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Best Practice Corner

Heparin Resistance During CPB: What Do You Do?

Roman Sniecinski, MD1; Elliott Bennett-Guerrero, MD2; Linda Shore-Lesserson, MD3

  1. Associate Professor of Anesthesiology, Emory University School of Medicine, Atlanta, GA
  2. Professor of Anesthesiology, Stony Brook School of Medicine, Stony Brook, NY
  3. Professor of Anesthesiology, Hofstra Northwell School of Medicine, Manhasset, NY

The use of unfractionated heparin (UFH) is ubiquitous to the practice of cardiac anesthesiology. For more than 60 years it has provided the necessary anticoagulation for cardiopulmonary bypass (CPB) and is administered on an almost daily basis by cardiovascular anesthesiologists. Despite its longevity of use, frequent users will admit that among the many advantages of UFH, there is a key disadvantage. It quickly achieves profound levels of reversible anticoagulation…except when it doesn’t.

Decreased heparin responsiveness, frequently termed “heparin resistance,” is essentially a flattening of the UFH dose-response curve’s slope. It is typically encountered after the initial bolus dose of heparin has been administered and manifests itself as a suboptimal activated clotting time (ACT) for the initiation of CPB. Virtually every cardiac anesthesiologist has experienced the frustration of trying to increase the level of patient anticoagulation while a surgeon, cannula in hand, waits impatiently to begin the operation. Although the scenario is familiar to all, the details of the problem and the employed solutions are highly variable and largely dependent on institutional practices.

Heparinization for CPB has a rather complex history, so it is not surprising that there is considerable variability in the administration and monitoring of UFH. In the early days of CPB, circa the 1950s, anesthesiologists were instructed to simply administer “3 mg/kg” of UFH;1 no monitoring was performed. It wasn’t until the 1970s that ACT was introduced into the operating room and the first “safe zone” for CPB anticoagulation was recommended.2 Since then, the use of aprotinin, the development of heparin-bonded circuits, and even changes in US potency standards of UFH have all impacted heparin management to varying degrees. The paucity of high-quality evidence for what constitutes the optimal level, and monitoring of anticoagulation for CPB, has resulted in a diverse range of local practices. A 2010 survey of North American cardiac centers reported that the “target ACT” for CPB ranged from <350 s to over 500 s, and the maximal UFH doses given before alternative anticoagulation strategies used ranged from 300 to 800 units/kg.3

This lack of agreement also makes it difficult to determine the extent of the problem of decreased heparin responsiveness. The incidence is quoted as being between 4% and 26% in cardiac surgical patients,4 although no consensus definition of “heparin resistance” exists in the literature (see Table 1). The 2011 STS/SCA blood conservation guidelines contain some information on how to treat decreased heparin responsiveness but provide no guidance with regard to an anticoagulation target.5

To better understand UFH management and anticoagulation targets prior to initiating, as well as during CPB, the Society of Cardiovascular Anesthesiologists (SCA) is currently conducting a survey of active and associate members. The goal is to describe current practice patterns and attitudes about diagnosing and treating decreased heparin responsiveness. Completed surveys will be entered into a drawing for prizes that include Apple gift cards and SCA memberships.

If you have not already done so, please complete the anticoagulation survey.

Table 1: Definitions of “Heparin Resistance” Used in Various Studies of Cardiac Surgical Patients on CPB

1st Author, Year

Study Population


Williams, MR, 20006

Aprotinin and EACA treated patients, mixture of procedures

450 u/kg UFH failed to achieve ACT≥480 s or ACT≥600 s if treated with aprotinin

Lemmer JH, 20027

Aprotinin-treated patients, mixture of procedures

600 u/kg UFH failed to achieve ACT >600 s

Koster A, 20038

No antifibrinolytics, mixture of procedures

500 u/kg UFH failed to achieve ACT≥480s

Avidan MS, 20059

No antifibrinolytics, mixture of procedures

400 u/kg UFH failed to achieve ACT≥480 s

Chan T, 200610

Mixture of procedures

5 mg/kg UFH failed to achieve ACT≥400 s

Knapik P, 201211

CABG patients

300 u/kg UFH failed to achieve ACT≥400 s or
400 u/kg UFH failed to achieve ACT≥480 s or
Heparin Sensitivity Index < 1.3 s/u

CPB=cardiopulmonary bypass; EACA=ε-aminocaproic acid; UFH=unfractionated heparin; ACT=activated clotting time; CABG=coronary artery bypass graft

  1. Patrick RT, Theye RA, Moffitt EA. Studies in extracorporeal circulation. V. Anesthesia and supportive care during intracardiac surgery with the Gibbon-type pump-oxygenator. Anesthesiology. 1957;18(5):673-685.
  2. Bull BS, Huse WM, Brauer FS, Korpman RA. Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg. 1975;69(5):685-689.
  3. Lobato RL, Despotis GJ, Levy JH, Shore-Lesserson LJ, Carlson MO, Bennett-Guerrero E. Anticoagulation management during cardiopulmonary bypass: a survey of 54 North American institutions. J Thorac Cardiovasc Surg. 2010;139(6):1665-1666.
  4. Finley A, Greenberg C. Review article: heparin sensitivity and resistance: management during cardiopulmonary bypass. Anesth Analg. 2013;116(6):1210-1222.
  5. Ferraris VA, Brown JR, Despotis GJ, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011;91(3):944-982.
  6. Williams MR, D'Ambra AB, Beck JR, et al. A randomized trial of antithrombin concentrate for treatment of heparin resistance. Ann Thorac Surg. 2000;70(3):873-877.
  7. Lemmer JH Jr, Despotis GJ. Antithrombin III concentrate to treat heparin resistance in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2002;123(2):213-217.
  8. Koster A, Fischer T, Gruendel M, et al. Management of heparin resistance during cardiopulmonary bypass: the effect of five different anticoagulation strategies on hemostatic activation. J Cardiothorac Vasc Anesth. 2003;17(2):171-175.
  9. Avidan MS, Levy JH, Scholz J, et al. A phase III, double-blind, placebo-controlled, multicenter study on the efficacy of recombinant human antithrombin in heparin-resistant patients scheduled to undergo cardiac surgery necessitating cardiopulmonary bypass. Anesthesiology. 2005;102(2):276-284.
  10. Chan T, Hwang NC, Lim CH. A statistical analysis of factors predisposing patients to heparin resistance. Perfusion. 2006;21(2):99-103.
  11. Knapik P, Ciesla D, Przybylski R, Knapik T. The influence of heparin resistance on postoperative complications in patients undergoing coronary surgery. Med Sci Monit. 2012;18(2):CR105-111.

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