Electromagnetic Stimulation of the Phrenic Nerve in Critically Ill Mechanically Ventilated Patients (STIMIT-II)

Study Overview
=================
Brief Summary
-----------------
Ventilator-induced diaphragmatic dysfunction is a common issue in critically ill patients. Muscle stimulation has shown to have beneficial effects in muscle groups on the extremities. A non-invasive way to stimulate the diaphragm would be the electromagnetic stimulation but it is currently unclear if that is feasible. In this proof-of-concept trial the primary aim is to show that it is possible to induce a diaphragmatic contraction in critically ill ICU patients via an external electromagnetic stimulation of the phrenic nerve, leading to an inspiration (i) with a sufficient tidal volume (3-6 ml/kg ideal body weight) and (ii) with verifiable muscular diaphragmatic contraction through ultrasound imaging.

Detailed Description
-----------------
During the time of first spontaneous breathing trial 60% of mechanically ventilated patients present with diaphragmatic weakness or also know as ventilator-induced diaphragmatic dysfunction (VIDD). The damage to the diaphragm in terms of muscle atrophy has been shown as early as 12 hours after initiation of mechanical ventilation. Recently, a correlation between diaphragmatic atrophy and mortality could be established. Induction of diaphragmatic contractions via stimulation of the phrenic nerve would be a possible method to prevent or treat VIDD. A possible modality would be the non-invasive electromagnetic stimulation but feasibility has not been established. In this proof-of-concept trial the primary aim is to show that it is possible to induce a diaphragmatic contraction in critically ill ICU patients via an external electromagnetic stimulation of the phrenic nerve, leading to an inspiration (i) with a sufficient tidal volume (3-6 ml/kg ideal body weight) and (ii) with verifiable muscular diaphragmatic contraction through ultrasound imaging.

Official Title
-----------------
Electromagnetic Stimulation of the Phrenic Nerve to Generate Contraction of the Diaphragm in Critically Ill Mechanically Ventilated Patients - a Proof-of-concept Study (STIMIT-II)

Conditions
-----------------
Muscle Weakness, Critical Illness, Mechanical Ventilation Complication

Intervention / Treatment
-----------------
* Device: Non-invasive electromagnetic stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients between 18 and 60 years old, hospitalized in ICU Mechanical ventilation < 36 h Prone to stay ventilated > 72 h Exclusion Criteria: Known neurological condition affecting motor neuron or muscle (e.g. ALS) Known paralysis of the phrenic nerve Proven or suspected spinal cord injury that contraindicates weight bearing on the spinal cord Conditions that limit diaphragm movement (high intra-abdominal pressure, ascites, obesity) Not able to read and understand the national language German Patients with Implanted cardiac support systems (pacemaker, implanted defibrillator) Patients with implanted medical pumps Pregnant patients Patients with skin lesions, infections or strictures in throat/neck area Patients with metallic implants

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 15 patients in control group, 15 patients in interventional group with sequential design in term of daily frequency of non-invasive electromagnetic phrenic nerve stimulation, i.e. starting with 5 patients with 2 stimulation per day, followed by 5 patients with 3 stimulations and 5 patients with 5 stimulations per day
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention, stimulated<br>Electromagnetic stimulation of the phrenic nerve in critically ill patients. | Device: Non-invasive electromagnetic stimulation<br>* Non-invasive bilateral electromagnetic stimulation of the phrenic nerve<br>|
| No Intervention: Control, not stimulated<br>Control group, no stimulation of the phrenic nerve. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of non-feasible stimulation, due to organisational or patient-specific reasons. | Percentage of non-feasible stimulation out of the total number of stimulations planned according to the investigation protocol. | 10 days | 
| Time to find the optimal stimulation point of the N. phrenicus | Time between first successful N. phrenicus stimulation and identification of the optimal stimulation locus in seconds | Study duration (10 days) | 
| Frequency of sufficient Tidal volume generated by electromagentical stimulation of the phrenic nerve (3-6 ml/kg ideal body weight) | Percentage of stimulated breaths above the cut-off Today volume (3-6 ml/kg ideal body weigh) out of the total number of stimulated breaths. Tidal volumes are measured by the mechanical ventilator. | Study duration (10 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variance of Tidal volume generated by electromagentical stimulation of the phrenic nerve | Measurement of variance among the Tidal volumes stimulated during the experimental therapy intervention; Tidal volumes are measured by the mechanical ventilator. | Study duration (10 days) | 
| Correlation between amplitude and duration of sEMG signals during stimulated breathing. | sEMG amplitude and duration are measured by a device (sEMG Amplificator) connected to electrodes applied to the patient's chest during electromagnetic phrenic nerve stimulation. | Study duration (10 days) | 
| Transpulmonary pressure during electromagnetical stimulation of the phrenic nerve | Transpulmonary pressure is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation. | Study duration (10 days) | 
| Occlusion pressure during electromagnetical stimulation of the phrenic nerve | Occlusion pressure is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation. | Study duration (10 days) | 
| Diaphragm thickening fraction | Diaphragm thickening fraction measured with ultrasound of the diaphragm. | approx. 28 days (till ICU discharge) | 
| Diaphragm excursion | Diaphragm excursion measured with ultrasound of the diaphragm. | approx. 28 days (till ICU discharge) | 
| Stimulated tracheal pressure during electromagentical stimulation of the phrenic nerve | Stimulated tracheal pressure is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation. | Study duration (10 days) | 
| Rapid Shallow Breathing Index (RSBI) record and evaluation. | Progression of RSBI during 10 days after subject inclusion, based on the mechanical ventilation parameters (Tidal volume) and the ICU continuous monitoring system (Respiratory Rate). | Study duration (10 days) | 
| Lung compliance during electromagentical stimulation of the phrenic nerve | Lung compliance is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation. | 10 days | 
| Lung resistance during electromagentical stimulation of the phrenic nerve | Lung resistance is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation. | 10 days | 
| Maximal inspiratory pressure (MIP) during electromagnetical stimulation of the phrenic nerve. | MIP is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation. | Study duration (10 days) | 
| Expiratory and Inspiratory Diaphragm Thickness measured by Ultrasound | Diaphragm Thickness measured by Ultrasound as a baseline parameter for muscle atrophy. | Study duration (10 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
VIDD, ICUAW, Muscle Weakness, Weaning