Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass.
BACKGROUND
Hemodynamic protamine reactions with heparin reversal during cardiac surgery are common and associated with adverse outcomes. As an alternative to protamine, the authors examined heparinase I reversal of heparin after aortocoronary bypass graft surgery.


METHODS
In a randomized, double-blind, double-dummy trial, 167 on- and off-pump aortocoronary bypass graft surgery patients received either heparinase I (maximum 35 microg/kg) or protamine (maximum 650 mg) for heparin reversal, monitored by activated clotting time values and clinical assessment. Hemodynamic parameters were recorded electronically; safety evaluation was to 30 days postoperatively. Noninferiority was predefined as 400 ml or less median 12-h chest tube drainage from intensive care unit arrival for heparinase I patients, after risk adjustment. Hemodynamic instability was defined as systemic hypotension (> or = 30 mmHg decrease) and/or pulmonary hypertension (> or = 40 mmHg with an increase > or = 10 mmHg) within 30 min of heparin reversal initiation.


RESULTS
Patient enrollment was terminated on advisement of the Data Safety Monitoring Board. Although heparinase I was noninferior for 12-h chest tube drainage, protamine had a superior safety profile. Overall, heparinase I subjects had longer hospital stays (P = 0.04), were more likely to experience a serious adverse event (P = 0.01), and were less likely to avoid transfusion (P = 0.006). A composite morbidity score was not different (P = 0.24), and similar rates of hemodynamic instability were observed between groups. Findings were consistent in analyses stratified by on- and off-pump surgery.


CONCLUSIONS
Heparinase I reverses heparin anticoagulation after aortocoronary bypass graft surgery but is not equivalent to protamine because of its inferior safety profile.
Stafford-Smith
Mark
M
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA. staff002@mc.duke.edu
Lefrak
Edward A
EA
Qazi
Anjum G
AG
Welsby
Ian J
IJ
Barber
Linda
L
Hoeft
Andreas
A
Dorenbaum
Alejandro
A
Mathias
Jasmine
J
Rochon
James J
JJ
Newman
Mark F
MF
D000293:Adolescent; D000328:Adult; D000368:Aged; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006494:Heparin Antagonists / Q000627:therapeutic use*; D019763:Heparin Lyase / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011479:Protamines / Q000009:adverse effects / Q000627:therapeutic use*
D006494:Heparin Antagonists; D011479:Protamines; D019763:Heparin Lyase