The Effect of Hyperoxemia on Neurological Outcomes of Adult Patients: A Systematic Review and Meta-Analysis

Abstract

Hyperoxemia commonly occurs in clinical practice and is often left untreated. Many studies have shown increased mortality in patients with hyperoxemia, but data on neurological outcome in these patients are conflicting, despite worsened neurological outcome found in preclinical studies. To investigate the association between hyperoxemia and neurological outcome in adult patients, we performed a systematic review and meta-analysis of observational studies. We searched MEDLINE, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and ClinicalTrials.gov from inception to May 2020 for observational studies correlating arterial oxygen partial pressure (PaO2) with neurological status in adults hospitalized with acute conditions. Studies of chronic pulmonary disease or hyperbaric oxygenation were excluded. Relative risks (RRs) were pooled at the study level by using a random-effects model to compare the risk of poor neurological outcome in patients with hyperoxemia and patients without hyperoxemia. Sensitivity and subgroup analyses and assessments of publication bias and risk of bias were performed. Maximum and mean PaO2 in patients with favorable and unfavorable outcomes were compared using standardized mean difference (SMD). Of 6255 records screened, 32 studies were analyzed. Overall, hyperoxemia was significantly associated with an increased risk of poor neurological outcome (RR 1.13, 95% confidence interval [CI] 1.05–1.23, statistical heterogeneity I2 58.8%, 22 studies). The results were robust across sensitivity analyses. Patients with unfavorable outcome also showed a significantly higher maximum PaO2 (SMD 0.17, 95% CI 0.04–0.30, I2 78.4%, 15 studies) and mean PaO2 (SMD 0.25, 95% CI 0.04–0.45, I2 91.0%, 13 studies). These associations were pronounced in patients with subarachnoid hemorrhage (RR 1.34, 95% CI 1.14–1.56) and ischemic stroke (RR 1.41, 95% CI 1.14–1.74), but not in patients with cardiac arrest, traumatic brain injury, or following cardiopulmonary bypass. Hyperoxemia is associated with poor neurological outcome, especially in patients with subarachnoid hemorrhage and ischemic stroke. Although our study cannot establish causality, PaO2 should be monitored closely because hyperoxemia may be associated with worsened patient outcome and consequently affect the patient’s quality of life.

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

“…Data on more than 36,000 mixed ICU patients mechanically ventilated with early arterial partial pressure of oxygen (PaO 2 ) suggested an independent U-shape association with hospital mortality [ 10 ]. A recent metanalysis of 32 studies in acute brain-damaged patients highlighted that hyperoxemia, differently defined across studies, was associated with an increased risk of poor neurological outcomes [ 11 ]. Patients with a poor neurological outcome also had a significantly higher maximum PaO 2 and mean PaO 2 .…”

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

“…Previous studies have questioned the effect of hyperoxemia on cerebral dynamics, but without focusing on the importance of cerebral autoregulation. This is clinically relevant, as recent evidence suggests that hyperoxemia can be detrimental to ABI patients and has been associated with poor neurological outcome and independently associated with higher in-hospital fatality ( Rincon et al, 2014 ; Hirunpattarasilp et al, 2022 ). Cerebral autoregulation is a compensatory mechanism of the brain that allows maintenance of constant cerebral blood flow (CBF) regardless of changes in perfusion pressure ( Claassen et al, 2021 ).…”

“…In patients with acute brain injuries, this range narrows and the risk of secondary damage increases ( Donnelly et al, 2015 ). Impaired CA has been shown to be associated with worse outcome, highlighting the importance of its assessment ( Rincon et al, 2014 ; Hirunpattarasilp et al, 2022 ).…”

Hyperoxia evokes pericyte-mediated capillary constriction

“…Moreover, when administering O 2 , clinicians should avoid generating hyperoxia which can result in a significant reduction of cerebral blood flow that might lead to poorer brain function, especially in critically ill patients who are at risk of receiving excess oxygen. 78 Reductions of cerebral blood flow occurring in spreading depression, 79 stroke. 80 cardiac arrest 81 and subarachnoid haemorrhage 82 have previously been shown to involve 20-HETE production.…”