Lung Volume Preservation During Extubation

Preserving Lung Volume During Weaning and Extubation. A Prospective, Multicenter Clinical Trial

Introduction: At present, the best spontaneous breathing trial (SBT) during weaning from mechanical ventilation is a 30-min test with pressure support (PSV) 8 cmH2O without positive end-expiratory pressure (PEEP). There is a debate about the possible collapse of some alveolar units during such SBT and during extubation with continuous suctioning. A few experiences show extubation without suctioning as feasible and safe. Lung ultrasound is a non invasive and useful exploration tool to assess the lung aeration.

Hypothesis: Techniques aimed at preserving lung volume during SBT and extubation can yield higher rates of successful extubation. The preserved lung volume of each SBT and extubation strategy can be assessed by using lung ultrasound.

Primary objective: To define the rates of successful extubation in two extubation approaches aiming at different levels of lung volume preservation: standard SBT (30-min PSV 8 cmH2O without PEEP followed by extubation with continuous suctioning) versus experimental SBT (PSV8+ PEEP 5 cmH2O followed by extubation without suctioning). To define the lung aeration levels using the modified Lung Ultrasound Score (LUS) of each SBT strategy.

Secondary objectives: Reintubation rate, ICU and hospital stays, and mortality in each group. To define the diaphragm and intercostal thickness and thickening fraction in different levels of lung volume preservation.

Design: Prospective, multicenter, randomized study. Two opposing extubation strategies are compared in randomly assigned patients.The level of aeration is assessed using lung ultrasound.

Study Overview

• Status: Completed
• Conditions: Weaning Failure; Pulmonary Collapse
• Intervention / Treatment: Other: Lung volume preservation

Detailed Description

HYPOTHESIS Techniques aimed at preserving lung volume during SBT and extubation can yield higher rates of successful extubation. Lung Ultrasound Score (LUS) might be lower in techniques aiming to preserve lung volume suggesting less lung collapse.

METHODS

Patients with inclusion criteria and none exclusion criteria will be randomized to the follow strategies:

• Standard: PSV 8 cmH2O, PEEP 0 cmH2O for 30 minutes and, when successful, followed by extubation with continuous suctioning.
• Lung volume preservation: PSV 8 cmH2O, PEEP 5 cmH2O for 30 minutes and, when successful, followed by direct extubation without suctioning.

The randomization will be done with the built-in tool of the RedCap® Platform with computerized random number tables and blocks of n patients for each hospital. The investigators of each center will have a profile and a password to log into the RedCap and proceed with randomization of each patient. The investigator of each center will have access only to the data and randomization of his/her center.

In extubation failure patients (those who does not tolerate the SBT or not extubated), the attending physician will decide on the treatment, either support with non-invasive ventilation or with high flow nasal cannula, or reintubation.

Patients who present extubation failure will not be randomized in later SBTs.

During the SBT, interventions that the physician considers necessary to monitor the success of the test, such as echocardiography or thoracic ultrasound, may be performed. In the event that the physician considers that the findings of these tests do not guarantee successful extubation despite fulfillment of extubation criteria according to the study protocol, the attending physician's decision will prevail over the study protocol. In these cases, it will be recorded in the case report form (CRF) as extubation failure due to "other causes of weaning failure".

Not all patients and participating centers will collect data from the lung, diaphragm and intercostal ultrasound assessment. Only those patients that showed interest and proved ultrasound skills, will participate in the ultrasound part of the nested study.

Those patients included in the Ultrasound assessment part, an ultrasonographic exploration will be performed at different times of the SBT and extubation: before starting the SBT, at the final of the SBT and after extubation.

To proof the hypothesis related to the LUS and considering a minimum difference of 1 point (LUSm ranges from 0 to 24 points), we anticipate that 93 in each arm are required .

OBJECTIVES:

Primary: To determine the rate of successful extubation in two opposite weaning strategies.

Secondary:To determine the LUS in two opposite weaning strategies. To determine the ICU stay, hospital stay, hospital survival, and 90-day survival in the two groups. To identify the causes of extubation failure (clinical and ultrasonographic).

Exploratory:To determine the diaphragm and intercostal thickness and thickening fraction in the two groups. To describe patterns of LUS, diaphragmatic and intercostal muscles in patients who fail weaning. To assess changes in LUS during SBT and extubation specifically in posterior-basal regions. To describe diaphragmatic thickening fraction during P0.1 and Pocc maneuvers.

• Study Type: Interventional
• Enrollment (Actual): 1753
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Bacelona
    • Manresa, Bacelona, Spain, 08243
      • Althaia Xarxa Assistencial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients> 18 years who meet weaning criteria (see below)
• More than 24 hours of mechanical ventilation (MV)
• Signed Informed Consent by a substitute decision maker (SDM).

