Neuromuscular Electrical Stimulation in ICU Patients

NCT04332263 | Terminated

• 1 other identifier: 36588914.4.1001.5347
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the present study is to evaluate the effects of neuromuscular electrical stimulation (NMES) combined with conventional physiotherapy (Experimental Group), compared to conventional physiotherapy only (Control Group) in critically ill Intensive Care Unit (ICU) patients, by means of a randomized controlled clinical trial. The investigators expect that the NMES program will be able to reduce muscle structure and function losses compared to control group, and will improve muscle quality faster, will reduce the ventilation time and the total time spent at the ICU, as well as improve functionality of these patients. In addition, the researchers expect to understand which mechanisms determine such adaptations in the musculoskeletal system of these patients.

Conditions

Intensive Care Unit Acquired Weakness

Outcome Measures

Primary Outcomes (8)

• Total ICU time

  Total time of stay at the ICU, from admission to discharge (an average of 7 up to 15 days). Total ICU time will be collected from the patient's medical record.

  Immediately after each patient discharge from the ICU (7 to 15 days after entry at the ICU, on average).

• Mechanical ventilation time

  Total time of mechanical ventilation, from patient intubation to weaning, will be collected from the patient's medical record.

  Immediately after each patient mechanical ventilation release (2 to 5 days from intubation start, on average).

• Weaning time

  Time and success of weaning post-mechanical ventilation, from weaning to ICU discharge, will be collected from the medical record of the patient. The maintenance of spontaneous ventilation for at least 48 hours after discontinuation of artificial ventilation will be considered a successful weaning.

  Immediately after each patient discharge from the ICU (7 to 15 days after entry at the ICU, on average).

• Change in knee extensor evoked force

  Knee extensor evoked force (EF) will be evaluated by means of isometric tests using a stainless steel dynamometry system instrumented with a load cell. EF will be evaluated through evoked contractions of the knee extensor muscles generated by supramaximal electrical stimuli with symmetrical rectangular biphasic current, applied in the form of single pulses (phase duration=1 ms, pulse duration=2 ms). At the beginning of the tests, the singular pulses will be applied with a manual trigger, and current intensity will be gradually increased (maximum 180 mA, inter-pulse interval = 3-5 second), until no further EF increase is observed. The current intensity required to reach the peak EF will then be increased by 10% to ensure supra-maximal stimulus during the tests. Three singular pulses will be applied and EF will be obtained by the mean value from the three evoked contractions. The change in knee extensor EF will be calculated as the difference in EF from ICU admission to ICU discharge.

  Change from the patient ICU admission to immediately before ICU discharge (e.g., from day 1 to day 7-15, on average).

• Knee extensor maximal voluntary isometric contraction

  Maximal knee extensor strength capacity during voluntary effort will be assessed only when the patient is discharged (POST) from ICU, by performing maximum voluntary isometric contractions (MVICs). To do so, once properly positioned on the dynamometer, subjects will perform three knee extensor MVICs, maintaining each contraction for a 5 sec period each. Subjects will be instructed to perform the contractions without any visual feedback, rapidly increasing the effort until they reach the maximum torque production, which should be maintained until the verbal command to cease contraction. Two-minute intervals will be given between contractions. The highest torque value recorded during the three MVICs will be adopted as the maximum voluntary effort (maximal torque). Mean and standard deviation values from the MVICs will be calculated for the experimental groups.

  Immediately before each patient ICU discharge (7 to 15 days after admission, on average).

• Knee extensor muscle quality: Real-time ultrasound 9 MHz frequency

  Real-time ultrasound (Vivid-I, General Electric, USA) obtained with a linear array probe (4 cm wide) and a 9 MHz sampling frequency will be used for the evaluation of muscle quality. Images from the rectus femoris (RF) muscle will be obtained with the participants at rest. Ultrasound images will be captured in the muscle's transverse plane, at 50% of the muscle's belly. To ensure the ultrasound images comparison at different times, the brightness and contrast settings will be maintained at 50% during all evaluations. Muscle quality will be determined using a standard function of the Image-J (National Institute of Health, USA) software. A region of interest that includes as much muscle area as possible, avoiding the fascia, will be selected from the RF muscle images. Muscle quality will be determined by analysing the image's average gray scale, which ranges from total black (0) to total white (255), and mean values from three ultrasound images will be determined.

  Immediately after each patient ICU admission and immediately before ICU discharge (7 to 15 days on average).

• Rectus femoris cross-sectional area

  RF cross-sectional area (CSA) will be captured at rest in the muscle's transverse plane, at 70% of the muscle belly. The probe will be positioned transversely to the muscle belly, with the image depth adjusted so that both the RF superficial and deep aponeuroses can be visualized. RF CSA will be obtained through the analysis of these transverse images. A standard function of the Image-J (National Institute of Health, USA) software will be used, which allows the demarcation of the muscular perimeter (excluding the aponeuroses), and calculates the internal selected area (cm2). The mean CSA value from three images will be calculated for each group at each time-point of the study.

  Immediately after each patient ICU admission and immediately before ICU discharge (7 to 15 days on average).

• Knee extensors muscle thickness

  Muscle thickness (MT) will be obtained at rest from ultrasound images of the RF, vastus intermedius (VI), vastus lateralis (VL) and vastus medialis (VM) muscles. Ultrasound images will be captured at 50% of the RF, VI and VL muscle bellies, and at 70% of the VM length. MT will be obtained by image analysis in the Image-J software (National Institute of Health, USA). Five equidistant measurements will be taken from the superficial to deep aponeurosis of the VI, VL and VM muscles. RF diameter will be obtained from the transverse image obtained for muscle quality evaluation and will represent its MT. The mean value of the five measures of the VI, VL and VM muscles will be calculated for each image. The mean MT value from three ultrasound images will be calculated and will be used as the MT from each evaluated muscle (in cm).

