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Completed

NCT Number: NCT05380687

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

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).

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Key information

Conditions

Ventilator Weaning Critical Care Pathologic Processes Pathological Conditions, Signs and Symptoms Respiration Disorders Respiration, Artificial Respiratory Aspiration Respiratory Failure Respiratory Insufficiency Respiratory Muscles Respiratory Tract Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Antwerp University Hospital

Edegem, Antwerp, 2650, Belgium

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

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

Treatment and study plan

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.

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.

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.

PEEP 10

Other

Positive End-Expiratory Pressure of 10cmH2O for 30 minutes

PEEP 5

Other

Positive End-Expiratory Pressure of 5cmH2O for 30 minutes

PEEP 0

Other

Positive End-Expiratory Pressure of 0cmH2O for 30 minutes

Primary outcomes

  1. 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

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

    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.

  2. 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

    Time frame: 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)

    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.

  3. 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

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

    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.

  4. 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

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

    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.

  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 5 cmH2O

    Time frame: 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)

    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.

Secondary outcomes

  1. Change in RSBI (ml*min)

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

    Rapid shallow breathing index, calculated as tidal volume divided by respiratory rate

  2. Change in P0.1 (cmH2O)

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

    Airway pressure at the first 100 milliseconds of a breath

  3. Change in Cdyn (ml / cmH2O)

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

    Dynamic respiratory system compliance, calculated as tidal volume divided by driving pressure

  4. Change in Raw (cmH2O * L / s)

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

    Respiratory system resistance, calculated as (peak inspiratory pressure - plateau pressure) / flow

  5. Change in PIP (cmH2O)

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

    Peak Inspiratory Pressure

  6. Change in DTF

    Time frame: Measured for 5 breaths in the 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)

    Diaphragm thickening fraction, calculated as (diaphragm thickness at end-inspiration - diaphragm thickness at end-expiration) / diaphragm thickness at end-expiration [dimensionless]. Muscle thickness will be measured in millimeters using M-mode ultrasound with the probe placed perpendicular to the muscle (not including the thickness of fascial muscle layers).

  7. Change in ICTF

    Time frame: Measured for 5 breaths in the 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)

    Parasternal intercostal muscle thickening fraction, calculated as (parasternal intercostal muscle thickness at end-inspiration - parasternal intercostal muscle thickness at end-expiration) / parasternal intercostal muscle thickness at end-expiration [dimensionless]. Muscle thickness will be measured in millimeters using M-mode ultrasound with the probe placed perpendicular to the muscle (not including the thickness of fascial muscle layers).

  8. Change in IOTF

    Time frame: Measured for 5 breaths in the 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)

    Internal oblique muscle thickening fraction, calculated as (internal oblique muscle thickness at end-inspiration - internal oblique muscle thickness at end-expiration) / internal oblique muscle thickness at end-expiration [dimensionless]. Muscle thickness will be measured in millimeters using M-mode ultrasound with the probe placed perpendicular to the muscle (not including the thickness of fascial muscle layers).

  9. Change in MIP (cmH2O)

    Time frame: Measured during an expiratory hold of ≤ 30 seconds between each training block (AH0-4 & BH0-4; cumulative ≤ 5 minutes)

    Maximal inspiratory pressure

  10. Change in MEP (cmH2O)

    Time frame: Measured during an inspiratory hold of ≤ 30 seconds between each training block (AH0-4 & BH0-4; cumulative ≤ 5 minutes)

    Maximal expiratory pressure

  11. Change in ∆Pocc (cmH2O)

    Time frame: Measured during an expiratory hold of ≤ 30 seconds between each training block (AH0-4 & BH0-4; cumulative ≤ 5 minutes)

    Airway occlusion pressure

  12. Change in NVE (ml/µv)

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

    Neuroventilatory efficiency, calculated as tidal volume divided by delta Edi. It is measured at a pressure support of 7 cmH2O, i.e. NOT during a zero assist manoeuvre.

  13. Change in TV (ml)

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

    Tidal volume

  14. Change in ∆Edi (µV)

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

    Increase in electrical activity of the diaphragm (Edi) during inspiration, calculated as Edi high - Edi low.

  15. Change in Pplat (cmH2O)

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

    Airway plateau pressure

  16. Change in static PEEP (cmH2O)

    Time frame: Measured during an expiratory hold of ≤ 30 seconds between each training block (AH0-4 & BH0-4; cumulative ≤ 5 minutes)

    Postive end-expiratory pressure as measured during an expiratory hold.

Sponsors and collaborators

Lead sponsor

University Hospital, Antwerp

Other

Collaborators

  • Research Foundation Flanders

Registry information

Acronym: TONES

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
May 19, 2022
Registry last updated
Apr 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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