naa a22 4500 510799981 CHVBK 20180411083351.0 cr unu---uuuuu 180411e20130201xx s 000 0 eng 10.1007/s12028-012-9710-4 doi (NATIONALLICENCE)springer-10.1007/s12028-012-9710-4 A Pilot Study of Darbepoetin Alfa for Prophylactic Neuroprotection in Aortic Surgery [Elektronische Daten] [Steven Messé, Michael McGarvey, Joseph Bavaria, Alberto Pochettino, Wilson Szeto, Albert Cheung, Elizabeth Leitner, Scott Miller, Scott Kasner] 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 1mg/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 48h comparing DARB patients to controls: S100β, median 214 versus 260ng/ml (p=0.69); glial fibrillary acidic protein (GFAP), median 0.022 versus 0.58ng/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 124ng/ml (p=0.04); GFAP, median 31.78 versus 0.31ng/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. Springer Science+Business Media, LLC, 2012 Neuroprotection nationallicence Aortic surgery nationallicence Stroke nationallicence Spinal ischemia nationallicence CSF biomarkers nationallicence Messé Steven Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut McGarvey Michael Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut Bavaria Joseph Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut Pochettino Alberto Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut Szeto Wilson Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut Cheung Albert Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut Leitner Elizabeth Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut Miller Scott Medical University of South Carolina, Charleston, SC, USA aut Kasner Scott Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut Neurocritical Care Humana Press Inc 18/1(2013-02-01), 75-80 1541-6933 18:1<75 2013 18 12028 https://doi.org/10.1007/s12028-012-9710-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12028-012-9710-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Messé Steven Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- McGarvey Michael Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Bavaria Joseph Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Pochettino Alberto Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Szeto Wilson Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Cheung Albert Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Leitner Elizabeth Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Miller Scott Medical University of South Carolina, Charleston, SC, USA aut NATIONALLICENCE 700 1- Kasner Scott Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 W. Gates Bldg, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 773 0- Neurocritical Care Humana Press Inc 18/1(2013-02-01), 75-80 1541-6933 18:1<75 2013 18 12028 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer