Original Article
Hypocarbia and Adverse Outcome in Neonatal Hypoxic-Ischemic Encephalopathy

https://doi.org/10.1016/j.jpeds.2010.10.019Get rights and content

Objective

To evaluate the association between early hypocarbia and 18- to 22-month outcome among neonates with hypoxic-ischemic encephalopathy.

Study design

Data from the National Institute of Child Health and Human Development Neonatal Research Network randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy were used for this secondary observational study. Infants (n = 204) had multiple blood gases recorded from birth to 12 hours of study intervention (hypothermia versus intensive care alone). The relationship between hypocarbia and outcome (death/disability at 18 to 22 months) was evaluated by unadjusted and adjusted analyses examining minimum PCO2 and cumulative exposure to PCO2 <35 mm Hg. The relationship between cumulative PCO2 <35 mm Hg (calculated as the difference between 35 mm Hg and the sampled PCO2 multiplied by the duration of time spent <35 mm Hg) and outcome was evaluated by level of exposure (none-high) using a multiple logistic regression analysis with adjustments for pH, level of encephalopathy, treatment group (±hypothermia), and time to spontaneous respiration and ventilator days; results were expressed as odds ratios and 95% confidence intervals. Alternative models of CO2 concentration were explored to account for fluctuations in CO2.

Results

Both minimum PCO2 and cumulative PCO2 <35 mm Hg were associated with poor outcome (P < .05). Moreover, death/disability increased with greater cumulative exposure to PCO2 <35 mm Hg.

Conclusions

Hypocarbia is associated with poor outcome after hypoxic-ischemic encephalopathy.

Section snippets

Methods

This is a secondary study to the NICHD randomized trial of whole-body cooling16 in encephalopathic infants ≥36 weeks gestational age admitted to the hospital within 6 hours of life with either severe acidosis or perinatal complications and resuscitation at birth. The study was performed in the participating centers of the Eunice Kennedy Shriver NICHD Neonatal Research Network and was approved by the institutional review board of each of the participating centers. Written informed consent was

Results

The average age at random assignment was 4.3 hours, and the average age at cooling was 5 hours (ie, 35.5 minutes after random assignment). Detailed blood gas analyses were available during the first 12 hours of study intervention, corresponding to the first 16.9 ± 2.2 hours of life (mean ± SD) for 204 of 208 infants. Primary outcome data were available for all 204 infants. The source of the blood gas was recorded for the first postnatal blood gas (150 arterial samples, 39 venous, 12 capillary,

Discussion

We report an association between hypocarbia soon after birth in neonates with hypoxic ischemic encephalopathy and poor outcome. Low PCO2 concentrations within the first 16 hours of life were associated with an increased risk of death or disability directly related to the degree and severity of hypocarbia. Both minimum PCO2 and cumulative PCO2 <35 mm Hg were associated with poor outcome at 18 to 22 months of age. Whether hypocarbia is an early marker or a risk factor for poor neurodevelopmental

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    Supported by the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) for the NICHD Neonatal Research Network’s Whole Body Cooling for Hypoxic Ischemic Encephalopathy Study.

    Participating Neonatal Research Network sites collected data and transmitted it to RTI International, the data coordinating center for the network, which stored, managed, and analyzed the data for this study. On behalf of the Neonatal Research Network, A.D. and J.L. had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. The authors declare no conflicts of interest.

    A list of additional members of Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network is available at www.jpeds.com (Appendix).

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