Transcutaneous Carbon Dioxide Monitoring in Neonates Receiving Therapeutic Hypothermia for Neonatal Encephalopathy

Neonatal encephalopathy (NE) affects 3 infants per 1000 live birth every year and can lead to death or permanent neurological deficit. Therapeutic hypothermia (33.5 oC) (TH) has been clearly proven to reduce mortality and adverse neurodevelopmental outcome in patients with moderate to severe NE. However, even with hypothermia, nearly half of the infants with NE are at risk of death or severe disability. Optimization of intensive care of these neonates might have the potential to prevent injury progression and further improve neurodevelopmental outcomes.

Multiple analyses noted a high rate (6 -89%) of incidence of hypocarbia during the first hours of postnatal life possibly due to the strong respiratory effort secondary to metabolic acidosis and the hypothermia treatment which causes a 20-30% reduction in metabolic rate. Furthermore, several studies have shown the association between hypocarbia and the increased risk of adverse neurodevelopmental outcome in infants with NE. Hypocarbia has the potential to exacerbate brain injury via multiple mechanisms. Hypocarbia was associated with nuclear DNA fragmentation in the cerebral cortex, membrane lipid peroxidation and increased neuronal excitability in animal models.

It is well established, that carbon dioxide is one of the most potent regulator of cerebral blood flow (CBF), with hypercarbia causing cerebral vasodilation and increased cerebral blood flow by 1 to 2 ml/100g/minute per 1 mmHg in PaCO2, whereas hypocarbia causes cerebral vasoconstriction. Reducing PaCO2 to 20 to 25 mmHg decreases CBF by 40 to 50%.

Hypocarbia may decrease oxygen supply further due to the cerebral vasoconstriction and the leftward shift of oxyhemoglobin curve.

It has been well known for decades that hypocarbia is associated with periventricular leukomalacia and, or, cerebral palsy in preterm neonates. In term, asphyxiated neonates the secondary analysis of the landmark CoolCap and NICHD hypothermia trials established that hypocarbia has a dose-dependent effect on long term neurodevelopmental outcomes. Both minimum and cumulative exposure to PCO2 less than 35 mmHg within the first 12 hours of life increased the risk of death and adverse neurodevelopmental outcome in the secondary analysis of NICHD trial. Consistent with this, the post-hoc analysis of CoolCap study showed that the probability of unfavorable outcome was raised dose-dependently with decreasing PCO2 in infants with moderate and severe NE. Moreover, a recent retrospective study also reported an association between hypocarbia over the first 4 days of life and brain injury on MRI. The consistent findings of an association between hypocarbia and adverse outcomes suggest that the close monitoring of carbon dioxide exchange and the avoidance of hypocarbia is highly important in this vulnerable patient population.