Associations between arterial oxygenation and oxidative stress markers in serum and bronchoalveolar lavage fluid of patients with severe brain injury.

BACKGROUND

Severe isolated brain injury can trigger systemic oxidative and inflammatory responses extending to distant organs, including the lungs. Supplemental oxygen therapy is routinely used in neurocritical care, but elevated arterial oxygenation may be associated with redox alterations.

OBJECTIVES

The primary objective was to characterize temporal dynamics of systemic and pulmonary oxidative stress in patients with severe traumatic brain injury during the first 7 days. Secondary objectives were to assess associations between oxidative stress marker concentrations and arterial oxygenation parameters, clinical severity scores, and 28-day mortality. This was an exploratory study and no causal inferences are drawn.

DESIGN

Prospective observational cohort study.

SETTING

First-level trauma centre intensive care unit over 12 months.

PATIENTS: Forty mechanically ventilated adult patients with isolated severe brain injury were enrolled.

INTERVENTIONS: No therapeutic intervention was applied. Standard intensive care management was maintained according to institutional protocols.

MAIN OUTCOME MEASURES: Primary outcomes were concentrations of superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) measured in serum and bronchoalveolar lavage fluid at three time points during the first 7 days. Secondary outcomes included correlations with arterial oxygen tension (PaO2), inspired oxygen fraction (FiO2), clinical severity scores, and 28-day mortality.

RESULTS

Antioxidant enzyme concentrations decreased and oxidative damage marker concentrations increased progressively (p < 0.001 for all). Repeated-measures correlation analysis showed that lower PaO2 values were associated with higher 8-OHdG levels in serum (r = -0.64) and bronchoalveolar lavage fluid (r = -0.55), and with lower SOD and CAT concentrations. The association between PaO2 and MDA was more complex: in mixed-effects models, PaO2 was positively associated with antioxidant enzyme concentrations and serum MDA concentration, suggesting that the relationship between oxygenation and lipid peroxidation is not straightforward. In an exploratory threshold-based analysis, PaO₂ values exceeding 100 mmHg at the earliest time point were associated with higher 28-day mortality (p < 0.05); however, this finding was not supported by a fully adjusted prognostic model and should be interpreted cautiously.

CONCLUSION

Severe isolated brain injury is associated with progressive systemic and pulmonary oxidative stress. The relationship between arterial oxygenation and oxidative stress appears complex and may depend on timing and oxygen exposure levels.