Open Heart Surgery
Conditions
Keywords
Protamine, Heparin, Activated clotting time, Postoperative bleeding, Cardiac surgery
Brief summary
Protamine sulfate is routinely used to reverse heparin anticoagulation after cardiopulmonary bypass (CPB). The conventional dosing strategy of 1 mg protamine per 100 IU of heparin may result in excess protamine exposure, which has been associated with anticoagulant effects, platelet dysfunction, and hemodynamic instability. Recent evidence suggests that lower protamine doses may provide adequate heparin reversal while reducing potential adverse effects.  This multicenter, prospective, randomized, double-blind, controlled trial aims to compare three protamine-to-heparin dosing ratios (1:1, 0.8:1, and 0.75:1) in adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. The primary outcome is activated clotting time (ACT) measured 5 minutes after protamine administration. Secondary outcomes include the need for additional protamine administration, protamine-related adverse events, postoperative bleeding, blood product transfusion requirements, and length of intensive care unit stay.  The results of this study may help determine whether reduced protamine dosing can safely achieve effective heparin reversal while minimizing drug exposure and potential complications after cardiopulmonary bypass. 
Detailed description
Heparin is routinely administered during cardiopulmonary bypass (CPB) to prevent clot formation in the extracorporeal circuit. At the end of CPB, protamine sulfate is used to neutralize the anticoagulant effect of heparin. The conventional protamine dosing strategy is 1 mg of protamine for every 100 IU of the initial heparin dose administered. However, emerging evidence suggests that this standard dosing regimen may result in excessive protamine exposure, which has been associated with adverse effects such as hypotension, pulmonary hypertension, platelet dysfunction, and paradoxical anticoagulation. Recent studies have suggested that reduced protamine dosing strategies may achieve adequate reversal of heparin anticoagulation while minimizing potential complications associated with protamine administration. However, the optimal protamine-to-heparin ratio remains uncertain. This randomized clinical study aims to compare different protamine dosing strategies for heparin reversal after cardiopulmonary bypass in adult patients undergoing cardiac surgery. Participants will be randomized to receive one of three protamine dosing regimens based on the initial heparin dose administered during CPB: the conventional 1:1 ratio (1 mg protamine per 100 IU heparin), a reduced dose ratio of 0.8:1, or a further reduced ratio of 0.75:1. The study will evaluate the effectiveness of these dosing strategies in achieving adequate heparin reversal as measured by activated clotting time (ACT), as well as clinical outcomes including the need for additional protamine administration, postoperative bleeding, transfusion requirements, protamine-related adverse events, re-exploration for bleeding, and duration of intensive care unit stay.
Interventions
Protamine sulfate will be administered intravenously for reversal of heparin anticoagulation after cardiopulmonary bypass. The dose will be calculated according to the randomized study group based on the initial heparin dose administered during cardiopulmonary bypass.
Sponsors
Sohag University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Protamine doses will be prepared by an unblinded perfusionist or pharmacist in indistinguishable syringes according to the randomized allocation. The surgical, anesthesia, and intensive care teams, as well as patients and outcome assessors, will remain blinded to group assignment.
Intervention model description
Participants undergoing elective cardiac surgery with cardiopulmonary bypass will be randomized in a 1:1:1 allocation to receive one of three protamine-to-heparin dosing ratios (1:1, 0.8:1, or 0.75:1) at the termination of cardiopulmonary bypass.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Patients scheduled for elective cardiac surgery requiring cardiopulmonary bypass (CABG, valve surgery, or combined procedures) * Patients receiving systemic heparinization according to the institutional cardiopulmonary bypass protocol * Ability to provide written informed consent before surgery
Exclusion criteria
* Known allergy or hypersensitivity to protamine * Pre-existing coagulopathy or bleeding disorders * Patients receiving chronic anticoagulation that cannot be safely discontinued before surgery * Severe renal dysfunction * Severe hepatic dysfunction * Emergency cardiac surgery * Pregnancy * Off-pump cardiac surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-protamine Activated Clotting Time (ACT) | 5 minutes after protamine administration | Activated clotting time measured 5 minutes after completion of protamine administration to assess adequacy of heparin reversal after cardiopulmonary bypass. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Need for additional protamine administration | 5 minutes after initial protamine administration | Requirement for additional protamine if activated clotting time exceeds 130 seconds after initial protamine administration. |
| Postoperative chest tube drainage | Within 24 hours after surgery | Total volume of chest tube drainage measured during the first 24 hours after cardiac surgery. |
| Blood transfusion requirements | Within 24 hours after surgery | Total number of blood product units (red blood cells, fresh frozen plasma, platelets, or cryoprecipitate) transfused within the first 24 hours after surgery. |
| Protamine-related adverse events | From protamine administration until 24 hours after surgery | Incidence of protamine-related adverse events including hypotension requiring vasopressors, allergic reactions, or anaphylaxis. |
| Re-exploration for bleeding | Within 24 hours after surgery | Need for surgical re-exploration due to postoperative bleeding. |
Countries
Egypt
Contacts
CONTACTAsmaa S Farghaly, MD
PRINCIPAL_INVESTIGATORAsmaa S Farghaly, MD
Faculty of Medicine, Sohag University
Outcome results
None listed