Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation

A Pilot Randomized Trial

Cecile Aubron, Zoe McQuilten, Michael Bailey, Jasmine Board, Heidi Buhr, Bruce Cartwright, Mark S. Dennis, Carol L. Hodgson, Paul Forrest, David McIlroy, Deirdre A. Murphy, Lynnette Murray, Vincent Pellegrino, David V. Pilcher, Jayne Sheldrake, Huyen Tran, Shirley Vallance, D. James Cooper, endorsed by the International ECMO Network (ECMONet)

Research output: Contribution to journalArticleResearchpeer-review

Abstract

OBJECTIVES: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. DESIGN: Randomized, controlled, unblinded study. SETTING: Two ICUs of two university hospitals. PATIENTS: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. INTERVENTIONS: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601-16,031 U] vs 20,710 U [95% CI, 15,343-27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5-53.2 s] vs 55.5 s [95% CI, 50.4-61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07-0.18] vs 0.27 [95% CI, 0.17-0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. CONCLUSIONS: Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.

Original languageEnglish
Pages (from-to)e563-e571
Number of pages9
JournalCritical Care Medicine
Volume47
Issue number7
DOIs
Publication statusPublished - 1 Jul 2019

Cite this

Aubron, Cecile ; McQuilten, Zoe ; Bailey, Michael ; Board, Jasmine ; Buhr, Heidi ; Cartwright, Bruce ; Dennis, Mark S. ; Hodgson, Carol L. ; Forrest, Paul ; McIlroy, David ; Murphy, Deirdre A. ; Murray, Lynnette ; Pellegrino, Vincent ; Pilcher, David V. ; Sheldrake, Jayne ; Tran, Huyen ; Vallance, Shirley ; Cooper, D. James ; endorsed by the International ECMO Network (ECMONet). / Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation : A Pilot Randomized Trial. In: Critical Care Medicine. 2019 ; Vol. 47, No. 7. pp. e563-e571.
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title = "Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation: A Pilot Randomized Trial",
abstract = "OBJECTIVES: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. DESIGN: Randomized, controlled, unblinded study. SETTING: Two ICUs of two university hospitals. PATIENTS: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. INTERVENTIONS: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95{\%} CI, 8,601-16,031 U] vs 20,710 U [95{\%} CI, 15,343-27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95{\%} CI, 43.5-53.2 s] vs 55.5 s [95{\%} CI, 50.4-61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95{\%} CI, 0.07-0.18] vs 0.27 [95{\%} CI, 0.17-0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. CONCLUSIONS: Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.",
author = "Cecile Aubron and Zoe McQuilten and Michael Bailey and Jasmine Board and Heidi Buhr and Bruce Cartwright and Dennis, {Mark S.} and Hodgson, {Carol L.} and Paul Forrest and David McIlroy and Murphy, {Deirdre A.} and Lynnette Murray and Vincent Pellegrino and Pilcher, {David V.} and Jayne Sheldrake and Huyen Tran and Shirley Vallance and Cooper, {D. James} and {endorsed by the International ECMO Network (ECMONet)}",
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Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation : A Pilot Randomized Trial. / Aubron, Cecile; McQuilten, Zoe; Bailey, Michael; Board, Jasmine; Buhr, Heidi; Cartwright, Bruce; Dennis, Mark S.; Hodgson, Carol L.; Forrest, Paul; McIlroy, David; Murphy, Deirdre A.; Murray, Lynnette; Pellegrino, Vincent; Pilcher, David V.; Sheldrake, Jayne; Tran, Huyen; Vallance, Shirley; Cooper, D. James; endorsed by the International ECMO Network (ECMONet).

In: Critical Care Medicine, Vol. 47, No. 7, 01.07.2019, p. e563-e571.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation

T2 - A Pilot Randomized Trial

AU - Aubron, Cecile

AU - McQuilten, Zoe

AU - Bailey, Michael

AU - Board, Jasmine

AU - Buhr, Heidi

AU - Cartwright, Bruce

AU - Dennis, Mark S.

AU - Hodgson, Carol L.

AU - Forrest, Paul

AU - McIlroy, David

AU - Murphy, Deirdre A.

AU - Murray, Lynnette

AU - Pellegrino, Vincent

AU - Pilcher, David V.

AU - Sheldrake, Jayne

AU - Tran, Huyen

AU - Vallance, Shirley

AU - Cooper, D. James

AU - endorsed by the International ECMO Network (ECMONet)

PY - 2019/7/1

Y1 - 2019/7/1

N2 - OBJECTIVES: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. DESIGN: Randomized, controlled, unblinded study. SETTING: Two ICUs of two university hospitals. PATIENTS: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. INTERVENTIONS: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601-16,031 U] vs 20,710 U [95% CI, 15,343-27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5-53.2 s] vs 55.5 s [95% CI, 50.4-61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07-0.18] vs 0.27 [95% CI, 0.17-0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. CONCLUSIONS: Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.

AB - OBJECTIVES: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. DESIGN: Randomized, controlled, unblinded study. SETTING: Two ICUs of two university hospitals. PATIENTS: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. INTERVENTIONS: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601-16,031 U] vs 20,710 U [95% CI, 15,343-27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5-53.2 s] vs 55.5 s [95% CI, 50.4-61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07-0.18] vs 0.27 [95% CI, 0.17-0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. CONCLUSIONS: Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.

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DO - 10.1097/CCM.0000000000003780

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JO - Critical Care Medicine

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