Hypocapnia in asphyxiated infants

Some of my posts are not necessarily going to be about very new publications, sometimes a clinical event or question stimulates me to review the literature, and I will share my findings with the readers.

Spontaneous hypocapnia is not rare in asphyxiated infants. Although it is possible to hyperventilate an infant more easily when their metabolism and CO2 production is reduced by hypothermia, they also frequently hyperventilate themselves. This may be in response so a systemic metabolic acidosis, but may go beyond that stimulus and lead to a systemic respiratory alkalosis. Exactly why this happens I am unsure, perhaps there is brain stem acidosis which over-drives respiration.

The well characterized neonatal rat carotid artery ligation and hypoxia model has similar responses. This model, developed by Dr R Vannucci, hyperventilates in response to metabolic acidosis, and will become spontaneously seriously hypocapnic. They may completely correct their acidosis with a mean PCO2 as low as 25 mmHg. In 1995 Dr Vannucci showed that just giving CO2 gas, as a 3, 6, or 9% mixture, prevented much of the brain damage, 3% gave normocapnia and reduced brain injury, the best effect was at 6% CO2 which caused mild hypercapnia (mean PCO2 about 56 mmHg), a slight reduction in the benefit was noted with 9% CO2, (mean PCO2 about 68 mmHg).

Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM: Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: An experimental study in the immature rat. Pediatrics 1995, 95(6):868-874. http://pediatrics.aappublications.org/content/95/6/868.full.pdf+html

Subsequently he showed that the rats with normocapnia and mild hypercapnia had better cardiac function and improved cerebral blood flow, and major improvements in cellular metabolism. http://www.nature.com/pr/journal/v42/n1/full/pr19972265a.html

Recent clinical studies show a link between hypocania and severity of brain damage in human infants also.

Pappas A, Shankaran S, Laptook AR, Langer JC, Bara R, Ehrenkranz RA, Goldberg RN, Das A, Higgins RD, Tyson JE et al: Hypocarbia and adverse outcome in neonatal hypoxic-ischemic encephalopathy. J Pediatr 2011, 158(5):752-758 e751. http://pediatrics.aappublications.org/content/95/6/868.full.pdf+html

Klinger G, Beyene J, Shah P, Perlman M: Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? Arch Dis Child Fetal Neonatal Ed 2005, 90(1):F49-52. http://fn.bmjjournals.com/content/90/1/F49.full

It therefore seems prudent to avoid inducing hypocapnia in asphyxiated infants. But what to do when they hyperventilate themselves? After weaning an infant to minimal respiratory support, even to endotracheal CPAP, and finding continuing hypocapnia, what to do next? There are 4 alternatives, either leave the situation as it is and accept hypocapnia, extubate the infant to see if the CO2 will increase a little, add a dead space to the ETT to elevate the CO2, or administer CO2 gas (the latter would be difficult as a source of medical grade CO2 might be difficult to find.) I have not in the past added a dead space in this circumstance. Would a trial be feasible?

Of course the animal model is not exactly what we are dealing with in asphyxiated babies, Vannucci et al give the CO2 during the hypoxic insult,  not afterward, but I think the combination of the animal data, the physiologic rationale, and the human observations make such a trial a reasonable idea.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged . Bookmark the permalink.

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