Whether variability restoration could be used to adapt NAVA settings also warrants further studies, as well as the development Wortmannin structure of specific tools for assessing variability at the bedside.Patients with respiratory failure probably adjust their breathing activity to achieve the best compromise between the muscular effort needed to breathe and the sensory cost of tolerating elevated PaCO2 levels. NAVA acts as an additional external cost-free muscle controlled by the central respiratory command. NAVA therefore does not seem to alter the closed loop that controls the PaCO2 and respiratory pattern optimization. Accordingly, when introducing NAVA in patients with respiratory failure, progressively increasing the NAVA level allows the PaCO2 (that is, VT) to improve to the optimal value.

Further NAVA level increases then lead to respiratory effort adjustments aimed at maintaining this optimal PaCO2 value, but do not change VT [20].Moreover, Karagiannidis and colleagues intended recently to evaluate the physiological effect of extracorporeal membrane oxygenation on the pattern of breathing in patients with severe lung failure treated with NAVA [78]. They demonstrated that a downregulation of extracorporeal exchange gas transfer caused an immediate upregulation of ventilation. Eucapnia under NAVA was preserved because the patients adjusted their minute ventilation to their needs. These interesting data highlighted once again that the ventilatory adaptation to maintain normocapnia remains under NAVA.How can the optimal NAVA level be determined?Determining the optimal NAVA level remains challenging, and several methods have been suggested.

Contrary to PSV and as already described, NAVA generates VT levels that can remain constant independent of the assist level once the patient’s ventilation needs appear to be satisfied [20]. Consequently, NAVA settings cannot be adjusted based solely on VT (and/or the corresponding PaCO2 target).Brander and colleagues tried to find the best NAVA level using breathing pattern analysis during a titration procedure [20]. Titration consisted of starting at a minimal assist level of around 3 cmH2O and then increasing the NAVA level every 3 minutes in steps of 1 cmH2O per arbitrary unit (the amount of microvolts recorded from the EAdi signal). The response in terms of VT and Paw was biphasic.

During the first phase, Batimastat VT and Paw increased while the esophageal pressure-time product (that is, inspiratory muscle effort) and EAdi decreased. Further increases in the NAVA level (second phase) did not significantly change Paw or VT but continued to decrease the esophageal pressure-time product and EAdi. The first phase may thus indicate an insufficient NAVA level to supplement the patient’s weak breathing effort, while the beginning of the second phase may correspond to the minimal assist level that satisfies the patient’s respiratory demand.