The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology

Clinical Practice Guidelines—Anticoagulation During Cardiopulmonary Bypass

Linda Shore-Lesserson, MD; Robert A. Baker, PhD, CCP; Victor A. Ferraris, MD, PhD; Philip E. Greilich, MD; David Fitzgerald, MPH, CCP; Philip Roman, MD, MPH; John W. Hammon, MD

Disclosures

Anesth Analg. 2018;126(2):413-424. 

In This Article

Bivalirudin

Bivalirudin, a recombinant direct thrombin inhibitor, is not currently approved by the Food and Drug Administration for use during CPB (albeit approved for this use outside the United States). Bivalirudin effectively inhibits the coagulation cascade and has a short 25-minute half-life in patients with normal renal function. Monitoring of anticoagulation with bivalirudin is more challenging than with heparin. The ecarin clotting time (ECT) correlates strongly (R2 = 0.91) with therapeutic bivalirudin concentrations but is not commonly available as a point-of-care test.[65] In a comparative analysis study of 10 patients undergoing cardiopulmonary bypass, three different methods of the ACT test were compared with ECT.[66] Although not as accurate as the ECT, the more commonly available celite-ACT was found to have an acceptable correlation with ECT-determined bivalirudin concentration (R 2 = 0.93).

Bivalirudin has the broadest experience in patients undergoing cardiac surgery (with and without CPB) and in patients with HIT and patients with HIT with thrombosis requiring CPB.[67] This includes procedures requiring deep hypothermic circulatory arrest.[68] Controlled trials suggest that bivalirudin provides adequate anticoagulation in all patients.[69,70] In these trials, secondary endpoints including mortality, 24-hour blood loss, overall incidence of transfusions, and duration of surgery were similar for bivalirudin-treated patients and for patients having CPB with heparin anticoagulation and protamine reversal. Several studies—for example, the Evaluation of Patients During Coronary Artery Bypass Graft Operation: Linking Utilization of Bivalirudin to Improved Outcomes and New Anticoagulant Strategies (EVOLUTION-ON) and the Coronary Artery Bypass Grafting Heparin-Induced Thrombocytopenia Thrombosis Syndrome On- and Off-Pump Safety and Efficacy (CHOOSE-ON) trials—propose a reliable therapeutic protocol for bivalirudin.[69,70] Bivalirudin dosing in the CHOOSE-ON and EVOLUTION-ON trials included a loading dose of 1.0 mg/kg, infusion of 2.5 mg · kg−1 · h−1, and pump prime of 50 mg. The adequacy of anticoagulation was monitored using 2.5 times the baseline ACT. In many centers, target ACT levels were achieved with lower loading dose and infusion rates.

In the EVOLUTION-ON multicenter, open label trial, 101 patients were randomly assigned to either bivalirudin or heparin with protamine reversal. Both groups were successfully anticoagulated, and there were no significant differences in morbidity or mortality between groups at 7 days, 30 days, or 12 weeks. Postoperative blood loss was statistically higher at 2 hours (238 mL versus 160 mL, p = 0.0009), but not at 24 hours (793 mL versus 668 mL, p = 0.15). Postoperative reexploration occurred in 6.1% versus 1.9%, but was not statistically significant.[70] Anticoagulation with the direct thrombin inhibitor bivalirudin appears to provide a safe and effective alternative to heparin and protamine reversal, even though it may increase the risk of excessive bleeding. In extreme cases, a combination of modified ultrafiltration, hemodialysis, and administration of recombinant factor VIIa in addition to balanced hemostatic resuscitation with fresh frozen plasma, cryoprecipitate and platelets may be required until the anticoagulant effects of bivalirudin are reversed.[68,71,72]

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