Clinical trial NCT05211661: Diaphragm Atrophy and Dysfunction in Mechanical Ventilation
Official title: Development of Diaphragm Atrophy, Dysfunction and Inhibited Cortical Control in Mechanical Ventilation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diaphragm Issues
Mechanical Ventilation Complication
Respiratory Failure
Intensive Care (ICU) Myopathy
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2022-01-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Comprehensive assessment of diaphragm atrophy, function, strength and control in patients in whom invasive mechanical ventilation in the Intensive Care Unit had been initiated within 48 hours. Then, serial measurements every third day including 2 measurements after extubation.

Brief summary: The gold standard of twitch transdiaphragmatic pressure recordings would ultimately clear the fog around the rate of development of Ventilator induced Diaphragm Dysfunction (VIDD) in mechanically ventilated patients over time.

Through measurements made even after mechanical ventilation (MV) it could be clarified to what extent patients recover from VIDD.

Paired with cortical stimulation and electromyographic recordings of diaphragm muscle potentials, it could be explored to what extent decreased diaphragm excitability due to long term MV contributes to VIDD on the level of motor cortex.

Against that background the present project aims at determining the rate of decline in diaphragm function, strength and control in patients undergoing MV (including measurements after extubation).

Detailed description: Evidence both from animal and human studies support the development of ventilator induced diaphragm dysfunction (VIDD) from as early as 24 hours of mechanical ventilation (MV) in the intensive care unit (ICU).

However, while the concept of VIDD seems to be proven now, several questions remain unanswered regarding its actual rate of development and (potentially) recovery after MV.

The gold standard of twitch transdiaphragmatic pressure recordings would ultimately clear the fog around the rate of development of VIDD over time.

Through measurements made even after MV it could be clarified to what extent patients recover from VIDD.

Paired with cortical stimulation and electromyographic recordings of diaphragm muscle potentials, it could be explored to what extent decreased diaphragm excitability due to long term MV contributes to VIDD on the level of motor cortex.

Against that background the present project aims at determining the rate of decline in diaphragm function, strength and control in patients undergoing MV (including measurements after extubation).

Eligibility criteria: Inclusion Criteria:

* Initiation of invasive mechanical ventilation in the Intensive Care Unit within 48 hours.
* Expected duration of invasive mechanical ventilation of at least 5 days.

Exclusion Criteria:

* Body-mass-index (BMI) \>40
* Expected absence of active participation of the patient in study-related measurements after extubation
* Alcohol or drug abuse
* Non MRI compatible implant in the body
* Slipped disc
* Epilepsy
* Patients in an interdependence or with an employment contract with the principal investigator, Co-PI or his deputy.

Primary outcomes:
measure: Twitch transdiaphragmatic pressure in response to supramaximal magnetic stimulation of the phrenic nerve roots.
timeFrame: 2 years
measure: Cortical control of diaphragm function
timeFrame: 2 years
Secondary outcomes:
measure: Diaphragm ultrasound
timeFrame: 2 years
measure: Systemic inflammation
timeFrame: 2 years
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: RWTH Aachen University
Study officials:
affiliation: RWTH Aachen University Hospital
name: Michael Dreher, Professor
role: STUDY_CHAIR
affiliation: RWTH Aachen University Hospital
name: Jens Spiesshoefer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Spiesshoefer J, Herkenrath S, Henke C, Langenbruch L, Schneppe M, Randerath W, Young P, Brix T, Boentert M. Evaluation of Respiratory Muscle Strength and Diaphragm Ultrasound: Normative Values, Theoretical Considerations, and Practical Recommendations. Respiration. 2020;99(5):369-381. doi: 10.1159/000506016. Epub 2020 May 12.
citation: Spiesshoefer J, Henke C, Herkenrath S, Randerath W, Brix T, Young P, Boentert M. Assessment of Central Drive to the Diaphragm by Twitch Interpolation: Normal Values, Theoretical Considerations, and Future Directions. Respiration. 2019;98(4):283-293. doi: 10.1159/000500726. Epub 2019 Jul 26.
citation: Spiesshoefer J, Henke C, Herkenrath S, Brix T, Randerath W, Young P, Boentert M. Transdiapragmatic pressure and contractile properties of the diaphragm following magnetic stimulation. Respir Physiol Neurobiol. 2019 Aug;266:47-53. doi: 10.1016/j.resp.2019.04.011. Epub 2019 Apr 25.
citation: Sharshar T, Ross ET, Hopkinson NS, Porcher R, Nickol AH, Jonville S, Dayer MJ, Hart N, Moxham J, Lofaso F, Polkey MI. Depression of diaphragm motor cortex excitability during mechanical ventilation. J Appl Physiol (1985). 2004 Jul;97(1):3-10. doi: 10.1152/japplphysiol.01099.2003. Epub 2004 Mar 12.
citation: Windisch W, Geiseler J, Simon K, Walterspacher S, Dreher M; on behalf of the Guideline Commission. German National Guideline for Treating Chronic Respiratory Failure with Invasive and Non-Invasive Ventilation: Revised Edition 2017 - Part 1. Respiration. 2018;96(1):66-97. doi: 10.1159/000488001. Epub 2018 Jun 26.
citation: Windisch W, Geiseler J, Simon K, Walterspacher S, Dreher M; on behalf of the Guideline Commission. German National Guideline for Treating Chronic Respiratory Failure with Invasive and Non-Invasive Ventilation - Revised Edition 2017: Part 2. Respiration. 2018;96(2):171-203. doi: 10.1159/000488667. Epub 2018 Jun 26.