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.
Highlights
Oxygen is frequently prescribed for the prevention and/ or treatment of hypoxemia and tissue hypoxia [1]
The post hoc meta-analysis to determine whether an increase in Arterial oxygen partial pressure (PaO2) leads to a greater odds of poor neurological outcome showed a significant correlation, with a substantial heterogeneity, when we considered all possible PaO2 levels including hypoxemia
Main Findings Our meta-analysis reveals two key points: (1) hyperoxemia was significantly associated with poorer neurological prognoses in patients with a range of acute illnesses (Figs. 2a, 3) with high robustness across all sensitivity analyses and types of outcome and (2) there was a trend for poorer outcome in higher PaO2 groups, regardless of the inclusion of hypoxemia in controls (Supplementary Fig. 3b), P aO2 criteria used (Supplementary Figs. 4a, 5) or the ventilation status of the patients (Supplementary Fig. 4b)
Summary
Oxygen is frequently prescribed for the prevention and/ or treatment of hypoxemia and tissue hypoxia [1]. A P aO2 of 300 mm Hg or more was reported in 11–26% of the patients [15,16,17,18,19] and 46% of PaO2 measurements were hyperoxic [12] (defined as PaO2 > 110 mm Hg in that study). Hyperoxemia is sometimes left uncorrected [2, 12, 14]. This might reflect ICU culture, precautionary oxygen use, limited opportunities for quality improvement and revision of outdated practices (such as unnecessary oxygen supplementation), and the lack of a formal process for oxygen titration [10, 14, 20, 21]
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