Effectiveness of local anticoagulation of the ECMO oxygenator during flow reduction trial in patients on V-A ECMO: a prospective observational cohort study

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is a support modus
for patients with severe cardiogenic shock to maintain systemic haemodynamics
and oxygenation/ventilation. It is applied in patients with cardiogenic shock,
i.e. after large myocardial infarction, after complicated open heart surgery,
or to restore circulation in refractory cardiac arrest. The V-A ECMO system
consists of a multi-hole venous cannula, connected to a pump achieving a flow
of 4-5 l/min, which pumps the blood through a membrane where oxygenation and
CO2 removal takes place, after which it is reinfused though an arterial cannula
(usually a retrograde cannula in the femoral artery). An antegrade (smaller)
leg cannula is in place to provide oxygenated blood to the leg, to prevent
ischaemia due to (partial) occlusion of the femoral artery by the retrograde
cannula. Patients are on intravenous heparin to prevent clot formation in the
oxygenator and cannulas. To improve efficiency of heparin to prevent oxygenator
clot formation, in the Erasmus MC, heparin is given directly before the
oxygenator.
ECMO is a temporary support measure, aiming to bridge the patient to cardiac
recovery or long term mechanical support. It is important to decide as early as
possible if the patient can be weaned from ECMO support, since ECMO puts
patients at risk for serious complications (bleeding, CVA, vascular
complications). The decision to remove the ECMO is based on improvement of
organ function and the result of a flow reduction trial.
In this flow reduction trial, the ECMO flow is reduced in steps to minimal
support (<1 l/min), while monitoring haemodynamic and echocardiographic
parameters. However, with low flow, the risk of clot formation is increased and
flow < 1l/min can therefore only can be maintained for a short period,
hampering assessment of organ function in this very short period.
During low ECMO blood flow in a weaning trial, heparin administration is
increased by a factor 2-3 by increasing the perfusor speed. As this higher
heparin administration is only maintained for 30 min, we assume that systemic
effects of this small extra amount of heparin are neglectable. However, since
the heparin is connected straight to the oxygenator, and the flow through the
oxygenator is reduced at the same time, the ratio of heparin to blood flow
increases, thereby probably increasing locoregional anticoagulation in the
oxygenator.

In this prospective observational study, the effects of our anticoagulation
strategy during flow reduction trials will be studied. The results may help in
performing safe flow reduction trials of adequate length, to be able to better
decide whether the ECMO can be removed safely in the individual patient.
Furthermore, most hospitals do not infuse their heparin close to the
oxygenator, so if our results indicate local intense anticoagulation without
systemic effects, this of interest for the care for patients on V-A ECMO in
general, especially for patients with a tendency for bleeding where systemic
over-anticoagulation needs to be avoided.

Primary Objective:
The aim of this observational study is to evaluate the increase in APTT in the
oxygenator at the end of a flow reduction trial when heparin infusion rate has
been increased during the trial.

Secondary Objective(s):
The secondary aim is to evaluate the change in systemic APTT, and the change in
aXa and Intem CT- Heptem CT (ROTEM) systemically and in the oxygenator after a
flow reduction trial when heparin infusion has been increased during the trial.

This is a prospective observational cohort study. In the Erasmus MC, the above
described procedure of connecting heparin to the oxygenator is standardized per
local protocol. As well, increasing the speed of heparin infusion during a flow
reduction trial is routine care.
Flow reduction trials will be performed when indicated according to hospital
protocol, i.e. as soon as organ function has stabilized and improvement in
cardiac function has been noted.
Before starting the flow reduction trial, blood samples will be taken from the
arterial line and ECMO circuit for the above mentioned coagulation parameters.
After this the heparin infusion rate will be doubled/tripled and the
flow-reduction trial will be performed. At the end of the flow reduction trial
the blood test will be repeated (and ECMO flow and heparin dose will be set
back to baseline values)
In the first 8 patients the heparin infusion rate will be doubles. If indeed
there is no/limited change in APTT (<10s increase), the heparin infusion rate
will be tripled in the consecutive 8 patients.

The burden and risk for the patient is minimal, since normal care will be
delivered, including standardised flow reduction trials. The only study related
procedures are obtaining blood samples,using acces points that are already in
place in this patient category.
There is no benefit for the individual patient, there is potential benefit for
patients supported in V-A ECMO, since performing this study adds on our
knowledge of safely performing flow reduction trials.