Subtle differences in commercial heparins can have serious consequences for cardiopulmonary bypass patients: A randomized controlled trial Kyle A. Arsenault, BHSc, a Jeremy S. Paikin, MD, b Jack Hirsh, MD, b,c Brian Dale, PhD, d Richard P. Whitlock, MD, e Kevin Teoh, MD, e Ed Young, PhD, f,g Jeffrey S. Ginsberg, MD, b Jeffrey I. Weitz, MD, b,g and John W. Eikelboom, MBBS b,g Objective: To compare the potency, reversibility, and perioperative bleeding risk of Hepalean with those of PPC heparin. Methods: Because in vitro testing failed to detect differences in the potency or protamine reversibility of the 2 heparin preparations, we conducted a parallel group, single-center, double-blind, randomized, controlled trial to compare the anticoagulant effects of Hepalean to those of PPC heparin in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Results: From June 1, 2011, to June 30, 2011, we randomly assigned 11 patients to receive PPC heparin and 10 to receive Hepalean. Despite similar initial doses of heparin, the median initial activated clotting time was nu- merically lower in the PPC heparin group than in the Hepalean group (median, 516.0 seconds; interquartile range, 481.0-633.0; vs median, 584.0 seconds, interquartile range, 520.0-629.0; P ¼ .418). Those given PPC heparin required a greater total heparin dose (median, 46,000.0 U; interquartile range, 39,500.0-60,000.0 vs me- dian, 34,500.0 U; interquartile range, 32,250.0-37,000.0; P ¼ .011) and a greater dose of heparin per kilogram than those given Hepalean (median, 572.9 U/kg; interquartile range, 443.0-659.7 vs median, 401.1 U/kg; inter- quartile range, 400.0-419.4; P ¼ .003). The key secondary results included an increased median total protamine dose (median, 600.0 mg; interquartile range, 550.0-700.0; vs median, 500.0 mg; interquartile range, 425.0- 542.5; P ¼ .026) and a trend toward increased chest tube output within 24 hours (median, 830.0 mL; interquartile range, 425.0-1135.0; vs median, 702.5 mL; interquartile range, 550.0-742.5; P ¼ .324). Conclusions: PPC heparin use was associated with greater heparin and protamine dose requirements than Hepalean. These findings indicate that heparin preparations are not interchangeable and suggest that a direct comparison of the potency with the brand in use is needed if a change is made to ensure that the agents exert similar anticoagulant effects in vivo. (J Thorac Cardiovasc Surg 2012;144:944-50) Supplemental material is available online. Most cardiac surgical operations are performed using car- diopulmonary bypass (CPB) that maintains the systemic blood circulation during cardioplegia. Heparin is routinely used to inhibit coagulation and prevent thrombus forma- tion on the surfaces of the bypass circuitry and the oxygenator. In patients undergoing cardiac surgery, the first dose of heparin is given before CPB, and the anticoagulant response is monitored using a point-of-care device that measures the activated clotting time (ACT). 1,2 The usual target ACT before CPB is at least 480 seconds. 3,4 The ACT is monitored throughout the procedure, and additional heparin doses are given to maintain this ACT target. At the end of the procedure, the anticoagulant effect of heparin is reversed with protamine sulfate. 5 Heparin is most commonly derived from porcine intesti- nal mucosa, and several brands are commercially available. Hamilton Health Sciences recently switched from Hepalean (Organon Teknika, Toronto, Ontario, Canada) to Pharma- ceutical Partners of Canada (PPC) heparin (PPC, Richmond Hill, Ontario, Canada) because the production of Hepalean From the McMaster University Michael G. DeGroote School of Medicine, a Hamilton, Ontario, Canada; Departments of Medicine, b Surgery, e and Pathology and Molec- ular Medicine, f McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, c Hamilton, Ontario, Canada; University of South Australia School of Pharmacy and Medical Sciences, d Adelaide, Australia; and Thrombosis and Atherosclerosis Research Institute, g Hamilton, Ontario, Canada. B. Dale was supported by grants from the Australasian Society of Thrombosis and Haemostasis and the University of South Australia. K. Arsenault was supported by the Beamish Family Foundation Chair in Vascular Surgery, held by Dr J. G. Titt- ley. J. I. Weitz holds the Tier I Canada Research Chair in Thrombosis and the Heart & Stroke Foundation of Ontario/J. Fraser Mustard Chair in Cardiovascular Re- search. J. Eikelboom holds a Tier II Canada Research Chair in Cardiovascular Medicine from the Canadian Institutes for Health Research. Internal funds were provided by Drs Eikelboom, Whitlock, and Teoh. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Dec 21, 2011; revisions received April 26, 2012; accepted for publication May 17, 2012; available ahead of print June 28, 2012. Address for reprints: John W. Eikelboom, MBBS, David Braley Cardiac, Vascular, and Stroke Research Institute, 237 Barton St East, Hamilton, ON L8L 2X2, Canada (E-mail: eikelbj@mcmaster.ca). 0022-5223/$36.00 Copyright Ó 2012 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2012.05.065 944 The Journal of Thoracic and Cardiovascular Surgery c October 2012 Perioperative Management Arsenault et al PM