Dyspnea During Mechanical VentilationNCT07877350
Association of Inspiratory Effort With Dyspnea During Assisted Mechanical Ventilation in Critically Ill Patients
An observational study of Dyspnea During Mechanical Ventilation and Inspiratory Effort, run by University of Crete at 1 site in Greece.
Trial summary
During assisted mechanical ventilation, breathing results from the interaction between the patient and the ventilator. Optimal titration of pressure support is essential to maintain a balance between over-assistance and under-assistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dyspnea During Mechanical Ventilation, Inspiratory Effort, Mechanical Ventilation
- How many people
- 50 participants
- Where
- 1 siteGreece
- Study dates
- 18 Jun 2026to 28 May 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population will consist of adult patients admitted to the Adult Intensive Care Unit of the University Hospital of Heraklion, Crete, Greece, who are receiving invasive assisted mechanical ventilation during prolonged or difficult liberation from mechanical ventilation. Participants will be identified from consecutively treated ICU patients undergoing routine clinical assessment and pressure-support titration by the treating ICU team.
Who may be able to join
- Adult patient admitted to the ICU.
- Receiving invasive assisted mechanical ventilation in a pressure-support mode or another assisted mode permitting measurement of the prespecified variables.
- Prolonged or difficult weaning.
- Receiving pressure support of at least 5 cmH2O at screening.
- Written informed consent from the participant or legally authorized representative, in accordance with local ethics requirements.
- Ability to undergo the planned physiological monitoring and dyspnea assessment.
Who cannot join
- Contraindication to nasogastric placement or to placement/use of an esophageal-gastric balloon catheter for Pes and Pgas measurement.
- Refusal of consent by the participant or legally authorized representative.
- Any clinical condition in which the treating physician considers study measurements or pressure-support titration unsafe (unstable hemodynamics, uncontrolled arrhythmia, severe hypoxemia, active myocardial ischemia etc.)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Greece1 site, 1 recruiting
- Recruiting
University Hospital of Heraklion
Heraklion, 71110
Katerina Vaporidi, MD, PhD, +30 2810 392718 / 2810 394729, vaporidi@uoc.gr
About this study
Official title: Association of Inspiratory Effort With Dyspnea During Assisted Mechanical Ventilation in Critically Ill Patients: A Single-Center Prospective Observational Physiological Study
During assisted mechanical ventilation, breathing results from the interaction between the patient and the ventilator. Optimal titration of pressure support is essential to maintain a balance between over-assistance and under-assistance. Excessive respiratory may lead to dyspnea and cause respiratory muscle fatigue, whereas excessive assistance promotes muscle atrophy and delays weaning. Although normal inspiratory effort values in healthy subjects are well defined, acceptable limits in critically ill patients remain unclear. Inspiratory effort is traditionally quantified by the pressure-time product (PTP), but its measurement is technically demanding. Simpler indices such as swings of esophageal pressure (δPes) and airway occlusion pressure at 100 ms (P0.1) are used more often, both with important limitations. Dyspnea, a frequent and distressing symptom among mechanically ventilated critically ill patients, may serve as a physiological marker of unacceptably high effort. This single-center prospective observational study conducted in the intensive care unit (ICU) of the University Hospital of Heraklion aims to (1) determine whether the ratio mean to maximal inspiratory pressure (Pmean/Pmax) correlates more strongly with dyspnea intensity than PTP, δPmus, P0.1 and (2) identify a Pmean/Pmax threshold predictive of clinically significant dyspnea. These findings are expected to define objective upper limits of acceptable inspiratory effort and guide ventilator titration to improve patient comfort and safety.
