Effects of Levosimendan on Cellular Metabolic Alterations in Patients With Septic Shock: A Randomized Controlled Pilot Study.

"The authors report no conflicts of interest."

"After the approval by the Institutional Ethics Authorities, the study was performed in the intensive care unit of the Tunis Military Hospital and registered in Clinicaltrials.gov as NCT02963454. Written informed consent was obtained from the patients’ next of kin or from the legally authorized representatives. Enrolment of patients started in August 2011 and ended in May 2014. We enrolled patients who fulfilled the criteria of septic shock requiring norepinephrine (NE) to maintain a mean arterial pressure (MAP) of at least 65 mm Hg despite appropriate volume resuscitation (pulmonary arterial occlusion pressure [PAOP] = 12 mm Hg to 18 mm Hg and central venous pressure [CVP] = 8 mm Hg to 12 mm Hg) (). Septic shock criteria were defined according to current Surviving Sepsis Campaign guidelines () which include the presence of sepsis-related refractory hypotension (MAP < 65 mm Hg) unresponsive to fluid challenge (20 mL/kg–40 mL/kg). Exclusion criteria were pregnancy, uncontrolled hemorrhage, terminal heart failure, significant valvular heart disease, documented or suspected acute coronary syndrome, and limitations on the use of inotropes: left ventricle outflow obstruction, systolic anterior motion of the mitral valve. Methods:: The study was designed as a prospective, double-blind, controlled, clinical pilot trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mm Hg, 20 septic shock patients were randomized to receive either levosimendan 0.2 μg/kg/min (n = 10), or dobutamine 5 μg/kg/min as active comparator (n = 10). Interstitial tissue concentrations of lactate, pyruvate, glucose, and glycerol were obtained by using muscle microdialysis. All measurements, including data from right heart catheterization, were obtained at baseline and every 6 h for the following 72 h after randomization.: The trial is registered with Clinicaltrials.gov, number NCT02963454."