Effects of Mechanical Ventilation on the Diaphragm in COVID-19 Intensive Care Patients. A Post-mortem Pathology Study

Effects of Mechanical Ventilation on the Diaphragm in COVID-19 Intensive Care Patients. A Post-mortem Pathology Study.

The diaphragm is the fundamental muscle of the respiratory system. The diaphragmatic dysfunction is present in 60% of critical patients at hospital admission and up to 80% after prolonged mechanical ventilation and difficult weaning.

Risk factors associated with diaphragm dysfunction and atrophy are sepsis, trauma, sedatives, steroids, and muscle relaxants.

The main pathology characteristics of diaphragm biopsies of mechanically ventilated patients are atrophy and a reduction in contractility, determining an impact on the clinical outcome.

Shi et al. found a higher section area of the diaphragm muscle fiber in biopsies of post mortem COVID-19 patients versus negative patients, independently from days of mechanical ventilation.

The hypothesis of our study is to identify different clusters of pathological presentation in post-mortem COVID-19 mechanically ventilated patients.

Study Overview

• Status: Recruiting
• Conditions: COVID-19 Acute Respiratory Distress Syndrome; Ventilation Therapy; Complications; Diaphragm Injury; Pathology

• Study Type: Observational
• Enrollment (Anticipated): 41

Contacts and Locations

• Study Contact: Name: Luigi Vetrugno, MD; Phone Number: + 39 0432559509; Email: luigi.vetrugno@asufc.sanita.fvg.it

Study Locations

• Italy
  • Udine, Italy, 33100
    • Recruiting
    • Anesthesiology and Intensive Care Clinic - Department of Medicine - ASUIUD
    • Contact: Luigi Vetrugno, M.D.; Phone Number: +393382873386; Email: luigi.vetrugno@asuiud.sanita.fvg.it
  • Udine, Italy
    • Recruiting
    • Azienda ospedaliero universitaria Friuli Centrale, Clinica di Anestesia e Rianimazione
    • Contact: Tiziana Bove

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Deceased COVID-19 patients admitted to the intensive care unit and mechanically ventilated.

Description

Inclusion Criteria:

• patients deceased in the intensive care unit positive to SARS-CoV-2 and mechanically ventilated
• post-mortem examination of the diaphragm

Exclusion Criteria:

• patients with a terminal disease and a prognosis of less than 48 hours at admission.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical characteristics	Evaluate if there are specific clusters in the study population and find different clinical characteristics.	One week post mortem
Blood test characteristics	Evaluate if there are specific clusters in the study population and find different blood test characteristics.	One week post mortem
Pathology characteristics	Evaluate if there are specific clusters in the study population and find different pathology characteristics.	One week post mortem

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical ventilation	Verify if there are correlations between the clusters characteristics and the other variables in the study population mechanical ventilation.	One week post mortem
Therapy	Verify if there are correlations between the clusters characteristics and therapy in the study population.	One week post mortem
Arterial blood gas analysis	Verify if there are correlations between the clusters characteristics and arterial blood gas in the study population.	One week post mortem

Collaborators and Investigators

• Sponsor: Azienda Sanitaria-Universitaria Integrata di Udine

Publications and helpful links

General Publications

• Goligher EC, Dres M, Fan E, Rubenfeld GD, Scales DC, Herridge MS, Vorona S, Sklar MC, Rittayamai N, Lanys A, Murray A, Brace D, Urrea C, Reid WD, Tomlinson G, Slutsky AS, Kavanagh BP, Brochard LJ, Ferguson ND. Mechanical Ventilation-induced Diaphragm Atrophy Strongly Impacts Clinical Outcomes. Am J Respir Crit Care Med. 2018 Jan 15;197(2):204-213. doi: 10.1164/rccm.201703-0536OC.
• Dres M, Goligher EC, Heunks LMA, Brochard LJ. Critical illness-associated diaphragm weakness. Intensive Care Med. 2017 Oct;43(10):1441-1452. doi: 10.1007/s00134-017-4928-4. Epub 2017 Sep 15.
• McCool FD, Manzoor K, Minami T. Disorders of the Diaphragm. Clin Chest Med. 2018 Jun;39(2):345-360. doi: 10.1016/j.ccm.2018.01.012.
• Supinski GS, Morris PE, Dhar S, Callahan LA. Diaphragm Dysfunction in Critical Illness. Chest. 2018 Apr;153(4):1040-1051. doi: 10.1016/j.chest.2017.08.1157. Epub 2017 Sep 5.
• Hooijman PE, Beishuizen A, Witt CC, de Waard MC, Girbes AR, Spoelstra-de Man AM, Niessen HW, Manders E, van Hees HW, van den Brom CE, Silderhuis V, Lawlor MW, Labeit S, Stienen GJ, Hartemink KJ, Paul MA, Heunks LM, Ottenheijm CA. Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients. Am J Respir Crit Care Med. 2015 May 15;191(10):1126-38. doi: 10.1164/rccm.201412-2214OC.
• Shi Z, Bogaards SJP, Conijn S, Onderwater Y, Espinosa P, Bink DI, van den Berg M, van de Locht M, Bugiani M, van der Hoeven H, Boon RA, Heunks L, Ottenheijm CAC. COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients. BMJ Open Respir Res. 2021 Sep;8(1):e001052. doi: 10.1136/bmjresp-2021-001052.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Actual): March 31, 2021
• Study Completion (Anticipated): January 20, 2022

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: January 11, 2022
• First Posted (Actual): January 13, 2022

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: COVID DIAPHRAGM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No