Domenico Luca Grieco1,2, Salvatore Maurizio Maggiore3, Giacomo Bellani4,5, Savino Spadaro6, Elena Spinelli7, Tommaso Tonetti8, Luca S Menga9,10, Marco Pozzi11, Denise Battaglini12,13, Rosa Di Mussi14, Andrea Bruni15, Andrea De Gaetano16, Carmine Giovanni Iovino3, Matteo Brioni7, Francesco Mojoli11, Giuseppe Foti4,5, Carlo Aberto Volta6, Paolo Pelosi12,13, Paolo Navalesi17,18, Salvatore Grasso14, V Marco Ranieri8, Massimo Antonelli9,10. 1. Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go F. Vito, 00168, Rome, Italy. dlgrieco@outlook.it. 2. Istituto di Anestesiologia e Rianimazione, Università Cattolica del Sacro Cuore, L.go F. Vito, 00168, Rome, Italy. dlgrieco@outlook.it. 3. Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences, Section of Anesthesia, Analgesia, Perioperative and Intensive Care, SS. Annunziata Hospital, Gabriele d'Annunzio University of Chieti-Pescara, Chieti, Italy. 4. Department of Medicine and Surgery, University of Milan-Bicocca, Via Cadore 48, Monza, Italy. 5. Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy. 6. Department Morphology, Surgery and Experimental medicine, Anesthesia and Intensive care section, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna, Ferrara, Italy. 7. Dipartimento di Anestesia, Rianimazione ed Emergenza-Urgenza, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli studi di Milano, Milan, Italy. 8. Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Critical Care Medicine, Policlinico di Sant'Orsola, Alma Mater Studiorum University of Bologna, Bologna, Italy. 9. Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go F. Vito, 00168, Rome, Italy. 10. Istituto di Anestesiologia e Rianimazione, Università Cattolica del Sacro Cuore, L.go F. Vito, 00168, Rome, Italy. 11. Anesthesia and Intensive Care, Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy. 12. Department of Surgical Sciences and Integrated Diagnostics, DISC, University of Genoa, Genoa, Italy. 13. Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy. 14. Department of Emergency and Organ Transplant (D.E.T.O.), University of Bari Aldo Moro, Bari, Italy. 15. Anesthesia and Intensive Care Unit, Department of Medical and Surgical Sciences, University Hospital Mater Domini, Magna Graecia University, Catanzaro, Italy. 16. CNR-IASI BioMatLab, Consiglio Nazionale delle Ricerche, Istituto di Analisi dei Sistemi ed Informatica, Laboratorio di Biomatematica (Italian National Research Council, Institute for System Analysis and Computer Science, Biomathematics Laboratory), Rome, Italy. 17. Department of Anesthesia and Intensive Care, Azienda Ospedaliera-Università di Padova, Padua, Italy. 18. Dipartimento di Medicina-DIMED, Università degli Studi di Padova, Via Giustiniani 2, 35128, Padova, Italy.
Abstract
BACKGROUND: In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial). METHODS: IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment. DISCUSSION: The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04012073 . Registered 9 July 2019.
BACKGROUND: In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial). METHODS: IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment. DISCUSSION: The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04012073 . Registered 9 July 2019.
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Authors: Domenico Luca Grieco; Filippo Bongiovanni; Lu Chen; Luca S Menga; Salvatore Lucio Cutuli; Gabriele Pintaudi; Simone Carelli; Teresa Michi; Flava Torrini; Gianmarco Lombardi; Gian Marco Anzellotti; Gennaro De Pascale; Andrea Urbani; Maria Grazia Bocci; Eloisa S Tanzarella; Giuseppe Bello; Antonio M Dell'Anna; Salvatore M Maggiore; Laurent Brochard; Massimo Antonelli Journal: Crit Care Date: 2020-08-28 Impact factor: 9.097