Inclusion Criteria:

1. age ≥ 16 years;

2. anticipated survival > 24 hours;

3. need for mechanical ventilation for at least 12 hours and

4. hemodynamic stability (MAP>65 mmHg, HR<100 beats/min, diuresis > 1 ml/kg/h, no
catecholamine requirement or fluid challenge).

Exclusion Criteria:

1. history of any lung disease, use of immunosuppressive medication, recent infections,
previous thromboembolic disease, recent ventilatory support, and participation in another
clinical trial. Absence of lung disease was defined by the following clinical criteria:
(a) no evidence of respiratory infection (white blood cell count <10x103/µl, temperature >
380C, purulent sputum), (b) normal chest roentgenogram, (c) PaO2/FIO2 ratio > 300, (d) and
a normal clinical respiratory history.