  Immediately after each patient ICU admission and immediately before ICU discharge (7 to 15 days on average).

Secondary Outcomes (20)

• Sit to stand test

  Immediately after each patient ICU discharge (7 to 15 days after admission, on average).

• Waking Speed Test

  Immediately after each patient ICU discharge, until study completion (about 30 months).

• Heart rate variability

  Immediately before and during NMES intervention protocols (daily, from 7 to 15 days on average).

• Peripheral polyneuropathy

  Immediately before ICU discharge (7 to 15 days after admission, on average).

• Inflammatory profile

  Immediately after each patient ICU admission and immediately before ICU discharge (7 to 15 days on average).

Study Arms (2)

Neuromuscular Electrical Stimulation - NMES

EXPERIMENTAL

NMES will be applied bilaterally on the quadriceps femoris muscle of ICU patients. An electrical stimulation system and an ICU-designed dynamometer will be used with the patients lying in bed, with the hips and the knees flexed at 60 and 90 degrees, respectively. Supramaximal single-pulse's peak force will be used to determine the NMES intervention level. NMES (alternating biphasic current, stimulation frequency = 80 Hz, 1 ms pulse duration) will be used to evoke tetanic forces (EF) at 50% of the supra-maximal single-pulse EF (i.e., 10-12% of a maximal voluntary isometric contraction). NMES protocol will be performed five times a week, lasting 20 min. Muscle fatigue will be evaluated every 5 min of the intervention, and will be determined as a 10 % decrease in the single-pulse evoked torque between the evoked force produced pre- and during the NMES protocol. If and when a 10% reduction of the single-pulse EF is achieved, the intervention protocol will be terminated before the 20 min.

Other: Neuromuscular Electrical Stimulation - NMES

Control Group - CG

NO INTERVENTION

The control group (CG) will only perform conventional physiotherapy and will not receive any NMES training, but will be evaluated through the same evaluations and in the same moments of the two above mentioned intervention groups. Conventional physiotherapy will be given to all three groups.

Interventions

Neuromuscular Electrical Stimulation - NMES OTHER

NMES will be applied through an alternating biphasic current, with a stimulation frequency of 80 Hz and 1 ms pulse duration. Tetanic evoke forces (EF) at a 50% level of a supra-maximal single-pulse peak EF (i.e., 10-12% of a maximal voluntary isometric contraction) will be used. NMES protocol will be performed five times a week, lasting 20 minutes. Muscle fatigue will be evaluated every 5 min of the intervention, and will be used to determine the NMES protocol termination. A 10 % decrease in the single-pulse evoked torque between the evoked force produced pre- and during the NMES protocol will be used to terminate the fatigue protocol.

Also known as: Artificial electrical stimulation

Neuromuscular Electrical Stimulation - NMES

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with any clinical condition hospitalized in the ICU, which are monitored by the Physiotherapy Service:
• Cerebrovascular diseases
• Other bacterial diseases
• Circulatory and respiratory diseases
• Digestive and abdominal diseases
• Liver diseases
• Time between the patient's ICU entry and the onset of the NMES intervention less than one week.
• Patients may be in mechanical ventilation, non-invasive ventilation, oxygen therapy or oxygen ambient ventilation (no ventilatory add). Patients re-admitted to the ICU within the same hospitalization period (i.e., did not leave the hospital) may also be included, as well as patients with previous tracheostomy.

You may not qualify if:

• Previously diagnosed neuromuscular diseases:
• ALS
• Guillain Barre
• Chronic stroke
• TRM
• End-stage malignant disease
• Lower limbs' amputation
• Body mass index above 40 kg/m2
• Cachexia (defined as the presence of chronic disease and weight loss ≥ 5% in a period shorter than 12 months or BMI \< 20 kg/m2, associated with at least three of the following criteria: (1) decreased muscle strength; (2) fatigue; (3) anorexia; (4) reduction of fat free mass index; and (5) biochemical abnormalities such as inflammation, anemia or reduction of serum albumin concentration).
• Lesions on the skin at the electrode placement and/or dynamometer support points
• Post-operative transplantation
• Patients using a neuromuscular blocker
• Hemodynamic instability (nora \> 10; ABCDE criteria)
• Height \< 1.50m
• Rhabdomyolysis

Sponsors & Collaborators

• Federal University of Rio Grande do Sul: lead

Study Sites (1)

Universidade Federal do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, 90690-200, Brazil

Location

Study Officials

• Marco A Vaz, PhD

  Federal University of Rio Grande do Sul

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be randomized through data generated by a computer program containing the coded distribution (Randomizer, USA). The software takes into account one of the main objectives of randomization, which is to prevent the researcher from identifying which intervention will be performed on each patient. A researcher blinded to the study will do the generation of the sequence of numbers, after the patients' selection by the inclusion and exclusion criteria. The numbers sequence used for randomization will be kept confidential until the exact moment of the beginning of the intervention. In addition, a second blinded researcher, who will not be aware of the subjects' names in the three experimental groups, will perform the data analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Model Details: The present study is a randomized controlled trial, which followed the recommendations proposed by the CONSORT Statement

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: April 2, 2020
• Study Start: March 1, 2022
• Primary Completion: March 1, 2022
• Study Completion: June 6, 2024
• Last Updated: June 10, 2024

Record last verified: 2024-06

Locations

BR (1)