An observational study in Dyspnea During Mechanical Ventilation, Inspiratory Effort and Mechanical Ventilation, sponsored by University of Crete. Recruiting at 1 site in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-16.
Sponsored by University of Crete · Observational
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.
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.
681 studies on the registry are indexed under Dyspnea; 159 are open to participants now.
This study's planned enrollment of 50 is below the median of 120 across 212 observational studies indexed under Dyspnea.
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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.
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Exclusion Criteria:
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.
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
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.
Time frame: 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.
Time frame: During each study observation session, an average 2-6 hours
Prevalence of clinically significant dyspnea
Proportion of participants with clinically significant dyspnea at any observed pressure-support level.
Time frame: During the study observation session
Plan to share: 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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University of Crete