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

Respiratory Failure Clinical Trial

— TONES  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05380687
• Other study ID #: 002418
• Status: Recruiting
• Phase: N/A
• Start date: June 15, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: University Hospital, Antwerp
• Contact: Petra Vertongen
• Phone: 3 821 4404
• Email: icu-research[@]uza.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 31, 2024
• Est. primary completion date: October 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Critical Care
• Respiration, Artificial
• Respiratory Failure
• Respiratory Insufficiency
• Respiratory Muscles
• Ventilator Weaning

Intervention

Diagnostic Test:
• Inspiratory hold
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
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
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.

Other:
• PEEP 10
Positive End-Expiratory Pressure of 10cmH2O for 30 minutes
• PEEP 5
Positive End-Expiratory Pressure of 5cmH2O for 30 minutes
• PEEP 0
Positive End-Expiratory Pressure of 0cmH2O for 30 minutes

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Edegem	Antwerp

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Antwerp	Research Foundation Flanders

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Change in RSBI (ml*min)	Rapid shallow breathing index, calculated as tidal volume divided by respiratory rate	Measured at each breath during 30 minutes in block B3 (at zero PEEP; cumulative 30 minutes)
Secondary	Change in P0.1 (cmH2O)	Airway pressure at the first 100 milliseconds of a breath	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in Cdyn (ml / cmH2O)	Dynamic respiratory system compliance, calculated as tidal volume divided by driving pressure	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in Raw (cmH2O * L / s)	Respiratory system resistance, calculated as (peak inspiratory pressure - plateau pressure) / flow	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in PIP (cmH2O)	Peak Inspiratory Pressure	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in DTF	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).	Measured for 5 breaths in the 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in ICTF	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).	Measured for 5 breaths in the 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in IOTF	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).	Measured for 5 breaths in the 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in MIP (cmH2O)	Maximal inspiratory pressure	Measured during an expiratory hold of = 30 seconds between each training block (AH0-4 & BH0-4; cumulative = 5 minutes)
Secondary	Change in MEP (cmH2O)	Maximal expiratory pressure	Measured during an inspiratory hold of = 30 seconds between each training block (AH0-4 & BH0-4; cumulative = 5 minutes)
Secondary	Change in ?Pocc (cmH2O)	Airway occlusion pressure	Measured during an expiratory hold of = 30 seconds between each training block (AH0-4 & BH0-4; cumulative = 5 minutes)
Secondary	Change in NVE (ml/µv)	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.	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in TV (ml)	Tidal volume	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in ?Edi (µV)	Increase in electrical activity of the diaphragm (Edi) during inspiration, calculated as Edi high - Edi low.	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in Pplat (cmH2O)	Airway plateau pressure	Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)
Secondary	Change in static PEEP (cmH2O)	Postive end-expiratory pressure as measured during an expiratory hold.	Measured during an expiratory hold of = 30 seconds between each training block (AH0-4 & BH0-4; cumulative = 5 minutes)