REMAP ECMO - Beta Receptor Modulation Trial

Despite the great benefits of Venoarterial ExtraCorporeal Membrane Oxygenation (V-A ECMO) and its rapidly increasing usage, even today, 30 till 70 percent of patients cannot be weaned from ECMO support and up to 50 percent of patients will eventually die in the first year. These high incidences of mortality and failure to wean from V-A ECMO support seem largely attributable to failure of the heart to recover in the context of inotropic drug administration and high sympathetic drive due to severe illness (further stressing an already failing heart). As V-A ECMO support creates a "safety window" where organ perfusion no longer relies on native cardiac output, therapeutic focus could be shifted to cardioprotective treatments. Cardioprotective treatments typically include beta blockers (BB) which have unequivocally shown benefits on mortality and morbidity in other patient categories with heart failure with reduced ejection fraction (HFrEF).

The investigators hypothesize that, in selected patients with cardiogenic shock undergoing V-A ECMO support, application of BBs is feasible and safe, and can effectively reduce heart rate.

Inclusion criteria

• Age ≥ 18 years,
• Having received V-A ECMO support for severe circulatory insufficiency due to left- or bi-ventricular failure.
• ≤ 16 hours after initiation of V-A ECMO support
• Receiving ≥ 2 mcg/kg/min of dobutamine.
• Norepinephrine infusion ≤ 0.4 mcg/kg/min
• Heart rate ≥ 80 bpm (being sinus rhythm, atrial fibrillation or atrial flutter) after V-A ECMO initiation

Exclusion criteria

• Objection during the deferred consent procedure
• V-A ECMO usage confined to the period during surgery or another intervention (the ECMO was removed at the end of the intervention).
• Concomitant durable Left Ventricular Assist Device (LVAD)
• Polymorphic ventricular tachycardia necessitating BB therapy
• Isolated right ventricular failure (e.g. due to pulmonary embolism)
• Need of high dose dobutamine > 6.0 mcg/kg/min
• Epinephrine infusion
• Signs of insufficient trans cardiac flow:

• Absence of aortic valve opening
• Pulse pressure <10 mmHg (with intra-aortic balloon pump (IABP) standby)
• Spontaneous contrast in the heart at echocardiography
• Contraindications for-, intolerance to- or allergy to esmolol
• Second- or third- degree AV block
• Pregnancy
• Life expectancy of less than 24 hours
• Participation in another randomized clinical trial (e.g. On Scene trial or Left Ventricular unloading trial)
• Inability to start study treatment within 4 hours after randomization
• Post heart transplantation patients