Read the detailed description
During assisted mechanical ventilation, the patient and the ventilator jointly contribute to inspiratory pressure generation. Appropriate titration of pressure support is required to avoid both insufficient assistance (under-assistance) and excessive assistance (over-assistance). Under-assistance may expose patients to excessive inspiratory effort and increased transpulmonary pressure (PL), dyspnea, stress, respiratory-muscle fatigue, and increased left ventricular (LV) afterload, whereas excessive assistance may result in excessive unloading of the inspiratory muscles, diaphragmatic dysfunction, and delayed liberation from mechanical ventilation. Although physiological ranges of inspiratory effort have been described in healthy individuals, the range of inspiratory effort that is acceptable and sustainable in critically ill patients receiving assisted mechanical ventilation remains uncertain. This gap limits the ability to individualize pressure-support settings during difficult or prolonged weaning. Inspiratory effort can be quantified using pressure-time product (PTP), derived from inspiratory pressure over time. However, PTP measurement requires specialized monitoring and offline waveform analysis. Alternative bedside measures include airway occlusion pressure at 100 milliseconds (P0.1), obtained from the ventilator, and changes in esophageal pressure. Although these indices may correlate with inspiratory effort, each has important physiological and technical limitations. The definition of unacceptably high inspiratory effort during assisted mechanical ventilation is therefore unresolved. Proposed thresholds have been based either on the upper physiological range observed in healthy individuals or on effort levels reported in patients who are successfully weaned. However, a fixed absolute pressure threshold may be inadequate for critically ill patients, particularly those with reduced inspiratory-muscle strength or diaphragmatic dysfunction. The effort that can be sustained without distress may depend on the relationship between the effort generated during tidal breathing and the patient's maximal inspiratory pressure-generating capacity. Dyspnea is a highly distressing symptom in critically ill patients receiving assisted ventilation and may be a clinically meaningful indicator of excessive or non-tolerable inspiratory effort. Dyspnea during mechanical ventilation has been associated with anxiety, increased sedative requirements, difficult weaning, and potentially persistent psychological morbidity after critical illness. In healthy individuals and in patients with chronic obstructive pulmonary disease, dyspnea has been related to the fraction of maximal inspiratory capacity used during tidal breathing. Accordingly, the ratio between mean inspiratory pressure generated during a breath and maximal inspiratory pressure, expressed as Pmean/Pmax, may provide a patient-specific measure of relative inspiratory effort. This prospective, single-center, observational physiological study will be conducted in the adult Intensive Care Unit of the University Hospital of Heraklion, Crete, Greece. The study will enroll adult patients receiving invasive assisted mechanical ventilation who have prolonged or difficult weaning and require pressure support of at least 5 cmH2O. In this ICU, these patients are routinely monitored with esophageal and gastric catheter as part of an extended respiratory monitoring. Patients will be excluded if they have a contraindication to placement or use of an esophageal-gastric balloon catheter, including severe coagulation disorders or skull-base fracture, or if consent cannot be obtained. Participants will receive standard clinical care. Pressure-support titration will be performed by the treating ICU clinicians according to usual clinical practice, based on the patient's respiratory mechanics, patient-ventilator interaction, clinical condition, hemodynamic status, and gas exchange. The study does not mandate a specific pressure-support strategy and does not require pressure-support changes for research purposes. In the absence of clinical or laboratory contraindications, the local usual-care approach consists of gradual reductions in pressure support, generally by 2-3 cmH2O. Pressure-support reduction will be discontinued whenever the treating clinician judges that further reduction is inappropriate. At baseline and at each clinically implemented pressure-support level, respiratory physiological measurements will be obtained. Flow and airway-pressure waveforms, esophageal pressure, and gastric pressure will be recorded using dedicated acquisition equipment and analyzed offline with AcqKnowledge software. Measurements will include PTP, Pmean/Pmax, and the change in respiratory-muscle pressure (delta Pmus). Additional measures of respiratory drive, breathing pattern, diaphragmatic contribution, and patient-ventilator interaction will also be recorded where technically feasible. The study will also collect ventilator-derived P0.1 and maximal inspiratory pressure/negative inspiratory force, ventilator settings, vital signs, arterial blood gas values including pH, PaO2, and PaCO2, and