Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression

Objective: Calcium desensitization plays an important part in the pathophysiology of septic myocardial depression. We postulated that levosimendan, a new calcium sensitizer, would be beneficial in sepsis-induced cardiac dysfunction. Design and setting: Prospective, randomized, controlled study in two university hospital intensive care units Patients and participants: Twenty-eight patients with persisting left ventricular dysfunction related to septic shock after 48 h of conventional treatment including dobutamine (5 mu g/kg per minute). Interventions: After 48 h of conventional treatment patients were randomized to receive a 24-h infusion of either levosimendan (0.2 mu g/kg per minute, n=15) or dobutamine (5 mu g/kg per minute, n=13). Measurements and results: Data from right heart catheterization, echocardiography, gastric tonometry, laser-Doppler flowmetry, and lactate concentrations and creatinine clearance were obtained before and after the 24-h drug infusion. Dobutamine did not change systemic or regional hemodynamic variables. By contrast, at the same mean arterial pressure levosimendan decreased pulmonary artery occlusion pressure and increased cardiac index. Levosimendan decreased left ventricular end-diastolic volume and increased left ventricular ejection fraction. Levosimendan increased gastric mucosal flow, creatinine clearance, and urinary output while it decreased lactate concentrations. Conclusions: These findings show that levosimendan improves systemic hemodynamics and regional perfusion in patients with septic cardiac dysfunction under conditions where administration of 5 mu g/kg dobutamine per minute is no longer efficacious. Accordingly, our results suggest that levosimendan can be an alternative to the strategy of increasing the dose of dobutamine under such conditions.