Clinical trial NCT03108118: Diaphragm Injury and Dysfunction During Mechanical Ventilation
Official title: Diaphragm Injury and Dysfunction During Mechanical Ventilation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Insufficiency
Diaphragm Injury
Mechanical Ventilation Complication
Keywords: Diaphragm dysfunction
Acute respiratory failure
Weaning
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2017-04-11
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Critically ill patients who are receiving invasive mechanical ventilation for less than 36 hours.

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Diaphragm dysfunction
timeFrame: 7 days
Secondary outcomes:
measure: Diaphragm thickness
timeFrame: 7 days
measure: Diaphragm neuromuscular coupling
timeFrame: 7 days
measure: Duration of inactivity (hours)
timeFrame: 7 days
measure: Patient-ventilator asynchrony rate
timeFrame: 7 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Ewan C Goligher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.