Weaning Criteria:

• Suitable cough (Ability to raise secretions to the endotracheal tube) (or Maximal inspiratory pressure (MIP) < -15 cmH2O).
• Absence of excessive secretions (<3 aspirations in the last 8 hours).
• Resolution or improvement of the pathology that led to intubation.
• Clinical stability (Heart Rate (HR) <140 bpm, Systolic Blood Pressure (SBP) 90-160, without vasopressors or at minimum doses).
• Adequate oxygenation (SatO2> 90% with Inspiratory Fraction of oxygen (FiO2) <0.4).
• Adequate ventilatory mechanics (Respiratory rate (RR) <35 rpm, Tidal Volume (TV) > 5 ml / kg, RR / TV <100 rpm/l).
• Confident awareness level (Glasgow Coma Scale (GCS)> 13).

Exclusion Criteria:

• tracheostomy, do-not-reintubate orders, decision of the responsible physician (e.g., due to a preference for a particular weaning technique according to the underlying pathology), absence of informed consent, mental incapacity without legal representation.
• For ultrasound assessment: skilled explorer not present at the time of the SBT, inadequate ultrasound window. Known diaphragmatic paralysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard; SBT: PSV 8 cmH2O, PEEP 0 cmH2O for 30 minutes and, when successful, followed by extubation with continuous suctioning. Patients included in the ultrasound nested study: Diaphragm and intercostal thickness and thickening fraction at the beginning and the end of the SBT.; Modified LUS at the beginning of the SBT, at the end of the SBT and after extubation if successful SBT.
Experimental: Lung Volume Preservation; SBT: PSV 8 cmH2O, PEEP 5 cmH2O for 30 minutes and, when successful, followed by direct extubation without suctioning and connected to the ventilator with PEEP 5 cmH2O. Patients included in the ultrasound part: Diaphragm and intercostal thickness and thickening fraction at the beginning and the end of the SBT.; Modified LUS at the beginning of the SBT, at the end of SBT and after extubation if successful SBT.	Other: Lung volume preservation; Extubate the patient connected to the ventilator and PEEP of 5 cmH2O after a successful SBT also using PEEP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Successful extubation	Number of patients free of mechanical ventilation	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Reintubation	Number of patients who need reintubation after successful SBT	72 hours
Rate of ICU Mortality	Patient's Mortality during ICU stay	90 days
Rate of Hospital Mortality	Patient's Mortality during hospital stay	90 days
Rate of Long term survival	Number of patients alive at 90 days after randomization	90 days
ICU length of stay	Mean of days in the ICU	90 days
Hospital length of stay	Mean of days in the hospital	90 days
Number of patients with tracheostomy	Patients who need tracheostomy	90 days
Logistic regression for successful extubation	By using a multilogistic regression, the variables related to successful extubation will be identified.	90 days
Modified Lung Ultrasound Score (LUSm) at the end of the SBT and after extubation.	Ultrasound exploration of anterior-superior, anterior-inferior, lateral and posterior-basal. From 0 (no collapse) to 36 (no areation)	72 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diaphragm thickness at the beginning and at the end of the SBT.	Maximal thickness measured in M-mode in millimeters.	72 hours
Diaphragm thickening fraction at the beginning and at the end of the SBT.	Thickening fraction= (maximal thickness - minimal thickness)/minimal thickness (%)	72 hours
Intercostal thickness at the beginning and at the end of the SBT.	Maximal thickness measured in M-mode in millimeters.	72 hours
Intercostal thickening fraction at the beginning and at the end of the SBT.	Thickening fraction= (maximal thickness - minimal thickness)/minimal thickness (%)	72 hours

Collaborators and Investigators

• Sponsor: Althaia Xarxa Assistencial Universitària de Manresa
• Investigators: Study Director: Rafael Fernandez, PhD, ALTHAIA Xarxa Assistencial de Manresa; Principal Investigator: Carlos Subira, PhD, Althaia Xarxa Assitencial de Manresa

