Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study)

doi:10.1016/j.pulmoe.2022.11.002

Multicenter Study

. 2023 Nov-Dec;29(6):457-468.

doi: 10.1016/j.pulmoe.2022.11.002. Epub 2022 Nov 24.

Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study)

Luigi Vetrugno¹, Nadia Castaldo², Alberto Fantin², Cristian Deana³, Andrea Cortegiani⁴, Federico Longhini⁵, Francesco Forfori⁶, Gianmaria Cammarota⁷, Domenico Luca Grieco⁸, Miriam Isola⁹, Paolo Navalesi¹⁰, Salvatore Maurizio Maggiore¹¹, Matteo Bassetti¹², Alfredo Chetta¹³, Marco Confalonieri¹⁴, Maria De Martino⁹, Giovanni Ferrari¹⁵, Daniela Francisi¹⁶, Roberto Luzzati¹⁷, Simone Meini¹⁸, Mariano Scozzafava¹⁹, Emanuela Sozio²⁰, Carlo Tascini²¹, Flavio Bassi³, Vincenzo Patruno²; Italian COVI-MIX Study Group²²; Edoardo De Robertis⁷, Chiara Aldieri²³, Lorenzo Ball²⁴, Elisa Baratella¹⁴, Michele Bartoletti²⁵, Annalisa Boscolo²⁶, Barbara Burgazzi¹³, Vito Catalanotti²⁵, Paola Confalonieri¹⁴, Silvia Corcione²⁷, Francesco Giuseppe De Rosa²⁸, Alessandro De Simoni¹³, Valerio Del Bono²³, Roberta Di Tria¹⁵, Sara Forlani²⁹, Daniele Roberto Giacobbe¹², Bianca Granozzi²⁵, Laura Labate¹², Sara Lococo³⁰, Tommaso Lupia³¹, Carola Matellon³, Sara Mehrabi³², Sabrina Morosi¹⁶, Silvia Mongodi³³, Maddalena Mura¹⁸, Stefano Nava³⁴, Riccardo Pol¹⁷, Tommaso Pettenuzzo²⁶, Nguyen Hoang Quyen³⁵, Carolina Rescigno³⁶, Elda Righi³⁵, Barbara Ruaro¹⁴, Francesco Salton¹⁴, Silvia Scabini²⁷, Angelo Scarda³⁷, Marcella Sibani³⁵, Evelina Tacconelli³⁵, Gennaro Tartaglione³⁷, Beatrice Tazza²⁵, Eleonora Vania²⁰, Pierluigi Viale²⁵, Andrea Vianello³⁵, Alessandro Visentin³⁵, Umberto Zuccon³⁷, Francesco Meroi⁹, Danilo Buonsenso³⁸

