Mucus RetentionNCT06491017
Effects of Mechanical Insufflation-Exsufflation With Optimized Settings on Wet Mucus Volume During Invasive Ventilation
A study testing MI-E Intervention protocol and Standard MI-E setting in people with Mucus Retention and Mechanical Ventilation Complication, run by Hospital Clinic of Barcelona at 1 site in Spain.
Trial summary
Retention of airway secretions is a frequent complication in critically ill patients requiring invasive mechanical ventilation (MV).This complication is often due to excessive secretion production and ineffective secretion clearance. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mucus Retention, Mechanical Ventilation Complication
- What is being tested?
- MI-E Intervention protocol and Standard MI-E setting
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteSpain
- Study dates
- 8 May 2026to Dec 2028
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults (> 18yo).
- Endotracheal intubation and invasive mechanical ventilation for > 48h and active humidification for > 24h.
- Richmond Agitation-Sedation Scale -3 to -5.
- Signed informed consent.
Who cannot join
- Patients with hemodynamic instability (MAP < 60 or > 110, Heart Rate < 50 or > 130, new onset arrhythmias), respiratory instability (PEEP > 12cmH2O, SpO2 < 90% or fraction of inspired oxygen (FiO2) > 60%).
- Undrained pneumothorax/pneumomediastinum.
- Unstable intracranial pressure (ICP > 20mmHg or MAP < 60).
- Severe bronchospasm.
- Post cardiothoracic surgical patients.
- Active pulmonary tuberculosis.
Show all 9Show fewer
- Bronchoesophageal or bronchopleural fistulas.
- Prone position.
- Pregnancy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital Clinic de Barcelona
Barcelona, 08036
Joan-Daniel Martí, PhD, 0034627954827, jd.martibcn@gmail.com
About this study
Official title: Effects of Mechanical Insufflation-Exsufflation With Optimized Settings on Suctioned Wet Mucus Volume During Invasive Ventilation
Retention of airway secretions is a frequent complication in critically ill patients requiring invasive mechanical ventilation (MV).This complication is often due to excessive secretion production and ineffective secretion clearance.
Mechanical insufflator-exsufflator (MI-E) is a respiratory physiotherapy technique that aims to assist or simulate a normal cough by using an electro-mechanical dedicated device. A positive airway pressure is delivered to the airways, in order to hyperinflate the lungs, followed by a rapid change to negative pressure that promotes a rapid exhalation and enhances peak expiratory flows.
Read more
However, there is no consensus on the best MI-E settings to facilitate secretion clearance in these patients. Inspiratory and expiratory pressures of ±40 cmH2O and inspiratory-expiratory time of 3 and 2 seconds, respectively, are often used as a standard for MI-E programming in the daily routine practice, but recent laboratory studies have shown significant benefits when MI-E setting is optimized to promote an expiratory flow bias.
The investigators designed this study to compare the effects of MI-E with an optimized setting versus a standard setting on the wet volume of suctioned sputum in intubated critically ill patients on invasive MV for more than 48 hours.
Read the detailed description
Retention of airway secretions is a frequent complication in critically ill patients requiring invasive mechanical ventilation (MV). This complication is often due to excessive secretion production and ineffective secretion clearance. One of the main causes is the presence of an endotracheal tube (ETT) which has been shown to decrease mucociliary clearance and hinders the generation of adequate peak expiratory flows when coughing. Other factors such as suboptimal airway humidification, inspiratory flow bias, semi-recumbent position, prolonged immobilization and respiratory muscles weakness further impair sputum clearance. Mucus retention may impede optimal gas exchange, and lead to atelectasis, increased work of breathing, bacterial colonization and development of pulmonary infections, prolonging the need for MV. These conditions, added to initial factors, increase morbidity and mortality in critically ill patients, making secretion clearance an essential factor for patients' prognosis.
Secretion removal techniques, such as, manual or mechanical hyperinflations, chest vibrations or expiratory rib cage compressions, prior to suctioning, are commonly used by physiotherapists in intensive care units (ICU). However, the evidence assessing respiratory physiotherapy techniques in critically ill patients is scant and sometimes inconsistent, making it difficult to extrapolate the results and standardize the clinical practice. Moreover, the execution of these techniques often differs among professionals based on their experience, training, and resources availability.
