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Resuscitation with 100% oxygen counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

Presented at the Neonatal Society 2011 Spring Meeting.

Dalen M2, Liu X1, Elstad M1,5, Løberg EM3, Saugstad OD2, Rootwelt T4, Thoresen M1

1 Child Health, School of Clinical Sciences, University of Bristol, Level D,St Michaels Hospital, Southwell street, Bristol, BS2 8EG, United Kingdom
2 Department of Paediatric Research, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway
3 Department of Pathology, Oslo University Hospital, N-0407 Oslo, Norway
4 Department of Paediatrics, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway
5 Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway

Background: Mild therapeutic hypothermia (HT) reduces brain injury in survivors after perinatal asphyxia. The 2010 International Liaison Committee on Resuscitation (ILCOR) guidelines recommend that resuscitation of term infants should begin with air and that HT should be considered for moderate-to-severe hypoxic-ischaemic (HI) encephalopathy. It is not known if supplemental oxygen during resuscitation affects hypothermic neuroprotection. We wanted to study whether 30 min of reoxygenation in air or 100% oxygen would affect hypothermic neuroprotection starting after reoxygenation. 

Methods: Hypoxia-ischemia in an established neonatal rat hypoxia-ischemia model was followed by 30 minutes of reoxygenation in either 21%O2 or 100%O2, before 5 hours of either normothermia 37ºC (NT) or 32ºC (HT). The effects of HT and hyperoxia on histopathological injury in hippocampus, basal ganglia and cortex, and on postural reflex performance 7 days after the insult were estimated by linear regression.

Results: Wilcoxon-median (95% confidence interval, CI) hippocampal injury-scores (range 0.0-4.0; 0% to >90% injury) were for 21%O2-NT: 2.00 (1.25-2.50), 100%O2-NT: 2.50 (1.50-3.25), 21%O2-HT: 1.00 (0.50-1.50), and 100%O2-HT: 2.00 (1.25-2.50). HT significantly reduced injury in hippocampus (B=-0.721, SEM=0.297, p=0.018), while 100%O2 significantly increased injury (B=+0.647, SEM=0.297, p=0.033). The regression constant was 1.896, SEM 0.257, and the residuals were normally distributed. Reoxygenation in 100%O2 also worsened postural reflex performance (p=0.041).

Conclusion: We confirm a ~50% neuroprotective effect of therapeutic hypothermia starting after a 30 min delay of breathing 21%O2 in the immature rat, assessed one week after hypoxia-ischaemia. Breathing 100%O2 during reoxygenation cancelled the HT protection seen when reoxygenation was in 21%O2.

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

Saugstad OD, Ramji S, Soll RF, Vento M. Resuscitation of Newborn Infants with 21% or 100% Oxygen: An Updated Systematic Review and Meta-Analysis. Neonatology. 2008;94:176-82.
Thoresen M, Baagenholm R, Loberg EM, Apricena F, Kjellmer I. Posthypoxic cooling of neonatal rats provides protection against brain injury. Arch Dis Child Fetal Neonatal Ed. 1996;74:F3-F9.

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