Cardiac Surgery: In Vivo Titration of Protamine

University of Montreal

Status: Completed

Conditions: Bleeding

Treatments: Procedure: Titration protamine; Drug: Standard administration of protamine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00684450

ICM 07-997

Details and patient eligibility

About

Safe use of cardiopulmonary bypass (CPB) requires massive doses of intravenous unfractionated heparin. At end-CPB, residual heparin is neutralized with intravenous injection of protamine sulfate. This prospective, randomized, controlled study will be conducted in 82 voluntary subjects admitted for elective, first intention, cardiac surgery requiring cardiopulmonary bypass. Each will be randomly assigned to one of two groups. The control group will be submitted to a standard protamine infusion of 1.3mg :100U of the total heparin dose given during bypass. The test group will receive an infusion of protamine (over 15 minutes) until activated clotting time (ACT) values (determined every 3 minutes) depict a plateau, sign that the optimal protamine to heparin ratio has been attained. The investigators hypothesize this new in vivo titration method to be as efficient as the standard protocol (adequacy of heparin neutralization, % heparin rebound, bleeding, and transfusion), and potentially safer by its ability to prevent protamine overdose and its deleterious impact on platelet function.15

Principal Objective

Evaluate a new in vivo method of titration of protamine sulfate.

Secondary Objective

Evaluate the impact of this method on the adequacy of heparin neutralization by measuring:

1. platelet count
2. postoperative bleeding
3. transfusion exposure a
4. incidence of heparin rebound

Full description

Protamine sulfate is administered to reverse the anticoagulant effects of heparin upon completion of cardiopulmonary bypass (CPB). In most cases, protamine is given in amounts sufficient to neutralize the total dose of heparin.9 This dose is usually calculated with a ratio of 1.3mg protamine for every 100U heparin given.10 In the literature, reported doses of intraoperatively administered protamine range from 0 to 8mg per 100U of heparin. Given in excess, protamine can, in addition to complement activation and hemodynamic instability,11 induce platelet dysfunctions.12-16 The latter significantly increases both the cost and morbidity of cardiac interventions as it is one of the main causes of postoperative bleeding. The optimal protamine/heparin ratio is difficult to individualize for each patient because of the great interpatient variability in heparin's metabolism4-7 and of the absence of correlation between ACT and heparin's plasma concentration.8 Consumption of heparin may vary from 0.01 to 3.86U/Kg per minute during CPB.30 The exact concentration of remaining circulating heparin at the end of bypass is not easily obtained.

Enrollment: 138 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• First intention, elective, cardiac surgery: either Coronary Artery Bypass Graft (CABG)or valve repair/replacement.
• Patients on preoperative aspirin, clopidogrel or heparin will be included.

Exclusion criteria

• Combination of CABG and valve surgery
• Second intention cardiac surgery
• ASA 5 patients
• Pre-existing hemostatic disorder (as evidenced by history)
• Pregnancy
• PLavix < 5 days before de surgery

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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138 participants in 2 patient groups

1

Active Comparator group

Description:

in vivo protamine titration in cardiac surgery. The titration is done during administration of protamine each 3 minutes to reach 2 consecutive ACT defined as 2 similar ACT values, within 10% variability, and ACT ≤ to 160 seconds. .The protamine is stopped when this values are obtain. Follow-up is done 15 minutes and 3 hours post-protamine

Treatment:

Procedure: Titration protamine

2

Active Comparator group

Description:

standard protamine administration ACT is done during administration of protamine each 3 minutes the values are recorded but the totality of protamine is given. Follow-up is done 15 minutes and 3 hours post-protamine

Treatment:

Drug: Standard administration of protamine