Affiliations

¹ Department of Anesthesiology, Critical Care Medicine and Emergency, SS. Annunziata Hospital, Chieti, Italy; Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy. Electronic address: luigi.vetrugno@unich.it.
² Pulmonology Unit, Department of Cardiothoracic Surgery, Health Integrated Agency of Friuli Centrale, Udine, Italy.
³ Department of Anesthesia and Intensive Care, Health Integrated Agency of Friuli Centrale, Udine, Italy.
⁴ Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Palermo, Italy; Department of Anesthesia Intensive Care and Emergency, Policlinico Paolo Giaccone, Palermo, Italy.
⁵ Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
⁶ Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, AOUP-Pisa, Italy.
⁷ Anesthesia and Intensive Care Service 2, University Hospital of Perugia, Perugia, Italy; Department of Medicine and Surgery, Universiy of Perugia, Perugia, Italy.
⁸ Department of Anesthesiology and Intensive Care Medicine, Catholic University of The Sacred Heart, Rome, Italy; Department of Anesthesia, Emergency and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁹ Department of Medicine, University of Udine, Udine, Italy.
¹⁰ Institute of Anaesthesia and Intensive Care, Padua University Hospital, Padua, Italy; Department of Medicine (DIMED), University of Padua, Padua, Italy.
¹¹ Department of Anesthesiology, Critical Care Medicine and Emergency, SS. Annunziata Hospital, Chieti, Italy; Department of Innovative Technologies in Medicine and Dentistry, Gabriele d'Annunzio University of Chieti Pescara, Chieti, Italy.
¹² Infectious Diseases Unit, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy; Department of Health Sciences, University of Genoa, Genoa, Italy.
¹³ Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
¹⁴ Department of Pulmonology, University Hospital of Cattinara, Trieste, Italy; University of Trieste, Trieste, Italy.
¹⁵ Pneumologia e Unità di Terapia Semi Intensiva Respiratoria, AO Umberto I Mauriziano, Turin, Italy.
¹⁶ Department of Infectious Disease "S. Maria della Misericordia" Hospital, University of Perugia, Perugia, Italy.
¹⁷ Infectious Disease Unit, University of Trieste, Trieste, Italy.
¹⁸ U.O. Medicina Interna, Felice Lotti Hospital, Azienda USL Toscana Nord-Ovest, Pontedera, Italy.
¹⁹ Respiratory High Dependecy Unit - General Hospital Lodi, Lodi, Italy.
²⁰ Infectious Diseases Division, Health Integrated Agency of Friuli Centrale, Udine, Italy.
²¹ Department of Medicine, University of Udine, Udine, Italy; Infectious Diseases Division, Health Integrated Agency of Friuli Centrale, Udine, Italy.
²² Department of Anesthesiology, Critical Care Medicine and Emergency, SS. Annunziata Hospital, Chieti, Italy.
²³ Division of Infectious Diseases, Department of Medicine, Hospital Santa Croce e Carle, Cuneo, Italy.
²⁴ Anesthesia and Intensive Care, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy; Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.
²⁵ Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola, Bologna, Italy.
²⁶ Institute of Anaesthesia and Intensive Care, Padua University Hospital, Padua, Italy.
²⁷ Department of Medical Sciences, University of Turin, Infectious Diseases, City of Health and Sciences, Turin, Italy.
²⁸ Infectious Diseases Unit, Cardinal Massaia Hospital, Asti, Italy; Infectious Diseases Unit, Cardinal Massaia Hospital, Asti, Italy.
²⁹ Pulmonary Medicine Unit, Lodi General Hospital, Lodi, Italy.
³⁰ Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.
³¹ Infectious Diseases Unit, Cardinal Massaia Hospital, Asti, Italy.
³² Infectious Diseases Division, Diagnostics and Public Health Department, University of Verona, Verona, Italy.
³³ Anaesthesia and Intensive Care, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
³⁴ Department of Clinical, Integrated and Experimental Medicine (DIMES), University of Bologna, Bologna, Italy; Respiratory and Critical Care Unit, Sant Orsola University Hospital, Bologna, Italy.
³⁵ Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
³⁶ UOC Malattie Infettive ad Indirizzo Neurologico, AORN Ospedali dei Colli, P.O. "D. Cotugno", Naples, Italy.
³⁷ Respiratory Disease Unit, "Santa Maria degli Angeli" Hospital, Pordenone, Italy.
³⁸ Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

PMID: 36669936
PMCID: PMC9684110
DOI: 10.1016/j.pulmoe.2022.11.002

Multicenter Study

Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study)

Luigi Vetrugno et al. Pulmonology. 2023 Nov-Dec.

. 2023 Nov-Dec;29(6):457-468.

doi: 10.1016/j.pulmoe.2022.11.002. Epub 2022 Nov 24.

