Dose for Reversal of Heparin After Cardiopulmonary Bypass

Официальное название

Lower Protamine Dose for Reversal of Heparin After Cardiopulmonary Bypass: Is it Safe? Comparative Prospective Randomized Trial.

Обзор

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. 

Подробное описание

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.

Вмешательства

• Препарат Protamine sulfate
  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.

Первичные конечные точки

• Post-protamine Activated Clotting Time (ACT) [Срок оценки: 5 minutes after protamine administration]

Вторичные конечные точки (5)

• Need for additional protamine administration [Срок оценки: 5 minutes after initial protamine administration]
• Postoperative chest tube drainage [Срок оценки: Within 24 hours after surgery]
• Blood transfusion requirements [Срок оценки: Within 24 hours after surgery]
• Protamine-related adverse events [Срок оценки: From protamine administration until 24 hours after surgery]
• Re-exploration for bleeding [Срок оценки: Within 24 hours after surgery]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Sohag University Hospital — Sohag

Идентификаторы

NCT: NCT07477977 · Soh-Med-26-1-5PD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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