Diaphragm Atrophy and Dysfunction in Mechanical Ventilation

Respiratory Failure Clinical Trial

— DAM  

Official title:

Development of Diaphragm Atrophy, Dysfunction and Inhibited Cortical Control in Mechanical Ventilation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05211661
• Other study ID #: CTCA 21-279
• Status: Recruiting
• Start date: October 10, 2022
• Est. completion date: December 1, 2023

Study information

• Verified date: October 2022
• Source: RWTH Aachen University
• Contact: Michael Dreher, Professor
• Phone: +4924180
• Email: mdreher[@]ukaachen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2023
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Diaphragm Issues
• Intensive Care (ICU) Myopathy
• Mechanical Ventilation Complication
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Diagnostic Test:
• Respiratory Muscle Testing
Comprehensive assessment of respiratory muscle function. Comprehensive assessment of respiratory muscle function to the point of its invasive assessment with recordings of twitch transdiaphragmatic pressure in response to magnetic phrenic nerve stimulation and stimulation of the lower thoracic nerve roots.

Locations

Country	Name	City	State
Germany	RWTH Aachen University	Aachen

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

References & Publications (6)

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. Epub 2004 Mar 12. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Twitch transdiaphragmatic pressure in response to supramaximal magnetic stimulation of the phrenic nerve roots.		2 years
Primary	Cortical control of diaphragm function	Amplitude of the diaphragm motor evoked potentials (measured by surface electrodes attached to the diaphragm) following cortical magnetic stimulation of the phrenic nerve roots.	2 years
Secondary	Diaphragm ultrasound	Diaphragm thickening fraction on ultrasound	2 years
Secondary	Systemic inflammation	Concentration of circulating Interleukin, high-sensitivity C-reactive protein (analyzed quantitatively based on a Levels venous blood sample).	2 years