Mechanical insufflator-exsufflator (MI-E) is a respiratory physiotherapy technique that aims to assist or simulate a normal cough by using an electro-mechanical dedicated device. A positive airway pressure is delivered to the airways, in order to hyperinflate the lungs, followed by a rapid change to negative pressure that promotes a rapid exhalation and enhances peak expiratory flows. MI-E is commonly used in patients with ineffective cough mainly due to respiratory pump failure (i.e: neuromuscular patients), and has been proposed in recent years as a technique with great potential to non-invasively clear secretions in the critically ill. Indeed, recent studies have evaluated safety and efficacy of MI-E in intubated critically ill patients with promising results and no associated adverse events. However, there is no consensus on the best MI-E settings to facilitate secretion clearance in these patients. Inspiratory and expiratory pressures of ±40 cmH2O and inspiratory-expiratory time of 3 and 2 seconds, respectively, are often used as a standard for MI-E programming in the daily routine practice, but recent laboratory studies have shown significant benefits when MI-E setting is optimized to promote an expiratory flow bias. For instance, Volpe et al. achieved significant differences in artificial mucus displacement when inspiratory flows were lowered, inspiratory time was increased to 4 seconds, and expiratory flow bias was enhanced by increasing the expiratory pressure over the inspiratory pressure. More recently, evidence from a swine model confirmed the improvement in mucus movement velocity when expiratory pressure was enhanced to increase the difference between inspiratory and expiratory pressures (i.e: +40/-70cmH2O). Importantly, increased inspiratory pressures should be avoided to prevent movement of mucus toward the lungs and potential associated detrimental effects such as alveolar damage or hemodynamic impairment.
The investigators designed this study to compare the effects of MI-E with an optimized setting versus a standard setting on the wet volume of suctioned sputum in intubated critically ill patients on invasive MV for more than 48 hours.
- Being tested
- MI-E Intervention protocol, Standard MI-E setting
- Keywords
- Mechanical insufflation-exsufflation, Physiotherapy, Mucus retention, mechanical ventilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MI-E Intervention protocolDevice
The endotracheal tube cuff will be inflated to 40 cmH2O and MI-E device will be used to deliver MI-E in automatic mode, with 4 sets of 5 respiratory cycles each and a 1-minute interval between each set.
Before initiation of the MI-E intervention protocol, the investigators will carry out a short-period test to find the appropriate MI-E settings to achieve inspiratory volumes of ≥1 liter and PEF ≥80 L/min. Concretely, inspiratory and expiratory time will always be set at 4 seconds and 2 seconds, respectively, and inspiratory flow will always be in slow mode. Once the appropriate inspiratory pressure will be found, the expiratory pressure will be initially set to exceed in 30 cmH2O the inspiratory pressure and, if required, this will be increased by 5 cmH2O until achieving a PEF ≥80 L/min with a maximum expiratory pressure of 70 cmH2O.
Standard MI-E settingDevice
Cough Assist E70 device (Philips Respironics, USA, Andover, Massachusetts) will be used to deliver MI-E in automatic mode, with 4 sets of 5 respiratory cycles each and a 1-minute interval between each set. During the 1-minute pause between sets, the patient will be reconnected to the ventilator to avoid desaturation and de-recruitment during procedures. PEEP will remain stable during the protocol.
The standard MI-E setting will consist of in-expiratory pressures of +40/-40 cmH2O, medium inspiratory flow, with 3 seconds and 2 seconds of in-expiratory time, respectively, and 1-second pause.
| Study group | Role | What they receive |
|---|---|---|
| MI-E intervention protocol | Experimental | The optimized MI-E setting will consist of in-expiratory pressures defined during the previous short-period test to achieve inspiratory volumes of ≥1 liter and PEF ≥80 L/min Receives: Device: MI-E Intervention protocol |
| Standard MI-E setting | Active comparator | The standard MI-E setting will consist of in-expiratory pressures of +40/-40 cmH2O, medium inspiratory flow, with 3 seconds and 2 seconds of in-expiratory time, respectively, and 1-second pause Receives: Device: Standard MI-E setting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wet volume of sputum
Airway suctioning will be carried out using an open aspiration procedure, using a 12French catheter connected to a sterile collection container. The suction procedure will be performed according to international guidelines . If necessary, 5 ml of saline solution will be used to rinse the catheter in case of impacted secretions inside the catheter; later this volume will be subtracted from the final volume of secretions, thus obtaining the exact amount of wet sputum.