relevant clinical data. Baseline characteristics, comorbidities, medications, laboratory findings, Richmond Agitation-Sedation Scale score, Confusion Assessment Method for the ICU status, and other clinically relevant variables will be retrieved from the ICU electronic record. Dyspnea will be assessed at the same time points as physiological measurements. In patients able to communicate and cooperate, dyspnea intensity will be assessed using a numerical rating scale (NRS) from 0 to 10, where 0 indicates no breathing discomfort and 10 indicates the worst imaginable breathing discomfort. In patients unable to self-report, dyspnea-related respiratory distress will be assessed using the Mechanical Ventilation-Respiratory Distress Observation Scale (MV-RDOS). Physiological and clinical measurements will be recorded approximately 5 minutes and again 30-60 minutes after each clinically indicated reduction in pressure support. The primary objective is to determine whether Pmean/Pmax has a stronger association with dyspnea intensity than P0.1, delta Pmus, and PTP. The principal analysis will account for repeated within-patient measurements obtained across pressure-support levels using mixed-effects models. A further objective is to determine whether Pmean/Pmax more accurately identifies clinically significant dyspnea than the comparator inspiratory-effort indices. Receiver-operating-characteristic analyses will be used to assess discrimination, compare areas under the curve between indices using the DeLong method, and identify an optimal Pmean/Pmax threshold for clinically significant dyspnea. Secondary analyses will explore associations between dyspnea and respiratory drive, breathing pattern, diaphragmatic contribution, gas exchange, and patient-ventilator interaction. The study is planned to enroll 50 participants. This sample size is based on the anticipated comparison of dependent associations between inspiratory-effort indices and dyspnea, while recognizing the limited prior literature available to estimate these relationships precisely. This study is intended to identify a clinically meaningful, patient-specific physiological marker of excessive inspiratory effort during assisted mechanical ventilation. If Pmean/Pmax shows a stronger relationship with dyspnea than conventional measures, it may help define an upper acceptable limit of inspiratory effort and support more individualized titration of ventilatory assistance.
- Keywords
- Dyspnea, Inspiratory Effort, assisted mechanical ventilation, Pmean/Pmax
- Medical subject headings
- Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Adult Critically Ill Patients on assisted mechanical ventilation | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Association between Pmean/Pmax and dyspnea intensity
Association of Pmean/Pmax, calculated from recorded inspiratory-pressure waveforms and maximal inspiratory pressure, with dyspnea intensity assessed by a 0-10 numerical rating scale in communicative participants or by MV-RDOS in non-communicative participants. The association will be evaluated with repeated-measures mixed-effects modeling.
Measured: At baseline and at each clinically indicated pressure-support level during the study observation session, approximately 5 minutes and 30-60 minutes after each adjustment
Comparative association of inspiratory-effort indices with dyspnea intensity
Comparison of the strength of association between dyspnea intensity and Pmean/Pmax versus P0.1, δPmus, and PTP.
Measured: During each study observation session, an average of 2-6 hours
Discrimination of clinically significant dyspnea by Pmean/Pmax
Diagnostic/discriminative performance of Pmean/Pmax for clinically significant dyspnea, defined prospectively as numerical rating scale score greater than 4 in communicative participants and/or the prespecified MV-RDOS threshold in non-communicative participants. The optimal threshold will be estimated using receiver-operating-characteristic analysis.
Measured: During each study observation session, an average 2-6 hours
Secondary outcomes (1)
Prevalence of clinically significant dyspnea
Proportion of participants with clinically significant dyspnea at any observed pressure-support level.
Measured: During the study observation session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2026
- Study start18 Jun 2026
- Primary completion30 Nov 2028 (estimated)
- Study completion28 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Dyspnea During Mechanical VentilationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Crete
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katerina Vaporidi, University of Crete
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07877350
- Sponsor's protocol ID
- 25718-2026
- Status last verified
- Sep 2026
- First submitted
- 4 Oct 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be made publicly available. De-identified data may be considered for sharing with qualified researchers following completion of the study and publication of the primary results, subject to approval by the study investigators, institutional and ethics requirements, applicable data-protection legislation, and a formal data-sharing agreement.
