Impact of oxygen and carbon dioxide levels on mortality in moderate to severe traumatic brain injury: a systematic review and meta-analysis

Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality worldwide. Secondary brain insults related to oxygenation and ventilation may affect outcomes in this high-risk population. The aim of this study was to perform a comprehensive review examining the relationship between oxygen and carbon dioxide thresholds and mortality to guide clinical care. Eleven databases, including: MEDLINE, MEDLINE In-Process, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, CINAHL, APA PsycINFO, Web of Science, Biosys, Scopus, and the Global Index Medicus, were systematically searched from inception to October 23, 2024. Included studies reported on adults ( $$\ge$$ 18 years) with moderate to severe TBI (msTBI) (Glasgow Coma Scale <13 or Head Abbreviated Injury Scale $$\ge$$ 3) and exposure to hypoxia, hypocapnia, or hypercapnia, with mortality or vegetative state data reported within 6 months. Vegetative state data was not reported, so all analyses were based on mortality. Pediatric or mild TBI studies, stroke-focused studies, and studies without mortality outcomes were excluded. The data were screened via Covidence software with multiple reviewers. No language or regional restrictions were applied. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality was assessed via the Newcastle-Ottawa Scale (NOS) for Cohort Studies, and certainty of evidence was rated using GRADE. Four authors independently extracted data with verification by a second reviewer. The primary outcome was measured using odds ratios (ORs) with 95% confidence intervals (CIs), calculated separately for crude and adjusted effect estimates. Twenty-one cohort studies with 41,980 patients were included. Hypoxia and hypocapnia were significantly associated with increased mortality (aOR, 1.39; 95% CI 1.11–1.75; p =.005; aOR, 1.64; 95% CI 1.25–2.15; p <.001). Hypercapnia was not significantly associated with mortality (aOR, 1.74; 95% CI 0.91–3.32; p =.09). In adults with msTBI, hypoxia and hypocapnia were independently associated with increased mortality, underscoring the importance of prompt recognition and targeted management of these secondary injuries. The role of hypercapnia remains unclear, warranting further investigation.