Measured: Immediately after each intervention
Secondary outcomes (12)
Respiratory parameters: Inspiratory flow (PIF)
Flow will be measured with a heated pneumotachograph (Fluxmed GrH monitor MBMED, Buenos Aires, Argentina) inserted between the proximal tip of the endotracheal tube and the Y-piece of the breathing circuit. All signals will be recorded on a personal computer for subsequent analysis with dedicated software (FluxReview software MBMED, Buenos Aires, Argentina)
Measured: Before and during MI-E interventions, delivered tidal volumes will be recorded, PIF and PEF will be assessed for each insufflation-exsufflation cycle, and the PEF-PIF difference and the PEF:PIF ratio will be calculated
Respiratory parameters: Peak expiratory flow (PEF)
Flow will be measured with a heated pneumotachograph (Fluxmed GrH monitor MBMED, Buenos Aires, Argentina) inserted between the proximal tip of the endotracheal tube and the Y-piece of the breathing circuit. All signals will be recorded on a personal computer for subsequent analysis with dedicated software (FluxReview software MBMED, Buenos Aires, Argentina)
Measured: Before and during MI-E interventions, delivered tidal volumes will be recorded, PIF and PEF will be assessed for each insufflation-exsufflation cycle, and the PEF-PIF difference and the PEF:PIF ratio will be calculated
Respiratory parameters: difference between PEF-PIF;
Flow will be measured with a heated pneumotachograph (Fluxmed GrH monitor MBMED, Buenos Aires, Argentina) inserted between the proximal tip of the endotracheal tube and the Y-piece of the breathing circuit. All signals will be recorded on a personal computer for subsequent analysis with dedicated software (FluxReview software MBMED, Buenos Aires, Argentina)
Measured: Before and during MI-E interventions, delivered tidal volumes will be recorded, PIF and PEF will be assessed for each insufflation-exsufflation cycle, and the PEF-PIF difference and the PEF:PIF ratio will be calculated
Respiratory parameters: PEF:PIF ratio
Flow will be measured with a heated pneumotachograph (Fluxmed GrH monitor MBMED, Buenos Aires, Argentina) inserted between the proximal tip of the endotracheal tube and the Y-piece of the breathing circuit. All signals will be recorded on a personal computer for subsequent analysis with dedicated software (FluxReview software MBMED, Buenos Aires, Argentina)
Measured: Before and during MI-E interventions, delivered tidal volumes will be recorded, PIF and PEF will be assessed for each insufflation-exsufflation cycle, and the PEF-PIF difference and the PEF:PIF ratio will be calculated
Pulmonary mechanics parameters: Static Compliance (Cst)
Pressure signals will be measured with a heated pneumotachograph (Fluxmed GrH monitor MBMED, Buenos Aires, Argentina) inserted between the proximal tip of the endotracheal tube and the Y-piece of the breathing circuit. All signals will be recorded on a personal computer for subsequent analysis with dedicated software (FluxReview software MBMED, Buenos Aires, Argentina)
Measured: Airway pressures will be recorded before, immediately after MI-E intervention, after endotracheal suctioning, and 1h after endotracheal suctioning. Respiratory system compliance and airway resistance will be calculated using standard formulas.
Pulmonary mechanics parameters: Airway resistance (Raw)
Pressure signals will be measured with a heated pneumotachograph (Fluxmed GrH monitor MBMED, Buenos Aires, Argentina) inserted between the proximal tip of the endotracheal tube and the Y-piece of the breathing circuit. All signals will be recorded on a personal computer for subsequent analysis with dedicated software (FluxReview software MBMED, Buenos Aires, Argentina)
Measured: Airway pressures will be recorded before, immediately after MI-E intervention, after endotracheal suctioning, and 1h after endotracheal suctioning. Respiratory system compliance and airway resistance will be calculated using standard formulas.
Hemodynamics values: Heart rate
Hemodynamics parameters will be recorder from the patient's monitor.
Measured: Before, immediately after MI-E interventions and after endotracheal suctioning.
Hemodynamics values: Mean arterial pressure
Hemodynamics parameters will be recorded from the patient's monitor.