Publications
Bureau C, Nierat MC, Decavele M, Rivals I, Dangers L, Beurton A, Virolle S, Deleris R, Delemazure J, Mayaux J, Morelot-Panzini C, Dres M, Similowski T, Demoule A. Sensory interventions to relieve dyspnoea in critically ill mechanically ventilated patients. Eur Respir J. 2024 Jan 18;63(1):2202215. doi: 10.1183/13993003.02215-2022. Print 2024 Jan.
PubMed 37678956Bureau C, Dres M, Morawiec E, Mayaux J, Delemazure J, Similowski T, Demoule A. Dyspnea and the electromyographic activity of inspiratory muscles during weaning from mechanical ventilation. Ann Intensive Care. 2022 Jun 10;12(1):50. doi: 10.1186/s13613-022-01025-5.
PubMed 35688999Decavele M, Gay F, Persichini R, Mayaux J, Morelot-Panzini C, Similowski T, Demoule A. The Mechanical Ventilation-Respiratory Distress Observation Scale as a surrogate of self-reported dyspnoea in intubated patients. Eur Respir J. 2018 Oct 10;52(4):1800598. doi: 10.1183/13993003.00598-2018. Print 2018 Oct. No abstract available.
PubMed 30209199Smits FE, Rietveld PJ, Snoep JWM, van der Velde-Quist F, de Jonge E, Schoe A. P0.1 is an Unreliable Measure of Effort in Support Mechanical Ventilation in Comparison With Esophageal-Derived Measures of Effort: A Comparison Study. Crit Care Med. 2025 Aug 1;53(8):e1650-e1658. doi: 10.1097/CCM.0000000000006745. Epub 2025 Jun 11.
PubMed 40638487Worsham CM, Banzett RB, Schwartzstein RM. Dyspnea, Acute Respiratory Failure, Psychological Trauma, and Post-ICU Mental Health: A Caution and a Call for Research. Chest. 2021 Feb;159(2):749-756. doi: 10.1016/j.chest.2020.09.251. Epub 2020 Oct 1.
PubMed 33011205Le Marec J, Hajage D, Decavele M, Schmidt M, Laurent I, Ricard JD, Jaber S, Azoulay E, Fartoukh M, Hraiech S, Mercat A, Similowski T, Demoule A. High Airway Occlusion Pressure Is Associated with Dyspnea and Increased Mortality in Critically Ill Mechanically Ventilated Patients. Am J Respir Crit Care Med. 2024 Jul 15;210(2):201-210. doi: 10.1164/rccm.202308-1358OC.
PubMed 38319128Schmidt M, Demoule A, Polito A, Porchet R, Aboab J, Siami S, Morelot-Panzini C, Similowski T, Sharshar T. Dyspnea in mechanically ventilated critically ill patients. Crit Care Med. 2011 Sep;39(9):2059-65. doi: 10.1097/CCM.0b013e31821e8779.
PubMed 21572329Demoule A, Clavel M, Rolland-Debord C, Perbet S, Terzi N, Kouatchet A, Wallet F, Roze H, Vargas F, Guerin C, Dellamonica J, Jaber S, Brochard L, Similowski T. Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial. Intensive Care Med. 2016 Nov;42(11):1723-1732. doi: 10.1007/s00134-016-4447-8. Epub 2016 Sep 30.
PubMed 27686347Tonelli R, Protti A, Spinelli E, Grieco DL, Yoshida T, Jonkman AH, Akoumianaki E, Telias I, Docci M, Rodrigues A, Perez J, Piquilloud L, Beitler J, Liu L, Roca O, Pisani L, Goligher E, Carteaux G, Bellani G, Clini E, Zhou JX, Grasselli G, Jaber S, Demoule A, Talmor D, Heunks L, Brochard L, Mauri T. Assessing inspiratory drive and effort in critically ill patients at the bedside. Crit Care. 2025 Jul 31;29(1):339. doi: 10.1186/s13054-025-05526-0.
