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

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. 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.