on June 25, 2009
Published online before print June 25, 2009, doi: 10.1161/STROKEAHA.109.549436
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Submitted on February 9, 2009
From the Department of Critical Care Medicine (G.H., D.Z.), the Division of Cardiac Surgery (A.M.), the Department of Psychology (M.K.), the Department of Anesthesia (J.H.), the Division of Nephrology (B.C.), and the Centre for Advancement of Health (P.F.), the University of Calgary, Calgary Health Region, Alberta, Canada; the Cardiac Sciences Program (R.C.A.), University of Manitoba, Winnipeg, Canada; and the Nuffield Department of Medicine (A.B.), University of Oxford, UK. * To whom correspondence should be addressed. E-mail: dzygun{at}ucalgary.ca.
Background and Purpose—Neurocognitive dysfunction complicates coronary artery bypass surgery. Erythropoietin may be neuroprotective. We sought to determine whether human recombinant erythropoietin would reduce the incidence of neurocognitive dysfunction after surgery. Methods—We randomly assigned 32 elective first-time coronary artery bypass graft patients to receive placebo or 375 U/kg, 750 U/kg, or 1500 U/kg of recombinant human erythropoietin divided in 3 daily doses, starting the day before surgery. Primary outcomes were feasibility and safety, and secondary outcomes were neurocognitive dysfunction at discharge and 2 months. Results—All subjects were male, mean age 60 years (range 46 to 73). No significant differences were found in pump time, cross-clamp time, or hospital length of stay. Mortality and pure red cell aplasia were not observed. One patient in the 375 U/kg group had ST changes compatible with myocardial injury immediately postoperative, but no other thrombotic complications were observed. Neurocognitive dysfunction occurred in 21/32 (66%) of patients at discharge and 5/32 (16%) at 2 months. Neurocognitive dysfunction at discharge by group was: placebo 6/8 (75%), 375 U/kg 4/8 (50%), 750 U/kg 6/8 (75%), and 1500 U/kg 5/8 (63%). Neurocognitive dysfunction at 2 months by group was: placebo 3/8 (38%), 375 U/kg 1/8 (13%), 750 U/kg 1/8 (13%), and 1500 U/kg 0/8 (0%). Neurocognitive dysfunction at 2 months for erythropoietin at any dose was 2/24 (8.3%) versus 3/8 (38%) for placebo (P=0.085). Conclusions—This study demonstrates feasibility and safety for the use of human recombinant erythropoietin as a neuroprotectant in coronary artery bypass graft surgery. A trend in the reduction of neurocognitive dysfunction at 2 months was associated with erythropoietin use. A multicenter randomized controlled trial is warranted.
Accepted on February 24, 2009
The Erythropoietin NeuroProtective Effect: Assessment in CABG Surgery (TENPEAKS). A Randomized, Double-Blind, Placebo Controlled, Proof-of-Concept Clinical Trial
Gregory Haljan MD, FRCPC;
Key words: neuroprotective agents • coronary artery bypass • recombinant erythropoietin