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

Not Applicable

Completed

• Conditions: Respiratory Muscles; Respiratory Failure; Ventilator Weaning; Respiration, Artificial; Critical Care
• Interventions: Diagnostic Test: Inspiratory hold; Diagnostic Test: Expiratory hold; Diagnostic Test: Ultrasound of respiratory muscles; Other: PEEP 10; Other: PEEP 5; Other: PEEP 0

• Registration Number: NCT05380687
• Lead Sponsor: University Hospital, Antwerp

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-09
• Study First Submitted QC: 2022-05-13
• Study First Posted: 2022-05-19
• Study Start: 2022-06-15
• Status Verified: 2023-06
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Training A - PEEP 10-5-5-5	Ultrasound of respiratory muscles	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.
Training B - PEEP 10-5-0-5	PEEP 5	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.
Training A - PEEP 10-5-5-5	Inspiratory hold	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.
Training A - PEEP 10-5-5-5	Expiratory hold	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.
Training B - PEEP 10-5-0-5	PEEP 0	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.
Training A - PEEP 10-5-5-5	PEEP 10	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.
Training A - PEEP 10-5-5-5	PEEP 5	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.
Training B - PEEP 10-5-0-5	Inspiratory hold	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.
Training B - PEEP 10-5-0-5	Expiratory hold	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.
Training B - PEEP 10-5-0-5	Ultrasound of respiratory muscles	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.
Training B - PEEP 10-5-0-5	PEEP 10	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.

Primary Outcome Measures

Name	Time	Method
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 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.
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 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.
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 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 Outcome Measures

Name	Time	Method
Change in MEP (cmH2O)	Measured during an inspiratory hold of ≤ 30 seconds between each training block (AH0-4 & BH0-4; cumulative ≤ 5 minutes)	Maximal expiratory pressure
Change in NVE (ml/µv)	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.
Change in ICTF	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).
Change in RSBI (ml*min)	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
Change in P0.1 (cmH2O)	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
Change in IOTF	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).
Change in ∆Pocc (cmH2O)	Measured during an expiratory hold of ≤ 30 seconds between each training block (AH0-4 & BH0-4; cumulative ≤ 5 minutes)	Airway occlusion pressure
Change in static PEEP (cmH2O)	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.
Change in Cdyn (ml / cmH2O)	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
Change in PIP (cmH2O)	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)	Peak Inspiratory Pressure
Change in MIP (cmH2O)	Measured during an expiratory hold of ≤ 30 seconds between each training block (AH0-4 & BH0-4; cumulative ≤ 5 minutes)	Maximal inspiratory pressure
Change in ∆Edi (µV)	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.
Change in Pplat (cmH2O)	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)	Airway plateau pressure
Change in Raw (cmH2O * L / s)	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
Change in DTF	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).
Change in TV (ml)	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)	Tidal volume

Trial Locations

Locations (1)

Antwerp University Hospital; 🇧🇪 Edegem, Antwerp, Belgium