TONES: Time Course of Neuro-ventilatory Efficiency During a Spontaneous Breathing Training
Study Details
Study Description
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
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the NVE during a zero-assist maneuver has a low variability and high repeatability at the same level of PEEP (within subjects, within blocks)
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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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Training A - PEEP 10-5-5-5 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. |
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.
Diagnostic Test: 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.
Diagnostic Test: 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
Other: PEEP 5
Positive End-Expiratory Pressure of 5cmH2O for 30 minutes
|
| Experimental: Training B - PEEP 10-5-0-5 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. |
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.
Diagnostic Test: 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.
Diagnostic Test: 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
Other: PEEP 5
Positive End-Expiratory Pressure of 5cmH2O for 30 minutes
Other: PEEP 0
Positive End-Expiratory Pressure of 0cmH2O for 30 minutes
|
Outcome Measures
Primary Outcome Measures
- 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 5 cmH2O [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.
- 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 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.
- 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
- 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 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 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 PIP (cmH2O) [Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)]
Peak Inspiratory Pressure
- 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 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 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 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 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 ∆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 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 TV (ml) [Measured at each breath during 30 minutes for each training block (A1-4 & B1-4; cumulative 4hours)]
Tidal volume
- 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 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.
Eligibility Criteria
Criteria
Inclusion criteria:
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adult (18-80 yrs.)
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admitted to the ICU
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intubated and mechanically ventilated
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Edi catheter (Maquet, Solna, Sweden) in situ as part of their clinical care
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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.
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can participate in the trial as judged by their attending physician
Exclusion criteria:
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pregnancy
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refusal of participation
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pre-existing neuromuscular disorders (e.g., Guillain-Barré)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Antwerp University Hospital | Edegem | Antwerp | Belgium | 2650 |
Sponsors and Collaborators
- University Hospital, Antwerp
- Research Foundation Flanders
Investigators
- Principal Investigator: Philippe G Jorens, MD, PhD, Head of the department of critical care medicine, Antwerp University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 002418