Measured: Before, immediately after MI-E interventions and after endotracheal suctioning.
Gas exchange: Arterial blood gas analysis
Parameters will be recorded from the patient's monitor arterial blood gas analysis.
Measured: Before, immediately after endotracheal suctioning and 1 hour after interventions.
Gas exchange: Pulseoximeter oxygen saturation (SpO2)
Parameters will be recorded from patient's pulseoximetry.
Measured: Before, immediately after endotracheal suctioning and 1 hour after interventions.
Adverse events
All adverse events that force the interruption of the interventions will be recorded. Reasons to stop MI-E will be haemodynamic instability, severe desaturation, structural damage caused to the airway (i.e. pneumothorax), airway obstruction or difficulty in correct ventilation of the patient.
Measured: During the intervention/procedure and immediately after the intervention/procedure.
Numbers of participants with adverse events
Relationship between the participants who have reported adverse effects and the number of adverse effects in the study.
Measured: During the intervention/procedure and immediately after the intervention/procedure.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2024
- Study start8 May 2026
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Mucus RetentionStudies of the same condition, open and under way.
- More trials run by Hospital Clinic of BarcelonaThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Clinic of Barcelona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joan-Daniel Martí Romeu, Hospital Clinic of Barcelona
- Investigators
- Joan Daniel Martí, PhD, Principal investigator, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06491017
- Sponsor's protocol ID
- HCB/2023/1101
- Status last verified
- May 2026
- First submitted
- 15 Feb 2024
- Last updated
- 8 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Konrad F, Schreiber T, Brecht-Kraus D, Georgieff M. Mucociliary transport in ICU patients. Chest. 1994 Jan;105(1):237-41. doi: 10.1378/chest.105.1.237.
PubMed 8275739Sackner MA, Hirsch J, Epstein S. Effect of cuffed endotracheal tubes on tracheal mucous velocity. Chest. 1975 Dec;68(6):774-7. doi: 10.1378/chest.68.6.774.
PubMed 1192854Gal TJ. Effects of endotracheal intubation on normal cough performance. Anesthesiology. 1980 Apr;52(4):324-9. doi: 10.1097/00000542-198004000-00008.
PubMed 7362053Kilgour E, Rankin N, Ryan S, Pack R. Mucociliary function deteriorates in the clinical range of inspired air temperature and humidity. Intensive Care Med. 2004 Jul;30(7):1491-4. doi: 10.1007/s00134-004-2235-3. Epub 2004 Mar 16.
PubMed 15024566American Association for Respiratory Care; Restrepo RD, Walsh BK. Humidification during invasive and noninvasive mechanical ventilation: 2012. Respir Care. 2012 May;57(5):782-8. doi: 10.4187/respcare.01766.
PubMed 22546299Li Bassi G, Zanella A, Cressoni M, Stylianou M, Kolobow T. Following tracheal intubation, mucus flow is reversed in the semirecumbent position: possible role in the pathogenesis of ventilator-associated pneumonia. Crit Care Med. 2008 Feb;36(2):518-25. doi: 10.1097/01.CCM.0000299741.32078.E9.
PubMed 18176317Wu MF, Wang TY, Chen DS, Hsiao HF, Hu HC, Chung FT, Lin TY, Lin SM. The effects of mechanical insufflation-exsufflation on lung function and complications in cardiac surgery patients: a pilot study. J Cardiothorac Surg. 2021 Dec 9;16(1):350. doi: 10.1186/s13019-021-01738-x.
PubMed 34886881Kuroiwa R, Tateishi Y, Oshima T, Inagaki T, Furukawa S, Takemura R, Kawasaki Y, Murata A. Mechanical Insufflation-exsufflation for the Prevention of Ventilator-associated Pneumonia in Intensive Care Units: A Retrospective Cohort Study. Indian J Crit Care Med. 2021 Jan;25(1):62-66. doi: 10.5005/jp-journals-10071-23508.
PubMed 33603304Pneumatikos IA, Dragoumanis CK, Bouros DE. Ventilator-associated pneumonia or endotracheal tube-associated pneumonia? An approach to the pathogenesis and preventive strategies emphasizing the importance of endotracheal tube. Anesthesiology. 2009 Mar;110(3):673-80. doi: 10.1097/ALN.0b013e31819868e0.
