A Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation.

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.

• Authors: Mauro Panigada, Alberto Cucino, Elena Spinelli, Giovanna Occhipinti, Giovanna Panarello, Cristina Novembrino, Dario Consonni, Alessandro Protti, Alfredo Lissoni, Antonio Arcadipane, Antonio Pesenti, Giacomo Grasselli
• Journal: Critical care medicine (Crit Care Med) Vol. 48 Issue 11 Pg. 1636-1644 (11 2020) ISSN: 1530-0293 [Electronic] United States
• PMID: 32947474 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Antithrombins
• Heparin

Topics

• Anticoagulants (administration & dosage, therapeutic use)
• Antithrombins (blood, therapeutic use)
• Extracorporeal Membrane Oxygenation (methods)
• Female
• Heparin (administration & dosage, therapeutic use)
• Humans
• Intensive Care Units
• Male
• Middle Aged
• Respiratory Insufficiency (therapy)