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.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 (PaO 2 ) and the oxygen inspired fraction (FiO 2 ). We explored the association between high PaO 2 and FiO 2 levels within the first week with clinical outcomes. Furthermore, in the CENTER-TBI cohort, we investigate whether PaO 2 and FiO 2 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). 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 2 ranged from 93 to 166 mmHg. Exposure to higher PaO 2 and FiO 2 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 PaO 2 levels, which remained independently associated with 6-month mortality.

Effects of short-term hyperoxemia on cerebral autoregulation and tissue oxygenation in acute brain injured patients

“…However, in TBI, the vascular and tissue responses to hyperoxemia may work differently and may potentially lead to an alteration of the vasomotor response and therefore of autoregulation ( Johnston et al, 2003 ). As discussed by Rezoagli et al (2022) in their study with TBI patients, increasing PaO 2 does not necessarily increase the delivery of oxygen in the injured brain parenchyma. This is related to the fact that oxygen flux is complexly governed by a combination of diffusion and consumption rather than simply tissue difusion ( Ercole, 2022 ).…”

“…This is related to the fact that oxygen flux is complexly governed by a combination of diffusion and consumption rather than simply tissue difusion ( Ercole, 2022 ). These considerations indicate that the use of hyperoxia, even in the presence of low PbtO 2 may be harmful rather than beneficial, given hyperoxia was independently associated with a higher 6-month mortality rate ( Ercole, 2022 ; Rezoagli et al, 2022 ). At present, findings regarding which hyperoxemia target should be used in ABI patients are inconclusive, and current guidelines only suggest targeting PaO 2 values to a range of 80–120 mm·Hg 8 .…”

“…In patients with traumatic brain injury (TBI), PaO 2 values of 150–200 mm·Hg seem to be associated with better functional and cognitive outcome at 6 months, while PaO 2 >200 mm·Hg was found to be independently associated with 6-months mortality ( Alali et al, 2019 ). Furthermore, more recently, Rezoagli et al ( Rezoagli et al, 2022 ) demonstrated that in a large multicenter cohort of TBI patients ( n = 1,084) the exposure to higher PaO 2 and fraction of inspired oxygen (FiO 2 ) in the first 7 days after ICU admission was independently associated with a higher 6-month mortality, independently of injury severity.…”

An exploratory study investigating the effect of targeted hyperoxemia in a randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma and hemorrhagic shock in cardiovascular healthy pigs

“…Current concepts suggest that severe hyperoxemia (arterial blood oxygen tension (PaO 2 ) > 300 mmHg (40 kPa)) should be avoided ( 15 , 17 , 18 ). However, a potential ‘sweet spot’ of mild hyperoxemia remains unknown.…”

Back to basics with newer technology: Should we focus on reducing work of breathing earlier?

“…While hypoxemic patients benefit from oxygen supplementation, additional oxygen alone has not been shown to improve clinical outcomes in non-hypoxic patients (15)(16)(17)(18). Collectively, clinicians have focused on making oxygen delivery supranormal with hyperoxia, fluids, blood transfusion, and vasoactive drugs; however, this has been unsuccessful in improving patient outcomes and may pose potential harms (15,(18)(19)(20)(21).…”