PubMed 40745324de Vries H, Jonkman A, Shi ZH, Spoelstra-de Man A, Heunks L. Assessing breathing effort in mechanical ventilation: physiology and clinical implications. Ann Transl Med. 2018 Oct;6(19):387. doi: 10.21037/atm.2018.05.53.
PubMed 30460261Demoule A, Decavele M, Antonelli M, Camporota L, Abroug F, Adler D, Azoulay E, Basoglu M, Campbell M, Grasselli G, Herridge M, Johnson MJ, Naccache L, Navalesi P, Pelosi P, Schwartzstein R, Williams C, Windisch W, Heunks L, Similowski T. Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement. Intensive Care Med. 2024 Feb;50(2):159-180. doi: 10.1007/s00134-023-07246-x. Epub 2024 Feb 22.
PubMed 38388984Demoule A, Hajage D, Messika J, Jaber S, Diallo H, Coutrot M, Kouatchet A, Azoulay E, Fartoukh M, Hraiech S, Beuret P, Darmon M, Decavele M, Ricard JD, Chanques G, Mercat A, Schmidt M, Similowski T; REVA Network (Research Network in Mechanical Ventilation). Prevalence, Intensity, and Clinical Impact of Dyspnea in Critically Ill Patients Receiving Invasive Ventilation. Am J Respir Crit Care Med. 2022 Apr 15;205(8):917-926. doi: 10.1164/rccm.202108-1857OC.
PubMed 35061577Mancini DM, Henson D, LaManca J, Levine S. Respiratory muscle function and dyspnea in patients with chronic congestive heart failure. Circulation. 1992 Sep;86(3):909-18. doi: 10.1161/01.cir.86.3.909.
PubMed 1516204O'Donnell DE, Banzett RB, Carrieri-Kohlman V, Casaburi R, Davenport PW, Gandevia SC, Gelb AF, Mahler DA, Webb KA. Pathophysiology of dyspnea in chronic obstructive pulmonary disease: a roundtable. Proc Am Thorac Soc. 2007 May;4(2):145-68. doi: 10.1513/pats.200611-159CC.
PubMed 17494725Karageorgos V, Proklou A, Vaporidi K. Lung and diaphragm protective ventilation: a synthesis of recent data. Expert Rev Respir Med. 2022 Apr;16(4):375-390. doi: 10.1080/17476348.2022.2060824. Epub 2022 Apr 5.
PubMed 35354361
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association of Inspiratory Effort With Dyspnea During Assisted Mechanical Ventilation in Critically Ill Patients: A Single-Center Prospective Observational Physiological Study
- ClinicalTrials.gov ID
- NCT07877350
- Acronym / sponsor ID
- 25718-2026
- Keywords
- Dyspnea, Inspiratory Effort, assisted mechanical ventilation, Pmean/Pmax
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of CreteUniversity, hospital or other
- Study start
- 18 Jun 2026 (actual)
- Primary completion
- 30 Nov 2028 (estimated)
- Study completion
- 28 May 2029 (estimated)
- First posted
- 16 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
During assisted mechanical ventilation, breathing results from the interaction between the patient and the ventilator. Optimal titration of pressure support is essential to maintain a balance between over-assistance and under-assistance. Excessive respiratory may lead to dyspnea and cause respiratory muscle fatigue, whereas excessive assistance promotes muscle atrophy and delays weaning. Although normal inspiratory effort values in healthy subjects are well defined, acceptable limits in critically ill patients remain unclear. Inspiratory effort is traditionally quantified by the pressure-time product (PTP), but its measurement is technically demanding. Simpler indices such as swings of esophageal pressure (δPes) and airway occlusion pressure at 100 ms (P0.1) are used more often, both with important limitations. Dyspnea, a frequent and distressing symptom among mechanically ventilated critically ill patients, may serve as a physiological marker of unacceptably high effort. This single-center prospective observational study conducted in the intensive care unit (ICU) of the University Hospital of Heraklion aims to (1) determine whether the ratio mean to maximal inspiratory pressure (Pmean/Pmax) correlates more strongly with dyspnea intensity than PTP, δPmus, P0.1 and (2) identify a Pmean/Pmax threshold predictive of clinically significant dyspnea. These findings are expected to define objective upper limits of acceptable inspiratory effort and guide ventilator titration to improve patient comfort and safety.
