Effect of Early Extracorporeal Diaphragm Pacing Combined With Tilt Table in Ventilated Patients.

Study Overview
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Brief Summary
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The aim of this study is to test the effect of 1week of extracorporeal diaphragm pacing (EDP) combined either with or without tilt table verticalization (TTV) on diaphragm function in patients with mechanical ventilation compared to conventional physiotherapy (CPT).

Detailed Description
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In order to explore whether extracorporeal diaphragm pacing (EDP) combined with tilt table verticalization (TTV) improves diaphragm function in mechanically ventilated patients, the investigators conducted a three-arms randomized controlled trial of 90 ventilated patients in the ICU of a general hospital in the southern China state of Guangzhou. After assessment of inclusion and exclusion criteria, patients were randomly assigned to one of the following three groups: (1) EDP with TTV and with conventional physiotherapy (CPT) (n = 30), (2) EDP without TTV and with CPT (n = 30), and (3) conventional physiotherapy (CPT; n = 30).

Official Title
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Effect of Early Extracorporeal Diaphragm Pacing （EDP） Combined With Tilt Table Verticalization （TTV) on Diaphragm Function in Critically Ill Patients With Mechanical Ventilation: a Randomized Controlled Trial.

Conditions
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Early Mobilization, Critically Ill, Mechanical Ventilation, Diaphragm Dysfunction

