In Vivo Protamine Titration Using Activated Coagulation Time to Neutralize Heparin Anticoagulation in Cardiac Surgery: Proof of Concept

Abstract

Objective: In vivo protamine titration (IVPT) is based on the observation of a plateau on the decay curve of the celite activated clotting times (ACTs) during protamine infusion for heparin reversal. The aim of the present study was to determine the optimal protamine/heparin ratio to reverse anticoagulation using IVPT curves.

Design: Prospective, randomized study.

Setting: Tertiary care university hospital.

Participants: The study comprised 138 patients undergoing elective cardiac surgery requiring cardiopulmonary bypass.

Interventions: The control group was given a protamine infusion of 1.3 mg per 1 mg (100 U) of heparin over 21 minutes. ACT was measured every 3 minutes. In the test group, the protamine dose was prepared using the same ratio as for the control group, and ACT values were measured every 3 minutes until a plateau was reached (2 consecutive ACT values <160 s), at which time the protamine infusion was stopped. The protamine/heparin ratio, blood losses, transfusions, and heparin concentrations were recorded.

Results: The protamine dose was lower in the test group (456.00 ± 105.66 mg [control group] v 295.25 ± 100.60 mg [test group]; p < 0.0001). The mean protamine/heparin ratios were 1.30 ± 0.10 (control group) and 0.81 ± 0.22 (test group) (p < 0.0001). Heparin concentrations were greater in the test group 15 minutes (0.10 [0-0.2] U/mL v 0 [0-0.1] U/mL; p = < 0.0001) and 3 hours (0 [0-0.1] U/mL v 0 [0-0] U/mL; p = 0.0002) after protamine infusion. There was no difference in the blood losses and transfusion requirements.

Conclusions: IVPT is safe and efficient in this low-risk population.

Keywords: cardiac surgery; heparin reversal; protamine.