https://doi.org/10.4081/monaldi.2024.2829

Diaphragmatic morphological post-mortem findings in critically ill COVID-19 patients: an observational study

Early Access
Submitted: October 20, 2023
Accepted: March 18, 2024
Published: April 23, 2024
COVID-19, invasive mechanical ventilation, diaphragm dysfunction, myosin, ventilation-induce diaphragm injury
Abstract Views: 86
PDF_EARLY VIEW: 52
SUPPLEMENTARY MATERIAL: 6
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Luigi Vetrugno
luigi.vetrugno@unich.it
https://orcid.org/0000-0003-3745-8368
Department of Medical, Oral and Biotechnological Sciences, Gabriele d’Annunzio University of Chieti Pescara, Chieti; Department of Anesthesiology, Critical Care Medicine and Emergency, Annunziata Hospital, Chieti, Italy.
Cristian Deana
Department of Anesthesia and Intensive Care, Health Integrated Agency Friuli Centrale, Academic Hospital of Udine, Italy.
Savino Spadaro
Department of Translational Medicine, University of Ferrara; Intensive Care Unit, Azienda Ospedaliera Universitaria Sant’Anna, Ferrara, Italy.
Gianmaria Cammarota
Department of Translational Medicine, Università degli Studi del Piemonte Orientale, Novara; Department of Anesthesiology and Intensive Care, Azienda Ospedaliero-Universitaria “Maggiore della Carità”, Novara, Italy.
Domenico Luca Grieco
https://orcid.org/0000-0002-4557-6308
Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; Department of Anesthesiology and Intensive Care Medicine, Catholic University of The Sacred Heart, Rome, Italy.
Annarita Tullio
https://orcid.org/0000-0003-3332-7459
Health Integrated Agency Friuli Centrale, Academic Hospital of Udine, Italy.
Tiziana Bove
https://orcid.org/0000-0002-5489-2898
Department of Anesthesia and Intensive Care, Health Integrated Agency Friuli Centrale, Academic Hospital of Udine; Department of Medicine, University of Udine, Italy.
Carla Di Loreto
Department of Medicine, University of Udine; Institute of Anatomic Pathology, Health Integrated Agency Friuli Centrale, Academic Hospital of Udine, Italy.
Salvatore Maurizio Maggiore
https://orcid.org/0000-0002-1828-9143
Department of Anesthesiology, Critical Care Medicine and Emergency, Annunziata Hospital, Chieti; Department of Innovative Technologies in Medicine and Dentistry, Gabriele d'Annunzio University of Chieti Pescara, Chieti, Italy.
Maria Orsaria
https://orcid.org/0000-0001-9978-8130
Institute of Anatomic Pathology, Health Integrated Agency Friuli Centrale, Academic Hospital of Udine, Italy.
DIASUS study group

