Relationship between PCO2 and unfavorable outcome in infants with moderate-to-severe hypoxic ischemic encephalopathy

Journal name:
Pediatric Research
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Abnormal PCO2 is common in infants with hypoxic ischemic encephalopathy (HIE). The objective was to determine whether hypocapnia was independently associated with unfavorable outcome (death or severe neurodevelopmental disability at 18 mo) in infants with moderate-to-severe HIE.


This was a post hoc analysis of the CoolCap Study in which infants were randomized to head cooling or standard care. Blood gases were measured at prespecified times after randomization. PCO2 and follow-up data were available for 196 of 234 infants. Analyses were performed to investigate the relationship between hypocapnia in the first 72h after randomization and unfavorable outcome.


After adjusting for pH, amplitude-integrated electroencephalogram background and seizures, birth weight, Apgar score at 5min, cooling status, and Sarnat stage, PCO2 was inversely associated with unfavorable outcome (P < 0.001). The probability of unfavorable outcome was 0.20±0.1 (point estimate ± SE), 0.53±0.23 and 0.89±0.16 for a PCO2 of 40, 30, and 20mm Hg respectively and was greater in infants with severe HIE than with moderate HIE.


Hypocapnia in infants with moderate-to-severe HIE was independently associated with unfavorable outcome. Future studies of controlled normocapnia will be important.

At a glance


  1. Figure 1:

    CONSORT chart showing flow of infants in the study.

  2. Figure 2:

    Temporal PCO2 pattern during treatment. (a) Temporal pattern of PCO2 between infants with moderate (solid line) or severe hypoxic ischemic encephalopathy (HIE) (dashed line). Significant differences in PCO2 compared to levels at randomization are represented by **P < 0.01. (b) Temporal pattern of PCO2 between infants with HIE who underwent head cooling (dashed line) compared to those managed with standard care (solid line). Significant differences in PCO2 (cooled vs. control groups) are represented by *P < 0.05. Values represented are mean and SD at each time point.

  3. Figure 3:

    Effect of PCO2 on the adjusted probability of an unfavorable outcome for infants with moderate (blue curve) and severe hypoxic ischemic encephalopathy (red curve) at randomization. The shaded areas around the curves represent the standard error of mean of the point estimate of the probability of unfavorable outcome at a given PCO2. The darkly shaded area indicates the overlap in the distribution.


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Author information


  1. Department of Pediatrics (Neonatology), Baylor College of Medicine, Houston, Texas

    • Krithika Lingappan
  2. Departments of Pediatrics (Neonatology) and Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas

    • Jeffrey R. Kaiser
  3. Department of Pediatrics (Cardiology), University of Texas Medical School, Houston, Texas

    • Chandra Srinivasan
  4. Department of Physiology, University of Auckland, Auckland, New Zealand

    • Alistair J. Gunn

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