Pressure support ventilation + sigh in acute hypoxemic respiratory failure patients: study protocol for a pilot randomized controlled trial, the PROTECTION trial

Tommaso Mauri, Giuseppe Foti, Carla Fornari, Jean-Michel Constantin, Claude Guerin, Paolo Pelosi, Marco Ranieri, Sara Conti, Daniela Tubiolo, Egle Rondelli, Federica Lovisari, Tommaso Fossali, Savino Spadaro, Domenico Luca Grieco, Paolo Navalesi, Italo Calamai, Tobias Becher, Oriol Roca, Yu-Mei Wang, Rihard Knafelj, Andrea Cortegiani, Jordi Mancebo, Laurent Brochard, Antonio Pesenti, Protection Study Group, Giacomo Grasselli, Elena Spinelli, Chiara Abbruzzese, Roberto Rona, Alfio Bronco, Silvia Villa, Stefano Gianni, Alessandra Papoff, Riccardo Pinciroli, Riccardo Colombo, Chiara Sproccati, Pietro Mandelli, Federico Villa, Nicolo' Patroniti, Iole Brunetti, Lorenzo Ball, Carlo Alberto Volta, Marta Lazzeri, Elisabetta Maragoni, Davide Eleuteri, Giuseppe Bello, Antonio dell'Anna, Eugenio Garofalo, Andrea Bruni, Eugenio Biamonte, Rocco D'Andrea, Lorenzo Querci, Elisabetta Pierucci, Rosario Spina, Irene Mori, Francesco Tomeo, Alain Mercat, François Beloncle, Sebastien Jochmans, Sandie Mazerand, Loredana Baboi, Hodane Yonis, Matthieu Jabaudon, Thomas Godet, Tomas Jovaisa, Tom Barnes, Usman Tariq, Norbert Weiler, Dirk Schädler, Inéz Frerichs, Marina García-de-Acilu, Anxela Vidal, Emilia Rosas, César Pérez Calvo, Jian-Xin Zhou, Spiridon Karagiannis, Vasiliki Zisopoulou, Ioannis Staikos, Marko Noc, Misa Fister, Peter Radsel, Cesare Gregoretti, Ignazio Sabella, Santi Maurizio Raineri, Tommaso Mauri, Giuseppe Foti, Carla Fornari, Jean-Michel Constantin, Claude Guerin, Paolo Pelosi, Marco Ranieri, Sara Conti, Daniela Tubiolo, Egle Rondelli, Federica Lovisari, Tommaso Fossali, Savino Spadaro, Domenico Luca Grieco, Paolo Navalesi, Italo Calamai, Tobias Becher, Oriol Roca, Yu-Mei Wang, Rihard Knafelj, Andrea Cortegiani, Jordi Mancebo, Laurent Brochard, Antonio Pesenti, Protection Study Group, Giacomo Grasselli, Elena Spinelli, Chiara Abbruzzese, Roberto Rona, Alfio Bronco, Silvia Villa, Stefano Gianni, Alessandra Papoff, Riccardo Pinciroli, Riccardo Colombo, Chiara Sproccati, Pietro Mandelli, Federico Villa, Nicolo' Patroniti, Iole Brunetti, Lorenzo Ball, Carlo Alberto Volta, Marta Lazzeri, Elisabetta Maragoni, Davide Eleuteri, Giuseppe Bello, Antonio dell'Anna, Eugenio Garofalo, Andrea Bruni, Eugenio Biamonte, Rocco D'Andrea, Lorenzo Querci, Elisabetta Pierucci, Rosario Spina, Irene Mori, Francesco Tomeo, Alain Mercat, François Beloncle, Sebastien Jochmans, Sandie Mazerand, Loredana Baboi, Hodane Yonis, Matthieu Jabaudon, Thomas Godet, Tomas Jovaisa, Tom Barnes, Usman Tariq, Norbert Weiler, Dirk Schädler, Inéz Frerichs, Marina García-de-Acilu, Anxela Vidal, Emilia Rosas, César Pérez Calvo, Jian-Xin Zhou, Spiridon Karagiannis, Vasiliki Zisopoulou, Ioannis Staikos, Marko Noc, Misa Fister, Peter Radsel, Cesare Gregoretti, Ignazio Sabella, Santi Maurizio Raineri

Abstract

Background: Adding 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).

Methods: PROTECTION 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.

Discussion: PROTECTION 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 registration: ClinicalTrials.gov, NCT03201263 . Registered on 28 June 2017.

Keywords: Intervention study; Mechanical ventilation; Positive-pressure ventilation; Pressure support; Recruitment; Sigh; Ventilator-induced lung injury; Weaning.

Conflict of interest statement

Ethics approval and consent to participate

The Institutional Review Board of the coordinating center approved the protocol on 12 June 2017 under reference number 318_2017bis. The trial was registered at www.clinicaltrials.gov with code NCT03201263. Informed consent will be abtained from all the patients enrolled following local regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Standard protocol items: recommendation for interventional trials (SPIRIT) figure. Schedule of enrolment, interventions, and assessments for the PROTECTION trial. PSV, pressure support ventilation
Fig. 2
Fig. 2
The Consolidated Standards of Reporting Trials (CONSORT) diagram of the PROTECTION trial. PaO2, partial pressure of arterial oxygen; FiO2, fraction of inspired oxygen; PEEP, positive end-expiratory pressure; RASS, Richmond Agitation-Sedation Scale; PaCO2, partial pressure of arterial carbon dioxide; COPD, chronic obstructive pulmonary disease; PSV, pressure support ventilation

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Source: PubMed

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