Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass

Mark Stafford-Smith, Edward A. Lefrak, Anjum G. Qazi, Ian J. Welsby, Linda Barber, Andreas Hoeft, Alejandro Dorenbaum, Jasmine Mathias, James J. Rochon, Mark F. Newman

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

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 μg/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 denned as systemic hypotension (≥ 30 mmHg decrease) and/or pulmonary hypertension (≥ 40 mmHg with an increase ≥ 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.

Original languageEnglish
Pages (from-to)229-240
Number of pages12
JournalAnesthesiology
Volume103
Issue number2
DOIs
StatePublished - Aug 2005

Bibliographical note

Funding Information:
Received from the Global Perioperative Research Organization, Durham, North Carolina. Submitted for publication October 27, 2004. Accepted for publication February 28, 2005. Supported by BioMarin Pharmaceutical Inc., Novato, California, and the Global Perioperative Research Organization, Durham, North Carolina. A potential alternate to protamine is heparinase I, an agent that deactivates heparin by a different mechanism. BioMarin Pharmaceuticals Inc. owns the rights to heparinase I. In addition, Dr. Dorenbaum is an employee of BioMarin Inc. who was involved in the conception of this project and editing of the final manuscript.

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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