Detailed description
During assisted mechanical ventilation, the patient and the ventilator jointly contribute to inspiratory pressure generation. Appropriate titration of pressure support is required to avoid both insufficient assistance (under-assistance) and excessive assistance (over-assistance). Under-assistance may expose patients to excessive inspiratory effort and increased transpulmonary pressure (PL), dyspnea, stress, respiratory-muscle fatigue, and increased left ventricular (LV) afterload, whereas excessive assistance may result in excessive unloading of the inspiratory muscles, diaphragmatic dysfunction, and delayed liberation from mechanical ventilation. Although physiological ranges of inspiratory effort have been described in healthy individuals, the range of inspiratory effort that is acceptable and sustainable in critically ill patients receiving assisted mechanical ventilation remains uncertain. This gap limits the ability to individualize pressure-support settings during difficult or prolonged weaning. Inspiratory effort can be quantified using pressure-time product (PTP), derived from inspiratory pressure over time. However, PTP measurement requires specialized monitoring and offline waveform analysis. Alternative bedside measures include airway occlusion pressure at 100 milliseconds (P0.1), obtained from the ventilator, and changes in esophageal pressure. Although these indices may correlate with inspiratory effort, each has important physiological and technical limitations. The definition of unacceptably high inspiratory effort during assisted mechanical ventilation is therefore unresolved. Proposed thresholds have been based either on the upper physiological range observed in healthy individuals or on effort levels reported in patients who are successfully weaned. However, a fixed absolute pressure threshold may be inadequate for critically ill patients, particularly those with reduced inspiratory-muscle strength or diaphragmatic dysfunction. The effort that can be sustained without distress may depend on the relationship between the effort generated during tidal breathing and the patient's maximal inspiratory pressure-generating capacity. Dyspnea is a highly distressing symptom in critically ill patients receiving assisted ventilation and may be a clinically meaningful indicator of excessive or non-tolerable inspiratory effort. Dyspnea during mechanical ventilation has been associated with anxiety, increased sedative requirements, difficult weaning, and potentially persistent psychological morbidity after critical illness. In healthy individuals and in patients with chronic obstructive pulmonary disease, dyspnea has been related to the fraction of maximal inspiratory capacity used during tidal breathing. Accordingly, the ratio between mean inspiratory pressure generated during a breath and maximal inspiratory pressure, expressed as Pmean/Pmax, may provide a patient-specific measure of relative inspiratory effort. This prospective, single-center, observational physiological study will be conducted in the adult Intensive Care Unit of the University Hospital of Heraklion, Crete, Greece. The study will enroll adult patients receiving invasive assisted mechanical ventilation who have prolonged or difficult weaning and require pressure support of at least 5 cmH2O. In this ICU, these patients are routinely monitored with esophageal and gastric catheter as part of an extended respiratory monitoring. Patients will be excluded if they have a contraindication to placement or use of an esophageal-gastric balloon catheter, including severe coagulation disorders or skull-base fracture, or if consent cannot be obtained. Participants will receive standard clinical care. Pressure-support titration will be performed by the treating ICU clinicians according to usual clinical practice, based on the patient's respiratory mechanics, patient-ventilator interaction, clinical condition, hemodynamic status, and gas exchange. The study does not mandate a specific pressure-support strategy and does not require pressure-support changes for research purposes. In the absence of clinical or laboratory contraindications, the local usual-care approach consists of gradual reductions in pressure support, generally by 2-3 cmH2O. Pressure-support reduction will be discontinued whenever the treating clinician judges that further reduction is inappropriate. At baseline and at each