Objectives: Supplementation of antithrombin might decrease the amount of heparin needed to achieve a given anticoagulation target during extracorporeal membrane oxygenation. However, exogenous antithrombin itself may increase the risk of bleeding. We conceived a study to evaluate the effect of antithrombin supplementation in adult patients requiring venovenous extracorporeal membrane oxygenation for respiratory failure on heparin dose, adequacy of anticoagulation, and safety. Design: Prospective randomized controlled trial. Setting: ICUs of two Italian referral extracorporeal membrane oxygenation centers. Patients: Adult patients requiring venovenous extracorporeal membrane oxygenation for severe respiratory failure and unfractionated heparin for systemic anticoagulation. Interventions: Before extracorporeal membrane oxygenation start, patients were randomized to either receive antithrombin concentrate to maintain a plasmatic level 80-120% (treatment) or not (control) during the extracorporeal membrane oxygenation course. Measurements and Main Results: The primary outcome was the total amount of heparin required to maintain activated partial thromboplastin time ratio 1.5-2. Secondary outcomes were anti-factor Xa, the incidence of hemorrhagic and thrombotic events, and the amount of blood products transfused. Twenty-four patients in the treatment group and 24 in the control group were included in the intention-to-treat analysis. Antithrombin was 109.5% (93.0-123.0%) in the treatment group and 84.0% (68.5-98.0%) in the control group (p= 0.001). Supplementation of antithrombin did not decrease heparin dose (13.5 international units/kg/hr [9.6-17.9 international units/kg/hr] vs 15.1 international units/kg/hr [10.7-18.3 international units/kg/hr] in the treatment and control group, respectively;p= 0.33) and anti-Factor Xa levels (0.4 international units/mL [0.3-0.5 international units/mL] vs 0.3 international units/mL [0.2-0.5 international units/mL] in the treatment group and control group respectively;p= 0.65). Bleeding, blood product transfusions, and thrombosis were not different in the two groups. Conclusions: Antithrombin supplementation may not decrease heparin requirement nor diminish the incidence of bleeding and/or thrombosis in adult patients on venovenous extracorporeal membrane oxygenation.

A Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation / M. Panigada, A. Cucino, E. Spinelli, G. Occhipinti, G. Panarello, C. Novembrino, D. Consonni, A. Protti, A. Lissoni, A. Arcadipane, A. Pesenti, G. Grasselli. - In: CRITICAL CARE MEDICINE. - ISSN 0090-3493. - 48:11(2020), pp. 1636-1644. [10.1097/CCM.0000000000004590]

A Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation

A. Cucino;A. Pesenti;G. Grasselli
2020

Abstract

Objectives: Supplementation of antithrombin might decrease the amount of heparin needed to achieve a given anticoagulation target during extracorporeal membrane oxygenation. However, exogenous antithrombin itself may increase the risk of bleeding. We conceived a study to evaluate the effect of antithrombin supplementation in adult patients requiring venovenous extracorporeal membrane oxygenation for respiratory failure on heparin dose, adequacy of anticoagulation, and safety. Design: Prospective randomized controlled trial. Setting: ICUs of two Italian referral extracorporeal membrane oxygenation centers. Patients: Adult patients requiring venovenous extracorporeal membrane oxygenation for severe respiratory failure and unfractionated heparin for systemic anticoagulation. Interventions: Before extracorporeal membrane oxygenation start, patients were randomized to either receive antithrombin concentrate to maintain a plasmatic level 80-120% (treatment) or not (control) during the extracorporeal membrane oxygenation course. Measurements and Main Results: The primary outcome was the total amount of heparin required to maintain activated partial thromboplastin time ratio 1.5-2. Secondary outcomes were anti-factor Xa, the incidence of hemorrhagic and thrombotic events, and the amount of blood products transfused. Twenty-four patients in the treatment group and 24 in the control group were included in the intention-to-treat analysis. Antithrombin was 109.5% (93.0-123.0%) in the treatment group and 84.0% (68.5-98.0%) in the control group (p= 0.001). Supplementation of antithrombin did not decrease heparin dose (13.5 international units/kg/hr [9.6-17.9 international units/kg/hr] vs 15.1 international units/kg/hr [10.7-18.3 international units/kg/hr] in the treatment and control group, respectively;p= 0.33) and anti-Factor Xa levels (0.4 international units/mL [0.3-0.5 international units/mL] vs 0.3 international units/mL [0.2-0.5 international units/mL] in the treatment group and control group respectively;p= 0.65). Bleeding, blood product transfusions, and thrombosis were not different in the two groups. Conclusions: Antithrombin supplementation may not decrease heparin requirement nor diminish the incidence of bleeding and/or thrombosis in adult patients on venovenous extracorporeal membrane oxygenation.
acute respiratory distress syndrome; antithrombin; coagulation; extracorporeal membrane oxygenation; hemorrhage; thrombosis
Settore MED/41 - Anestesiologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/773233
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