Hypoxic Respiratory FailureLUPONCT04648657
Lung Ultrasound, PEEP and Overdistension (LUPO)
An observational study of Hypoxic Respiratory Failure, run by University of Padova at 1 site in Italy.
Trial summary
The investigators suppose that lung sliding could be reduced in the same lung region moving from less ventilated to overinflated condition. This is supported by theoretical arguments by some authors but so far it has not been demonstrated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypoxic Respiratory Failure
- What is being tested?
- Lung Ultrasound and Electric impedance tomography
- Type of treatment
- Medical device
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 25 Feb 2021to 15 May 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
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: Mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) according to the Berlin definition (P/F ratio 100-300 with at least PEEP 5 cmH2O)
Who may be able to join
- Age > 18 years
- BMI < 35 kg/m2
Who cannot join
- Presence or history of pneumothorax, absence of lung pulse
- Pregnancy
- Patients with Pressure arterial O2/FiO2 (PaO2/FiO2) < 100 mmHg with at least 5 cmH2O of PEEP
- Pacemaker and/or internal cardiac defibrillator
- Hemodynamic parameters: systolic blood pressure <100 mmHg and >180 mmHg, or if systolic blood pressure is between 100-180 mmHg on high dose of IV continuous infusion of norepinephrine (>0,2 μg/kg/min), or dobutamine (>5 μg/kg/min ), or dopamine (>5 μg/kg/min), or epinephrine (>0,1 μg/kg/min)
- Hemodynamic instability (systolic blood pressure < 70 mmHg, heart rate increase to >140 bpm or decrease to <60 bpm, appearance of cardiac arrhythmias, (peripheral saturation O2 (SpO2) decrease to < 88%) during RM
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Lung Ultrasound for Diagnosis of Lung Overdistension in Acute Hypoxaemic Respiratory Failure
The investigators suppose that lung sliding could be reduced in the same lung region moving from less ventilated to overinflated condition. This is supported by theoretical arguments by some authors but so far it has not been demonstrated.
The investigators suppose that speckle tracking applied to LUS is able to demonstrate a reduction or abolition in pleural sliding when lung tissue is overinflated by higher PEEP after lung recruitment maneuver. The overinflation is diagnosed by Electric Impedance Tomography (EIT) and mechanical respiratory measurements (reduction in compliance as ratio between tidal volume over difference between plateau pressure and PEEP) and localized by EIT.
Read the detailed description
Lung ultrasonography (LUS) is a rapid, easy and non-invasive bedside tool for the detection of specific ultrasound patterns, associated with several pulmonary and pleural disorders. The main limitation of studies assessing lung recruitability and lung monitoring during mechanical ventilation is the lack of detection of lung overinflation: the A pattern doesn't change if the lung tissue is completely re-aerated or is overinflated. Considering this, the investigators could not use LUS to guide lung recruitment due to the risk of lung damage. Speckle tracking echocardiography is a gray-scale based technique used for quantification of myocardial strain to provide a quantitative, objective measure of left ventricle (LV) systolic function.
The investigators suppose that lung sliding could be reduced in the same lung region moving from less ventilated to overinflated condition. This is supported by theoretical arguments by some authors but so far it has not been demonstrated.
The investigators suppose that speckle tracking is able to demonstrate a reduction or abolition in pleural sliding when lung tissue is overinflated by higher PEEP after lung recruitment maneuver. The overinflation is diagnosed by EIT and mechanical respiratory measurements (reduction in compliance as ratio between tidal volume over difference between plateau pressure and PEEP) and localized by EIT.
Primary endpoint: agreement between LUS and EIT to diagnose lung overdistension in Acute Hypoxaemic Respiratory failure patients during a PEEP trial.
Patients are ventilated in pressure controlled mode with a tidal volume of 6 mL/kg predicted body weight (PBW), respiratory rate (RR) is maintained as set per clinical management, I:E = 1:2, PEEP level is set at 5 cmH2O and inspiratory fraction of O2 (FiO2) at 100% before starting the protocol.