clinically implemented pressure-support level, respiratory physiological measurements will be obtained. Flow and airway-pressure waveforms, esophageal pressure, and gastric pressure will be recorded using dedicated acquisition equipment and analyzed offline with AcqKnowledge software. Measurements will include PTP, Pmean/Pmax, and the change in respiratory-muscle pressure (delta Pmus). Additional measures of respiratory drive, breathing pattern, diaphragmatic contribution, and patient-ventilator interaction will also be recorded where technically feasible. The study will also collect ventilator-derived P0.1 and maximal inspiratory pressure/negative inspiratory force, ventilator settings, vital signs, arterial blood gas values including pH, PaO2, and PaCO2, and relevant clinical data. Baseline characteristics, comorbidities, medications, laboratory findings, Richmond Agitation-Sedation Scale score, Confusion Assessment Method for the ICU status, and other clinically relevant variables will be retrieved from the ICU electronic record. Dyspnea will be assessed at the same time points as physiological measurements. In patients able to communicate and cooperate, dyspnea intensity will be assessed using a numerical rating scale (NRS) from 0 to 10, where 0 indicates no breathing discomfort and 10 indicates the worst imaginable breathing discomfort. In patients unable to self-report, dyspnea-related respiratory distress will be assessed using the Mechanical Ventilation-Respiratory Distress Observation Scale (MV-RDOS). Physiological and clinical measurements will be recorded approximately 5 minutes and again 30-60 minutes after each clinically indicated reduction in pressure support. The primary objective is to determine whether Pmean/Pmax has a stronger association with dyspnea intensity than P0.1, delta Pmus, and PTP. The principal analysis will account for repeated within-patient measurements obtained across pressure-support levels using mixed-effects models. A further objective is to determine whether Pmean/Pmax more accurately identifies clinically significant dyspnea than the comparator inspiratory-effort indices. Receiver-operating-characteristic analyses will be used to assess discrimination, compare areas under the curve between indices using the DeLong method, and identify an optimal Pmean/Pmax threshold for clinically significant dyspnea. Secondary analyses will explore associations between dyspnea and respiratory drive, breathing pattern, diaphragmatic contribution, gas exchange, and patient-ventilator interaction. The study is planned to enroll 50 participants. This sample size is based on the anticipated comparison of dependent associations between inspiratory-effort indices and dyspnea, while recognizing the limited prior literature available to estimate these relationships precisely. This study is intended to identify a clinically meaningful, patient-specific physiological marker of excessive inspiratory effort during assisted mechanical ventilation. If Pmean/Pmax shows a stronger relationship with dyspnea than conventional measures, it may help define an upper acceptable limit of inspiratory effort and support more individualized titration of ventilatory assistance.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adult Critically Ill Patients on assisted mechanical ventilation | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will consist of adult patients admitted to the Adult Intensive Care Unit of the University Hospital of Heraklion, Crete, Greece, who are receiving invasive assisted mechanical ventilation during prolonged or difficult liberation from mechanical ventilation. Participants will be identified from consecutively treated ICU patients undergoing routine clinical assessment and pressure-support titration by the treating ICU team.
Key inclusion criteria (6 listed)
- Adult patient admitted to the ICU.
- Receiving invasive assisted mechanical ventilation in a pressure-support mode or another assisted mode permitting measurement of the prespecified variables.
- Prolonged or difficult weaning.
- Receiving pressure support of at least 5 cmH2O at screening.
- Written informed consent from the participant or legally authorized representative, in accordance with local ethics requirements.
Key exclusion criteria (3 listed)
- Contraindication to nasogastric placement or to placement/use of an esophageal-gastric balloon catheter for Pes and Pgas measurement.
