Late Breaking Abstract - Effects of levosimendan on diaphragm contractile efficiency in patients weaning from mechanical ventilation

Introduction: Respiratory muscle weakness frequently develops in critically ill patients and is associated with difficult weaning from mechanical ventilation and increased mortality. No drug has been approved to improve respiratory muscle function. However, we have previously shown that the calcium sensitizer levosimendan improves contractility of diaphragm muscle fibers in vitro and diaphragm contractility in healthy subjects in vivo. Objectives: To investigate the effects of levosimendan on diaphragm contractile efficiency in mechanically ventilated patients. Methods: In a double-blind placebo-controlled trial mechanically ventilated patients (N=39) performed two continuous positive airway pressure (CPAP) trials for 30-minutes each with 5 hour interval. After the first CPAP trial, study medication (either levosimendan 0.2 µg/kg/min or placebo) was administered. During both trials electrical activity of the diaphragm (EAdi), transdiaphragmatic pressure (Pdi) and tidal volume (TV) were continuously measured. Neuromechanical efficiency (primary outcome parameter) was defined as ΔPdi/ΔEAdi. Results: Neuromechanical efficiency did not improve after levosimendan. However, ΔEAdi and tidal volume were higher after levosimendan administration (31% and 11%, respectively). P0.1, a measure for respiratory load, increased in the placebo group by 41%, while it remained constant in the levosimendan group. PaCO2 significantly decreased (44 mmHg vs 42 mmHg) in response to levosimendan administration. Conclusions: Although levosimendan did not improve diaphragm contractile efficiency, tidal volume increased, while P0.1 and PaCO2 decreased.