Topical TXA Does Not Reduce Peri-Operative Seizures but Increases Risk of Transfusion in Cardiac Surgery Compared to Intravenous TXA

By Leah Kosyakovsky on

Key Points:

  • IV TXA is used to prevent peri-operative bleeding in cardiac surgery, but it carries a risk of seizure. It is hypothesized that topical TXA may reduce this risk of seizure.
  • In DEPOSITION, topical and IV TXA were compared in individuals undergoing cardiac surgery. The primary endpoint was seizure. Authors also investigated differences in RBC transfusions between arms.
  • Topical TXA did not result in a significant difference in peri-operative seizures, but it did increase RBC transfusion requirement relative to IV TXA.

Perioperative bleeding is a major source of morbidity and mortality in cardiac surgery. However, the use of intravenous TXA for bleeding has several limitations, including increasing the risk of peri-operative seizures. Topical TXA on the source of bleeding has been utilized in other forms of surgery to minimize systemic absorption, but it has not been well tested in cardiac surgery. In a breaking presentation at the 2024 ACC conference today, Dr. Andre Lamy and his team presented their study: “DEPOSITION: Topical Tranexamic Acid to Reduce Seizures in Cardiac Surgery.”

The DEPOSITION study (NCT03954314) was an investigator-initiated, randomized, double-blinded trial examining the safety and efficacy of topical vs IV TXA in cardiac surgery. Participants were required to be undergoing cardiac surgery with cardiopulmonary bypass and a median sternotomy approach. Key exclusions were active endocarditis, bleeding disorders, eGFR <30ml/min, pre-operative Hb >170 or <110 g/L or thrombocytopenia (<50,000). The primary efficacy outcome was seizure. Key secondary outcomes included RBC transfusions, any blood product transfusions, composite MACE, re-operation for bleeding or tamponade, and ICU length of stay. 

A total of 3,242 patients were 1:1 randomized to either topical or IV TXA. Both arms were given 2 dummy or treatment syringes for both topical and systemic use to maintain blinding. The IV bolus was given at the start and during surgery, whereas the topical treatment was given at the end of surgery. A total of 96.5% of patients received the active treatment allocation, and 100% of patients completed follow-up. The mean age was 66 with 23% women; most patients (70%) were receiving CABG, and the mean time on bypass was 88 minutes. 

The study was stopped in November 2023 for safety. There was no reduction in seizures with topical TXA treatment relative to IV therapy (RR 0.36, 95% CI [0.12, 1.14]; p=0.07). In post-hoc analyses, the authors were more inclusive with their seizure definition and also included individuals who developed both seizures and strokes. In this analysis, topical TXA resulted in a reduction in “any seizure” (RR 0.29, 95% CI [0.09, 0.86]; p=0.02). There was, however, an increase in RBC transfusions in the topical TXA arm (RR 1.31, 95% CI [1.18, 1.46]; p<0.001), but no difference in any other secondary outcomes.

When discussing the clinical implications of the study at the ACC conference, Dr. Lamy stated: “Topical TXA  does not reduce risk of seizure….but does increase the risk of transfusion…the mechanism of seizure with TXA is likely more complex….probably mediated by embolism of air or debris.”