title: A pilot study of darbepoetin alfa for prophylactic neuroprotection in aortic surgery.
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.
  
  
  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.
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. messe@mail.med.upenn.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Messé
authors.forename: Michael L
authors.initials: ML
authors.lastname: McGarvey
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Bavaria
authors.forename: Alberto
authors.initials: A
authors.lastname: Pochettino
authors.forename: Wilson Y
authors.initials: WY
authors.lastname: Szeto
authors.forename: Albert T
authors.initials: AT
authors.lastname: Cheung
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Leitner
authors.forename: Scott W
authors.initials: SW
authors.lastname: Miller
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
mesh_terms: D000368:Aged; D001011:Aorta / Q000601:surgery*; D000068256:Darbepoetin alfa; D057239:Early Termination of Clinical Trials; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010865:Pilot Projects; D011446:Prospective Studies; D020760:Spinal Cord Ischemia / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D020521:Stroke / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D004921:Erythropoietin; D000068256:Darbepoetin alfa