Publications and helpful links

General Publications

• Brochard L, Rauss A, Benito S, Conti G, Mancebo J, Rekik N, Gasparetto A, Lemaire F. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med. 1994 Oct;150(4):896-903. doi: 10.1164/ajrccm.150.4.7921460.
• Esteban A, Anzueto A, Frutos F, Alia I, Brochard L, Stewart TE, Benito S, Epstein SK, Apezteguia C, Nightingale P, Arroliga AC, Tobin MJ; Mechanical Ventilation International Study Group. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA. 2002 Jan 16;287(3):345-55. doi: 10.1001/jama.287.3.345.
• Soummer A, Perbet S, Brisson H, Arbelot C, Constantin JM, Lu Q, Rouby JJ; Lung Ultrasound Study Group. Ultrasound assessment of lung aeration loss during a successful weaning trial predicts postextubation distress*. Crit Care Med. 2012 Jul;40(7):2064-72. doi: 10.1097/CCM.0b013e31824e68ae.
• Perren A, Domenighetti G, Mauri S, Genini F, Vizzardi N. Protocol-directed weaning from mechanical ventilation: clinical outcome in patients randomized for a 30-min or 120-min trial with pressure support ventilation. Intensive Care Med. 2002 Aug;28(8):1058-63. doi: 10.1007/s00134-002-1353-z. Epub 2002 Jul 13.
• Esteban A, Anzueto A, Alia I, Gordo F, Apezteguia C, Palizas F, Cide D, Goldwaser R, Soto L, Bugedo G, Rodrigo C, Pimentel J, Raimondi G, Tobin MJ. How is mechanical ventilation employed in the intensive care unit? An international utilization review. Am J Respir Crit Care Med. 2000 May;161(5):1450-8. doi: 10.1164/ajrccm.161.5.9902018.
• Esteban A, Alia I, Tobin MJ, Gil A, Gordo F, Vallverdu I, Blanch L, Bonet A, Vazquez A, de Pablo R, Torres A, de La Cal MA, Macias S. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med. 1999 Feb;159(2):512-8. doi: 10.1164/ajrccm.159.2.9803106.
• Fernandez MM, Gonzalez-Castro A, Magret M, Bouza MT, Ibanez M, Garcia C, Balerdi B, Mas A, Arauzo V, Anon JM, Ruiz F, Ferreres J, Tomas R, Alabert M, Tizon AI, Altaba S, Llamas N, Fernandez R. Reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial reduces reintubation in critically ill patients: a multicenter randomized controlled trial. Intensive Care Med. 2017 Nov;43(11):1660-1667. doi: 10.1007/s00134-017-4911-0. Epub 2017 Sep 22.
• Andreu M, Bertozzi M, Bezzi M, Borello S, Castro D, Giorgio VD, Aguirre M; ExtubAR group; ExtubAR group is composed by. Comparison of Two Extubation Techniques in Critically Ill Adult Subjects: The ExtubAR Randomized Clinical Trial. Respir Care. 2022 Jan;67(1):76-86. doi: 10.4187/respcare.09276. Epub 2021 Nov 3.
• Tenza-Lozano E, Llamas-Alvarez A, Jaimez-Navarro E, Fernandez-Sanchez J. Lung and diaphragm ultrasound as predictors of success in weaning from mechanical ventilation. Crit Ultrasound J. 2018 Jun 18;10(1):12. doi: 10.1186/s13089-018-0094-3.
• Esteban A, Alia I, Gordo F, Fernandez R, Solsona JF, Vallverdu I, Macias S, Allegue JM, Blanco J, Carriedo D, Leon M, de la Cal MA, Taboada F, Gonzalez de Velasco J, Palazon E, Carrizosa F, Tomas R, Suarez J, Goldwasser RS. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. The Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):459-65. doi: 10.1164/ajrccm.156.2.9610109.
• Subira C, Hernandez G, Vazquez A, Rodriguez-Garcia R, Gonzalez-Castro A, Garcia C, Rubio O, Ventura L, Lopez A, de la Torre MC, Keough E, Arauzo V, Hermosa C, Sanchez C, Tizon A, Tenza E, Laborda C, Cabanes S, Lacueva V, Del Mar Fernandez M, Arnau A, Fernandez R. Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2019 Jun 11;321(22):2175-2182. doi: 10.1001/jama.2019.7234.
• Subira C, Rognoni G, Baquerizo H, Garcia C, Cabanes S, de la Torre M, Quevedo B, Pedros C, Tizon AI, Murillo N, Parro L, Eiras F, Rialp G, Altaba S, Gonzalez-Castro A, Pacheco AF, Bayoumi P, Gomez-Medrano N, Vallverdu I, Higon A, Navarro MD, Falcon A, Keough E, Arizo D, Martinez JF, Duran N, Rodriguez R, Popoviciu-Koborzan MR, Guerrero I, Concha P, Barral P, Batlle M, Cano S, Garcia-Castrillon S, Andorra X, Tua Y, Arnau A, Fernandez R. Effect of lung volume preservation during spontaneous breathing trial on successful extubation in patients receiving mechanical ventilation: protocol for a multicenter clinical trial. Trials. 2024 Jul 16;25(1):481. doi: 10.1186/s13063-024-08297-1.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2023
• Primary Completion (Actual): August 13, 2024
• Study Completion (Actual): August 13, 2024

Study Registration Dates

• First Submitted: August 29, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Reintubation; Weaning from Mechanical Ventilation; Lung Ultrasound Score; Diaphragm and intercostal thickness and thickening fraction
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pulmonary Atelectasis
• Other Study ID Numbers: CEI 22/67

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: If any researcher is interested on exploratory analysis, it should be presented to the principal investigator to get the approval for it.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No