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Increased inspired oxygen in the first hours of life is associated with poor outcome in newborns treated with therapeutic hypothermia after perinatal asphyxia

Presented at the Neonatal Society 2012 Spring Meeting.

Sabir H1, Jary S1,2, Tooley J2, Liu X1, Thoresen M1,3

1 School of Clinical Sciences, University of Bristol, St Michael’s Hospital, Bristol, United Kingdom
2 University Hospitals Bristol, St Michael’s Hospital, Neonatal Unit, Bristol, United Kingdom
3 Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway

Background: Term newborns affected by perinatal asphyxia usually need resuscitation and ventilatory support. Therapeutic hypothermia (HT) reduces brain injury and has become standard of care after moderate or severe perinatal asphyxia. In non cooled newborns hyperoxia and hypocarbia after birth are associated with poor outcome. In a cohort born at least 18 months before the new ILCOR guideline of resuscitation in air was implemented, we assessed whether increased inspired oxygen and/or hypocarbia during the first 6h of life were associated with poor outcome at 18 months in term neonates treated with therapeutic hypothermia.

Methods: Sixty one newborns with moderate or severe perinatal asphyxia, fulfilling the entry criteria as laid out by the CoolCap and TOBY trial, were cooled for 72h using whole body cooling. Blood gases were analysed and ventilatory settings monitored hourly for 6h after birth. We investigated if there was any association between increased inspired oxygen and/or hypocarbia and poor outcome (death or disability (examined by Bayley Scales of Infant Development II at 18-20 months)).

Results: Presented as median (IQR): HT was undertaken from 3h 45min (10min-10h) and lowest pCO2 level within the first six hours of life was 30mmHg (16.5–96mmHg). The highest FiO2 within the first hour of life was 0.43 (0.21–1.00). The area-under-the-curve (AUC) -FiO2 and -PaO2 for hours 1-6 of life was 0.23 (0.21–1.0) and 86.1mmHg (21.6-196.6mmHg), respectively. We did not find any association between any measures of hypocapnia (lowest value, time average over 6h) and poor outcome (p>0.05), but we found a significant correlation between AUC-FiO2 hours 1-6 of life and outcome, even when excluding newborns with initial oxygenation failure (e.g. meconium aspiration) (p<0.05).

Conclusion: Discussion: We did not find a association between PaO2 and outcome. It is not possible in a clinical setting to standardize the measurements, because arterial samples are not available at all times in each newborn and the frequency of sample analysis is dependent on the sickness of each child. Because we only have PaO2 values from 67% of samples, this weakens the dataset with regards to PaO2 and may explain why we did not find a correlation of AUC-PaO2 and outcome (1). Increased fraction of inspired oxygen within the first 6h of life is significantly associated with poor outcome in newborns treated with therapeutic hypothermia following hypoxic ischemic encephalopathy. These results are in keeping with our recent study in rats where resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat (2).

Corresponding author: marianne.thoresen@bristol.ac.uk

References
1. Sabir H et al. J Ped. 2012 Apr 18
2. Dalen M et al., Pediatr Res. 2012 Mar;71 (3): 247-52

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