What are the benefits and administration guidelines of tranexamic acid (TXA) in on-pump Coronary Artery Bypass Grafting (CABG) patients pre and post-operatively?

Tranexamic Acid in On-Pump CABG: Benefits and Administration

Tranexamic acid is recommended during on-pump cardiac surgical procedures to reduce bleeding, blood transfusions, and reoperation rates without increasing thrombotic complications. 1

Primary Benefits

Blood Loss Reduction:

• TXA reduces postoperative chest tube drainage by approximately 206 mL in the first 24 hours compared to placebo 2
• In on-pump CABG specifically, TXA reduces total postoperative bleeding by 43% 3
• Bleeding exceeding 600 mL is reduced by 80% 3

Transfusion Requirements:

• The frequency of any allogeneic blood transfusion is reduced by 36% (RR 0.64) 2
• This reduction occurs without increasing prothrombotic complications 2

Reoperation for Bleeding:

• TXA reduces the incidence of reoperation for bleeding by 54% (RR 0.46) 2
• This represents a clinically significant reduction in a major postoperative complication 2

Mechanism and Fibrinolytic Effects

• TXA works by inhibiting fibrinolysis, as evidenced by significant reductions in plasma D-dimer levels (P <0.0001) 3
• The antifibrinolytic effect is particularly pronounced in on-pump CABG due to the fibrinolytic activation caused by cardiopulmonary bypass 3
• TXA may also modulate inflammation, with reductions in interleukin-6 levels observed 3

Administration Protocol

Dosing Regimen (Class I, Level A recommendation): 1

Loading Dose:

• 10 mg/kg IV bolus over 10-20 minutes before skin incision 4, 3, 5

Maintenance Infusion:

• 1 mg/kg/h continuous infusion until end of surgery 6
• Alternative regimen: 6-15 mg/kg/h (both low and high dose protocols show similar efficacy) 4

Cardiopulmonary Bypass Circuit:

• Add 500 mg to 1 mg/kg to the CPB priming solution 4, 3

Maximum Total Dose:

• Do not exceed 100 mg/kg total dose to minimize seizure risk 1

Safety Profile

Cardiovascular Safety:

• No significant increase in cerebrovascular accidents (RR 0.93) 2
• No increase in mortality (RR 0.82) 2
• No increase in myocardial infarction (RR 0.90) 2
• No increase in acute renal insufficiency (RR 1.01) 2

Critical Safety Concern - Seizures:

• TXA may increase the risk of postoperative seizures (RR 6.67) 2
• Higher doses are associated with increased seizure risk 1
• This risk is dose-dependent, making adherence to the maximum 100 mg/kg limit essential 1

Clinical Context and Special Considerations

Preferred Over Aprotinin:

• TXA is preferred over aprotinin, which has been associated with increased renal failure requiring dialysis, 55% increase in MI or heart failure risk, and 181% increase in stroke or encephalopathy risk 1
• Neither TXA nor aminocaproic acid shows these adverse renal, cardiac, or cerebral events 1

Use in Antiplatelet Therapy:

• For patients on dual antiplatelet therapy (aspirin and clopidogrel) requiring urgent CABG, TXA is part of a comprehensive hemostatic approach 1
• TXA can be used safely in this high-bleeding-risk population 1

Low-Dose vs High-Dose:

• Low-dose protocols (15 mg/kg loading, 6 mg/kg/h infusion, 1 mg/kg in bypass circuit) are as effective as high-dose protocols for antifibrinolysis 4
• Given the dose-dependent seizure risk, lower effective doses should be preferred 1, 4

Common Pitfalls to Avoid

• Exceeding maximum dose: Always calculate total cumulative dose to ensure it remains below 100 mg/kg to minimize seizure risk 1
• Omitting bypass circuit dose: Remember to add TXA to the CPB priming solution for optimal effect in on-pump cases 3
• Delaying administration: Give loading dose before skin incision to ensure adequate levels during the period of maximal fibrinolytic activation 3, 6
• Confusing with DDAVP: TXA (lysine analogue) is the first-line agent; DDAVP shows minimal clinical benefit and should not be substituted 7