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Citation
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HERO ID
1340244
Reference Type
Journal Article
Title
A pilot study of darbepoetin alfa for prophylactic neuroprotection in aortic surgery
Author(s)
Messé, SR; McGarvey, ML; Bavaria, JE; Pochettino, A; Szeto, WY; Cheung, AT; Leitner, E; Miller, SW; Kasner, SE
Year
2013
Is Peer Reviewed?
1
Journal
Neurocritical Care
ISSN:
1541-6933
EISSN:
1556-0961
Volume
18
Issue
1
Page Numbers
75-80
Language
English
PMID
22528284
DOI
10.1007/s12028-012-9710-4
Abstract
BACKGROUND: Descending aortic (DA) surgery poses a high risk for spinal and cerebral infarction and routine use of lumbar drains allows for measurement of CSF markers of neurologic injury. Erythropoiesis medications have extensive preclinical data demonstrating neuroprotection. We hypothesized that prophylactic darbepoetin alfa (DARB) given before surgery reduces neurologic injury in patients undergoing DA repair. METHODS AND RESULTS: We performed a prospective adaptive dose-finding trial of prophylactic DARB ( www.clinicaltrials.gov NCT00647998) that terminated prematurely following publication of an erythropoietin stroke study showing possible harm. Enrollment halted before dose adjustments; nine patients each received 1 mg/kg IV DARB immediately before surgery. A prospective cohort of nine untreated patients was subsequently obtained for comparison. The primary outcome of death or neurologic impairment at discharge occurred in 1/9 (11 %) DARB patients and 3/9 (33 %) controls (p = 0.58). There were no statistical differences in changes of CSF biomarkers from baseline to 48 h comparing DARB patients to controls: S100β, median 214 versus 260 ng/ml (p = 0.69); glial fibrillary acidic protein (GFAP), median 0.022 versus 0.58 ng/ml (p = 0.45). In patients with early perioperative neurologic ischemia, there were greater changes in CSF biomarkers, compared to those without ischemia: S100β, median 2301 versus 124 ng/ml (p = 0.04); GFAP, median 31.78 versus 0.31 ng/ml (p = 0.34). CONCLUSIONS: There were no significant effects of prophylactic DARB on clinical outcome or CSF markers of neurologic injury in this pilot study, although all point estimates favored treatment. DA repair is a promising model of prophylactic neuroprotection.
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1. Initial Lit Search
PubMed
PubMed
Considered New
2. Lit Search Updates through Oct 2015
PubMed
Considered
4. Considered through Oct 2015
6. Cluster Filter through Oct 2015
7. Other Studies through Oct 2015
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Arsenic (Inorganic)
1. Literature
PubMed
Lit search updates through Oct 2015
3. Hazard ID Screening
Other potentially supporting studies
4. Adverse Outcome Pathways/Networks Screening
Excluded/Not relevant
Electronic discard
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2. Electronic Discard
1. MOA Literature Screening
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