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