Cardiogenic Shock, Heart Failure
Conditions
Keywords
Veno-Arterial ExtraCorporeal Membrane Oxygenation, Betablocker, Esmolol, Cardiogenic shock
Brief summary
In this phase 2, single center, randomized clinical pilot trial, investigators will study the effect of a strategy involving a reduction of beta receptor (BR) stimulation (by decreasing dobutamine dosages) and subsequent BR inhibition (through ultra-short acting betablockers), versus a (routine) strategy with continued BR stimulation through dobutamine infusion, on heart rate in patients with cardiogenic shock due to left- or bi-ventricular failure being supported by V-A ECMO.
Detailed description
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.
Interventions
DRUGEsmolol
A vey cardioselective, short-acting betablocker, with an ultra-short half life time.
Sponsors
Erasmus Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change (delta) in heart rate 24 hours after randomization. | 24 hours after randomization | The average heart rate on basis of all observations during 5 minutes at both time points (t=0 and t=24h). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vasopressor score | at baseline, 24 and 48 hours | using the calculation as described in literature, excluding inotropic medication |
| Occurrence of new onset ventricular and/or atrial arrhythmias after randomization | during the first 48 hours | — |
| Left ventricular outflow tract velocity time integral (LVOT VTI) | at baseline, 24 and 48 hours | Echocardiography parameters |
| Cardiac output | at baseline, 24 and 48 hours | Pulmonary arterial catheter parameter |
| Stroke volume index | at baseline, 24 and 48 hours | Pulmonary arterial catheter parameter |
| Pulmonary capillary wedge pressure | at baseline, 24 and 48 hours | Pulmonary arterial catheter parameter |
| Central venous pressure | at baseline, 24 and 48 hours | Pulmonary arterial catheter parameter |
| Mixed venous oxygen saturation (SvO2) | at baseline, 24 and 48 hours | Pulmonary arterial catheter parameter |
| Lactate level | at baseline, 24 and 48 hours | — |
| Troponin | At 24 and 48 hours after randomization | measured at baseline, 24- and 48- hours after randomization, and Area Under the Curve (AUC) |
| Percentage of patients having received esmolol | after 48 hours | — |
| Plasma NT-proBNP levels | At baseline and 48 hours after randomization | Biomarker for cardiac stretch |
| Plasma Creatine Kinase MB levels | At baseline and 48 hours after randomization | Biomarker for cardiac injury |
| FiO2 suppletion | At 24 and 48 hours after randomization | — |
| Plasma metanephrine levels | At baseline and 24 after randomization | — |
| Plasma normetanephrines levels | At baseline and 24 after randomization | — |
| Maximum median dosages of esmolol | after 48 hours | — |
| Ejection fraction (EF) | at baseline, 24 and 48 hours | Echocardiography parameters |
| Tricuspid annular plane systolic excursion (TAPSE). | at baseline, 24 and 48 hours | Echocardiography parameters |
| Positive End Expiratory Pressure (PEEP) level | At 24 and 48 hours after randomization | — |
| Myocardial oxygen consumption | At 24 and 48 hours after randomization | Estimated by calculating the pressure volume (PV) area on basis of non-invasive PV loop assessments using echocardiography and pulmonary artery catheter measurements |
Countries
Netherlands
Contacts
Primary ContactChristiaan L. Meuwese, MD, PhD
Backup ContactMyrthe PJ van Steenwijk, MD
Outcome results
None listed