EFFECTS OF LEVOSIMENDAN ON CELLULAR METABOLIC ALTERATIONS IN PATIENTS WITH SEPTIC SHOCK: A RANDOMIZED CONTROLLED PILOT STUDY

Introduction: Mitochondrial dysfunction and consequent cellular energetic failure play a key role in the development of sepsis-related organs failure. Evidence suggests that the pleiotropic effects of levosimendan may positively affect cellular metabolism during septic shock. Objectives: To investigate changes in the concentration of glucose, lactate, pyruvate, and glycerol in the extracellular fluid of the skeletal muscle following levosimendan administration in patients with septic shock. 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 mu g/kg/min (n = 10), or dobutamine 5 mu g/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. Results: Compared with dobutamine, levosimendan increased interstitial tissue pyruvate concentration (153.3 +/- 73 and 187.2 +/- 13.5 vs. 210.7 +/- 76.2 and 161 +/- 64.6; P< 0.05), and lactate clearance (55 vs. 10). Lactate/pyruvate ratio was lower in the levosimendan group at the end of study period (37.7 +/- 18.9 and 29.3 +/- 12.7 vs. 10.9 +/- 4.5 and 31.4 +/- 13.2; P< 0.05). Conclusion: Although we investigated a small number of patients, our preliminary results suggest that levosimendan may improve cellular metabolic alterations in patients with septic shock.