Effect of Peripheral VA-ECMO Flow Variations on the Pulmonary Arterial Occlusion Pressure (PAPO) in Patients With Refractory Cardiogenic Shock.

Cardiogenic shock is the most severe form of heart failure. It is characterized by acute and profound myocardial contractile dysfunction, leading to a severe decrease in cardiac index (<2.2 L/min) associated with signs of peripheral hypoperfusion. In its most severe forms, the impairment of cardiac contractile function is associated with an intense systemic inflammatory response syndrome (SIRS), leading to multiorgan failure and patient death. The mortality rate for patients in this situation is very high, approaching 50%.

Over the last decades, mechanical circulatory support techniques have gained interest, and their use in patients with cardiogenic shock refractory to medical treatments has significantly increased worldwide. Peripheral Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is the main temporary cardiac support technique used to maintain sufficient blood perfusion to the organs while awaiting myocardial recovery or heart transplantation. Its principle involves draining venous blood near the right atrium through a cannula inserted percutaneously or surgically into the patient's femoral vein. The venous blood is then reinfused after extracorporeal oxygenation into the descending aorta, countering the natural blood flow, via another cannula inserted into the femoral artery.

It has been postulated that the retrograde blood reinfusion by ECMO could increase cardiac afterload, enhance cardiac workload, and consequently reduce its own perfusion and recovery capabilities. Additionally, it has been suggested that, through this same effect, Pulmonary Artery Occlusion Pressure (PAOP) could rise, leading to acute pulmonary edema (APE), found in 30% of patients under peripheral ECMO. This, in turn, worsens the patient's tissue oxygenation and, ultimately, prognosis. According to this principle, this effect would amplify as the ECMO flow, set by the clinician, increases.

Several authors have written about this phenomenon, considering these hypothetical physiological considerations. However, to date, no prospective study has confirmed that the sequential increase in ECMO flow leads to a correlated elevation in PAOP in patients placed under peripheral VA-ECMO for refractory cardiogenic shock. Moreover, several factors may oppose this principle.

Firstly, as VA-ECMO retrogradely injects blood into the aorta via the arterial route, it simultaneously unloads the right cardiac chambers by an equivalent amount (in liters/minute) and reduces cardiac preload. Consequently, the filling of the left cardiac chambers and the left ventricular end-diastolic volume, both determinants of PAOP, are diminished. Secondly, arterial reinfusion by peripheral ECMO occurs more than 30 cm from the aortic valve, and its effect on cardiac afterload may be minimal, especially in patients with residual cardiac ejection. Finally, patients in cardiogenic shock under ECMO often present severe circulatory insufficiency, leading to significant volume expansion. They may have a markedly positive sodium-water balance, which alone could explain the elevation of PAOP and the occurrence of APE independently of the ECMO effect.

Thus, to date, the investigators do not have enough scientific evidence to certify that the variation in peripheral VA-ECMO flow alone induces an increase in PAOP in patients with refractory cardiogenic shock under peripheral VA-ECMO It is with the aim of addressing this question that the investigators are considering the PAPO-Flow study.

All eligible patients from the medical intensive care unit of the Pitié-Salpêtrière Hospital Group will be included after verification of inclusion and exclusion criteria by the investigator, explanation of the study, and provision of the information sheet. After allowing the patient a necessary reflection period to make their decision, written and voluntary consent will be obtained. If the patient is not able to understand the information or express written consent at the time of inclusion, information and consent will be obtained from their relative. Emergency inclusion will be possible if the patient is unable to understand the information or express consent, and if contacting a relative is not possible at the time of patient inclusion. Patient information and consent collection to continue participation will be sought as soon as their condition allows.

Patient demographic data, clinical data including medical history, vital signs, fluid and sodium balance, and administered treatments will be collected at the time of patient inclusion.

The protocol unfolds in 5 steps as follows, each step lasting between 10 and 15 minutes to allow for the patient's hemodynamic adaptation. At each step, invasive and non-invasive hemodynamic evaluation is performed.

1. The 1st step is called "100% flow": it involves recording the patient's hemodynamic measurements at the baseline, i.e., at 100% of their ECMO-VA flow, previously set by the clinician entirely independently of the study.
2. The 2nd step is called "125% flow": the patient's ECMO-VA flow is increased to 125% of the initial flow.
3. The 3rd step is called "150% flow": the patient's ECMO-VA flow is increased to 150% of the initial flow.
4. The 4th step is called "175% flow": the patient's ECMO-VA flow is increased to 175% of the initial flow.
5. The 5th and final step is called "200% flow": the patient's ECMO-VA flow is increased to 200% of the initial flow.

At the end of the protocol, the ECMO flow is returned to its initial value (100%) without posing any risk to the patient.

At each step of the protocol, hemodynamic tolerance is assessed through continuous monitoring of vital signs on the patient's scope by the study investigators. The protocol is interrupted in case of poor patient tolerance, and the ECMO-VA flow is immediately returned to its initial value. The patient then continues their follow-up as planned.