High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI

Abstract

Purpose The effect of high arterial oxygen levels and supplemental oxygen administration on outcomes in traumatic brain injury (TBI) is debated, and data from large cohorts of TBI patients are limited. We investigated whether exposure to high blood oxygen levels and high oxygen supplementation is independently associated with outcomes in TBI patients admitted to the intensive care unit (ICU) and undergoing mechanical ventilation. <p><p>Methods This is a secondary analysis of two multicenter, prospective, observational, cohort studies performed in Europe and Australia. In TBI patients admitted to ICU, we describe the arterial partial pressure of oxygen (PaO₂) and the oxygen inspired fraction (FiO₂). We explored the association between high PaO₂ and FiO₂ levels within the first week with clinical outcomes. Furthermore, in the CENTER-TBI cohort, we investigate whether PaO₂ and FiO₂ levels may have differential relationships with outcome in the presence of varying levels of brain injury severity (as quantified by levels of glial fibrillary acidic protein (GFAP) in blood samples obtained within 24 h of injury).<p> Results The analysis included 1084 patients (11,577 measurements) in the CENTER-TBI cohort, of whom 55% had an unfavorable outcome, and 26% died at a 6-month follow-up. Median PaO<p>2</sub> ranged from 93 to 166 mmHg. Exposure to higher PaO₂ and FiO₂ in the first seven days after ICU admission was independently associated with a higher mortality rate. A trend of a higher mortality rate was partially confirmed in the OzENTER-TBI cohort (n = 159). GFAP was independently associated with mortality and functional neurologic outcome at follow-up, but it did not modulate the outcome impact of high PaO₂ and FiO₂ levels, which remained independently associated with 6-month mortality. <p>Conclusions In two large prospective multicenter cohorts of critically ill patients with TBI, levels of PaO₂ and FiO₂ varied widely across centers during the first seven days after ICU admission. Exposure to high arterial blood oxygen or high supplemental oxygen was independently associated with 6-month mortality in the CENTER-TBI cohort, and the severity of brain injury did not modulate this relationship. Due to the limited sample size, the findings were not wholly validated in the external OzENTER-TBI cohort. We cannot exclude the possibility that the worse outcomes associated with higher PaO₂ were due to use of higher FiO₂ in patients with more severe injury or physiological compromise. Further, these findings may not apply to patients in whom FiO₂ and PaO₂ are titrated to brain tissue oxygen monitoring (PbtO₂) levels. However, at minimum, these findings support the need for caution with oxygen therapy in TBI, particularly since titration of supplemental oxygen is immediately applicable at the bedside.