Our study investigates the post-mortem findings of the diaphragm's muscular structural changes in mechanically ventilated COVID-19 patients. Diaphragm samples of the right side from 42 COVID-19 critically ill patients were analyzed and correlated with the type and length of mechanical ventilation (MV), ventilatory parameters, prone positioning, and use of sedative drugs. The mean number of fibers was 550±626. The cross-sectional area was 4120±3280 μm2, while the muscular fraction was 0.607±0.126. The overall population was clustered into two distinct populations (clusters 1 and 2). Cluster 1 showed a lower percentage of slow myosin fiber and higher fast fiber content than cluster 2, 68% versus 82%, p<0.00001, and 29.8% versus 18.8%, p=0.00045 respectively. The median duration of MV was 180 (41-346) hours. In cluster 1, a relationship between assisted ventilation and fast myosin fiber percentage (R2=-0.355, p=0.014) was found. In cluster 2, fast fiber content increased with increasing the length of the controlled MV (R2=0.446, p=0.006). A high grade of fibrosis was reported. Cluster 1 was characterized by fibers’ atrophy and cluster 2 by hypertrophy, supposing different effects of ventilation on the diaphragm but without excluding a possible direct viral effect on diaphragmatic fibers.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
McCool FD, Manzoor K, Minami T. Disorders of the diaphragm. Clin Chest Med 2018;39:345-60. DOI: https://doi.org/10.1016/j.ccm.2018.01.012
Doorduin J, van Hees HW, van der Hoeven JG, Heunks LM. Monitoring of the respiratory muscles in the critically ill. Am J Respir Crit Care Med 2013;187:20-7. DOI: https://doi.org/10.1164/rccm.201206-1117CP
Telias I, Brochard LJ, Gattarello S, et al. The physiological underpinnings of life-saving respiratory support. Intensive Care Med 2022;48:1274-86. DOI: https://doi.org/10.1007/s00134-022-06749-3
Shanely RA, Zergeroglu MA, Lennon SL, et al. Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity. Am J Respir Crit Care Med 2002;166:1369-74. DOI: https://doi.org/10.1164/rccm.200202-088OC
Levine S, Nguyen T, Taylor N, et al. Rapid disuse atrophy of diaphragm fibres in mechanically ventilated humans. N Engl J Med 2008;358:1327-35. DOI: https://doi.org/10.1056/NEJMoa070447
Jaber S, Petrof BJ, Jung B, et al. Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. Am J Respir Crit Care Med 2011;183:364-71. DOI: https://doi.org/10.1164/rccm.201004-0670OC
Petrof BJ, Jaber S, Matecki S. Ventilator-induced diaphragmatic dysfunction. Curr Opin Crit Care 2010;16:19-25. DOI: https://doi.org/10.1097/MCC.0b013e328334b166
Dres M, Goligher EC, Heunks LMA, Brochard LJ. Critical illness-associated diaphragm weakness. Intensive Care Med 2017;43:1441-52. DOI: https://doi.org/10.1007/s00134-017-4928-4
Goligher EC, Dres M, Fan E, et al. Mechanical ventilation-induced diaphragm atrophy strongly impacts clinical outcomes. Am J Respir Crit Care Med 2018;197:204-13. DOI: https://doi.org/10.1164/rccm.201703-0536OC
Frutos-Vivar F, Esteban A, Apezteguia C, et al. Outcome of reintubated patients after scheduled extubation. J Crit Care 2011;26:502-9. DOI: https://doi.org/10.1016/j.jcrc.2010.12.015
Shi Z, de Vries HJ, Vlaar APJ, et al. Dutch COVID-19 diaphragm investigators. diaphragm pathology in critically ill patients with COVID-19 and postmortem findings from 3 medical centers. JAMA Intern Med 2021;181:122-4. DOI: https://doi.org/10.1001/jamainternmed.2020.6278
Regmi B, Friedrich J, Jörn B, et al. Diaphragm muscle weakness might explain exertional dyspnea 15 months after hospitalization for COVID-19. Am J Respir Crit Care Med 2023;207:1012-21. DOI: https://doi.org/10.1164/rccm.202206-1243OC
Guérin C, Papazian L, Reignier J, et al. Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials. Crit Care 2016;20:384. DOI: https://doi.org/10.1186/s13054-016-1556-2
Costa ELV, Slutsky AS, Brochard LJ, et al. Ventilatory variables and mechanical power in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2021;204:303-11. DOI: https://doi.org/10.1164/rccm.202009-3467OC
Mizuno M. Human respiratory muscles: fibre morphology and capillary supply. Eur Respir J 1991;4:587-601. DOI: https://doi.org/10.1183/09031936.93.04050587
Vetrugno L, Castaldo N, Fantin A, et al. Ventilatory associated barotrauma in COVID-19 patients: a multicenter observational case control study (COVI-MIX-study). Pulmonology 2022;29:457-68. DOI: https://doi.org/10.1016/j.pulmoe.2022.11.002
Vetrugno L, Orso D, Corradi F, et al. Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study. Respir Res 2022;23:210. DOI: https://doi.org/10.1186/s12931-022-02138-y
