NMES Role to Prevent Respiratory Muscle Weakness in Critically Ill Patients and Its Association to Changes in Myokines.

NCT05536531 | Recruiting

• 2 other identifiers: 52-c50ID 210602003
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Particularly, muscle respiratory wasting will occur early (18 to 69 hours) in up to 60% of patients with mechanical ventilation (MV), leading rapidly to diaphragmatic weakness, which is associated with prolonged MV use, longer ICU and hospital stay, and higher mortality risk. Sepsis and muscle inactivity, derived from sedation and MV use, are key driver mechanisms for developing these consequences, which can be avoided through early physical activation. However, exercise is limited at the early stages of care, where sedation and MV are needed, delaying muscle activation. Neuromuscular electrical stimulation (NMES) represents an alternative to achieve early muscle contraction in non-cooperative patients, being able to prevent local muscle wasting and, according to some reports, has the potential to shorten the time on MV, suggesting a systemic effect through myokines, a diverse range of cytokines and chemokines secreted by myocytes during muscle contraction. However, no studies have evaluated whether NMES applied to peripheral muscles can exert distant muscle effects over the diaphragm, ameliorating its weakness and if this protective profile is associated with myokine's change in ICU patients. This proposal comprises a randomized controlled study of NMES applied twice daily, for three days, compared to standard care (no NMES). Thirty-two patients will be recruited in the first 48 hours after MV and randomly assigned to the control group or NMES group (16 subjects each). Muscle characterization of quadriceps and diaphragm will be performed at baseline (Day 1, before the first NMES session) and after the last NMES session (morning of day 4). Myokine measurements \[IL-1, IL-6, IL-15, Brain-Derived Neurotrophic Factor (BDNF), Myostatin and Decorin\], through blood serum obtained from peripheric blood samples, will be performed just before starting NMES (T0) at the end of the session (T0.5), and 2 and 6 hours later (T2 and T6). These myokine curves will be repeated on days 1 and 3 at the first NMES session of the day. The Control group will be assessed in the same way and timing, except that blood samples will be at T0 and T6. Additionally, functional outcomes such as MV time and ICU length of stay will be registered for all patients at ICU discharge. Standard care won´t be altered.

Conditions

Muscle Weakness or Atrophy; Mechanical Ventilation Complication; Electrical Stimulations

Keywords

Neuromuscular electrical stimulation; Critical care

Outcome Measures

Primary Outcomes (2)

• Change in Tracheal twitch pressure (centimeters of water)

  Sub Maximal diaphragmatic strength measured trough tracheal twitch pressure derived from magnetic stimulation of phrenic nerve.

  Change from begining (Day one) and at the end (Day three)

• Change in Diaphragmatic thickness fraction (centimeter percentage change)

  Diaphragmatic function derived from ultrasonography measurement of diaphragmatic muscle thickness between inspiration and expiration (during twitch manoeuvre)

  Change from begining (Day one) and at the end (Day three)

Secondary Outcomes (10)

• IL-1 myokine

  through Study, at begining (Day one) and at the end (Day three). Before and after intervención

• IL-6 myokine

  through Study, at begining (Day one) and at the end (Day three). Before and after intervención

• Decorin myokine

  through Study, at begining (Day one) and at the end (Day three). Before and after intervención

• Myostatin myokine

  through Study, at begining (Day one) and at the end (Day three). Before and after intervención

• IL-15 myokine

  through Study, at begining (Day one) and at the end (Day three). Before and after intervención

Study Arms (2)

NMES group

EXPERIMENTAL

NMES will be implemented simultaneously on quadriceps femoris muscles of both lower limbs using an electrical stimulator (TRAINFES 6 ADVANCED, Biomedical devices Spa, Santiago, Chile). Four rubber surface electrodes will be placed over motor points. However, since the electrodes will cover big proportion of muscle surface, anatomical distribution of the belly muscle plus visible contraction of it will be considered for correct setting. The stimulation will be delivered by biphasic current, symmetric (compensated) impulses of 45-50 Hz frequency, 400 μsec pulse duration. With a stimulus duration of 25 minutes, and an on-off programming of 5 seconds on (including 0.8 second rise time, 3.4 seconds of plateau and 0.8 second of fall time) and 5 seconds off, at current intensities able to cause maximal visible contractions. The session duration will be 30 minutes and will be applied twice a day.