PubMed 19212256Shapiro M, Wilson RK, Casar G, Bloom K, Teague RB. Work of breathing through different sized endotracheal tubes. Crit Care Med. 1986 Dec;14(12):1028-31. doi: 10.1097/00003246-198612000-00007.
PubMed 3780244Branson RD. Secretion management in the mechanically ventilated patient. Respir Care. 2007 Oct;52(10):1328-42; discussion 1342-7.
PubMed 17894902Martinez-Alejos R, Marti JD, Li Bassi G, Gonzalez-Anton D, Pilar-Diaz X, Reginault T, Wibart P, Ntoumenopoulos G, Tronstad O, Gabarrus A, Quinart A, Torres A. Effects of Mechanical Insufflation-Exsufflation on Sputum Volume in Mechanically Ventilated Critically Ill Subjects. Respir Care. 2021 Sep;66(9):1371-1379. doi: 10.4187/respcare.08641. Epub 2021 Jun 8.
PubMed 34103385Rose L, McKim D, Leasa D, Nonoyama M, Tandon A, Kaminska M, O'Connell C, Loewen A, Connolly B, Murphy P, Hart N, Road J. Monitoring Cough Effectiveness and Use of Airway Clearance Strategies: A Canadian and UK Survey. Respir Care. 2018 Dec;63(12):1506-1513. doi: 10.4187/respcare.06321. Epub 2018 Sep 11.
PubMed 30206128Goni-Viguria R, Yoldi-Arzoz E, Casajus-Sola L, Aquerreta-Larraya T, Fernandez-Sangil P, Guzman-Unamuno E, Moyano-Berardo BM. Respiratory physiotherapy in intensive care unit: Bibliographic review. Enferm Intensiva (Engl Ed). 2018 Oct-Dec;29(4):168-181. doi: 10.1016/j.enfi.2018.03.003. Epub 2018 Jun 15. English, Spanish.
PubMed 29910086Swingwood E, Tume L, Cramp F. A survey examining the use of mechanical insufflation-exsufflation on adult intensive care units across the UK. J Intensive Care Soc. 2020 Nov;21(4):283-289. doi: 10.1177/1751143719870121. Epub 2019 Sep 5.
PubMed 34093728
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Mechanical Insufflation-Exsufflation With Optimized Settings on Suctioned Wet Mucus Volume During Invasive Ventilation
- ClinicalTrials.gov ID
- NCT06491017
- Acronym / sponsor ID
- HCB/2023/1101
- Keywords
- Mechanical insufflation-exsufflation, Physiotherapy, Mucus retention, mechanical ventilation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Hospital Clinic of BarcelonaUniversity, hospital or other
- Study start
- 8 May 2026 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 8 Jul 2024 (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.
Retention of airway secretions is a frequent complication in critically ill patients requiring invasive mechanical ventilation (MV).This complication is often due to excessive secretion production and ineffective secretion clearance.
Mechanical insufflator-exsufflator (MI-E) is a respiratory physiotherapy technique that aims to assist or simulate a normal cough by using an electro-mechanical dedicated device. A positive airway pressure is delivered to the airways, in order to hyperinflate the lungs, followed by a rapid change to negative pressure that promotes a rapid exhalation and enhances peak expiratory flows.
However, there is no consensus on the best MI-E settings to facilitate secretion clearance in these patients. Inspiratory and expiratory pressures of ±40 cmH2O and inspiratory-expiratory time of 3 and 2 seconds, respectively, are often used as a standard for MI-E programming in the daily routine practice, but recent laboratory studies have shown significant benefits when MI-E setting is optimized to promote an expiratory flow bias.
The investigators designed this study to compare the effects of MI-E with an optimized setting versus a standard setting on the wet volume of suctioned sputum in intubated critically ill patients on invasive MV for more than 48 hours.
Detailed description
Retention of airway secretions is a frequent complication in critically ill patients requiring invasive mechanical ventilation (MV). This complication is often due to excessive secretion production and ineffective secretion clearance. One of the main causes is the presence of an endotracheal tube (ETT) which has been shown to decrease mucociliary clearance and hinders the generation of adequate peak expiratory flows when coughing. Other factors such as suboptimal airway humidification, inspiratory flow bias, semi-recumbent position, prolonged immobilization and respiratory muscles weakness further impair sputum clearance. Mucus retention may impede optimal gas exchange, and lead to atelectasis, increased work of breathing, bacterial colonization and development of pulmonary infections, prolonging the need for MV. These conditions, added to initial factors, increase morbidity and mortality in critically ill patients, making secretion clearance an essential factor for patients' prognosis.
