Abstract
BackgroundAdding cyclic short sustained inflations (sigh) to assisted ventilation yields optimizes lung recruitment, decreases heterogeneity and reduces inspiratory effort in patients with acute hypoxemic respiratory failure (AHRF). These findings suggest that adding sigh to pressure support ventilation (PSV) might decrease the risk of lung injury, shorten weaning and improve clinical outcomes. Thus, we conceived a pilot trial to test the feasibility of adding sigh to PSV (the PROTECTION study).MethodsPROTECTION is an international randomized controlled trial that will be conducted in 23 intensive care units (ICUs). Patients with AHRF who have been intubated from 24 h to 7 days and undergoing PSV from 4 to 24 h will be enrolled. All patients will first undergo a 30-min sigh test by adding sigh to clinical PSV for 30 min to identify early oxygenation responders. Then, patients will be randomized to PSV or PSV + sigh until extubation, ICU discharge, death or day 28. Sigh will be delivered as a 3-s pressure control breath delivered once per minute at 30 cmH2O. Standardized protocols will guide ventilation settings, switch back to controlled ventilation, use of rescue treatments, performance of spontaneous breathing trial, extubation and reintubation. The primary endpoint of the study will be to verify the feasibility of PSV + sigh evaluated through reduction of failure to remain on assisted ventilation during the first 28 days in the PSV + sigh group versus standard PSV (15 vs. 22%). Failure will be defined by switch back to controlled ventilation for more than 24 h or use of rescue treatments or reintubation within 48 h from elective extubation. Setting the power to 80% and first-risk order to 5%, the computed size of the trial is 129 patients per arm.DiscussionPROTECTION is a pilot randomized controlled trial testing the feasibility of adding sigh to PSV. If positive, it will provide physicians with an effective addition to standard PSV for lung protection, able to reduce failure of assisted ventilation. PROTECTION will provide the basis for a future larger trial aimed at verifying the impact of PSV + sigh on 28-day survival and ventilator-free days.Trial registrationClinicalTrials.gov, NCT03201263. Registered on 28 June 2017.
Highlights
Adding cyclic short sustained inflations to assisted ventilation yields optimizes lung recruitment, decreases heterogeneity and reduces inspiratory effort in patients with acute hypoxemic respiratory failure (AHRF)
Ever since a landmark study demonstrated the association between the use of high tidal volumes during controlled mechanical ventilation and increased mortality [2], “protective” controlled ventilation with limited volume and pressure has become the recommended treatment for patients with AHRF, in order to minimize the risk of ventilation-induced lung injury (VILI) [3]
PROTECTION is a pilot randomized controlled trial to test the long-term clinical feasibility of the addition of sigh to pressure support ventilation (PSV) in comparison to standard PSV. It will provide the basis for a future larger trial aimed at verifying the impact of PSV + sigh on a composite outcome endpoint including 28-day survival and ventilator-free days
Summary
Design The PROTECTION (Pressure support ventilation + sigh in acute hypoxemic respiratory failure patients) trial is an investigator-initiated, international, multicenter, parallel randomized controlled two-arm trial that will be performed in intubated and ventilated patients with AHRF, who are admitted to the intensive care unit (ICU). Data collection At enrollment, before the sigh test we will anonymously collect patients’ demographic information (e.g., age, sex, height, weight), past (e.g., hypertension, chronic medications) and recent (e.g., etiology of the acute respiratory failure, days since intubation) medical history, severity of lung injury (e.g., ventilation setting, arterial blood gases, respiratory system compliance, diagnosis of acute respiratory distress syndrome (ARDS)) and of systemic involvement (e.g., presence of shock, number of organ failures) and ventilation data (e.g., RR, Vt, PEEP, FiO2, PSV level) In both groups, for the first 24 h, we will assess the SpO2/FiO2 ratio, RR and PSV tidal volume every 4 h to further characterize physiologic response to sigh over time. To assess the feasibility of PSV + sigh as compared to PSV (i.e., the primary endpoint), we will compute the proportion of patients experiencing at least one of the following events in each arm: switch to controlled ventilation for ≥ 24 h consecutively; use of PEEP ≥ 15 cmH2O, prone positioning, inhaled nitric oxide, extracorporeal membrane oxygenation or reintubation within 48 h from extubation. Specific patient insurance will be granted to cover all unexpected adverse events caused by the study interventions and all adverse events will be monitored by and reported to the coordinating center
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