Authors

Affiliations

¹ Department of Anesthesiology, Critical Care Medicine and Emergency, SS. Annunziata Hospital, Chieti, Italy; Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy. Electronic address: luigi.vetrugno@unich.it.
² Pulmonology Unit, Department of Cardiothoracic Surgery, Health Integrated Agency of Friuli Centrale, Udine, Italy.
³ Department of Anesthesia and Intensive Care, Health Integrated Agency of Friuli Centrale, Udine, Italy.
⁴ Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Palermo, Italy; Department of Anesthesia Intensive Care and Emergency, Policlinico Paolo Giaccone, Palermo, Italy.
⁵ Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
⁶ Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, AOUP-Pisa, Italy.
⁷ Anesthesia and Intensive Care Service 2, University Hospital of Perugia, Perugia, Italy; Department of Medicine and Surgery, Universiy of Perugia, Perugia, Italy.
⁸ Department of Anesthesiology and Intensive Care Medicine, Catholic University of The Sacred Heart, Rome, Italy; Department of Anesthesia, Emergency and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁹ Department of Medicine, University of Udine, Udine, Italy.
¹⁰ Institute of Anaesthesia and Intensive Care, Padua University Hospital, Padua, Italy; Department of Medicine (DIMED), University of Padua, Padua, Italy.
¹¹ Department of Anesthesiology, Critical Care Medicine and Emergency, SS. Annunziata Hospital, Chieti, Italy; Department of Innovative Technologies in Medicine and Dentistry, Gabriele d'Annunzio University of Chieti Pescara, Chieti, Italy.
¹² Infectious Diseases Unit, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy; Department of Health Sciences, University of Genoa, Genoa, Italy.
¹³ Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
¹⁴ Department of Pulmonology, University Hospital of Cattinara, Trieste, Italy; University of Trieste, Trieste, Italy.
¹⁵ Pneumologia e Unità di Terapia Semi Intensiva Respiratoria, AO Umberto I Mauriziano, Turin, Italy.
¹⁶ Department of Infectious Disease "S. Maria della Misericordia" Hospital, University of Perugia, Perugia, Italy.
¹⁷ Infectious Disease Unit, University of Trieste, Trieste, Italy.
¹⁸ U.O. Medicina Interna, Felice Lotti Hospital, Azienda USL Toscana Nord-Ovest, Pontedera, Italy.
¹⁹ Respiratory High Dependecy Unit - General Hospital Lodi, Lodi, Italy.
²⁰ Infectious Diseases Division, Health Integrated Agency of Friuli Centrale, Udine, Italy.
²¹ Department of Medicine, University of Udine, Udine, Italy; Infectious Diseases Division, Health Integrated Agency of Friuli Centrale, Udine, Italy.
²² Department of Anesthesiology, Critical Care Medicine and Emergency, SS. Annunziata Hospital, Chieti, Italy.
²³ Division of Infectious Diseases, Department of Medicine, Hospital Santa Croce e Carle, Cuneo, Italy.
²⁴ Anesthesia and Intensive Care, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy; Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.
²⁵ Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola, Bologna, Italy.
²⁶ Institute of Anaesthesia and Intensive Care, Padua University Hospital, Padua, Italy.
²⁷ Department of Medical Sciences, University of Turin, Infectious Diseases, City of Health and Sciences, Turin, Italy.
²⁸ Infectious Diseases Unit, Cardinal Massaia Hospital, Asti, Italy; Infectious Diseases Unit, Cardinal Massaia Hospital, Asti, Italy.
²⁹ Pulmonary Medicine Unit, Lodi General Hospital, Lodi, Italy.
³⁰ Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.
³¹ Infectious Diseases Unit, Cardinal Massaia Hospital, Asti, Italy.
³² Infectious Diseases Division, Diagnostics and Public Health Department, University of Verona, Verona, Italy.
³³ Anaesthesia and Intensive Care, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
³⁴ Department of Clinical, Integrated and Experimental Medicine (DIMES), University of Bologna, Bologna, Italy; Respiratory and Critical Care Unit, Sant Orsola University Hospital, Bologna, Italy.
³⁵ Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
³⁶ UOC Malattie Infettive ad Indirizzo Neurologico, AORN Ospedali dei Colli, P.O. "D. Cotugno", Naples, Italy.
³⁷ Respiratory Disease Unit, "Santa Maria degli Angeli" Hospital, Pordenone, Italy.
³⁸ Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

PMID: 36669936
PMCID: PMC9684110
DOI: 10.1016/j.pulmoe.2022.11.002

Abstract

Background: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication.

Methods: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death.

Results: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001).

Conclusions: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality.

Trial registration: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

Keywords: Acute respiratory failure; Barotrauma; COVID-19; High flow nasal cannula; Invasive mechanical ventilation; Pneumothorax.

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Conflict of interest statement

Declaration of Competing Interest None.

