Angiomax (Bivalirudin) in Cardiothoracic Surgery
Primary Recommendation
Bivalirudin should be considered as an alternative anticoagulant to unfractionated heparin in cardiothoracic surgery, particularly for patients with heparin-induced thrombocytopenia (HIT) or those at high bleeding risk, though it requires specialized protocols and experienced teams. 1
Indications for Bivalirudin in Cardiac Surgery
Primary Indication: Heparin-Induced Thrombocytopenia
- Bivalirudin is the preferred anticoagulant for patients with confirmed or suspected HIT undergoing cardiac surgery (Class IIa, Level of Evidence B). 1
- For patients with acute HIT requiring urgent cardiac surgery, bivalirudin is recommended over other alternatives including argatroban, plasma exchange with heparin, or heparin with antiplatelet agents. 1
- The FDA has approved bivalirudin for use in patients with HIT and HIT with thrombosis syndrome undergoing PCI, and this extends to cardiac surgery in clinical practice. 2
Secondary Considerations
- Bivalirudin may be considered as a primary anticoagulant in critically ill cardiac surgery patients to reduce bleeding complications and potentially improve mortality outcomes. 3
- In propensity-matched analysis, primary bivalirudin anticoagulation (versus switching from heparin) was associated with reduced minor bleeding (p=0.04) and mortality (p=0.01). 3
Dosing Protocols for Cardiac Surgery
On-Pump Cardiac Surgery (with CPB)
- Initial bolus: 1 mg/kg IV plus 50 mg in pump priming fluid. 1
- Maintenance infusion: 2.5 mg/kg/hour during the procedure. 1
- Target ACT: 2.5 times baseline ACT. 1
- If ACT remains below target, administer additional bolus of 0.1 to 0.5 mg/kg. 1
- Stop infusion 15 minutes before anticipated end of CPB. 1
- If CPB continues beyond 20 minutes after stopping infusion, give bolus of 0.5 mg/kg IV and restart infusion at 2.5 mg/kg/hour. 1
Off-Pump Cardiac Surgery
- Initial bolus: 0.75 mg/kg IV. 1
- Maintenance infusion: 1.75 mg/kg/hour during the procedure. 1
- Target ACT: >300 seconds. 1
- If ACT <300 seconds, increase infusion rate by 0.25 mg/kg/hour. 1
Renal Impairment Adjustments
- Severe renal failure (CrCl <30 mL/min): Bivalirudin is contraindicated. 1
- Moderate renal impairment (CrCl 30-59 mL/min): Reduce maintenance infusion to 1.4 mg/kg/hour for PCI procedures. 4
- Hemodialysis patients: Reduce infusion to 0.25 mg/kg/hour. 2
Monitoring Requirements
Activated Clotting Time (ACT)
- Baseline ACT must be measured before bivalirudin administration. 1
- Target ACT during CPB: 2.5 times baseline (typically >480 seconds with uncoated equipment). 1
- ACT should be checked 5 minutes after initial bolus and regularly throughout the procedure. 1, 2
- Unlike heparin, bivalirudin monitoring with ACT has not been standardized, and some centers use ecarin clotting time. 1
Bivalirudin Levels
- Whole blood bivalirudin level measurement is possible but remains an expert opinion recommendation. 1
- No routine functional clotting assay has been validated for optimal bivalirudin monitoring during cardiac surgery. 5
Critical Operative Considerations
Perfusion Management
- Avoid blood stagnation in the CPB circuit - bivalirudin undergoes enzymatic degradation by thrombin, and stagnant blood increases thrombosis risk. 1
- Do not aspirate pericardial blood - this can introduce activated thrombin and degrade bivalirudin. 1
- Continuous circuit flow must be maintained to prevent clot formation. 6
- The CPB circuit setup requires modification compared to heparin protocols. 1
Surgical Technique Modifications
- Minimize cardiotomy suction use due to risk of thrombin activation. 6
- Maintain meticulous hemostasis throughout the procedure. 6
- Consider cell salvage techniques carefully, as bivalirudin may be present in salvaged blood. 6
Reversal and Post-Operative Management
No Specific Reversal Agent
- Bivalirudin has no reversal agent - unlike heparin, which is reversed with protamine. 1
