title: Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass.
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 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.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA. staff002@mc.duke.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
authors.forename: Edward A
authors.initials: EA
authors.lastname: Lefrak
authors.forename: Anjum G
authors.initials: AG
authors.lastname: Qazi
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Welsby
authors.forename: Linda
authors.initials: L
authors.lastname: Barber
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeft
authors.forename: Alejandro
authors.initials: A
authors.lastname: Dorenbaum
authors.forename: Jasmine
authors.initials: J
authors.lastname: Mathias
authors.forename: James J
authors.initials: JJ
authors.lastname: Rochon
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
mesh_terms: 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*
chemical_list: D006494:Heparin Antagonists; D011479:Protamines; D019763:Heparin Lyase