Effects of levosimendan on respiratory muscle function in patients weaning from mechanical ventilation

Purpose Respiratory muscle weakness frequently develops in critically ill patients and is associated with adverse outcome, including difficult weaning from mechanical ventilation. Today, no drug is approved to improve respiratory muscle function in these patients. Previously, we have shown that the calcium sensitizer levosimendan improves calcium sensitivity of human diaphragm muscle fibers in vitro and contractile efficiency of the diaphragm in healthy subjects. The main purpose of this study is to investigate the effects of levosimendan on diaphragm contractile efficiency in mechanically ventilated patients. Methods In a double-blind randomized placebo-controlled trial, mechanically ventilated patients performed two 30-min continuous positive airway pressure (CPAP) trials with 5-h interval. After the first CPAP trial, study medication (levosimendan 0.2 mu g/kg/min continuous infusion or placebo) was administered. During the CPAP trials, electrical activity of the diaphragm (EA(di)), transdiaphragmatic pressure (P-di), and flow were measured. Neuromechanical efficiency (primary outcome parameter) was calculated. Results Thirty-nine patients were included in the study. Neuromechanical efficiency was not different during the CPAP trial after levosimendan administration compared to the CPAP trial before study medication. Tidal volume and minute ventilation were higher after levosimendan administration (11 and 21%, respectively), whereas EA(di) and P-di were higher in both groups in the CPAP trial after study medication compared to the CPAP trial before study medication. Conclusions Levosimendan does not improve diaphragm contractile efficiency.