Association between hypocapnia and ventilation during the first days of life and brain injury in asphyxiated newborns treated with hypothermia

Abstract

Purpose: Therapeutic hypothermia is the standard treatment for asphyxiated newborns. Since hypocapnia is common in these newborns, the aim of this study was to assess the association among hypocapnia, ventilation, and brain injury.

Methods: We conducted a retrospective cohort study of all asphyxiated newborns treated with hypothermia from 2008 to 2014. Partial pressure of carbon dioxide (pCO₂), ventilatory status, and modes of ventilation were recorded during the first 4 days of life. Brain injury was evaluated using brain magnetic resonance imaging. Differences between intubated and nonintubated newborns and between the newborns who developed brain injury or not were assessed.

Results: One hundred ninety-eight asphyxiated newborns were treated with hypothermia. During the first 2 days of life, intubated newborns had consistently lower pCO₂ levels (respectively, 29.01 ± 8.55, p < .001 on day 1 of life and 33.65 ± 7.12, p = .004 on day 2 of life). Fifty-nine percent of the intubated newborns developed brain injury versus only 43% of the nonintubated newborns (p = .046). The lowest pCO₂ levels averaged over the first 4 days of life were significantly decreased in newborns developing brain injury (p = .02) and significantly associated with brain injury severity (p = .01). After adjusting for potential cofounders, the lowest pCO₂ averaged over days 1–4 of life remained significantly associated with an increased risk of brain injury (odds ratio [95%CI]: 1.07 [1.00–1.14]; p = .04).

Conclusions: Intubated and ventilated asphyxiated newborns experienced more severe hypocapnia, and had higher incidences of brain injury. Hypocapnia during the first 4 days of life was associated with an increased risk of developing (more severe) brain injury.

Keywords:

• Birth asphyxia
• carbon dioxide
• hypothermia
• magnetic resonance imaging
• neonatal encephalopathy

Acknowledgements

We thank Mr Wayne Ross Egers for his professional English correction of the manuscript.

Disclosure statement

The authors report no conflict of interest. This manuscript has been contributed to, seen, and approved by all the authors. All the authors fulfill the authorship credit requirements. The study sponsors had no involvement in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication. No honorarium, grant, or other form of payment was received for preparation of this manuscript.

Additional information

Funding

This work was supported by the FRSQ Clinical Research Scholar Career Award Junior 2 under grant number 32814; a New Investigator Research Grant from the SickKids Foundation and the CIHR Institute of Human Development, Child and Youth Health (IHDCYH) under grant number NI13-049R.