Intervention / Treatment
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* Device: Extracorporeal Diaphragm Pacing
* Device: Tilt Table Verticalization
* Other: Conventional Physiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Duration of mechanical ventilation prior to enrollment≤ 72 hours. Expected duration of mechanical ventilation≥72 hours. Participants (or their legal representatives) have signed informed consent. Exclusion Criteria: Pregnancy or breast-feeding. Prone ventilation or current extracorporeal membrane oxygenation. Hemodynamic instability: mean arterial pressure is less than 65 millimeters of mercury (mmHg) or higher than 85 millimeters of mercury (mmHg), heart rate > 150 beats / minute, intravenous use of larger doses of vasopressors (such as dopamine > 10 mg/ (kg· min) or norepinephrine/epinephrine >0.1 mg/ (kg· min)) or aortic balloon counter pulsation; respiratory rate< 5 breaths per minute; Oxygen saturation< 88%. New-onset myocardial ischemia. Unstable cervical spine fracture and spinal cord injury. Deterioration of neurological function, requiring intracranial pressure monitoring and ventricular drainage, or active control of intracranial hypertension. Current neuromuscular block treatment or pre-existing neuromuscular disease or neuromuscular junction disease affecting respiratory muscle (such as myasthenia gravis, Guillain-Barré syndrome, etc.). There are contraindications to diaphragmatic pacing (local skin, tissue incompleteness or infection, chest X-ray examination shows pneumothorax or pleural effusion accounting for 1/3 of bilateral chest cavity). Body mass index (BMI) ⩾40 kg/m2. Known / suspected phrenic nerve palsy. Patients who refuse active treatment or are in the terminal stage of malignant tumors, have an expected life expectancy of < 6 months, etc. Participated in other clinical studies related to mechanical ventilation within 2 months prior to the start of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>In the control condition, patients received conventional physiotherapy (CPT) according to standard clinic procedures. | Other: Conventional Physiotherapy<br>* Patients receive early mobilization, which refers to a series of clinical intervention protocols (such as passive movement or active exercises, etc.) that confers physical benefits at an early period in collaboration with a multidisciplinary team (intensive care physicians, rehabilitation physicians, physical therapists, occupational therapists, respiratory therapists, and nurses). The study intervention take place during working time between 8 a.m. and 17 p.m. Patients of all three study groups receive this rehabilitation program until they transfer out of ICU.<br>|
| Experimental: experimental group 1<br>the experimental group uses Extracorporeal Diaphragm Pacing (EDP) on the basis of the control group. | Device: Extracorporeal Diaphragm Pacing<br>* In the EDP group, a pacer using the extracorporeal diaphragm pacemaker provided by Guangzhou Xueliang Biotechnology Developing Co., Ltd., the pacing electrode is pasted on the body surface closest to the phrenic nerve at the outer edge of the lower end of the sternocleidomastoid muscle under ultrasound guidance, and the auxiliary electrode is placed between the second intercostal of the midline of the clavicle. The intensity of treatment parameters was set from low to high, and the intensity of treatment was increased when the patient could tolerate it, pacing 12-18 times/min at a frequency of 40 hertz (Hz)/30min/time, and performed every 12 hours for a week.<br>* Other names: External Diaphragm Pacing;Other: Conventional Physiotherapy<br>* Patients receive early mobilization, which refers to a series of clinical intervention protocols (such as passive movement or active exercises, etc.) that confers physical benefits at an early period in collaboration with a multidisciplinary team (intensive care physicians, rehabilitation physicians, physical therapists, occupational therapists, respiratory therapists, and nurses). The study intervention take place during working time between 8 a.m. and 17 p.m. Patients of all three study groups receive this rehabilitation program until they transfer out of ICU.<br>|
| Experimental: experimental group 2<br>the experimental group used Extracorporeal Diaphragm Pacing (EDP) combined with Tilt Table Verticalization (TTV) on the basis of the control group. | Device: Extracorporeal Diaphragm Pacing<br>* In the EDP group, a pacer using the extracorporeal diaphragm pacemaker provided by Guangzhou Xueliang Biotechnology Developing Co., Ltd., the pacing electrode is pasted on the body surface closest to the phrenic nerve at the outer edge of the lower end of the sternocleidomastoid muscle under ultrasound guidance, and the auxiliary electrode is placed between the second intercostal of the midline of the clavicle. The intensity of treatment parameters was set from low to high, and the intensity of treatment was increased when the patient could tolerate it, pacing 12-18 times/min at a frequency of 40 hertz (Hz)/30min/time, and performed every 12 hours for a week.<br>* Other names: External Diaphragm Pacing;Device: Tilt Table Verticalization<br>* VitalGo bed (VitalGo Systems Ltd., Fort Lauderdale） is used for verticalization. Verticalization was set to minimum 30°, depending on cardiopulmonary parameters (respiratory rate, heart rate, blood pressure, oxygen saturation), vertical position was gradually increased (in 5° steps) to a maximum of 90°, as long as the above-named cardiopulmonary parameters of the patient remained stable and remain this position for 30 minutes simultaneously with extracorporeal diaphragm pacing for a week.<br>* Other names: head-up tilt;Other: Conventional Physiotherapy<br>* Patients receive early mobilization, which refers to a series of clinical intervention protocols (such as passive movement or active exercises, etc.) that confers physical benefits at an early period in collaboration with a multidisciplinary team (intensive care physicians, rehabilitation physicians, physical therapists, occupational therapists, respiratory therapists, and nurses). The study intervention take place during working time between 8 a.m. and 17 p.m. Patients of all three study groups receive this rehabilitation program until they transfer out of ICU.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline on Diaphragm Thickening Fraction at Day 4 and Day 7. | The Diaphragm thickening fraction-DTf (%) was calculated as the difference between end-expiration and end-inspiration divided by end-inspiration × 100.Diaphragm thickening fraction (DTf) less than 20% is a measure of ultrasonographic diaphragmatic dysfunction in patients on mechanical ventilation. | Baseline, Day 4 and Day 7. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline on Ventilation mode at Day 4 and Day 7. | A ventilator mode is a way of describing how the mechanical ventilator assists the patient with taking a breath. | Baseline, Day 4 and Day 7. | 
| Change from Baseline on Positive End-expiratory Pressure (PEEP) at Day 4 and Day 7. | Positive end-expiratory pressure (PEEP) is the positive pressure that will remain in the airways at the end of the respiratory cycle (end of exhalation) that is greater than the atmospheric pressure in mechanically ventilated patients. | Baseline, Day 4 and Day 7. | 
| Change from Baseline on minute ventilation at Day 4 and Day 7. | It usually refers to the expired amount and can be calculated using the following equation: minute ventilation (VE)= tidal volume (VT) ×respiratory frequency(f) | Baseline, Day 4 and Day 7. | 
| Change from Baseline on tidal volume at Day 4 and Day 7. | Tidal volume is the amount of air that moves in or out of the lungs with each respiratory cycle. | Baseline, Day 4 and Day 7. | 
| Change from Baseline on Maximum Inspiratory Pressure (MIP） at Day 4 and Day 7. | The maximum inspiratory pressures measure the maximal efforts of the respiratory muscles. | Baseline, Day 4 and Day 7. | 
| Change from Baseline on airway occlusion pressure (P0.1) at Day 4 and Day 7. | P0.1 is a parameter for the neuro-muscular activation of the respiratory system, which is an important determinant for the work of breathing. | Baseline, Day 4 and Day 7. | 
| Change from Baseline on transdiaphragmatic pressure at Day 4 and Day 7. | Transdiaphragmatic pressure (Pdi) represents the pressure across the diaphragm, which can be expressed as the difference between abdominal pressure (Pab) and pleural pressure (Ppl):Pdi = Ppl- Pab. | Baseline, Day 4 and Day 7. | 
| Change from Baseline on MRC score at Day 4 and Day 7. | Medical Research Council (MRC)-sum score evaluates global muscle strength. Manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) is evaluated on both sides using MRC scale. Summation of scores gives MRC-sum score, ranging from 0 to 60. | Baseline, Day 4 and Day 7. | 
| Change from Baseline on Blood oxygen status at Day 4 and Day 7. | Oxygenation Index = (FiO2× Mean Airway Pressure) / partial pressure of oxygen in arterial blood (PaO2) The oxygenation index is used to assess the intensity of ventilatory support required to maintain oxygenation. | Baseline, Day 4 and Day 7. |