Abstract
Background
Cerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role in neuroinflammation and is a suggested source of tissue injury after aneurysm rupture. This study sought to determine whether patients with subarachnoid hemorrhage and cerebral vasospasm were more likely to have been exposed to early hyperoxemia than those without vasospasm.
Methods
This single-center retrospective cohort study included adult patients presenting with aneurysmal subarachnoid hemorrhage to Vanderbilt University Medical Center between January 2007 and December 2017. Patients with an ICD-9/10 diagnosis of aneurysmal subarachnoid hemorrhage were initially identified (N = 441) and subsequently excluded if they did not have intracranial imaging, arterial PaO2 values or died within 96 h post-rupture (N = 96). The final cohort was 345 subjects. The degree of hyperoxemia was defined by the highest PaO2 measured within 72 h after aneurysmal rupture. The primary outcome was development of cerebral vasospasm, which included asymptomatic vasospasm and delayed cerebral ischemia (DCI). Secondary outcomes were mortality and modified Rankin Scale.
Results
Three hundred and forty five patients met inclusion criteria; 218 patients (63%) developed vasospasm. Of those that developed vasospasm, 85 were diagnosed with delayed cerebral ischemia (DCI, 39%). The average patient age of the cohort was 55 ± 13 years, and 68% were female. Ninety percent presented with Fisher grade 3 or 4 hemorrhage (N = 310), while 42% presented as Hunt–Hess grade 4 or 5 (N = 146). In univariable analysis, patients exposed to higher levels of PaO2 by quintile of exposure had a higher mortality rate and were more likely to develop vasospasm in a dose-dependent fashion (P = 0.015 and P = 0.019, respectively). There were no statistically significant predictors that differentiated asymptomatic vasospasm from DCI and no significant difference in maximum PaO2 between these two groups. In multivariable analysis, early hyperoxemia was independently associated with vasospasm (OR = 1.15 per 50 mmHg increase in PaO2 [1.03, 1.28]; P = 0.013), but not mortality (OR = 1.10 [0.97, 1.25]; P = 0.147) following subarachnoid hemorrhage.
Conclusions
Hyperoxemia within 72 h post-aneurysmal rupture is an independent predictor of cerebral vasospasm, but not mortality in subarachnoid hemorrhage. Hyperoxemia is a variable that can be readily controlled by adjusting the delivered FiO2 and may represent a modifiable risk factor for vasospasm.
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Acknowledgements
The authors would like to thank the REDCap team for assistance with secure data storage.
Funding
Dr. Ware was funded by NIH HL103836. Drs. Ware and Bastarache are funded by HL135849.
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RAR contributed to study conception, data collection, and manuscript preparation. SNA, SVJ, ART, and ML contributed to data collection and manuscript preparation. CW assisted with statistical analysis and critical revision of the manuscript. JAB, LBW, and RCT contributed to study conception and critical review of the manuscript.
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Author LB Ware has received research support from Global Blood Therapeutics, CSL Behring, and Boehringer Ingelheim in the past and currently receives research support from Genentech. She also has received consulting fees from Citius, Foresee, Boehringer Ingelheim, Quark, CSL Behring and Merck.
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An Institutional Review Board waiver was granted by Vanderbilt University as the study did not meet the definition of human subjects research.
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Supplemental Fig. 1.
Flowchart of study population (JPEG 38 kb)
Supplemental Fig. 2.
Maximum PaO2 and modified Rankin Scale. Boxplot summary of maximum PaO2 in the first 3 days by modified Rankin Scale at discharge among survivors (N = 336). Nine patients without available modified Rankin Scales were excluded. P = 0.067 by Kruskal–Wallis test (JPEG 68 kb)
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Reynolds, R.A., Amin, S.N., Jonathan, S.V. et al. Hyperoxemia and Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care 35, 30–38 (2021). https://doi.org/10.1007/s12028-020-01136-6
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DOI: https://doi.org/10.1007/s12028-020-01136-6