LEVOSIMENDAN to Facilitate Weaning From ECMO in Severe Cardiogenic Shock Patients
Status:
Recruiting
Trial end date:
2023-11-01
Target enrollment:
Participant gender:
Summary
In the last decade, venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become the
first-line therapy in patients with refractory cardiogenic shock. VA-ECMO provides both
respiratory and cardiac support, is easy to insert, even at the bedside, provides stable flow
rates, and is associated with less organ failure after implantation compared to large
biventricular assist-devices that require open-heart surgery. In patients with potentially
reversible cardiac failure (e.g. myocarditis, myocardial stunning post-myocardial infarction,
post-cardiotomy or post-cardiac arrest), VA-ECMO might be weaned after a few days of support
and used as a bridge to recovery.
Although considered as the ultimate life-saving technology for refractory cardiac failure,
veno-arterial ECMO is still associated with severe complications. Specifically, excessive LV
afterload and lack of LV unloading under VA-ECMO might induce LV stasis with thrombus
formation, pulmonary edema, myocardial ischemia caused by ventricular distension and
ultimately increase mortality. ECMO support also exposes to many complications such as
infections, hemorrhage or peripheral vascular embolism. These complications are more frequent
with prolonged support and are responsible for significant morbidity and mortality, prolonged
ICU and hospital stays and higher costs.
Levosimendan, which acts to sensitize myocardial contractile proteins to calcium, improves
cardiac contractility without increasing the intracellular calcium concentration. Unlike
traditional inotropes such as dobutamine, levosimendan neither increases myocardial oxygen
consumption nor impairs diastolic function or possess proarrhythmic effects. It also
influences the opening of ATP-dependent potassium channels, including those in vascular
smooth muscle cells, leading to coronary, pulmonary, and peripheral vasodilation and
antiinflammatory, antioxidative, antiapoptotic, anti-stunning and cardioprotective effects.
Additionally, Levosimendan which has a long lasting action (up to 7-9 d), resulting from the
formation of active metabolite, may be used as a single 24h perfusion.
In recent preliminary studies, the drug was associated with accelerated weaning from VA-ECMO
and even improved survival. Therefore, a multicenter randomized trial with sufficient
statistical power is needed in refractory cardiogenic shock patients supported by VA-ECMO to
test if the early administration of Levosimendan can facilitate and accelerate VA-ECMO
weaning, and ultimately translate in significantly less morbidity, reduced ICU and hospital
length of stays and associated costs.