range in 100%O2-wean down compared to 21%O2-titrate up (p <0.05, figure 3) and cerebral oxygen extraction was not different (figure 4). Lower whole blood oxidized/reduced glutathione ratio and lower concentration of oxidized glutathione (suggesting less oxidative stress) with 21%O2-titrate up, and lower reduced GSH concentration with 100% O2-wean down (table 2) were observed at 10 min after ROSC.

Conclusion: Supraphysiological C-DO2 with 100% O2-wean down may exacerbate cerebral oxidative stress following ROSC that may be prevented by abrupt weaning to 21% O2. Clinical studies are needed to determine the impact on neurodevelopmental outcomes.


Figure 1: By study design, the inspired oxygen concentration was different between groups after ROSC. Data represented as mean and standard error of mean (SEM). *p value < 0.05.

Figure 2: Arterial partial pressure of oxygen (PaO2, figure 2A) and arterial hemoglobin oxygen saturation( SaO2, figure 2B) were higher with 100% O2-wean down.*p<0.05 ANOVA. 

  Figure 3: Cerebral oxygen delivery (C-DO2) was significantly higher with 100%-wean down compared to 21%-titrate up, potentially resulting in cerebral hyperoxia from supra-physiological C-DO2. Data represented as mean and SEM. *p< 0.01, ꝉ p<0.05 by ANOVA. ROSC: return of spontaneous circulation. The median (interquartile range) for C-DO2 in normal term lambs breathing room air is shown by the shaded area (median= 2.6 ml/kg/min; IQR-1.98 to 3.55 ml/kg/min).


Figure 4: Cerebral oxygen extraction or AV-DO2, reflective of cerebral metabolic demand, was not different between the two inspired O2 weaning strategies after ROSC. Data presented as mean and SEM.

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University of California, Davis
University of California Davis
University of California Davis
University of California Davis
University of California Davis
University of California Davis
University of California Davis

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