Sparing Red Blood Cells During Cardiac Surgery

Volume 18, Issue 1

Achieving effective hemostasis during cardiac surgery is like orchestrating a delicate symphony.

If patients are on anticoagulants prior to surgery, these must be completely reversed prior to skin incision. Once the patient is cannulated for bypass, high-dose heparin is given to prevent thrombotic complications that arise from contact with key plasma proteins and the prosthetic materials used for the bypass tubing. Coagulation is monitored closely during bypass, with additional heparin balanced with factor repletion via fresh frozen plasma, and with complimentary administration of platelets and cryoprecipitate as needed.

Additionally, antifibrinolytic therapy is used to prevent runaway fibrinolysis and uncontrolled hemorrhage. Traditionally this was done with aprotinin, but this agent was removed from the market in 2007 amid safety concerns for renal failure. Tranexamic acid has emerged as the preferred antifibrinolytic agent during cardiac surgery, but the optimal dose remains undetermined.

In this week's issue of Talking Therapeutics, we discuss a new clinical trial that compares 2 different dosing regimens for tranexamic acid during cardiac surgery. 

Point 1: Small But Significant Improvement in Transfusion Requirement

The new study compared a high-dose vs low-dose regimen of tranexamic acid during cardiac surgery.

“The high-dose tranexamic acid group received an intravenous bolus of 30 mg/kg after anesthesia induction, then a maintenance dosage of 16 mg/kg/h throughout the operation with a pump prime dose of 2 mg/kg,” researchers said. “The low-dose tranexamic acid group received an intravenous bolus and maintenance regimen of 10 mg/kg and 2 mg/kg/h, with a pump prime dose of 1 mg/kg.”

A smaller proportion of patients in the high-dose group required allogeneic red blood cell transfusion compared to the low-dose group, at 21.8% vs 26.0% of patients, respectively (risk difference [RD], −4.1% [1-sided 97.55% CI, −∞ to −1.1%]; relative risk, 0.84 [1-sided 97.55% CI, −∞ to 0.96; P = .004]). 

With respect to safety, the composite outcome of postoperative seizure, thrombotic events, kidney dysfunction, and death occurred in 265 out of 1525 patients in the high-dose cohort (17.6%) vs 249 out of 1506 patients in the low-dose cohort (16.8%) (RD, 0.8%; 1-sided 97.55% CI, −∞ to 3.9%; P = .003 for noninferiority).

Point 2: Questions Remain

Red blood cell transfusion is an important endpoint. However, there are more robust measures of effective surgical hemostasis.

For example, reoperation for bleeding occurred in 16 patients in the high-dose group (1.0%) vs 21 patients in the low-dose group (1.4%) (risk difference, −0.4% [95% CI, −1.2% to 0.5%; P = .39]; relative risk, 0.75 [95% CI, 0.39-1.43]). This endpoint is a more valuable measure of the benefit of tranexamic acid, and there was no difference between groups. 

I also found the seizure data to be a bit concerning. Fifteen patients in the high-dose group experienced seizures (1.0%), compared to 6 patients in the low-dose group (0.4%) (risk difference, 0.6% [95% CI, −0.0% to 1.2%]; relative risk, 2.47 [95% CI, 0.96-6.35; P = .05]. This difference was nearly statistically significant, indicating that a slightly larger trial may have found a signal for harm.

Given the potentially serious nature of seizures and the relatively mild benefit associated with a lower risk of blood transfusion, the value of a high-dose regimen may not be worth the risk.