Clinical trial NCT05191433: Effects of Mechanical Ventilation on the Diaphragm in COVID-19 Intensive Care Patients. A Post-mortem Pathology Study
Official title: Effects of Mechanical Ventilation on the Diaphragm in COVID-19 Intensive Care Patients. A Post-mortem Pathology Study.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diaphragm Injury
Pathology
COVID-19 Acute Respiratory Distress Syndrome
Ventilation Therapy; Complications
Lead sponsor: Azienda Sanitaria-Universitaria Integrata di Udine
Sponsor class: OTHER
First posted: 2022-01-13
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Deceased COVID-19 patients admitted to the intensive care unit and mechanically ventilated.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical characteristics
timeFrame: One week post mortem
measure: Blood test characteristics
timeFrame: One week post mortem
measure: Pathology characteristics
timeFrame: One week post mortem
Secondary outcomes:
measure: Mechanical ventilation
timeFrame: One week post mortem
measure: Therapy
timeFrame: One week post mortem
measure: Arterial blood gas analysis
timeFrame: One week post mortem
Other outcomes:
Locations:
city: Udine
country: Italy
facility: Anesthesiology and Intensive Care Clinic - Department of Medicine - ASUIUD
city: Udine
country: Italy
facility: Azienda ospedaliero universitaria Friuli Centrale, Clinica di Anestesia e Rianimazione
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.