To check the presence of areas with reduced or absent pleural sliding not depending on overdistention, and to exclude absence of lung pulse due to pneumothorax, a basal LUS examination is performed before recruiting manoeuvre (RM): the ultrasound linear probe (12 megahertz, GE) is positioned parallel into the 4th-5th right intercostal space next to the sternal margin for the first acquisition; then other two acquisitions along the intercostal space from the medial part to the lateral side of the thorax are recorded; the procedure is repeated on the left side resulting in a final acquisition of 3 ultrasound clips of 10 seconds for each hemithorax. If the presence of pneumothorax is suspected or diagnosed (absence of lung pulse), the patient is excluded from the study according to exclusion criteria.
Then at the same level, marked with a dermographic pen, the EIT belt is positioned and a basal assessment of lung impedance is recorded.
After that a 40x40 RM is performed, setting a PEEP of 40 cmH2O for 40 seconds on continuous positive airway pressure mode mode. If hemodynamic instability or decrease in oxygen saturation occurs during the maneuver, RM is interrupted and previous ventilator settings restored until stability is obtained and the patient discharged from the protocol. If the presence of pneumothorax is suspected or diagnosed (absence of lung pulse), the patient is excluded from the study according to exclusion criteria and clinically managed.
Ventilation is then set again in volume controlled mode with a tidal volume of 6 ml/kg and a PEEP set to reach a maximum plateau pressure of 30 cmH20. I:E ratio and RR are left unchanged.
A decremental PEEP trial is performed reducing PEEP value of 2 cmH2O, static compliance is calculated with an inspiratory pause of 3 seconds just before PEEP modification, and a registration of EIT is acquired for each PEEP level. The PEEP trial starts with the maximum PEEP level (PEEPmax, which is 30 cmH2O minus the pressure generated by 6 ml/kg of tidal volume) and stops at 2 cmH2O less than the best PEEP (PEEPmin), identified according to the static compliance value.
At the same time ultrasound linear probe is transversely set 1 cm above or below the EIT belt and clips recorded at each PEEP level as described above (Fig.2). A total of 6 LUS clips for each level of PEEP is recorded.
Once best PEEP is identified, LUS clips are encoded stored on an external memory stick.
EIT images
Ultrasound setting pre-defined are fixed. Clips are analyzed using GE software and longitudinal speckle tracking applied for each pleural clip. A-lines are numbered per clip Measurements Maximal strain, strain rate and time to peak are calculated and stored by a second investigator blinded to respiratory maneuvers. Differences between parameters calculated on basal and on PEEP trial clips are analyzed.
EIT session is analyzed by dedicated software and lung impedance assessed; each LUS clip is matched with correspondent part of EIT image considered two Region of Interest on the upper part of each hemithorax.
Intra-observer variability on speckle-tracking is assessed by intra-class coefficient correlation; correlation between speckle tracking values and PEEP level is assessed by Spearman correlation test; receiving operating characteristic (ROC) curve (Youden's index) is calculated to predict the accuracy of speckle tracking for predicting hyperinflation. EIT and LUS clips are compared with Cohen's K.
A-lines are numbered at different level of PEEP to investigate if the number of A-lines could be related to lung overdistention
- Conditions
- Hypoxic Respiratory Failure
- Being tested
- Lung Ultrasound, Electric impedance tomography
- Keywords
- lung ultrasound, lung overdistention, electric impedance tomography
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lung UltrasoundDevice
Also called LUS
Echography of Lungs based on artifacts study
Electric impedance tomographyDevice
Also called EIT
Low alternating electrical currents (usually <5 milliampere at 50-80 kHz) applied through different pair of electrodes on thorax
| Study group | Role | What they receive |
|---|---|---|
| acute hypoxemic respiratory failure patients | Mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) with P/F ratio < 300 with at least PEEP 5 cmH2O) Receives: Device: Lung Ultrasound; Device: Electric impedance tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
agreement between LUS+Speckle tracking and EIT in diagnosis of lung overdistension
LUS with speckle tracking applied and EIT are able to diagnose lung overdistension in the same lung zone
Measured: 5 months
Secondary outcomes (2)
quantification of lung sliding by speckle tracking at different levels of PEEP
Speckle tracking applied to LUS is able to quantify lung sliding at different PEEP levels
Measured: 5 months
correlation between number of A-lines and lung overdistention
the number of A-lines per clip at different level of PEEP is related to the lung overdistention diagnosed by EIT
Measured: 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2020
- Study start25 Feb 2021
- Primary completion30 Apr 2021
- Study completion15 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hypoxic Respiratory FailureStudies 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
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Padova
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paolo Persona, University of Padova
- Investigators
- Paolo Navalesi, MD, Study chair, University of Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04648657
- Sponsor's protocol ID
- 0021712
- Acronym
- LUPO
- Status last verified
- Apr 2022
- First submitted
- 23 Nov 2020
- Last updated
- 26 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bikker IG, Leonhardt S, Reis Miranda D, Bakker J, Gommers D. Bedside measurement of changes in lung impedance to monitor alveolar ventilation in dependent and non-dependent parts by electrical impedance tomography during a positive end-expiratory pressure trial in mechanically ventilated intensive care unit patients. Crit Care. 2010;14(3):R100. doi: 10.1186/cc9036. Epub 2010 May 30.
