Norepinephrine vs Norepinephrine and Dobutamine in Cardiogenic Shock (SHOCK-NORDOB)

Norepinephrine vs Norepinephrine and Dobutamine in Cardiogenic Shock : a Randomised, Opened, Cross-over Study. Heart SHOCK-NORDOB Study

Cardiogenic shock is a frequent cause of admission and death in the intensive care unit. Mortality is about 50%. Once the etiologic treatment has been done, for instance coronary revascularization, management of the shock state is the cornerstone of the treatment. Norepinephrine is the first-line vasopressor therapy because of its minor effect on heart rhythm. Morever norepinephrine is a inotrope. In a previous study, we demonstrated that increasing the norepinephrine dose increases cardiac index, cardiac power index, SVO2 and tissue perfusion without acceleration of heart rate. Nevertheless, dobutamine remains the first-line inotropic treatment. Dobutamine has a positive chronotropic effect that might cause higher myocardial oxygen consumption. As a result, combination of vasopressor / inotrope is still controversial. The aim of this study was to compare hemodynamics and metabolics effects of 2 treatments strategies (norepinephrine dose increasing or addition of dobutamine) in patients with cardiogenic shock and optimised blood pressure level (MAP≥65 mmHg) under norepinephrine treatment. The secondary objectives were : To evaluate the efficacy of the treatments on micro- and macrocirculation parameters To evaluate the tolerance of the treatments To evaluate the dose and the admistration's kinetics of the treatments

3 first hours : strategy 1, norepinephrine alone with increased dose or norepinephrine + dobutamine 0.5 hour : wash-out (decrease of norepinephrine dose or weaning of dobutamine) 3 last hours : strategy 2, crossover, norepinephrine alone with increased dose or norepinephrine + dobutamine

After obtention of a mean arterial pressure (MAP) of 65 mmHg with infusion of norepinephrine, patients with cardiogenic shock receive for 3 hours either increasing doses of norepinephrine (with a maximal MAP of 85 mmHg) or dobutamine. There is a wash-out phase of 30 minutes (decrease of norepinephrine dose or weaning of dobutamine). The third phase of the study is the administration of the comparator treatment during 3 hours. After the 6.5 hours of the study, the hemodynamic management is up to the physician.

Measure of increase of cardiac index > 15% (L/min/m²), increase of organ perfusion assessed by : lactate clearance > 15% (mmoL/L), decrease of mottling (decrease of 2 points of Mottling score), increase of musculaire oxygen saturation measured by NIRS > 15% (rSo2%), increase of urine output > 50% (mL/h), increase of SVcO2 > 15%(%) Evaluation of occurence of side effects : Increase of heart rate > 15% (bpm) , increase of oxygen consumption evaluated by decrease of ratio mean arterial pressure / heart rate > 15% (Buffington ratio). The primary endpoint is defined by the presence of 2 efficacy criterias without any side effects.

Inclusion Criteria: Patients with cardiogenic shock (ischemic, rythmic, valvular) defined : by cardiac index (CI) < 2,2 L/min/m² or CI < 2,5 L/min/m² under vasopressor/inotropic treatment and organ hypoperfusion signs : mottles, capillary refill time , urine output < 0,5 mL/kg/hour during at least one hour ou renal replacement therapy, consciouness impairment, pulmonary oedema, hyperlactatemia (> 2 mmoL/L) Mean arterial pressure > 65 mmHg under norepinephrine treatment Patients with social coverage Exclusion Criteria: < 18 years old Pregnancy Inclusion in other drug study Poisonings with cardiotoxicants Patient with intra-aortic ballon pump, extracorporeal life support Patient under guardianship