Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients

Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients

Levosimendan is a relatively new drug that improves cardiac contractility in patients with heart failure. Its main mechanism of action is enhanced binding of calcium to the myocardial contractile proteins. Recent data from our lab showed that levosimendan improves contractility of human diaphragm in vitro (muscle fibers from COPD patient diaphragm) and in vivo (healthy subjects). Accordingly, levosimendan may appear of value in the treatment of disorders associated with impaired respiratory muscle function, such as mechanically ventilated patients.We hypothesize that levosimendan could improve respiratory muscle function in mechanically ventilated patients commencing a CPAP trial.

Inclusion Criteria:

• mechanical ventilation > 3 days
• informed consent
• able to sustain a CPAP trial for 30 minutes
• PaO2/FiO2 ratio > 200 mmHg
• ventilatory settings: positive end expiratory pressure <= 10 cmH2O, pressure support <= 10 cmH2O

Exclusion Criteria:

• pre-existent muscle disease (congenital or acquired) or diseases/disorders known to be associated with myopathy including auto-immune diseases
• pre-existent cardiac disease (based on history, electrocardiography and transthoracic echocardiography)
• upper airway/esophageal pathology (i.e. recent surgery, esophageal varices, diaphragmatic hernia)
• phrenic nerve lesions
• pregnancy, breast feeding
• severe renal failure (serum creatinine > 150 umol/L)
• severe hepatic failure
• recent (within 5 days) nasal bleeding
• systolic blood pressure < 120 mmHg