Comparison of Landiolol Versus Standard of Care for Prevention of Mortality in Patients Hospitalized for a Septic Shock With Hypercontractility
Comparison of Landiolol Versus Standard of Care for Prevention of Mortality in Patients Hospitalized for a Septic Shock With Hypercontractility
Several data emphasize the relation between tachycardia (>90/min) and high mortality during
 septic shock. The investigators previously demonstrated the high mortality associated with
 hypercontractility, tachycardia and the presence of a left ventricular obstruction. A severe
 hypovolemia, a hyper adrenergic stimulation or a severe vasoplegia can all explain this
 relation between tachycardia, hypercontractility and the mortality during septic shock.

 Landiolol is another short-term acting beta-blocker with a half-life of 4 minutes without any
 beta 2 activity or membrane stabilizing effect. The landiolol has been used in critically ill
 patients to control supraventricular tachycardia but not in this context of tachycardia and
 septic shock. The investigators hypothesize that landiolol by reducing the heart rate may
 improve the survival of patients treated for a septic shock and presenting with an
 hypercontractility state.
Inclusion Criteria:

 -  Age ≥ 18 years old

 -  Patient admitted for a septic shock (according to the SEPSIS3 definition: sepsis with
 persisting hypotension (MAP<65mmHg or SAP <90mmHg) requiring vasopressors to maintain
 MAP>65mmHg and having a serum lactate level >2 mmol/L

 -  Patient who received at least 30ml/kg of fluid and absence of fluid responsiveness

 -  Left ventricular ejection fraction >65% (visual or Simpson method using
 echocardiography)

 -  Tachycardia >100 bpm in sinus rhythm with a MAP 65mmHg for more than 1 hour

 -  Patient receiving invasive mechanical ventilation

 -  Patients adapted to the ventilator under sedation and analgesia

 -  Written informed consent

 -  Patient covered by French national health insurance

 Exclusion Criteria:

 -  Patients with inclusion criteria already present for more than 36 hours

 -  Patient treated with Dobutamine, adrenaline or isoprenaline

 -  Patient currently treated with beta blockers (previous home betablocker treatment is
 not an exclusion criteria)

 -  Supra ventricular (atrial fibrillation or flutter) or ventricular arrhythmias

 -  Patients with any form of cardiac pacing

 -  Sick sinus syndrome

 -  Severe atrioventricular (AV) nodal conductance disorders (without pacemaker): 2nd or
 3rd degree AV block

 -  Known pulmonary hypertension

 -  ScVO2 <70%

 -  Moribund

 -  Cardiac arrest

 -  Non-treated phaeochromocytoma

 -  Acute asthmatic attack

 -  Pregnant or breastfeeding woman

 -  Patient deprived of liberty by administrative or judicial decision or placed under
 judicial protection (guardianship or supervision),

 -  Age <18 years

 -  Hypersensitivity to the active substance or to any of the excipients

 -  Severe bradycardia (less than 50 beats per minute)

 -  Cardiogenic shock

 -  Severe hypotension

 -  Decompensated heart failure when considered not related to the arrhythmia

 -  Severe, uncorrectable metabolic acidosis

 -  Presence of significant bleeding, or

 -  Acute respiratory distress defined by increased oxygen dependency, polypnea > 30 /min,
 signs of struggle (pulling, thoraco-abdominal sway) if the patient is not intubated
 and ventilated.