NMES to Prevent Respiratory Muscle Atrophy in Mechanically Ventilated Patients

Breath Synchronized Electrical Stimulation of the Abdominal Wall Muscles to Prevent Respiratory Muscle Atrophy During the Acute Stages of Mechanical Ventilation Therapy

Patients requiring prolonged time on the ventilator are susceptible to a wide range of clinical complications and excess mortality. It is therefore imperative for them to wean at the earliest possible time.

Respiratory muscle weakness due to disuse of these muscles is a major underlying factor for weaning failure. Surprisingly, there is not much known about the impact of critical illness and MV on the expiratory abdominal wall muscles.These muscles are immediately activated as ventilation demands increase and are important in supporting respiratory function in patients with diaphragm weakness. Weakness of expiratory abdominal wall muscles will result in a decreased cough function and reduced ventilatory capacity. These are considerable causes of weaning failure and (re)hospitalisation for respiratory complications such as pneumonia.

Recent evidence shows that neuromuscular electrical stimulation (NMES) can be used as a safe therapy to maintain skeletal muscle function in critically ill patients. This study will be the first to test the hypothesis that breath-synchronized NMES of the abdominal wall muscles can prevent expiratory muscle atrophy during the acute stages of MV.

Study Overview

• Status: Unknown
• Conditions: Muscle Weakness; Mechanical Ventilation Complication; Neuromuscular Electrical Stimulation
• Intervention / Treatment: Device: VentFree prototype (VF03-K) active stimulation; Device: VentFree prototype (VF03-K) sham stimulation

Detailed Description

Approximately 30-40% of intubated patients at the intensive care unit (ICU) take more than one attempt to wean from mechanical ventilation (MV). 6-14% of intubated patients take longer than 7 days to wean from MV. Patients requiring prolonged time on the ventilator are susceptible to a wide range of clinical complications and excess mortality. It is therefore imperative for them to wean at the earliest possible time.

Respiratory muscle weakness due to disuse of these muscles is a major underlying factor for weaning failure. It is known that diaphragm strength rapidly declines within a few days after the initiation of MV. Surprisingly, there is not much known about the impact of critical illness and MV on the expiratory abdominal wall muscles.These muscles are immediately activated as ventilation demands increase and are important in supporting respiratory function in patients with diaphragm weakness. Weakness of expiratory abdominal wall muscles will result in a decreased cough function and reduced ventilatory capacity. These are considerable causes of weaning failure and (re)hospitalisation for respiratory complications such as pneumonia.

Recent evidence shows that neuromuscular electrical stimulation (NMES) can be used as a safe therapy to maintain skeletal muscle function in critically ill patients, e.g. by stimulating quadriceps muscles in patients receiving MV.

This study will be the first to test the hypothesis that exhalation synchronized NMES of the abdominal wall muscles can prevent expiratory muscle atrophy during the acute stages of MV. The investigators hypothesize that this approach will improve respiratory function and thereby will reduce the amount of time it takes to wean patients from mechanical ventilation.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Leo MA Heunks, MD, Prof; Phone Number: 0204442209; Email: l.heunks@vumc.nl
• Study Contact Backup: Name: Annemijn H Jonkman, MSc; Phone Number: 0204442209; Email: ah.jonkman@vumc.nl

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • UMC Nijmegen
      • Contact: Tim Frenzel, MD, PhD; Phone Number: +31 (0) 24 3665010; Email: tim.frenzel@radboudumc.nl
    • Nijmegen, Gelderland, Netherlands, 6532 SZ
      • Recruiting
      • Canisius Wilhelmina Hospital
      • Contact: Jeroen Schouten, MD; Phone Number: +31 (0)24 - 365 7915; Email: j.schouten@cwz.nl
      • Contact: Mirjam Evers; Phone Number: +31 (0)24 - 365 7915; Email: m.evers@cwz.nl
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • Recruiting
      • VU University Medical Center
      • Contact: Leo MA Heunks, MD, Prof; Email: l.heunks@vumc.nl
      • Contact: Angelique ME Spoelstra-de Man, MD, PhD; Email: am.spoelstra@vumc.nl
      • Sub-Investigator: Annemijn Jonkman, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age > 18 year
• invasive mechanical ventilation less than 72 hours
• expected duration of MV after inclusion > 72 hours

Exclusion Criteria:

• no clearly visible separate layers of the abdominal wall muscles (external oblique, internal oblique and transverse abdominal muscles), assessed with ultrasound during routine care
• cardiac pacemaker
• congenital myopathies and/or existing central or peripheral neuropathies
• refractory epilepsy
• recent abdominal surgery within four weeks prior to study inclusion
• body mass index (BMI) greater than 35 kg/m2
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: VF03-K active stimulation; NMES applied to the abdominal wall muscles using the VentFree prototype (VF03-K). Stimulation is applied twice daily for 30 minutes, 5 days per week, for 6 weeks or until the patient is weaned from mechanical ventilation, whichever occurs sooner.	Device: VentFree prototype (VF03-K) active stimulation; Abdominal wall muscle stimulation synchronised with mechanical ventilation. Stimulation frequency: 30 Hz, pulse width: 352us, max. intensity: 100mA (threshold intensity determined using ultrasound)
SHAM_COMPARATOR: VF03-K sham stimulation; Sham stimulation applied to the abdominal wall muscles using the VentFree prototype (VF03-K). Sham stimulation is applied twice daily for 30 minutes, 5 days per week, for 6 weeks or until the patient is weaned from mechanical ventilation, whichever occurs sooner.	Device: VentFree prototype (VF03-K) sham stimulation; Abdominal wall muscle sham-stimulation synchronised with mechanical ventilation. Stimulation frequency: 10 Hz, pulse width: 352us, intensity: 15 mA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thickness of the abdominal wall muscles	Thickness of the abdominal wall muscles over time, for both groups, as measured by ultrasound.	Until study completion, up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thickness of the diaphragm	Thickness of the diaphragm over time, for both groups, as measured by ultrasound.	Until study completion, up to 6 weeks
Thickness of the rectus abdominis muscle	Thickness of the rectus abdominis mucle over time, for both groups, as measured by ultrasound.	Until study completion, up to 6 weeks
Maximum expiratory pressure (MEP)	Maximum expiratory pressure (MEP) to assess expiratory muscle function	Within 24 hours after extubation
Maximum inspiratory pressure (MIP)	Maximum inspiratory pressure (MIP) to assess inspiratory muscle function	Within 24 hours after extubation
Vital capacity (Vc)	Vital capacity (Vc) to assess respiratory muscle strength	Within 24 hours after extubation
Peak expiratory flow	Peak expiratory flow (PEF) to assess cough strength	Within 24 hours after extubation
Number of patients with extubation failure	Weaning failure defined as the failure to pass a spontaneous-breathing trial or the need for reintubation within 48 hours following extubation	Within 24 hours after extubation
Systemic inflammatory markers	Among others, cytokines IL-6 and IL-1 will be determined from blood sample analysis	Within 24 hours after extubation
Number of patients with respiratory complications after ICU discharge	Number of patients with development of pneumonia, and readmission to the ICU due to atelectasis or respiratory problems that require mechanical ventilation.	Up to 6 weeks after ICU discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expiratory flow limitation (optional)	EFL test to determine flow limitation in COPD	Measured before the first NMES session and within 24 hours after extubation

Collaborators and Investigators

• Sponsor: University Medical Center Nijmegen
• Collaborators: Amsterdam UMC, location VUmc; Canisius-Wilhelmina Hospital; Liberate Medical
• Investigators: Principal Investigator: Angelique ME Spoelstra-de Man, MD, PhD, Amsterdam UMC, location VUmc

Publications and helpful links

General Publications

• Jonkman AH, Frenzel T, McCaughey EJ, McLachlan AJ, Boswell-Ruys CL, Collins DW, Gandevia SC, Girbes ARJ, Hoiting O, Kox M, Oppersma E, Peters M, Pickkers P, Roesthuis LH, Schouten J, Shi ZH, Veltink PH, de Vries HJ, Shannon Weickert C, Wiedenbach C, Zhang Y, Tuinman PR, de Man AME, Butler JE, Heunks LMA. Breath-synchronized electrical stimulation of the expiratory muscles in mechanically ventilated patients: a randomized controlled feasibility study and pooled analysis. Crit Care. 2020 Oct 30;24(1):628. doi: 10.1186/s13054-020-03352-0.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 9, 2017
• Primary Completion (ANTICIPATED): July 1, 2018
• Study Completion (ANTICIPATED): December 31, 2018

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (ACTUAL): March 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 5, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Mechanically ventilated patients; Neuromuscular electrical stimulation; Respiratory function; Expiratory muscles; Ventilator-acquired muscle atrophy
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscle Weakness; Muscular Atrophy; Atrophy
• Other Study ID Numbers: LM-RB-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No