- Refusal of consent by the participant or legally authorized representative.
- Any clinical condition in which the treating physician considers study measurements or pressure-support titration unsafe (unstable hemodynamics, uncontrolled arrhythmia, severe hypoxemia, active myocardial ischemia etc.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Association between Pmean/Pmax and dyspnea intensity
Time frame: At baseline and at each clinically indicated pressure-support level during the study observation session, approximately 5 minutes and 30-60 minutes after each adjustment
Association of Pmean/Pmax, calculated from recorded inspiratory-pressure waveforms and maximal inspiratory pressure, with dyspnea intensity assessed by a 0-10 numerical rating scale in communicative participants or by MV-RDOS in non-communicative participants. The association will be evaluated with repeated-measures mixed-effects modeling.
Comparative association of inspiratory-effort indices with dyspnea intensity
Time frame: During each study observation session, an average of 2-6 hours
Comparison of the strength of association between dyspnea intensity and Pmean/Pmax versus P0.1, δPmus, and PTP.
Discrimination of clinically significant dyspnea by Pmean/Pmax
Time frame: During each study observation session, an average 2-6 hours
Diagnostic/discriminative performance of Pmean/Pmax for clinically significant dyspnea, defined prospectively as numerical rating scale score greater than 4 in communicative participants and/or the prespecified MV-RDOS threshold in non-communicative participants. The optimal threshold will be estimated using receiver-operating-characteristic analysis.
1 secondary outcome
Prevalence of clinically significant dyspnea
Time frame: During the study observation session
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Background: PubMed 37678956Bureau C, Nierat MC, Decavele M, Rivals I, Dangers L, Beurton A, Virolle S, Deleris R, Delemazure J, Mayaux J, Morelot-Panzini C, Dres M, Similowski T, Demoule A. Sensory interventions to relieve dyspnoea in critically ill mechanically ventilated patients. Eur Respir J. 2024 Jan 18;63(1):2202215. doi: 10.1183/13993003.02215-2022. Print 2024 Jan.
- Background: PubMed 35688999Bureau C, Dres M, Morawiec E, Mayaux J, Delemazure J, Similowski T, Demoule A. Dyspnea and the electromyographic activity of inspiratory muscles during weaning from mechanical ventilation. Ann Intensive Care. 2022 Jun 10;12(1):50. doi: 10.1186/s13613-022-01025-5.
- Background: PubMed 30209199Decavele M, Gay F, Persichini R, Mayaux J, Morelot-Panzini C, Similowski T, Demoule A. The Mechanical Ventilation-Respiratory Distress Observation Scale as a surrogate of self-reported dyspnoea in intubated patients. Eur Respir J. 2018 Oct 10;52(4):1800598. doi: 10.1183/13993003.00598-2018. Print 2018 Oct. No abstract available.
- Background: PubMed 40638487Smits FE, Rietveld PJ, Snoep JWM, van der Velde-Quist F, de Jonge E, Schoe A. P0.1 is an Unreliable Measure of Effort in Support Mechanical Ventilation in Comparison With Esophageal-Derived Measures of Effort: A Comparison Study. Crit Care Med. 2025 Aug 1;53(8):e1650-e1658. doi: 10.1097/CCM.0000000000006745. Epub 2025 Jun 11.
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- Individual participant dataSharing planned: No. Individual participant data will not be made publicly available. De-identified data may be considered for sharing with qualified researchers following completion of the study and publication of the primary results, subject to approval by the study investigators, institutional and ethics requirements, applicable data-protection legislation, and a formal data-sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dyspnea During Mechanical Ventilation and Inspiratory Effort, run by University of Crete at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Katerina Vaporidi, MD, PhD (+30 2810 392718 / 2810 394729, vaporidi@uoc.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association between Pmean/Pmax and dyspnea intensity (time frame: At baseline and at each clinically indicated pressure-support level during the study observation session, approximately 5 minutes and 30-60 minutes after each adjustment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07877350, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.