Device: Neuromuscular electrical stimulation (NMES)

Control

NO INTERVENTION

Sham NMES will not be provided. Standard care won´t be altered and passive mobilization will be performed according to routine ICU procedures.

Interventions

Neuromuscular electrical stimulation (NMES) DEVICE

Electrical stimulator (Electrostimulator TRAINFES 6 ADVANCED, Biomedical devices Spa, Santiago, Chile.) to administer NMES

Also known as: Standard Care

NMES group

Eligibility Criteria

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

You may qualify if:

• Consecutively admission to Christus ICU between March 2021 and December 2021.
• Connected to invasive MV within the previous 24-48 hours
• Deep sedation \[non-cooperative state; Sedation-Agitation Scale (SAS) 1 or 2\].
• ICU-acquired weakness risk (One of the following risk factors: the need for invasive MV, sepsis, hyperglycemia, APACHE II admission score \>13 pts, use of corticosteroids, and/or muscle inactivity due to deep sedation).
• Written informed consent provided by patient/surrogate

You may not qualify if:

• Age \< 18 years
• Pregnancy
• Obesity (Body Mass Index \>35 kg/m2)
• Pre-existing Neuromuscular diseases (e.g., myasthenia Gravis, Guillain-Barré disease)
• Diseases with systemic vascular involvement such as systemic lupus erythematosus.
• Use of neuromuscular blockers
• Technical obstacles to the implementation of NMES such as bone fractures or skin lesions (e.g., burns)
• End-stage malignancy
• Presence of cardiac pacemakers
• Diagnosis of brain death.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, 8970117, Chile

RECRUITING

Related Publications (5)

• Dres M, Dube BP, Mayaux J, Delemazure J, Reuter D, Brochard L, Similowski T, Demoule A. Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients. Am J Respir Crit Care Med. 2017 Jan 1;195(1):57-66. doi: 10.1164/rccm.201602-0367OC.

  PMID: 27310484 BACKGROUND

• Goligher EC, Fan E, Herridge MS, Murray A, Vorona S, Brace D, Rittayamai N, Lanys A, Tomlinson G, Singh JM, Bolz SS, Rubenfeld GD, Kavanagh BP, Brochard LJ, Ferguson ND. Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort. Am J Respir Crit Care Med. 2015 Nov 1;192(9):1080-8. doi: 10.1164/rccm.201503-0620OC.

  PMID: 26167730 BACKGROUND

• Dirks ML, Hansen D, Van Assche A, Dendale P, Van Loon LJ. Neuromuscular electrical stimulation prevents muscle wasting in critically ill comatose patients. Clin Sci (Lond). 2015 Mar;128(6):357-65. doi: 10.1042/CS20140447.

  PMID: 25296344 BACKGROUND

• Truong AD, Kho ME, Brower RG, Feldman DR, Colantuoni E, Needham DM. Effects of neuromuscular electrical stimulation on cytokines in peripheral blood for healthy participants: a prospective, single-blinded Study. Clin Physiol Funct Imaging. 2017 May;37(3):255-262. doi: 10.1111/cpf.12290. Epub 2015 Oct 16.

  PMID: 26475418 BACKGROUND

• Routsi C, Gerovasili V, Vasileiadis I, Karatzanos E, Pitsolis T, Tripodaki E, Markaki V, Zervakis D, Nanas S. Electrical muscle stimulation prevents critical illness polyneuromyopathy: a randomized parallel intervention trial. Crit Care. 2010;14(2):R74. doi: 10.1186/cc8987. Epub 2010 Apr 28.

  PMID: 20426834 BACKGROUND

MeSH Terms

Conditions

Muscle Weakness; Atrophy

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pathological Conditions, Anatomical

Study Officials

• Yorschua Jalil, PT, MSc

  Facultad de Medicina, Pontificia Universidad Católica de Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yorschua Jalil, PT, MSc

CONTACT

96691771; yfjalil@uc.cl

Alejandro Bruhn, MD, PhD

CONTACT

23545649; alejandrobruhn@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Analysis of respiratory function (diaphragm) derived from Twitch maneuver and echography (posterior images analysis) will be performed blind to arm assignment. Given sedation, patients will be also be blinded to the intervention.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: September 13, 2022
• Study Start: July 11, 2022
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: January 14, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)