Neurological outcomes and mortality following hyperoxemia in adult patients with acute brain injury: an updated meta-analysis and meta-regression

Abstract

Background: The aim of this study was to evaluate the association of arterial hyperoxemia with neurological outcomes and mortality in adults with acute brain injury (ABI).

Methods: Six electronic databases, including MEDLINE, Embase and online registers of clinical trials, were systematically searched from inception to June 1 st, 2024. Studies comparing the effects of hyperoxemia versus no hyperoxemia on outcomes of hospitalized adult patients with ABI-related conditions (e.g. traumatic brain injury, post-cardiac arrest, subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke) were included according to PRISMA guidelines. Data were pooled using a random-effects model for unadjusted and covariate-adjusted odds ratios. The primary outcome was poor neurological outcome as defined by each individual study, and the secondary outcome was all-cause mortality. Subgroup analyses were conducted based on principal diagnosis, timing of outcome measures, oxygenation thresholds, among other factors. Meta-regression was applied to identify sources of heterogeneity.

Results: After 7,849 nonduplicated records were screened, 66 studies fulfilled eligibility criteria for systematic review. The meta-analysis including 24 studies (16,635 patients) revealed that patients with hyperoxemia are 1.29 times more likely to develop poor neurological outcomes (unadjusted OR, 1.295; 95% Confidence Interval, CI 1.040-1.616) compared with those with no hyperoxemia, particularly in subarachnoid hemorrhage and ischemic stroke subgroups. The meta-analysis including 35 studies (98,207 patients) revealed that all-cause mortality is 1.13 times more likely (OR 1.13; 95% CI 1.002-1.282) in patients with hyperoxemia compared with no hyperoxemia.

Conclusions: In our study we found that hyperoxemia is significantly associated with an increased risk of poor neurological outcomes and mortality in patients with acute brain injury compared to those with no hyperoxemia. Our results suggest the importance of carefully adjusting oxygenation strategies in neurocritical ICUs.

Keywords: Acute brain injury; Hyperoxemia; Meta-analysis; Mortality; Neurological outcomes.

Fig. 1

PRISMA flowchart diagram for identification and selection of studies. Excluded studies are listed in Table S3 in the Supplement

Fig. 2

Effect of hyperoxemia on poor neurological outcomes in patients with ABI. Forest plot for the meta-analysis based on unadjusted ORs for poor neurological outcomes in hyperoxemia versus no hyperoxemia in patients in ABI (n = 24 studies, 16,635 patients). The boxes show the effect estimates from the individual studies. The size of the boxes is inversely proportional to the size of the result study variance. The diamonds represent pooled results in each subgroup and overall analysis; the length of horizontal lines across the boxes and the width of the diamonds illustrates the 95% CI. The gray vertical line at one is the line of null effect, and the red vertical line shows the pooled effect estimate of the whole analysis. ABI: Acute brain injury, CI: confidence interval, ICH: Intracerebral hemorrhage, IS: Ischemic stroke, OR: odds ratio, PCA: Post-cardiac arrest, SAH: Subarachnoid hemorrhage, TBI: Traumatic brain injury

Fig. 3

Effects of hyperoxemia on mortality in patients with ABI. Forest plot for the meta-analysis based on unadjusted ORs for mortality in hyperoxemia versus no hyperoxemia in patients in ABI (n = 35 studies, 98,207 patients). ABI: Acute brain injury, CI: confidence interval, ICH: Intracerebral hemorrhage, IS: Ischemic stroke, OR: odds ratio, PCA: Post-cardiac arrest, SAH: Subarachnoid hemorrhage, TBI: Traumatic brain injury

Fig. 4

Group subanalysis for association of hyperoxemia and poor outcomes. (A) Forest plot of unadjusted ORs for hyperoxemia and poor neurological outcomes classified by different criteria: risk of bias, neurological outcome scale, time of outcome evaluation, hyperoxemia definition, control group definition, type and time of PaO₂ measure, type of ventilatory support. (B) Forest plot of unadjusted ORs and for mortality classified by different criteria: risk of bias, time of outcome evaluation, hyperoxemia definition, control group definition, type and time of PaO₂ measure, type of ventilatory support. P-values < 0.1 for intra-group comparisons are shown. Horizontal lines represent 95% CIs; size of the symbols are proportional to the number of studies (see Figures S5 and S6). HD: hospital discharge, IV: invasive ventilation, NA: not available, NIV: non-invasive ventilation, NOS: Newcastle Ottawa Scale, PaO₂: arterial partial pressure of oxygen