Diaphragm Injury and Dysfunction During Mechanical Ventilation (MYOTRAUMA)

This study is designed to evaluate the relationship between diaphragm activity during mechanical ventilation and the development of ventilator-induced diaphragm dysfunction (VIDD). Diaphragm structure, activity, and function are monitored longitudinally over the first 7 days of mechanical ventilation.

Study Overview

• Status: Completed
• Conditions: Respiratory Insufficiency; Mechanical Ventilation Complication; Diaphragm Injury

Detailed Description

Multiple factors are responsible for injury to the diaphragm during mechanical ventilation and critical illness. Suppression of respiratory drive and respiratory muscle activity can contribute to diaphragm dysfunction and increase the risk of prolonged mechanical ventilation.

The objective of this study is to determine whether diaphragm inactivity or injurious loading of hte diaphragm during mechanical ventilation leads to the development of diaphragm weakness. To address this question, we are monitoring the diaphragm longitudinally over the first week of mechanical ventilation.

Diaphragm activity is monitored by measurements of transdiaphragmatic pressure and diaphragm electrical activity. Diaphragm function is assessed by maximal transdiaphragmatic pressure generation and by measurements of diaphragm neuromuscular coupling. Diaphragm structure is assessed by daily ultrasound imaging.

Study measurments commence at enrolment (within 36 hours of intubation) and continue for the first 7 days of the study (or until extubation or death, if earlier).

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Critically ill patients who are receiving invasive mechanical ventilation for less than 36 hours.

Description

Inclusion Criteria:

• Adult patients (>18) with acute respiratory failure receiving invasive mechanical ventilation for less than 36 hours diagnosed with any of the following conditions: acute severe brain injury; moderate or severe ARDS; septic shock; pneumonia

Exclusion Criteria:

• Predicted probability of remaining alive and on the ventilator on ICU day 7 is less than 50%
• Liberation from mechanical ventilation is expected/planned within 24 hours
• High cervical spine injury (C5 or higher)
• Receiving mechanical ventilation for neuromuscular disease
• Acute exacerbation of an obstructive lung disease
• Known esophageal varices or any other condition for which the attending physician deems an orogastric catheter to be unsafe
• Esophageal, gastric or duodenal surgical procedures within the last 6 months
• Received mechanical ventilation for > 48 hours in the preceding 6 months

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Acute respiratory failure; We are enrolling patients who are intubated because of acute respiratory distress syndrome, pneumonia, septic shock, or severe acute brain injury (GCS ≤ 8 prior to intubation). This population is targeted for study because they are at relatively high risk of requiring prolonged mechanical ventilation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diaphragm dysfunction	Diaphragm dysfunction will be defined as maximal transdiaphragmatic pressure < 30 cm H2O and/or maximal diaphragm thickening fraction < 20% at study completion	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Diaphragm thickness	7 days
Diaphragm neuromuscular coupling	7 days
Duration of inactivity (hours)	7 days
Patient-ventilator asynchrony rate	7 days

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Publications and helpful links

General Publications

• Levine S, Nguyen T, Taylor N, Friscia ME, Budak MT, Rothenberg P, Zhu J, Sachdeva R, Sonnad S, Kaiser LR, Rubinstein NA, Powers SK, Shrager JB. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008 Mar 27;358(13):1327-35. doi: 10.1056/NEJMoa070447.
• Jaber S, Petrof BJ, Jung B, Chanques G, Berthet JP, Rabuel C, Bouyabrine H, Courouble P, Koechlin-Ramonatxo C, Sebbane M, Similowski T, Scheuermann V, Mebazaa A, Capdevila X, Mornet D, Mercier J, Lacampagne A, Philips A, Matecki S. Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. Am J Respir Crit Care Med. 2011 Feb 1;183(3):364-71. doi: 10.1164/rccm.201004-0670OC. Epub 2010 Sep 2.
• Goligher EC, Fan E, Herridge MS, Murray A, Vorona S, Brace D, Rittayamai N, Lanys A, Tomlinson G, Singh JM, Bolz SS, Rubenfeld GD, Kavanagh BP, Brochard LJ, Ferguson ND. Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort. Am J Respir Crit Care Med. 2015 Nov 1;192(9):1080-8. doi: 10.1164/rccm.201503-0620OC.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 25, 2013
• Primary Completion (ACTUAL): December 1, 2019
• Study Completion (ACTUAL): December 1, 2019

Study Registration Dates

• First Submitted: April 4, 2017
• First Submitted That Met QC Criteria: April 4, 2017
• First Posted (ACTUAL): April 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 15, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Weaning; Acute respiratory failure; Diaphragm dysfunction
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Wounds and Injuries
• Other Study ID Numbers: 12-5582-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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