- The anticoagulant effect subsides approximately one hour after discontinuation due to its 25-minute half-life. 2, 7
- Renal replacement therapy can reduce plasma concentrations of bivalirudin but has limited clinical utility. 1
Sheath/Line Removal Timing
- Remove arterial access sheaths 2-4 hours after stopping bivalirudin. 1
- This timing allows for adequate clearance while minimizing bleeding risk. 1
Post-Operative Bleeding Management
- Mean blood loss after on-pump surgery: 750 ± 494 mL with 56% transfusion rate. 8
- Mean blood loss after off-pump surgery: 833 ± 310 mL with 30% transfusion rate. 8
- Re-exploration rates for bleeding are low (approximately 1.4%) in experienced centers. 8
Comparison to Unfractionated Heparin
Advantages of Bivalirudin
- Predictable anticoagulation without need for antithrombin III. 5, 7
- No platelet activation (unlike heparin). 7
- Ability to inhibit clot-bound thrombin. 1, 7
- Reduced bleeding complications in critically ill patients (p=0.05). 3
- Eliminates risk of HIT. 5, 8
Disadvantages of Bivalirudin
- No reversal agent available. 1
- Requires specialized protocols and experienced team. 1, 8
- Risk of catheter/circuit thrombosis if blood stagnation occurs. 1
- Limited long-term outcome data in cardiac surgery compared to PCI. 5
- Higher cost compared to unfractionated heparin. 5
Contraindications and Precautions
Absolute Contraindications
- Significant active bleeding. 2
- Hypersensitivity to bivalirudin or its components. 2
- Severe renal failure (CrCl <30 mL/min) for cardiac surgery. 1
Relative Contraindications and Cautions
- Coronary artery brachytherapy: Increased risk of fatal thrombus formation. 2
- Inexperienced surgical/perfusion team - bivalirudin requires specialized knowledge. 1, 5
- Procedures requiring prolonged CPB times may increase complexity. 6
Special Clinical Scenarios
Urgent/Emergent Surgery in HIT Patients
- If surgery cannot be delayed until subacute HIT B or remote HIT, bivalirudin is the preferred option. 1
- The American Society of Hematology suggests delaying surgery when possible, but acknowledges bivalirudin as the best alternative when delay is not feasible. 1
- Postoperative platelet count monitoring is necessary even when postoperative heparin is avoided, as delayed-onset autoimmune HIT can occur 5-10 days after intraoperative heparin exposure. 1
Critically Ill Cardiac Surgery Patients
- Primary bivalirudin (versus secondary after heparin failure) showed reduced mortality (OR=19.2 for UFH versus bivalirudin, p=0.007). 3
- Predictors of mortality included urgent admission, septic shock, and primary therapy with UFH rather than bivalirudin. 3
Common Pitfalls and How to Avoid Them
Circuit Thrombosis
- Most critical complication - occurs with blood stagnation or inadequate dosing. 1
- Prevention: Maintain continuous circuit flow, avoid pericardial aspiration, ensure adequate ACT levels. 1, 6
- Monitor cardiotomy reservoir and pericardium for clot formation. 1
Inadequate Anticoagulation
- Unlike heparin, there is no validated point-of-care test for optimal bivalirudin levels. 5
- Rely on ACT monitoring with target of 2.5 times baseline. 1
- Be prepared to give additional boluses if ACT falls below target. 1
Excessive Bleeding Without Reversal
- Plan surgical hemostasis meticulously since no reversal agent exists. 1
- Consider tranexamic acid or other hemostatic adjuncts. 6
- Wait for drug clearance (approximately 1 hour after stopping infusion). 2
Switching Between Anticoagulants
- Bivalirudin may be used after unfractionated heparin bolus without adverse effects in PCI. 1
- However, in cardiac surgery, establish clear protocols for switching to avoid "stacking" effects. 6
Institutional Requirements for Safe Use
Team Experience
- Bivalirudin use should be restricted to skilled perfusionist/surgeon/anesthesiologist teams. 1
- Institutional protocols must be thoroughly developed and followed. 5, 6
- All team members must understand bivalirudin's unique pharmacology and management requirements. 6