Secretion removal techniques, such as, manual or mechanical hyperinflations, chest vibrations or expiratory rib cage compressions, prior to suctioning, are commonly used by physiotherapists in intensive care units (ICU). However, the evidence assessing respiratory physiotherapy techniques in critically ill patients is scant and sometimes inconsistent, making it difficult to extrapolate the results and standardize the clinical practice. Moreover, the execution of these techniques often differs among professionals based on their experience, training, and resources availability.
Mechanical insufflator-exsufflator (MI-E) is a respiratory physiotherapy technique that aims to assist or simulate a normal cough by using an electro-mechanical dedicated device. A positive airway pressure is delivered to the airways, in order to hyperinflate the lungs, followed by a rapid change to negative pressure that promotes a rapid exhalation and enhances peak expiratory flows. MI-E is commonly used in patients with ineffective cough mainly due to respiratory pump failure (i.e: neuromuscular patients), and has been proposed in recent years as a technique with great potential to non-invasively clear secretions in the critically ill. Indeed, recent studies have evaluated safety and efficacy of MI-E in intubated critically ill patients with promising results and no associated adverse events. However, there is no consensus on the best MI-E settings to facilitate secretion clearance in these patients. Inspiratory and expiratory pressures of ±40 cmH2O and inspiratory-expiratory time of 3 and 2 seconds, respectively, are often used as a standard for MI-E programming in the daily routine practice, but recent laboratory studies have shown significant benefits when MI-E setting is optimized to promote an expiratory flow bias. For instance, Volpe et al. achieved significant differences in artificial mucus displacement when inspiratory flows were lowered, inspiratory time was increased to 4 seconds, and expiratory flow bias was enhanced by increasing the expiratory pressure over the inspiratory pressure. More recently, evidence from a swine model confirmed the improvement in mucus movement velocity when expiratory pressure was enhanced to increase the difference between inspiratory and expiratory pressures (i.e: +40/-70cmH2O). Importantly, increased inspiratory pressures should be avoided to prevent movement of mucus toward the lungs and potential associated detrimental effects such as alveolar damage or hemodynamic impairment.
The investigators designed this study to compare the effects of MI-E with an optimized setting versus a standard setting on the wet volume of suctioned sputum in intubated critically ill patients on invasive MV for more than 48 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MI-E intervention protocol | Experimental | Device: MI-E Intervention protocolThe optimized MI-E setting will consist of in-expiratory pressures defined during the previous short-period test to achieve inspiratory volumes of ≥1 liter and PEF ≥80 L/min |
| Standard MI-E setting | Active comparator | Device: Standard MI-E settingThe standard MI-E setting will consist of in-expiratory pressures of +40/-40 cmH2O, medium inspiratory flow, with 3 seconds and 2 seconds of in-expiratory time, respectively, and 1-second pause |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults (> 18yo).
- Endotracheal intubation and invasive mechanical ventilation for > 48h and active humidification for > 24h.
- Richmond Agitation-Sedation Scale -3 to -5.
- Signed informed consent.
Key exclusion criteria (9 listed)
- Patients with hemodynamic instability (MAP < 60 or > 110, Heart Rate < 50 or > 130, new onset arrhythmias), respiratory instability (PEEP > 12cmH2O, SpO2 < 90% or fraction of inspired oxygen (FiO2) > 60%).
- Undrained pneumothorax/pneumomediastinum.
- Unstable intracranial pressure (ICP > 20mmHg or MAP < 60).
- Severe bronchospasm.
