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The impact of patient-ventilator asynchrony in adult mechanically ventilated patients on outcomes：A systematic review and meta-analysis v1

1. Background Patients-ventilator asynchrony (PVA) is defined as a mismatch between the patient breathing efforts with a ventilator’s breath delivery. (1) PVA is a common problem in mechanically ventilated patients, (2, 3) which could potentially induce the exhaustion of diaphragm and respiratory muscles and deliver high tidal volume to the lung leading to ventilator-induced lung injury (VILI). (4, 5) The impact of PVA on clinical outcomes varied depending on the timing of evaluating PVA. (6, 7) Utility of closedloop-ventilation such as Neurally Adjusted Ventilatory Assist (NAVA) and Proportional Assist Ventilation (PAV) which usually reduces PVA was shown to be associated with better outcomes in the weaning phase of mechanical ventilation using partial ventilation. (8, 9) In contrast, the impact of PVA in acute phase of mechanical ventilation on clinical outcomes were not similar across studies. Thille AW et al. reported that higher incidence of PVA was associated with longer duration of mechanical ventilation, while this was not associated with mortality. (2) Conversely, Blanch L et al. showed that ICU mortality of the patients with higher incidence of PVA was significantly higher than that with lower incidence of PVA. (10) Furthermore, to date, there is no systematic review regarding PVA in the acute phase of mechanical ventilation. Therefore, we will conduct this systematic review and meta-analysis to clarify the impact of PVA on specific clinical outcomes and the effect of interventions in order to improve PVA for mechanically ventilated patients in the acute phase of mechanical ventilation. 2. Review question Part A. The impact of PVA on clinical outcomes To clarify the impact of patient-ventilator asynchrony in adult mechanically ventilated patients in acute phase of mechanical ventilation on outcomes. Part B. The impact of interventions for mechanically ventilated patients on PVA To clarify the impact of interventions for adult mechanically ventilated patients in acute phase of mechanical ventilation on PVA. 3. Method 3.1.1 Types of study to be included Part A. The impact of PVA on clinical outcomes We will include published and unpublished observational studies and secondary analysis of randomized controlled trials (RCTs) including crossover trials, cluster-randomized trials, quasi-randomized trials. We will include studies presented only in abstract or letter form, in any language, from any country and with any length of follow-up. Part B. The impact of interventions for mechanically ventilated patients on PVA