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CARDIOVASCULAR ANESTHESIA

A Dose-Determining Trial of Heparinase-I (Neutralase^TM) for Heparin Neutralization in Coronary Artery Surgery

Edward K. Heres, MD^*, Jay Charles Horrow, MD, Glenn P. Gravlee, MD^*, Barbara E. Tardiff, MD, John Luber, Jr, MD, Joel Schneider, MD^||||, Thomas Barragry, MD^¶, and Richard Broughton, BSc^#

*Allegheny General Hospital, Pittsburgh, Pennsylvania; MCP-Hahnemann University, Philadelphia, Pennsylvania; Duke University Medical Center, Durham, North Carolina; Albany Medical Center, Albany, New York; ||||St. John’s Hospital, Springfield, Illinois; ¶St. Francis Hospital, Milwaukee, Wisconsin; and #IBEX Technologies, Montreal, Quebec, Canada

Address correspondence to Jay Charles Horrow, MD, MCP-Hahnemann University, 245 N. 15th St., MS 310, Philadelphia, PA 19102. Address e-mail to horrow{at}drexel.edu

Heparinase-I, a specific heparin-degrading enzyme, may represent an alternative to protamine. We explored the dose of heparinase-I for efficacy and safety in patients undergoing coronary artery surgery. At the conclusion of cardiopulmonary bypass, subjects received 5, 7, or 10 µg/kg of open-label heparinase-I instead of protamine. Activated clotting time (ACT) and its difference from a contemporaneous heparin-free sample (ACT) at 3 min before and 3, 6, and 9 min after heparinase-I determined reversal efficacy. After surgery, we recorded hourly chest tube drainage. Systemic and pulmonary arterial blood pressure and cardiac output measurements before and immediately after heparinase-I were used to evaluate hemodynamic safety. Coagulation measurements included anti-factor Xa and anti-factor IIa activities. Forty-nine patients from seven institutions participated: 12 received 5 µg/kg, 21 received 7 µg/kg, 4 received two doses of 7 µg/kg, 8 received 10 µg/kg, and 4 received two doses of 10 µg/kg. Treatment groups did not differ demographically. Median ACT 9 min later was 11, 7, and 4 s for the 5, 7, and 10 µg/kg groups, respectively. No adverse hemodynamic changes occurred with heparinase-I administration. The authors conclude that heparinase-I effectively restored the ACT after cardiopulmonary bypass. This effect appeared to be dose dependent.

IMPLICATIONS: Heparinase-I (Neutralase^TM) successfully restored activated coagulation time with no adverse hemodynamic events in patients undergoing coronary artery surgery with cardiopulmonary bypass in an open-label dose-determining trial.

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