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Normobaric Hyperoxia is Associated with Increased Cerebral Excitotoxicity After Severe Traumatic Brain Injury

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Abstract

Background

Normobaric oxygen therapy is frequently applied in neurocritical care, however, whether supplemental FiO2 has beneficial cerebral effects is still controversial. We examined in patients with severe traumatic brain injury (TBI) the effect of incremental FiO2 on cerebral excitotoxicity, quantified by cerebral microdialysis (CMD) glutamate.

Methods

This was a retrospective analysis of a database of severe TBI patients monitored with CMD and brain tissue oxygen (PbtO2). The relationship of FiO2—categorized into four separate ranges (<40, 41–60, 61–80, and >80 %)—with CMD glutamate was examined using ANOVA with Tukey’s post hoc test.

Results

A total of 1,130 CMD samples from 36 patients—monitored for a median of 4 days—were examined. After adjusting for brain (PbtO2, intracranial pressure, cerebral perfusion pressure, lactate/pyruvate ratio, Marshall CT score) and systemic (PaCO2, PaO2, hemoglobin, APACHE score) covariates, high FiO2 was associated with a progressive increase in CMD glutamate [8.8 (95 % confidence interval 7.4–10.2) µmol/L at FiO2 < 40 % vs. 12.8 (10.9–14.7) µmol/L at 41–60 % FiO2, 19.3 (15.6–23) µmol/L at 61–80 % FiO2, and 22.6 (16.7–28.5) µmol/L at FiO2 > 80 %; multivariate-adjusted p < 0.05]. The threshold of FiO2-related increase in CMD glutamate was lower for samples with normal versus low PbtO2 < 20 mmHg (FiO2 > 40 % vs. FiO2 > 60 %). Hyperoxia (PaO2 > 150 mmHg) was also associated with increased CMD glutamate (adjusted p < 0.001).

Conclusions

Incremental normobaric FiO2 levels were associated with increased cerebral excitotoxicity in patients with severe TBI, independent from PbtO2 and other important cerebral and systemic determinants. These data suggest that supra-normal oxygen may aggravate secondary brain damage after severe TBI.

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Acknowledgments

This work was supported by grants from the Swiss National Science Foundation (Grant No. 320030_138191, to Mauro Oddo), the Novartis Foundation for Biomedical Research (to Mauro Oddo) and the Société Française d’Anesthésie et Réanimation (SFAR) (to Hervé Quintard). The authors thank Professor Lucas Liaudet, MD, for helpful scientific discussion.

Conflict of interest

All authors declare they have no conflicts of interest to report.

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Authors and Affiliations

  1. Department of Intensive Care Medicine, Neuroscience Critical Care Research Group Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University Hospital, Rue du Bugnon 46, BH 08.623, 1011, Lausanne, Switzerland

    Hervé Quintard, Camille Patet, Tamarah Suys & Mauro Oddo

  2. Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University Hospital, 1011, Lausanne, Switzerland

    Pedro Marques-Vidal

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  1. Hervé Quintard
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Correspondence to Mauro Oddo.

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Quintard, H., Patet, C., Suys, T. et al. Normobaric Hyperoxia is Associated with Increased Cerebral Excitotoxicity After Severe Traumatic Brain Injury. Neurocrit Care 22, 243–250 (2015). https://doi.org/10.1007/s12028-014-0062-0

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