PubMed 20509966Duclos G, Bobbia X, Markarian T, Muller L, Cheyssac C, Castillon S, Resseguier N, Boussuges A, Volpicelli G, Leone M, Zieleskiewicz L. Speckle tracking quantification of lung sliding for the diagnosis of pneumothorax: a multicentric observational study. Intensive Care Med. 2019 Sep;45(9):1212-1218. doi: 10.1007/s00134-019-05710-1. Epub 2019 Jul 29.
PubMed 31359081Uematsu M. Speckle tracking echocardiography - Quo Vadis? Circ J. 2015;79(4):735-41. doi: 10.1253/circj.CJ-15-0049. Epub 2015 Mar 13.
PubMed 25766514Hickling KG. Best compliance during a decremental, but not incremental, positive end-expiratory pressure trial is related to open-lung positive end-expiratory pressure: a mathematical model of acute respiratory distress syndrome lungs. Am J Respir Crit Care Med. 2001 Jan;163(1):69-78. doi: 10.1164/ajrccm.163.1.9905084.
PubMed 11208628Adler A, Amyot R, Guardo R, Bates JH, Berthiaume Y. Monitoring changes in lung air and liquid volumes with electrical impedance tomography. J Appl Physiol (1985). 1997 Nov;83(5):1762-7. doi: 10.1152/jappl.1997.83.5.1762.
PubMed 9375349
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung Ultrasound for Diagnosis of Lung Overdistension in Acute Hypoxaemic Respiratory Failure
- ClinicalTrials.gov ID
- NCT04648657
- Acronym / sponsor ID
- LUPO / 0021712
- Conditions
- Hypoxic Respiratory Failure
- Keywords
- lung ultrasound, lung overdistention, electric impedance tomography
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of PadovaUniversity, hospital or other
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 15 May 2021 (actual)
- First posted
- 1 Dec 2020 (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.
The investigators suppose that lung sliding could be reduced in the same lung region moving from less ventilated to overinflated condition. This is supported by theoretical arguments by some authors but so far it has not been demonstrated.
The investigators suppose that speckle tracking applied to LUS is able to demonstrate a reduction or abolition in pleural sliding when lung tissue is overinflated by higher PEEP after lung recruitment maneuver. The overinflation is diagnosed by Electric Impedance Tomography (EIT) and mechanical respiratory measurements (reduction in compliance as ratio between tidal volume over difference between plateau pressure and PEEP) and localized by EIT.
Detailed description
Lung ultrasonography (LUS) is a rapid, easy and non-invasive bedside tool for the detection of specific ultrasound patterns, associated with several pulmonary and pleural disorders. The main limitation of studies assessing lung recruitability and lung monitoring during mechanical ventilation is the lack of detection of lung overinflation: the A pattern doesn't change if the lung tissue is completely re-aerated or is overinflated. Considering this, the investigators could not use LUS to guide lung recruitment due to the risk of lung damage. Speckle tracking echocardiography is a gray-scale based technique used for quantification of myocardial strain to provide a quantitative, objective measure of left ventricle (LV) systolic function.
