The erythropoietin neuroprotective effect: assessment in CABG surgery (TENPEAKS): a randomized, double-blind, placebo controlled, proof-of-concept clinical trial.
OBJECTIVE
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.
Haljan
Gregory
G
Foothills Medical Centre, Rm EG23, 1403-29 Street NW, Calgary, Alberta, Canada T2N2T9.
Maitland
Andrew
A
Buchan
Alastair
A
Arora
Rakesh C
RC
King
Michael
M
Haigh
John
J
Culleton
Bruce
B
Faris
Peter
P
Zygun
David
D
D000368:Aged; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D004311:Double-Blind Method; D004921:Erythropoietin / Q000627:therapeutic use*; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D011994:Recombinant Proteins
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin