Interaction of neurovascular protection of erythropoietin with age, sepsis, and statin therapy following aneurysmal subarachnoid hemorrhage

Clinical article

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Object

In a previous randomized controlled trial, the authors demonstrated that acute erythropoietin (EPO) therapy reduced severe vasospasm and delayed ischemic deficits (DIDs) following aneurysmal subarachnoid hemorrhage. In this study, the authors aimed to investigate the potential interaction of neurovascular protection by EPO with age, sepsis, and concurrent statin therapy.

Methods

The clinical events of 80 adults older than 18 years and with < 72 hours of aneurysmal subarachnoid hemorrhage, who were randomized to receive 30,000 U of intravenous EPO-β or placebo every 48 hours for a total of 3 doses, were analyzed by stratification according to age (< or ≥ 60 years), sepsis, or concomitant statin therapy. End points in the trial included cerebral vasospasm and impaired autoregulation on transcranial Doppler ultrasonography, DIDs, and unfavorable outcome at discharge and at 6 months measured with the modified Rankin Scale and Glasgow Outcome Scale. Analyses were performed using the t-test and/or ANOVA for repeated measurements.

Results

Younger patients (< 60 years old) or those without sepsis obtained benefits from EPO by a reduction in vasospasm, impaired autoregulation, and unfavorable outcome at discharge. Compared with nonseptic patients taking EPO, those with sepsis taking EPO had a lower absolute reticulocyte count (nonsepsis vs sepsis, 143.5 vs. 105.8 × 109/L on Day 6; p = 0.01), suggesting sepsis impaired both hematopoiesis and neurovascular protection by EPO. In the EPO group, none of the statin users suffered DIDs (p = 0.078), implying statins may potentiate neuroprotection by EPO.

Conclusions

Erythropoietin-related neurovascular protection appears to be attenuated by old age and sepsis and enhanced by statins, an important finding for designing Phase III trials.

Abbreviations used in this paper: aSAH = aneurysmal subarachnoid hemorrhage; DID = delayed ischemic deficit; EPO = erythropoietin; GOS = Glasgow Outcome Scale; mRS = modified Rankin Scale; TCD = transcranial Doppler.
Article Information

Contributor Notes

Address correspondence to: Ming-Yuan Tseng, M.D., Ph.D., Department of Neurosurgery, Box 167, Level 4, Block A, Addenbrooke's Hospital, Cambridge, United Kingdom CB2 2QQ. email: myt22@cam.ac.uk.Please include this information when citing this paper: published online November 20, 2009; DOI: 10.3171/2009.10.JNS09954.

© Copyright 1944-2019 American Association of Neurological Surgeons

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