- Post cardiothoracic surgical patients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MI-E Intervention protocolThe endotracheal tube cuff will be inflated to 40 cmH2O and MI-E device will be used to deliver MI-E in automatic mode, with 4 sets of 5 respiratory cycles each and a 1-minute interval between each set. Before initiation of the MI-E intervention protocol, the investigators will carry out a short-period test to find the appropriate MI-E settings to achieve inspiratory volumes of ≥1 liter and PEF ≥80 L/min. Concretely, inspiratory and expiratory time will always be set at 4 seconds and 2 seconds, respectively, and inspiratory flow will always be in slow mode. Once the appropriate inspiratory pressure will be found, the expiratory pressure will be initially set to exceed in 30 cmH2O the inspiratory pressure and, if required, this will be increased by 5 cmH2O until achieving a PEF ≥80 L/min with a maximum expiratory pressure of 70 cmH2O. | Device | MI-E intervention protocol |
| Standard MI-E settingCough Assist E70 device (Philips Respironics, USA, Andover, Massachusetts) will be used to deliver MI-E in automatic mode, with 4 sets of 5 respiratory cycles each and a 1-minute interval between each set. During the 1-minute pause between sets, the patient will be reconnected to the ventilator to avoid desaturation and de-recruitment during procedures. PEEP will remain stable during the protocol. The standard MI-E setting will consist of in-expiratory pressures of +40/-40 cmH2O, medium inspiratory flow, with 3 seconds and 2 seconds of in-expiratory time, respectively, and 1-second pause. | Device | Standard MI-E setting |
Primary outcome
Wet volume of sputum
Time frame: Immediately after each intervention
Airway suctioning will be carried out using an open aspiration procedure, using a 12French catheter connected to a sterile collection container. The suction procedure will be performed according to international guidelines . If necessary, 5 ml of saline solution will be used to rinse the catheter in case of impacted secretions inside the catheter; later this volume will be subtracted from the final volume of secretions, thus obtaining the exact amount of wet sputum.
12 secondary outcomes
Respiratory parameters: Inspiratory flow (PIF)
Time frame: Before and during MI-E interventions, delivered tidal volumes will be recorded, PIF and PEF will be assessed for each insufflation-exsufflation cycle, and the PEF-PIF difference and the PEF:PIF ratio will be calculated
Respiratory parameters: Peak expiratory flow (PEF)
Time frame: Before and during MI-E interventions, delivered tidal volumes will be recorded, PIF and PEF will be assessed for each insufflation-exsufflation cycle, and the PEF-PIF difference and the PEF:PIF ratio will be calculated
Respiratory parameters: difference between PEF-PIF;
Time frame: Before and during MI-E interventions, delivered tidal volumes will be recorded, PIF and PEF will be assessed for each insufflation-exsufflation cycle, and the PEF-PIF difference and the PEF:PIF ratio will be calculated
Respiratory parameters: PEF:PIF ratio
Time frame: Before and during MI-E interventions, delivered tidal volumes will be recorded, PIF and PEF will be assessed for each insufflation-exsufflation cycle, and the PEF-PIF difference and the PEF:PIF ratio will be calculated
Pulmonary mechanics parameters: Static Compliance (Cst)
Time frame: Airway pressures will be recorded before, immediately after MI-E intervention, after endotracheal suctioning, and 1h after endotracheal suctioning. Respiratory system compliance and airway resistance will be calculated using standard formulas.
Pulmonary mechanics parameters: Airway resistance (Raw)
Time frame: Airway pressures will be recorded before, immediately after MI-E intervention, after endotracheal suctioning, and 1h after endotracheal suctioning. Respiratory system compliance and airway resistance will be calculated using standard formulas.
Hemodynamics values: Heart rate
Time frame: Before, immediately after MI-E interventions and after endotracheal suctioning.
Hemodynamics values: Mean arterial pressure
Time frame: Before, immediately after MI-E interventions and after endotracheal suctioning.
Gas exchange: Arterial blood gas analysis
Time frame: Before, immediately after endotracheal suctioning and 1 hour after interventions.
Gas exchange: Pulseoximeter oxygen saturation (SpO2)
Time frame: Before, immediately after endotracheal suctioning and 1 hour after interventions.
Adverse events
Time frame: During the intervention/procedure and immediately after the intervention/procedure.
Numbers of participants with adverse events
Time frame: During the intervention/procedure and immediately after the intervention/procedure.
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 8 May 2026.
- Background: PubMed 8275739Konrad F, Schreiber T, Brecht-Kraus D, Georgieff M. Mucociliary transport in ICU patients. Chest. 1994 Jan;105(1):237-41. doi: 10.1378/chest.105.1.237.
