Excess cerebral oxygen delivery follows return of spontaneous circulation in near-term asphyxiated lambs

Shiraz Badurdeen,Martin Kluckow,Stuart B Hooper,Calum T Roberts,Andrew W Gill,Sarah Klink,Suzanne L Miller,Robert Galinsky,Peter G Davis,Georg M Schmölzer,Graeme R Polglase

doi:10.1038/s41598-020-73453-x

Abstract

Hypoxic-ischaemia renders the neonatal brain susceptible to early secondary injury from oxidative stress and impaired autoregulation. We aimed to describe cerebral oxygen kinetics and haemodynamics immediately following return of spontaneous circulation (ROSC) and evaluate non-invasive parameters to facilitate bedside monitoring. Near-term sheep fetuses [139 ± 2 (SD) days gestation, n = 16] were instrumented to measure carotid artery (CA) flow, pressure, right brachial arterial and jugular venous saturation (SaO2 and SvO2, respectively). Cerebral oxygenation (crSO2) was measured using near-infrared spectroscopy (NIRS). Following induction of severe asphyxia, lambs received cardiopulmonary resuscitation using 100% oxygen until ROSC, with oxygen subsequently weaned according to saturation nomograms as per current guidelines. We found that oxygen consumption did not rise following ROSC, but oxygen delivery was markedly elevated until 15 min after ROSC. CrSO2 and heart rate each correlated with oxygen delivery. SaO2 remained > 90% and was less useful for identifying trends in oxygen delivery. CrSO2 correlated inversely with cerebral fractional oxygen extraction. In conclusion, ROSC from perinatal asphyxia is characterised by excess oxygen delivery that is driven by rapid increases in cerebrovascular pressure, flow, and oxygen saturation, and may be monitored non-invasively. Further work to describe and limit injury mediated by oxygen toxicity following ROSC is warranted.

Highlights

Hypoxic-ischaemia renders the neonatal brain susceptible to early secondary injury from oxidative stress and impaired autoregulation
We evaluated whether the change in heart rate (HR), crSO2 and SaO2 between adjacent timepoints corresponded with fluctuations in oxygen delivery and carotid artery pressure
In this study we show that the immediate period following return of spontaneous circulation (ROSC) is characterised by an excess in oxygen delivery relative to consumption, driven by rapid increases in cerebrovascular pressure, flow, and oxygen saturation

Summary

Introduction

Hypoxic-ischaemia renders the neonatal brain susceptible to early secondary injury from oxidative stress and impaired autoregulation. We aimed to describe cerebral oxygen kinetics and haemodynamics immediately following return of spontaneous circulation (ROSC) and evaluate noninvasive parameters to facilitate bedside monitoring. Following induction of severe asphyxia, lambs received cardiopulmonary resuscitation using 100% oxygen until ROSC, with oxygen subsequently weaned according to saturation nomograms as per current guidelines. In response to severe hypoxic-ischaemia, cardiac output is redistributed to prioritise oxygen delivery to the brain through dilation of the cerebral vasculature. Lamb experiments have previously shown a rapid increase in both cerebral blood flow and oxygen delivery following ROSC14–17. A measure of the matching of delivery and consumption is the cerebral fractional oxygen extraction (cFOE). This is the proportion of oxygen unloaded from haemoglobin (Hb) into the tissue. Oxygen sufficiency may be defined as oxygen delivery that is well matched to oxygen consumption, and is seen in the relatively stable cFOE during normal transition[18,19,20]

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