Effect of Changes in Carbon Dioxide Levels on Cerebral and Cardiac Perfusion Post Extensive Resuscitation in a Term Ovine Model

Background: Extensive neonatal resuscitation with chest compressions leads to hypoxic injury as evidenced by encephalopathy, myocardial dysfunction, leading to morbidity and mortality. Although the blood flow to vital organs is pressure passive during the post-resuscitation phase following asphyxia, studies have shown that fluctuations in carbon dioxide could influence cerebral and myocardial perfusion and oxygenation. In a neonatal model of asphyxia with an open ductus, there are no studies evaluating the role of carbon dioxide fluctuations on cerebral, myocardial, pulmonary, and ductal hemodynamics and oxygenation. A multicenter RCT in 204 infants of GA ≥36weeks undergoing whole-body hypothermia for HIE, showed that cumulative exposure to hypocarbia was associated with increased death/disability at 18-22 months of age.

Methods: Blood gas and hemodynamic parameters (coronary blood flow (CoBF), carotid flow (CBF), pulmonary flow (PBF), ductal flow (DBF), mean blood pressure (MBP)) were obtained 30 min post-resuscitation from 7 term asphyxiated lambs (138 – 141 days).
The oxygen delivery to the brain and heart was calculated using blood gas parameters and blood flows. Correlation, parametric, and non-parametric analyses were performed.

Results: Eighty-four-time points between 30 & 150 min were analyzed. With stable MBP (~40 mmHg), there was a significant positive correlation between PaCO2 , Coronary blood flow (CoBF) (R-0.59), and Carotid blood flow (CBF) (R-0.64) as shown in fig 1A & 1B. The CoBF and CBF was significantly different with hypo, normo & hypercapnia (fig 1A & 1B). Along with changes in PaCO2 , the pH and ductal blood flow were significantly different between hypo and hypercapnia (fig 1C). Although there was no statistically significant difference in arterial oxygenation (PaO2 ) and pulmonary blood flow (PBF) (fig 1C), the oxygen delivery to the myocardium and brain was significantly affected by fluctuations in PaCO2.(fig 2A and 2B). The lowest oxygen delivery to the brain and heart was seen in the hypocapnia group compared to the normocapnia and hypercapnia group (fig 2A and 2B)

Conclusion: In the immediate post-resuscitation phase, avoiding hypocapnia is important to maintain perfusion, and oxygenation of the brain and heart. These findings confirm the higher risk of increased death/disability at 2y with hypocapnia in the post-resuscitation period (Pappas et al. 2011). With an open ductus, PBF and oxygenation are maintained with normocapnia. It remains unknown if higher flows and oxygenation associated with hypercapnia are beneficial or harmful given the risk of reperfusion injury in the immediate post-resuscitation phase.