The investigators suppose that lung sliding could be reduced in the same lung region moving from less ventilated to overinflated condition. This is supported by theoretical arguments by some authors but so far it has not been demonstrated.
The investigators suppose that speckle tracking is able to demonstrate a reduction or abolition in pleural sliding when lung tissue is overinflated by higher PEEP after lung recruitment maneuver. The overinflation is diagnosed by EIT and mechanical respiratory measurements (reduction in compliance as ratio between tidal volume over difference between plateau pressure and PEEP) and localized by EIT.
Primary endpoint: agreement between LUS and EIT to diagnose lung overdistension in Acute Hypoxaemic Respiratory failure patients during a PEEP trial.
Patients are ventilated in pressure controlled mode with a tidal volume of 6 mL/kg predicted body weight (PBW), respiratory rate (RR) is maintained as set per clinical management, I:E = 1:2, PEEP level is set at 5 cmH2O and inspiratory fraction of O2 (FiO2) at 100% before starting the protocol.
To check the presence of areas with reduced or absent pleural sliding not depending on overdistention, and to exclude absence of lung pulse due to pneumothorax, a basal LUS examination is performed before recruiting manoeuvre (RM): the ultrasound linear probe (12 megahertz, GE) is positioned parallel into the 4th-5th right intercostal space next to the sternal margin for the first acquisition; then other two acquisitions along the intercostal space from the medial part to the lateral side of the thorax are recorded; the procedure is repeated on the left side resulting in a final acquisition of 3 ultrasound clips of 10 seconds for each hemithorax. If the presence of pneumothorax is suspected or diagnosed (absence of lung pulse), the patient is excluded from the study according to exclusion criteria.
Then at the same level, marked with a dermographic pen, the EIT belt is positioned and a basal assessment of lung impedance is recorded.
After that a 40x40 RM is performed, setting a PEEP of 40 cmH2O for 40 seconds on continuous positive airway pressure mode mode. If hemodynamic instability or decrease in oxygen saturation occurs during the maneuver, RM is interrupted and previous ventilator settings restored until stability is obtained and the patient discharged from the protocol. If the presence of pneumothorax is suspected or diagnosed (absence of lung pulse), the patient is excluded from the study according to exclusion criteria and clinically managed.
Ventilation is then set again in volume controlled mode with a tidal volume of 6 ml/kg and a PEEP set to reach a maximum plateau pressure of 30 cmH20. I:E ratio and RR are left unchanged.
A decremental PEEP trial is performed reducing PEEP value of 2 cmH2O, static compliance is calculated with an inspiratory pause of 3 seconds just before PEEP modification, and a registration of EIT is acquired for each PEEP level. The PEEP trial starts with the maximum PEEP level (PEEPmax, which is 30 cmH2O minus the pressure generated by 6 ml/kg of tidal volume) and stops at 2 cmH2O less than the best PEEP (PEEPmin), identified according to the static compliance value.
At the same time ultrasound linear probe is transversely set 1 cm above or below the EIT belt and clips recorded at each PEEP level as described above (Fig.2). A total of 6 LUS clips for each level of PEEP is recorded.
Once best PEEP is identified, LUS clips are encoded stored on an external memory stick.
EIT images
Ultrasound setting pre-defined are fixed. Clips are analyzed using GE software and longitudinal speckle tracking applied for each pleural clip. A-lines are numbered per clip Measurements Maximal strain, strain rate and time to peak are calculated and stored by a second investigator blinded to respiratory maneuvers. Differences between parameters calculated on basal and on PEEP trial clips are analyzed.
EIT session is analyzed by dedicated software and lung impedance assessed; each LUS clip is matched with correspondent part of EIT image considered two Region of Interest on the upper part of each hemithorax.
Intra-observer variability on speckle-tracking is assessed by intra-class coefficient correlation; correlation between speckle tracking values and PEEP level is assessed by Spearman correlation test; receiving operating characteristic (ROC) curve (Youden's index) is calculated to predict the accuracy of speckle tracking for predicting hyperinflation. EIT and LUS clips are compared with Cohen's K.
