Low-Dose Heparin Anticoagulation During Extracorporeal Life Support for Acute Respiratory Distress Syndrome in Conscious Sheep

Abstract

Background:Over 32% of burned battlefield causalities develop trauma-induced hypoxic respiratory failure, also known as acute respiratory distress syndrome (ARDS). Recently, 9 out of 10 US combat soldiers’ survived life-threatening trauma-induced ARDS supported with extracorporeal membrane oxygenation (ECMO), a portable form of cardiopulmonary bypass. Unfortunately, the size, incidence of coagulation complications, and the need for systematic anticoagulation for traditional ECMO devices have prevented widespread use of this lifesaving technology. Therefore, a compact, mobile, ECMO system using minimal anticoagulation may be the solution to reduce ARDS in critically ill military and civilian patients.Methods:We conducted a prospective cohort laboratory investigation to evaluate the coagulation function in an ovine model of oleic acid induced ARDS supported with veno-venous ECMO. The experimental design approximated the time needed to transport from a battlefield setting to an advanced facility and compared bolus versus standard heparin anticoagulation therapy.Results:Comprehensive coagulation and hemostasis assays did not show any difference because of ECMO support over 10 h between the two groups but did show changes because of injury. Platelet count and function did decrease with support on ECMO, but there was no significant bleeding or clot formation during the entire experiment.Conclusions:A bolus heparin injection is sufficient to maintain ECMO support for up to 10 h in an ovine model of ARDS. With a reduced need for systematic anticoagulation, ECMO use for battlefield trauma could reduce significant morbidity and mortality from ventilator-induced lung injury and ARDS. Future studies will investigate the mechanisms and therapies to support patients for longer periods on ECMO without coagulation complications.Level of Evidence:V—therapeutic animal experiment.

Hemorrhage under veno-venous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients: a retrospective data analysis

“…In line with previous studies (23,24), ECMO was applied even in early post-traumatic or surgical patients and a relatively low aPTT of 35-40 was targeted. Lower and or delayed AC was safely used in experimental studies or in trauma patients (24,25). In one reported series of ECMO cases authors did not use any AC for a short time (26), although in one of these patients' multiple thrombus formations were detected in the inferior cava vein.…”

Electron Microscopy as a Tool for Assessment of Anticoagulation Strategies During Extracorporeal Life Support: The Proof Is on the Membrane

“…Our group recently published that ECMO without continuous heparinization could sustain a circuit up to 10 hours. 6 Moreover, several case reports have concluded that is safe to discontinue systemic heparinization in traumatic bleeding patients requiring ECMO. 18 We documented the first SEM analysis of MOs using a trauma-related ARDS ECMO model.…”

“…Based on other studies the change in shear stress applied to blood as it enters the MO activates the clotting cascade facilitating the greatest potential for clots. 6 Both methods achieved the goal of SEM analysis of the PMP fibers, allowing for a more conclusive post-ECMO assessment of the MOs. Although both methods differ in basic approach, we are confident that they are both useful in providing insight into the dynamics of clot formation on MOs.…”

“…In the standard heparin group, H+, a continuous heparin (APP Pharmaceuticals, USA) infusion maintained the ACT between 160 and 180 s after an initial bolus of 150 IU/kg during the dual-lumen catheter insertion. 6,10 In the low heparin group, H −, sheep received only the initial 150 IU/kg heparin bolus during ECMO catheter placement and another heparin bolus during the OA injection (300-900 IU). No continuous heparin administration took place in this group.…”

“…5 Reports in the literature document successful ECLS therapy with reduced or no heparin anticoagulation, and our laboratory have recently documented normal coagulation function in an animal model using low-dose heparin anticoagulation during ECLS for acute respiratory distress syndrome (ARDS). 6 The best way for real-time monitoring of anticoagulation is a challenge, as bedside assays such as activated clotting time (ACT) and thromboelastography (TEG); monitoring of antithrombin, D-dimer, and other functional coagulation parameters; have failed to accurately predict bleeding or clotting complications. 5 Ideally, anticoagulation therapy during ECLS would prevent circuit-related clot and bleeding problems by inhibiting platelet and coagulation factor activation.…”