Time Course of Neuro-ventilatory Efficiency During a Spontaneous Breathing Training

NCT05380687 | Completed

• 1 other identifier: 002418
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The TONES trial aims to evaluate the neuroventilatory efficiency (NVE = tidal volume / peak voltage of diaphragm contraction) measured during a zero-assist manoeuvre (ZAM, i.e. with PEEP but without pressure support). This novel parameter, NVE-ZAM, will be studied in a blocked, crossover, repeated measures design. Possible confounders, such as activity of respiratory muscles other than the diaphragm, are included. The investigators hypothesized that

• the NVE during a zero-assist maneuver has a low variability and high repeatability at the same level of PEEP (within subjects, within blocks)
• NVE-ZAM trends differ between participants (between subjects, within blocks) and between PEEP levels (within subjects, between blocks) The primary aim is to study the variability and repeatability of the NVE-ZAM within subjects and within blocks. Additionally, the effect of PEEP, muscle fatigue and recruitment of the accessory and expiratory muscles of respiration on the NVE-ZAM will be studied in an exploratory analysis (in multiple combinations of within and between subjects and/or blocks).

Conditions

Ventilator Weaning; Respiration, Artificial; Respiratory Muscles; Respiratory Failure; Critical Care

Outcome Measures

Primary Outcomes (5)

• Neuroventilatory efficiency (NVE) during a zero-assist breath in neural pressure support mode with a pressure support level of 7cmH2O and a PEEP of 10 cmH2O

  Measured using an Edi catheter (Maquet, Solna, Sweden) each 3 minutes as tidal volume / delta Edi. Zero assist is defined as a pressure support of 0 cmH2O during a single breath.

  Measured each 3 mintues during blocks A1 and B1: initial 30 minutes of training in both trainings A and B (cumulative: 2x 30 minutes)

• Neuroventilatory efficiency (NVE) during a zero-assist breath in neural pressure support mode with a pressure support level of 7cmH2O and a PEEP of 5 cmH2O

  Measured using an Edi catheter (Maquet, Solna, Sweden) each 3 minutes as tidal volume / delta Edi. Zero assist is defined as a pressure support of 0 cmH2O during a single breath.

  Measured each 3 mintues during blocks A2 and B2: second next 30 minutes of training in both trainings A and B (cumulative: 2x 30 minutes)

• Neuroventilatory efficiency (NVE) during a zero-assist breath in neural pressure support mode with a pressure support level of 7cmH2O and a PEEP of 5 cmH2O

  Measured using an Edi catheter (Maquet, Solna, Sweden) each 3 minutes as tidal volume / delta Edi. Zero assist is defined as a pressure support of 0 cmH2O during a single breath.

  Measured each 3 mintues during block A3: third next 30 minutes of training in training A (cumulative: 1x 30 minutes)

• Neuroventilatory efficiency (NVE) during a zero-assist breath in neural pressure support mode with a pressure support level of 7cmH2O and a PEEP of 0 cmH2O

  Measured using an Edi catheter (Maquet, Solna, Sweden) each 3 minutes as tidal volume / delta Edi. Zero assist is defined as a pressure support of 0 cmH2O during a single breath.

  Measured each 3 mintues during block B3: third next 30 minutes of training in training B (cumulative: 1x 30 minutes)

• Neuroventilatory efficiency (NVE) during a zero-assist breath in neural pressure support mode with a pressure support level of 7cmH2O and a PEEP of 5 cmH2O

  Measured using an Edi catheter (Maquet, Solna, Sweden) each 3 minutes as tidal volume / delta Edi. Zero assist is defined as a pressure support of 0 cmH2O during a single breath.

  Measured each 3 mintues during blocks A4 and B4: fourth next 30 minutes of training in both trainings A and B (cumulative: 2x 30 minutes)

Secondary Outcomes (16)

• Change in RSBI (ml*min)

  Measured at each breath during 30 minutes in block B3 (at zero PEEP; cumulative 30 minutes)

• Change in P0.1 (cmH2O)

  Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)

• Change in Cdyn (ml / cmH2O)

  Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)

• Change in Raw (cmH2O * L / s)

  Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)

• Change in PIP (cmH2O)

  Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)

Study Arms (2)

Training A - PEEP 10-5-5-5

EXPERIMENTAL

The respiratory muscles of all participants will be trained in 4 consecutive blocks of 30 minutes during ventilation in neural pressure support mode (NPS) with a pressure support of 7 cmH2O. During training A, the 4 blocks are A1. PEEP 10 cmH2O \| A2. PEEP 5 cmH2O \| A3. PEEP \*5\* cmH2O \| A4. PEEP 5 cmH2O During the training, ventilator data will be recorded and respiratory muscles will be imaged using ultrasound. Before and after each training block, an inspiratory and an expiratory hold (both ≤ 30 seconds) will be performed to assess fatigue.