A-lines are numbered at different level of PEEP to investigate if the number of A-lines could be related to lung overdistention
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| acute hypoxemic respiratory failure patients | – | Device: Lung Ultrasound, Device: Electric impedance tomographyMechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) with P/F ratio < 300 with at least PEEP 5 cmH2O) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) according to the Berlin definition (P/F ratio 100-300 with at least PEEP 5 cmH2O)
Key inclusion criteria (2 listed)
- Age > 18 years
- BMI < 35 kg/m2
Key exclusion criteria (6 listed)
- Presence or history of pneumothorax, absence of lung pulse
- Pregnancy
- Patients with Pressure arterial O2/FiO2 (PaO2/FiO2) < 100 mmHg with at least 5 cmH2O of PEEP
- Pacemaker and/or internal cardiac defibrillator
- Hemodynamic parameters: systolic blood pressure <100 mmHg and >180 mmHg, or if systolic blood pressure is between 100-180 mmHg on high dose of IV continuous infusion of norepinephrine (>0,2 μg/kg/min), or dobutamine (>5 μg/kg/min ), or dopamine (>5 μg/kg/min), or epinephrine (>0,1 μg/kg/min)
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 |
|---|---|---|
| Lung UltrasoundAlso: LUSEchography of Lungs based on artifacts study | Device | acute hypoxemic respiratory failure patients |
| Electric impedance tomographyAlso: EITLow alternating electrical currents (usually <5 milliampere at 50-80 kHz) applied through different pair of electrodes on thorax | Device | acute hypoxemic respiratory failure patients |
Primary outcome
agreement between LUS+Speckle tracking and EIT in diagnosis of lung overdistension
Time frame: 5 months
LUS with speckle tracking applied and EIT are able to diagnose lung overdistension in the same lung zone
2 secondary outcomes
quantification of lung sliding by speckle tracking at different levels of PEEP
Time frame: 5 months
correlation between number of A-lines and lung overdistention
Time frame: 5 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
- Background: PubMed 20509966Bikker IG, Leonhardt S, Reis Miranda D, Bakker J, Gommers D. Bedside measurement of changes in lung impedance to monitor alveolar ventilation in dependent and non-dependent parts by electrical impedance tomography during a positive end-expiratory pressure trial in mechanically ventilated intensive care unit patients. Crit Care. 2010;14(3):R100. doi: 10.1186/cc9036. Epub 2010 May 30.
- Background: PubMed 31359081Duclos G, Bobbia X, Markarian T, Muller L, Cheyssac C, Castillon S, Resseguier N, Boussuges A, Volpicelli G, Leone M, Zieleskiewicz L. Speckle tracking quantification of lung sliding for the diagnosis of pneumothorax: a multicentric observational study. Intensive Care Med. 2019 Sep;45(9):1212-1218. doi: 10.1007/s00134-019-05710-1. Epub 2019 Jul 29.
- Background: PubMed 25766514Uematsu M. Speckle tracking echocardiography - Quo Vadis? Circ J. 2015;79(4):735-41. doi: 10.1253/circj.CJ-15-0049. Epub 2015 Mar 13.
- Background: PubMed 11208628Hickling KG. Best compliance during a decremental, but not incremental, positive end-expiratory pressure trial is related to open-lung positive end-expiratory pressure: a mathematical model of acute respiratory distress syndrome lungs. Am J Respir Crit Care Med. 2001 Jan;163(1):69-78. doi: 10.1164/ajrccm.163.1.9905084.
- Background: PubMed 9375349Adler A, Amyot R, Guardo R, Bates JH, Berthiaume Y. Monitoring changes in lung air and liquid volumes with electrical impedance tomography. J Appl Physiol (1985). 1997 Nov;83(5):1762-7. doi: 10.1152/jappl.1997.83.5.1762.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Paolo Navalesi, MD study chair
University of Padova
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 Hypoxic Respiratory Failure, run by University of Padova at 1 site in Italy.
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 2 inclusion and 6 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: finished, as of the sponsor's last update on 26 Apr 2022. 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 Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
agreement between LUS+Speckle tracking and EIT in diagnosis of lung overdistension (time frame: 5 months). 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 NCT04648657, which also lists 5 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 26 Apr 2022.