Use of Neuromuscular Electrostimulation (NMES) for Treatment or Prevention of ICU-Associated Weakness

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether neuromuscular electrostimulation (NMES) will decrease ICU-associated weakness. The investigators believe that 60 minutes of daily NMES will improve strength and function in those who have had extended ICU stays, as well as decrease critical illness myopathy as an etiology of weakness in the critically ill.

Detailed Description
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Survivors of critical illness frequently have significant, debilitating and persistent weakness after discharge from the intensive care unit (ICU). This weakness can persist for up to 4 years after ICU discharge. There are few interventions that have been successful in reducing or preventing weakness. Neuromuscular electrostimulation (NMES) therapy is beneficial in other populations of weak and functionally limited patients, such as those with chronic respiratory failure requiring mechanical ventilation, severe chronic obstructive pulmonary disease and end-stage congestive heart failure. We propose a randomized clinical trial to evaluate the efficacy of 60 minutes of NMES versus sham therapy, applied to the bilateral lower extremities, to reduce ICU-associated weakness in patients with acute respiratory failure. Our specific aims are to determine if NMES therapy will: 1) increase strength of the 3 treated lower extremity muscle groups (i.e., pretibial, triceps surae, and quadriceps), 2) improve important clinical outcomes (i.e., functional status, duration of mechanical ventilation, length of ICU and hospital stay, in-hospital mortality, and total hospital charges), 3) reduce critical illness myopathy as an etiology of weakness in clinically weak ICU patients. The investigators hypothesize that NMES therapy will reduce ICU-associated weakness, and improve clinical and functional outcomes. Additionally, the rates of critical illness myopathy as an etiology of weakness in clinically weak ICU patients will be lower in those receiving NMES versus sham therapy. Since there is no single test that is optimal for measuring muscle strength in the critically ill, the investigators will employ four non-invasive measures: manual muscle testing (MMT), hand held dynamometry (HHD), handgrip dynamometry (HGD), and maximal inspiratory pressure (MIP). With no existing therapeutic options available, our study explores the potential of NMES as a feasible intervention to reduce ICU-associated weakness.

Official Title
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Use of Neuromuscular Electrostimulation (NMES) for Treatment or Prevention of ICU-Associated Weakness

Conditions
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Intensive Care Unit, Muscle Weakness

