Can Neurally Adjusted Ventilatory Assist improve the outcome of mechanical ventilation compared to Pressure Support Ventilation? A multicenter randomized clinical trial.

INTERVENTION: Neurally adjusted ventilatory assist (NAVA) is a new mode of mechanical ventilation controlled by diaphragmatic electrical signals. Brefly the application of NAVA requires the introduction of a catheter to measure the electrical activity of the diaphragm (EAdi). NAVA relies, opposite to conventional assisted ventilation modes, on the EAdi to trigger the ventilator breath and to adjust the ventilatory assist to the neural drive. The amplitude of the ventilator assist is determined by the instantaneous EAdi and the NAVA level set by the clinician. The NAVA level amplifies the Eadi signal and determines instantaneous ventilator assist on a breath‐to‐breath basis. In patients enrolled in the NAVA group, EAdi catheter will be positioned and NAVA ventilation will be kept continuously (24 hours per day) till extubation (on rough average 7 days expected). If no EAdi signal will be detected patients will be maintained in assist control mode until the signal will be detectable. If the signal will remain undetectable, the patient will anyway be included in the NAVA group (intention‐to‐treat analysis). The ventilator will be initially set according to the following criteria: Positive End‐Expiratory Pressure (PEEP) as set by the attending physician; NAVA level between 1 and 3 cmH2O/microV (to maintain Tidal Volume (VT) between 5‐8 ml/kg and mean peak EAdi between 7 and 15 microV); EAdi trigger 0.5 microV and flow trigger 5, assuring that the vast majority of the breaths are neurally triggered; peak Pressure airway (Paw) alarm set to 45 cm H2O. After enrollment, patients will be tested every day for readiness to wean according to following criteria: suctioning less than twice per hour; clearly audible cough during suctioning; Glasgow Coma Scale (GCS) equal or greater than 8; heart rate equal or less than 120 beats per minute (bpm) and systolic blood pressure (SBP) equal or greater than 90 mmHg and equal or less than 180 mmHg; dopamine or dobutamine equal or less than 5 mcg/kg/min or norepinephrine equal or less than 0.1 mcg/kg/min; PaO2/FiO2 equal or greater than 150 mmHg; PEEP equal or less than 8 cmH2O; VT equal or greater than 5ml/kg; respiratory rate (RR) < 40/min; absence of evident respiratory distress (diaphoresis, accessory muscle recruitment, thoraco‐abdominal paradox); pH equal or greater than 7.35; Richmond Agitation Sedation Scale (RASS) between ‐1 and + 1. If the patient will meet all the criteria, a spontaneous breathing trial (SBT) in Continuous Positive Airway Pressure (CPAP) 2 cmH2O will be performed for 30 minutes. At the end of SBT arterial blood gases (ABG) will be sampled and the patient will be considered ready for extubation if all the follow criteria will be excluded: agitation and anxiety and/or depressed mental status (RASS = +3 or = ‐4); increased accessory muscle activity and or dyspnoea (VAS equal or greater than 7); RR/VT equal or greater than 105 b*min‐1*L‐1; PaO2 equal or less than 60 mmHg on FiO2 > 50%; pH < 7.32; SBP < 90 mmHg; cardiac arrhythmias not previously present. If SBT will be stopped for failure the same mode will be started again with settings able to restore clinical stability. CONDITION: Duration of mechanical ventilation during acute respiratory failure Lenght of stay in intensive care unit in patient with acute respiratory failure PRIMARY OUTCOME: Duration of mechanical ventilation (expressed in days). ; These data can be assessed by looking at the bedside chart data. Intensive care unit lenght of stay (expressed in days). ; In both groups the lenght of stay in the Intensive care unit will be calculated as the number of days from the entrance to the discharge of the patients. ; These data can be assessed by looking at the medical records database available the recruiting hospitals. If the patient will be able to maintain spontaneous breathing for the 48 hours following extubation, he/she will be considered as extubation success and the protocol will be ended. Otherwise, the subject will be re‐intubated and data collection and observation will be continued. Criteria for re‐intubation are: emergency, such as respiratory or cardiac arrest and gasping for air; neurologic deterioration; need for continuous infusion of epinephrine, norepinephrine, vasopressine, or dopamine or dobutamine > 5 mcg/Kg/min to maintain SBP equal or greater than 90 mmHg despite adequate filling; upper airway obstruction with stridor and/or tirage; unmanageable tracheo‐bronchial secretions; respiratory distress (SpO2 <90%; RR > 35 bpm; visible accessory muscle recruitment or thoracic‐abdominal paradox, despite administration of oxygen). After extubation, it will be also possible to ventilate not‐invasively (NIV) the patient, either for preventing (i.e. NIV started immediately after extubation in at risk patients) or treating post‐extubation respiratory failure (i.e. NIV started at established respiratory failure). When feasible, NIV will be applied in NAVA mode for patients included in the NAVA group. Tracheotomy will be performed between 7 and 14 days of invasive mechanical ventilation without likelihood of prompt extubation. ; In both groups the days of invasive mechanical ventilation will be counted from the first day of intubation to the successful extubation. With successful extubation we intend an extubation followed by a 48 hours period of spontaneous breathing. SECONDARY OUTCOME: Hospital charges per patient during Intensive care unit stay. ; In both groups the cost per patient will be calculated in euro as the average charge for one day of intensive care unit stay of each centres. ; These data can be assessed by looking at the medical records database available in the recruiting hospitals. Hospital length of stay. ; In both group the lenght of stay in the hospital will be calculated as the number of days from the entrance to the discharge of the patient from the hospital. These data can be assessed by looking at the medical records database available in the recruiting hospitals. Number of tracheotomies. ; In both groups we will count the number of tracheotomies performed. ; These data can be assessed by looking at the medical records database available in the recruiting hospitals. Rate of re‐intubation. ; In both groups the rate of re‐intubation will be assessed as the number of patients intubated within 48 hours after extubation divided by the total number of patients included in that group. ; These data can be assessed by looking at the medical records database available in the recruiting hospitals. Weaning time. ; In both groups the weaning time will be calculated as the number of days spent both on NAVA and on PSV. ; These data can be assessed by looking at the medical records database available in the recruiting hospitals. INCLUSION CRITERIA: Intubated patients Previous mechanical ventilation >= 24 hours Ability to effectively trigger the ventilator Expected ventilatory assistance >= 48 hours No scheduled surgery No inclusion in other research protocol No neuromuscular or neurologic disease Absence of contraindications to feeding tube positioning (including esophageal surgery in the previous 12 months and/or history of esophageal varices) PaO2/FiO2 >150 with PEEP >= 5 cmH2O