Diagnostic Test: Inspiratory hold; Diagnostic Test: Expiratory hold; Diagnostic Test: Ultrasound of respiratory muscles; Other: PEEP 10; Other: PEEP 5

Training B - PEEP 10-5-0-5

EXPERIMENTAL

The respiratory muscles of all participants will be trained in 4 consecutive blocks of 30 minutes during ventilation in neural pressure support mode (NPS) with a pressure support of 7 cmH2O. During training B, the 4 blocks are B1. PEEP 10 cmH2O \| B2. PEEP 5 cmH2O \| B3. PEEP \*0\* cmH2O \| B4. PEEP 5 cmH2O During the training, ventilator data will be recorded and respiratory muscles will be imaged using ultrasound. Before and after each training block, an inspiratory and an expiratory hold (both ≤ 30 seconds) will be performed to assess fatigue.

Diagnostic Test: Inspiratory hold; Diagnostic Test: Expiratory hold; Diagnostic Test: Ultrasound of respiratory muscles; Other: PEEP 10; Other: PEEP 5; Other: PEEP 0

Interventions

Inspiratory hold DIAGNOSTIC_TEST

A short period (\< 30 seconds) during which both inspiratory and expiratory valves of the ventilator circuit are closed at the end of inspiration. It is used to asses expiratory force generation (maximal expiratory pressure, MEP) and frequently used in clinical practice.

Training A - PEEP 10-5-5-5; Training B - PEEP 10-5-0-5

Expiratory hold DIAGNOSTIC_TEST

A short period (\< 30 seconds) during which both inspiratory and expiratory valves of the ventilator circuit are closed at the end of expiration. It is used to asses static PEEP and inspiratory force generation (maximal inspiratory pressure, MIP \& occlusion pressure, ∆Pocc) and is frequently used in clinical practice.

Training A - PEEP 10-5-5-5; Training B - PEEP 10-5-0-5

Ultrasound of respiratory muscles DIAGNOSTIC_TEST

Ultrasound of the diaphragm, parasternal intercostal muscle and internal oblique muscle will be performed during each block. Thickening fractions, calculated as thickness at end-inspiration minus thickness at end-expiration divided by thickness at end-expiration, are used to assess the contribution of the muscle to the tidal volume. A median over 5 breaths will be calculated.

Training A - PEEP 10-5-5-5; Training B - PEEP 10-5-0-5

PEEP 10 OTHER

Positive End-Expiratory Pressure of 10cmH2O for 30 minutes

Training A - PEEP 10-5-5-5; Training B - PEEP 10-5-0-5

PEEP 5 OTHER

Positive End-Expiratory Pressure of 5cmH2O for 30 minutes

Training A - PEEP 10-5-5-5; Training B - PEEP 10-5-0-5

PEEP 0 OTHER

Positive End-Expiratory Pressure of 0cmH2O for 30 minutes

Training B - PEEP 10-5-0-5

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult (18-80 yrs.)
• admitted to the ICU
• intubated and mechanically ventilated
• Edi catheter (Maquet, Solna, Sweden) in situ as part of their clinical care
• ventilated in a support mode (e.g. pressure support) with a support between 7 and 15 cmH2O, a PEEP ≤10 cmH2O and an Fi02 \<0.6, all since ≥6 hours.
• can participate in the trial as judged by their attending physician

You may not qualify if:

• pregnancy
• refusal of participation
• pre-existing neuromuscular disorders (e.g., Guillain-Barré)

Sponsors & Collaborators

• University Hospital, Antwerp: lead
• Research Foundation Flanders: collaborator

Study Sites (1)

Antwerp University Hospital

Edegem, Antwerp, 2650, Belgium

Location

MeSH Terms

Conditions

Respiratory Aspiration; Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Philippe G Jorens, MD, PhD

  Head of the department of critical care medicine, Antwerp University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized crossover of 2 trainings (A and B)

Study Record Dates

• First Submitted: May 9, 2022
• First Posted: May 19, 2022
• Study Start: June 15, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: April 4, 2025

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)