Figures

Fig 2 — **Fig. 2**
Survival Kaplan Meier curves. In Fig. 2 (a) Kaplan-Meier survival curves show overall survival of patients with COVID-19 infection who developed barotrauma when on IMV and on NIRS. Patients in IMV and NIRS were represented by continuous and dotted curves respectively, with no difference in overall survival (p=0.37). In Fig. 2 (b) Kaplan-Meier survival curves describe overall survival of patients with COVID-19 infection when on IMV, and when in NIRS. Patients in IMV and NIRS were represented by continuous and dotted curves respectively, with no difference in overall survival (p=0.12). Legend. IMV: invasive mechanical ventilation; NIRS: non-invasive respiratory support

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References

1. Anzueto A., Frutos-Vivar F., Esteban A., Alia I., Brochard L., Stewart T., et al. Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients. Intensive Care Med. 2004;30(4):612–619. - PubMed
1. Udi J., Lang C.N., Zotzmann V., Krueger K., Fluegler A., Bamberg F., et al. Incidence of barotrauma in patients with COVID-19 pneumonia during prolonged invasive mechanical ventilation - a case-control study. J Intensive Care Med. 2021;36(4):477–483. - PubMed
1. McGuinness G., Zhan C., Rosenberg N., Azour L., Wickstrom M., Mason D.M., et al. Increased incidence of barotrauma in patients with COVID-19 on invasive mechanical ventilation. Radiology. 2020;297(2):E252–EE62. - PMC - PubMed
1. Miro O., Llorens P., Jimenez S., Pinera P., Burillo-Putze G., Martin A., et al. Frequency, risk factors, clinical characteristics, and outcomes of spontaneous pneumothorax in patients with coronavirus disease 2019: a case-control, emergency medicine-based multicenter study. Chest. 2021;159(3):1241–1255. - PMC - PubMed
1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. - PMC - PubMed

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[1] Anzueto A., Frutos-Vivar F., Esteban A., Alia I., Brochard L., Stewart T., et al. Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients. Intensive Care Med. 2004;30(4):612–619. - PubMed

[2] Anzueto A., Frutos-Vivar F., Esteban A., Alia I., Brochard L., Stewart T., et al. Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients. Intensive Care Med. 2004;30(4):612–619. - PubMed

[3] Udi J., Lang C.N., Zotzmann V., Krueger K., Fluegler A., Bamberg F., et al. Incidence of barotrauma in patients with COVID-19 pneumonia during prolonged invasive mechanical ventilation - a case-control study. J Intensive Care Med. 2021;36(4):477–483. - PubMed

[4] Udi J., Lang C.N., Zotzmann V., Krueger K., Fluegler A., Bamberg F., et al. Incidence of barotrauma in patients with COVID-19 pneumonia during prolonged invasive mechanical ventilation - a case-control study. J Intensive Care Med. 2021;36(4):477–483. - PubMed

[5] McGuinness G., Zhan C., Rosenberg N., Azour L., Wickstrom M., Mason D.M., et al. Increased incidence of barotrauma in patients with COVID-19 on invasive mechanical ventilation. Radiology. 2020;297(2):E252–EE62. - PMC - PubMed

[6] McGuinness G., Zhan C., Rosenberg N., Azour L., Wickstrom M., Mason D.M., et al. Increased incidence of barotrauma in patients with COVID-19 on invasive mechanical ventilation. Radiology. 2020;297(2):E252–EE62. - PMC - PubMed

[7] Miro O., Llorens P., Jimenez S., Pinera P., Burillo-Putze G., Martin A., et al. Frequency, risk factors, clinical characteristics, and outcomes of spontaneous pneumothorax in patients with coronavirus disease 2019: a case-control, emergency medicine-based multicenter study. Chest. 2021;159(3):1241–1255. - PMC - PubMed

[8] Miro O., Llorens P., Jimenez S., Pinera P., Burillo-Putze G., Martin A., et al. Frequency, risk factors, clinical characteristics, and outcomes of spontaneous pneumothorax in patients with coronavirus disease 2019: a case-control, emergency medicine-based multicenter study. Chest. 2021;159(3):1241–1255. - PMC - PubMed

[9] Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. - PMC - PubMed

[10] Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. - PMC - PubMed

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Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study)

Affiliations

Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study)

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