Cammarota G, Bruni A, Morettini G, et al. Lung ultrasound to evaluate aeration changes in response to recruitment maneuver and prone positioning in intubated patients with COVID-19 pneumonia: preliminary study. Ultrasound J 2023;15:3. DOI: https://doi.org/10.1186/s13089-023-00306-9
Polla B, D’Antona G, Bottinelli R, Reggiani C. Respiratory muscle fibres: specialisation and plasticity. Thorax 2004;59:808-17. DOI: https://doi.org/10.1136/thx.2003.009894
Haun CT, Vann CG, Roberts BM, et al. A critical evaluation of the biological construct skeletal muscle hypertrophy: size matters but so does the measurement. Front Physiol 2019;10:247 DOI: https://doi.org/10.3389/fphys.2019.00247
Roberts MD, Haun CT, Vann CG, et al. Sarcoplasmic hypertrophy in skeletal muscle: a scientific "unicorn" or resistance training adaptation?. Front Physiol 2020;11:816. DOI: https://doi.org/10.3389/fphys.2020.00816
Dhont S, Derom E, Van Braeckel E, et al. The pathophysiology of 'happy' hypoxemia in COVID-19. Respir Res 2020;21:198. DOI: https://doi.org/10.1186/s12931-020-01462-5
Deana C, Verriello L, Pauletto G, et al. Insights into neurological dysfunction of critically ill COVID-19 patients. Trends in Anaesthesia & Critical Care 2021;36:30-8. DOI: https://doi.org/10.1016/j.tacc.2020.09.005
Reid WD, Belcastro AN. Time course of diaphragm injury and calpain activity during resistive loading. Am J Respir Crit Care Med 2000;162:1801-6. DOI: https://doi.org/10.1164/ajrccm.162.5.9906033
Miyata H, Zhan WZ, et al. Myoneural interactions affect diaphragm muscle adaptations to inactivity. J Appl Physiol (1985) 1995;79:1640-9. DOI: https://doi.org/10.1152/jappl.1995.79.5.1640
Shi Z, Bogaards SJP, Conijn S, et al. COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients. BMJ Open Respir Res 2021;8:e001052. DOI: https://doi.org/10.1136/bmjresp-2021-001052
Lewis P, O'Halloran KD. Diaphragm muscle adaptation to sustained hypoxia: lessons from animal models with relevance to high altitude and chronic respiratory diseases. Front Physiol 2016;7:623. DOI: https://doi.org/10.3389/fphys.2016.00623
Deana C, Rovida S, Orso D, et al. Learning from the Italian experience during COVID-19 pandemic waves: be prepared and mind some crucial aspects. Acta Biomed 2021;92:e2021097.
Vetrugno L, Guadagnin GM, Barbariol F, et al. Ultrasound Imaging for diaphragm dysfunction: a narrative literature review. J Cardiothorac Vasc Anesth 2019;33:2525-36. DOI: https://doi.org/10.1053/j.jvca.2019.01.003
Poulard T, Bachasson D, Fossé Q, et al. Poor correlation between diaphragm thickening fraction and transdiaphragmatic pressure in mechanically ventilated patients and healthy subjects. Anesthesiology 2022;136:162-75. DOI: https://doi.org/10.1097/ALN.0000000000004042
Cammarota G, Rossi E, Vitali L, et al. Effect of awake prone position on diaphragmatic thickening fraction in patients assisted by noninvasive ventilation for hypoxemic acute respiratory failure related to novel coronavirus disease. Crit Care 2021;25:305. DOI: https://doi.org/10.1186/s13054-021-03735-x
Hadda V, Raja A, Suri TM, et al. Temporal evolution of diaphragm thickness and diaphragm excursion among subjects hospitalized with COVID-19: a prospective observational study. Respir Med Res 2022;83:100960. DOI: https://doi.org/10.1016/j.resmer.2022.100960
Hennigs JK, Huwe M, Hennigs A, et al. Respiratory muscle dysfunction in long-COVID patients. Infection 2022;50:1391-7. DOI: https://doi.org/10.1007/s15010-022-01840-9
Schepens T, Fard S, Goligher EC. Assessing diaphragmatic function. Respir Care 2020;65:807-19. DOI: https://doi.org/10.4187/respcare.07410
Deana C, Vetrugno L, Cortegiani A, et al. Quality of life in COVID-related ARDS patients one year after intensive care discharge (Odissea Study): a multicenter observational study. J Clin Med 2023;12:1058. DOI: https://doi.org/10.3390/jcm12031058

Ethics Approval

The study was approved by the Institutional Review Board of the University of Udine (IRB ID 086/2021, November 22, 2021). Consent to participation was waived due to the retrospective design of the study.

How to Cite

Vetrugno, Luigi, Cristian Deana, Savino Spadaro, Gianmaria Cammarota, Domenico Luca Grieco, Annarita Tullio, Tiziana Bove, Carla Di Loreto, Salvatore Maurizio Maggiore, Maria Orsaria, and DIASUS study group. 2024. “Diaphragmatic Morphological <i>post-mortem</i> Findings in Critically Ill COVID-19 Patients: An Observational Study”. Monaldi Archives for Chest Disease, April. https://doi.org/10.4081/monaldi.2024.2829.
Copyright (c) 2024 The Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.