- Background: PubMed 1192854Sackner MA, Hirsch J, Epstein S. Effect of cuffed endotracheal tubes on tracheal mucous velocity. Chest. 1975 Dec;68(6):774-7. doi: 10.1378/chest.68.6.774.
- Background: PubMed 7362053Gal TJ. Effects of endotracheal intubation on normal cough performance. Anesthesiology. 1980 Apr;52(4):324-9. doi: 10.1097/00000542-198004000-00008.
- Background: PubMed 15024566Kilgour E, Rankin N, Ryan S, Pack R. Mucociliary function deteriorates in the clinical range of inspired air temperature and humidity. Intensive Care Med. 2004 Jul;30(7):1491-4. doi: 10.1007/s00134-004-2235-3. Epub 2004 Mar 16.
- Background: PubMed 22546299American Association for Respiratory Care; Restrepo RD, Walsh BK. Humidification during invasive and noninvasive mechanical ventilation: 2012. Respir Care. 2012 May;57(5):782-8. doi: 10.4187/respcare.01766.
- Background: PubMed 18176317Li Bassi G, Zanella A, Cressoni M, Stylianou M, Kolobow T. Following tracheal intubation, mucus flow is reversed in the semirecumbent position: possible role in the pathogenesis of ventilator-associated pneumonia. Crit Care Med. 2008 Feb;36(2):518-25. doi: 10.1097/01.CCM.0000299741.32078.E9.
- Background: PubMed 34886881Wu MF, Wang TY, Chen DS, Hsiao HF, Hu HC, Chung FT, Lin TY, Lin SM. The effects of mechanical insufflation-exsufflation on lung function and complications in cardiac surgery patients: a pilot study. J Cardiothorac Surg. 2021 Dec 9;16(1):350. doi: 10.1186/s13019-021-01738-x.
- Background: PubMed 33603304Kuroiwa R, Tateishi Y, Oshima T, Inagaki T, Furukawa S, Takemura R, Kawasaki Y, Murata A. Mechanical Insufflation-exsufflation for the Prevention of Ventilator-associated Pneumonia in Intensive Care Units: A Retrospective Cohort Study. Indian J Crit Care Med. 2021 Jan;25(1):62-66. doi: 10.5005/jp-journals-10071-23508.
- Background: PubMed 19212256Pneumatikos IA, Dragoumanis CK, Bouros DE. Ventilator-associated pneumonia or endotracheal tube-associated pneumonia? An approach to the pathogenesis and preventive strategies emphasizing the importance of endotracheal tube. Anesthesiology. 2009 Mar;110(3):673-80. doi: 10.1097/ALN.0b013e31819868e0.
- Background: PubMed 3780244Shapiro M, Wilson RK, Casar G, Bloom K, Teague RB. Work of breathing through different sized endotracheal tubes. Crit Care Med. 1986 Dec;14(12):1028-31. doi: 10.1097/00003246-198612000-00007.
- Background: PubMed 17894902Branson RD. Secretion management in the mechanically ventilated patient. Respir Care. 2007 Oct;52(10):1328-42; discussion 1342-7.
- Background: PubMed 34103385Martinez-Alejos R, Marti JD, Li Bassi G, Gonzalez-Anton D, Pilar-Diaz X, Reginault T, Wibart P, Ntoumenopoulos G, Tronstad O, Gabarrus A, Quinart A, Torres A. Effects of Mechanical Insufflation-Exsufflation on Sputum Volume in Mechanically Ventilated Critically Ill Subjects. Respir Care. 2021 Sep;66(9):1371-1379. doi: 10.4187/respcare.08641. Epub 2021 Jun 8.
- Individual participant dataSharing planned: No
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.
Joan Daniel Martí, PhD principal investigator
Hospital Clinic of Barcelona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MI-E Intervention protocol and Standard MI-E setting in people with Mucus Retention and Mechanical Ventilation Complication, run by Hospital Clinic of Barcelona at 1 site in Spain.
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 4 inclusion and 9 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 8 May 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 Spain. 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 Dani M Romeu, PhD (93-2275400 ext. 5710, jd.martibcn@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Wet volume of sputum (time frame: Immediately after each intervention). 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 NCT06491017, which also lists 23 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 8 May 2026.