Evaluation of the Effect of Dexmedetomidine on Phenylephrine Response During Refractory Septic Shock

Inclusion Criteria:

• Age ≥ 18 years old
• Septic shock, defined by the "Sepsis-3" criteria
• proven or suspected infection, with modification of the SOFA score ≥ 2 points,
• with persistent hypotension requiring vasopressors to maintain MAP ≥ 65 mmHg
• and a serum lactate level > 2 mmol/L despite adequate vascular filling
• Adequate vascular filling: ≥ 30ml/kg, OR absence of preload-dependency criteria attime of assessment (respiratory variability of the inferior vena cava, passive leglift, pulsed pressure variation)
• Catecholamine resistance, defined by the need for a dose of norepinephrine ≥ 0,5 µg/kg/min for more than 2 consecutive hours within 24 hours of admission to intensivecare unit
• persistence of circulatory failure with at least one of the following criteria presentin the 2 hours prior to randomisation: hyperlactatemia > 2mmol/l, and/or mottling (≥ 1score), and/or oliguria (diuresis < 0,5 ml/kg/h over the last 2 hours)
• Invasive Mechanical ventilation
• Under sedation by midazolam or propofol
• Informed consent obtained from a relative for patient included in an emergency
• Patient affiliated to the national health insurance system

Exclusion Criteria:

• Cardiac arrest before inclusion and occurring before septic shock criteria are met
• Cardiac index < 2.2 l/min/m² after volume correction, or left ventricular ejectionfraction < 40% on echocardiography
• Bradycardia < 55 bpm (apart from treatment with β-blocker) or 2nd or 3rd degree BAVnot equipped
• Proven or suspected decompensation of coronary heart disease
• Acute cerebrovascular condition within 2 weeks prior to inclusion
• Severe hepatic insufficiency with TP and factor V <50% in the absence of DIC (disseminated intravascular coagulation)
• Patient on adrenaline or vasopressors at the time of inclusion (epinephrine orvasopressin stopped prior to inclusion is not a criterion for non-inclusion)
• Patient on non-selective MAOI iproniazid within 15 days of inclusion
• Patient for whom a decision has been made to limit the use of therapies
• Hypersensitivity to dexmedetomidine or phenylephrine
• Patient on dexmedetomidine before inclusion
• Person subject to a legal protection measure (curatorship, guardianship)
• Person subject to limited judicial protection
• Pregnant, parturient or breastfeeding woman
• Patient with suspected or confirmed mesenteric ischemia