Intervention / Treatment
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* Device: Neuromuscular Electrostimulation (NMES) CareStim Muscle Stimulation Device (Care Rehab; McLean, VA)
* Device: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1 day of mechanical ventilation with an expectation of requiring ≥2 additional days of ICU stay in a Johns Hopkins Intensive Care Unit (ICU) Exclusion Criteria: Unable to understand or speak English due to language barrier or cognitive impairment prior to admission Unable to independently transfer from bed to chair at baseline prior to hospital admission Known primary systemic neuromuscular disease (e.g. Guillian-Barre) at ICU admission Known intracranial process that is associated with localizing weakness (e.g. cerebral vascular accident) at ICU admission Transferred from another ICU outside of the Johns Hopkins system after >4 consecutive days of mechanical ventilation Moribund (i.e. >90% probability of patient mortality in the next 96 hours) Anticipated transfer to another ICU for care (e.g. awaiting organ transplantation and transfer to surgical ICU) Any pacemaker (e.g., cardiac, diaphragm) or implanted cardiac defibrillator Pregnancy Body mass index ≥35 kg/m2 Any limitation in life support other than a sole no-CPR order Known or suspected malignancy in the legs Unable to treat or evaluate both lower extremities (e.g., bilateral amputation, bilateral skin lesions) ICU length of stay >7 days prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NMES<br>60 minute daily NMES sessions every day for the duration of subject's ICU stay. | Device: Neuromuscular Electrostimulation (NMES) CareStim Muscle Stimulation Device (Care Rehab; McLean, VA)<br>* 60 minute NMES sessions will be applied to three muscle groups of the lower extremities (quadriceps, pretibial, and triceps surae). Sessions start at study entry, and will occur every day for the duration of subject's ICU stay.<br>* Other names: CareStim Muscle Stimulation Device (Care Rehab; McLean, VA);|
| Sham Comparator: Sham<br>60 minute sham sessions every day for the duration of subjects ICU stay. No voltage will be applied to those receiving sham sessions. | Device: Sham<br>* 60 minute NMES sessions will be applied to three muscle groups of the lower extremities (quadriceps, pretibial, and triceps surae). Sessions start at study entry, and will occur every day for the duration of subject's ICU stay. Sham groups will NOT have voltage applied.<br>* Other names: CareStim Muscle Stimulation Device (Care Rehab; McLean, VA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower Extremity Strength, at Hospital Discharge, of 3 Bilateral Muscle Groups (Pretibial, Triceps Surae, and Quadriceps) Measured Via MMT Using a Composite Medical Research Council (MRC) Score | Range 0 to 30 with higher score better. The composite score is a simple sum of the individual scores from the 3 bilateral muscle groups | At hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual Muscle Strength Using Handheld Dynamometry: Tibialis Anterior, Gastrocnemius, and Quadriceps Muscle Strength | Strength (in pounds) - measured via handheld dynamometry of tibialis anterior, gastrocnemius, and quadriceps | ICU and hospital discharge | 
| Overall Body Strength | Measuring strength of 6 muscle groups in arms and legs using Medical Research Council composite score (each muscle group scored from scale of 0 [no visible or noticeable contraction] to 5 [maximum strength] and the sum of the scores for the 6 muscle groups equate to a composite score ranging from 0 to 60, higher score is better). | ICU and hospital discharge | 
| Hand Grip Strength | Hand grip strength measured using a dynamometer (measured in kilograms, then compared to age- and sex-matched population norms to yield % predicted) | ICU and hospital discharge | 
| Respiratory Muscle Strength | Measured using maximal inspiratory pressure (MIP) measurements that is then compared to predicted values for each participant (i.e., % predicted) | ICU and hospital discharge | 
| Functional Status Measured Using Functional Status Score for the Intensive Care Unit | Evaluates a patient's physical function in the ICU setting. Each task is scored, ranging from 0 (unable to perform) to 7 (complete independence).The total score ranges from 0-35, with higher scores indicating better physical functioning. | ICU and hospital discharge | 
| Duration of Mechanical Ventilation | The number of days the patient was on mechanical ventilation. | Until hospital discharge | 
| ICU and Hospital Length of Stay | The number of days that the patient was in the ICU and hospital, respectively. | ICU and Hospital discharge | 
| ICU and In-hospital Mortality | The number of patients who died in the ICU and those who died by hospital discharge. | ICU discharge and Hospital discharge | 
| Total Hospital Charges | The total dollar amount of charges from hospital stay | Hospital discharge | 
| Hospital Discharge Destination (e.g., Home, Rehab Facility) | Discharge location after hospital stay. | Hospital discharge | 
| Lower Extremity Strength, at Hospital Discharge, of 3 Bilateral Muscle Groups (Pretibial, Triceps Surae, and Quadriceps) | Measured via manual muscle strength test using a composite Medical Research Council (MRC) score with each muscle group rated with score ranging from 0 (no visible or noticeable contraction of the muscle) to 5 (maximum strength). The sum of the scores for the lower limb muscle groups can range from 0 to 30 (higher score is better) | At hospital discharge | 
| Mean Change in Subject's Lower Extremity Muscle Strength Composite Score From Baseline | The mean change of the sum of the lower limb strength scores between awakening and ICU discharge and between ICU discharge and hospital discharge. Three lower limb muscle groups are assessed bilaterally (each muscle group scored from scale of 0 [no visible or noticeable contraction] to 5 [maximum strength]). The scores are then summed for each patient at each time point (range 0 -30, higher score is better). | At ICU and Hospital discharge | 
| ICU Delirium | Proportion of ICU days the patient had delirium | During ICU stay - on days with study (NMES/Sham) session | 
| Subgroup Analysis | For patients with >= 7 days of mechanical ventilation, we will compare the 2 groups for the following outcomes: Lower extremity muscle strength, mean change in whole body muscle strength score from baseline to ICU discharge, mean change in whole body muscle strength score from baseline to hospital discharge, and whole body muscle strength score at ICU discharge and at hospital discharge. Each muscle group is assessed bilaterally (scale of 0 [no visible or noticeable contraction] to 5 [maximum strength]). There are three muscle groups assessed bilaterally for lower extremity (hip flexion, knee extension, and ankle dorsiflexion) (score range 0-30, higher score is better i.e. stronger); while for whole body strength assessment (score range 0-360, higher score is better), the following additional muscles are assessed: shoulder abduction, elbow flexion and wrist extension. The scores are then summed for each patient at each time point. | ICU and hospital discharge and change over time | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiration, Artificial, Critical Illness, Intensive Care Units, Electric Stimulation Therapy, Muscle Weakness, Paresis, Mechanically, Ventilated, Patients, Admitted, Medical