Incidence and Risk Factors of Weaning-induced Cardiac Dysfunction: Results From a Multicenter, Observational Study (WIPO)

Incidence of Weaning-induced Pulmonary Oedema (The WIPO Study)

During weaning from mechanical ventilation, the shift from positive to negative pressure ventilation may be responsible for a cardiac dysfunction that can lead to the development of pulmonary oedema (weaning-induced pulmonary oedema, WIPO) and to the failure of spontaneous breathing trials. However, the incidence and risk factors for WIPO development are not well defined and have been investigated only by a few studies.

Study Overview

• Status: Completed
• Conditions: Weaning Failure; Spontaneous Breathing Trial; Weaning-induced Pulmonary Edema
• Intervention / Treatment: Procedure: Spontaneous breathing trial

Detailed Description

During weaning from mechanical ventilation, the shift from positive to negative pressure ventilation may be responsible for a cardiac dysfunction that can lead to the development of pulmonary oedema (weaning-induced pulmonary oedema, WIPO) and to the failure of spontaneous breathing trials. The mechanisms leading to WIPO have been described in many studies. The fact that the intrathoracic pressure becomes negative increases right ventricle preload and afterload, reduces right ventricle compliance and increases left ventricle afterload. Arterial hypertension, which results from adrenergic stress and possibly from hypercapnia, usually worsens this latter mechanism. Myocardial ischemia, resulting from the imbalance between the reduction of oxygen delivery (hypoxemia) and increased oxygen demand (unfavourable loading conditions, increase of inotropic and heart rate) may participate in this phenomenon, even though its incidence seems to be low. The means for detecting WIPO in a patient performing a spontaneous breathing trial (SBT) have been widely investigated. To avoid the insertion of a pulmonary artery catheter, which clinicians nowadays tend to avoid when the patient is ready to be extubated, many alternatives methods have been proposed. The increase of left ventricular filling pressure during an SBT was detected with echocardiography, the increase during the test either of B-type natriuretic peptide levels or of extravascular lung water measured by transpulmonary thermodilution can be used. The investigators have also demonstrated that the detection of haemoconcentration during a weaning test, which is related to the filtration of a significant amount of plasma through the alveolar-capillary barrier, allows the detection of WIPO.

Unresolved questions:

The incidence of WIPO is not well defined. In the studies where it has been reported, it ranged between 44% and 87% of SBT failures. However, these studies included a small number of patients and/or included a specific population of patients that had already failed one or more weaning tests. In a monocentric study, the investigators recently reported that WIPO occurred in 59% of cases of SBT failures.

The risk factors for WIPO development are not well defined and have been investigated only by a few studies. In the above-mentioned one, the investigators have identified the presence of pre-existing cardiopathy, pre-existing chronic respiratory failure and obesity as independent risk factors for developing WIPO. However, these results were obtained only from a monocentric cohort.

• Study Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• France
  • Le Kremlin-Bicêtre, France
    • Medical Intensive Care Unit

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

All the intubated patients who need to do a Spontaneous Breathing Trial

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Social coverage from health insurance (in France).
3. Decision of the attending physicians to perform an SBT.

Exclusion Criteria:

1. Presence of tracheostomy (in this case at the end of the test the patient could be connected to the ventilator, even in case of positivity of the weaning test. Thus, it is not possible to test the absence of reintubation at 48 hours, which is one of the criteria defining the success of weaning).
2. Refusal of the patient or, if the case, one of the relatives to participate to the study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of WIPO	The diagnosis of WIPO will be done a posteriori by a group of experts. They will establish the diagnosis of WIPO, based on the following elements: Failure or success of SBT; Clinical examination at the end of SBT; Variation during SBT of arterial blood gas variables, plasmatic protein and blood haemoglobin concentration, extravascular lung water (optional), B-type natriuretic peptide (optional), echocardiographic estimation of left ventricular preload (E and A waves of mitral flow, e' wave of the mitral valve annulus), pulmonary arterial occlusion pressure (optional).	30-120 mins during the Spontaneous Breathing Trial

Secondary Outcome Measures

Outcome Measure	Time Frame
Risk factors for developing WIPO	The risk factors for WIPO will be done a posteriori by multivaraite analysis

Collaborators and Investigators

• Sponsor: Bicetre Hospital

Publications and helpful links

General Publications

• Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina M, Vieillard-Baron A, Welte T. Weaning from mechanical ventilation. Eur Respir J. 2007 May;29(5):1033-56. doi: 10.1183/09031936.00010206.
• Dres M, Teboul JL, Monnet X. Weaning the cardiac patient from mechanical ventilation. Curr Opin Crit Care. 2014 Oct;20(5):493-8. doi: 10.1097/MCC.0000000000000131.
• Teboul JL. Weaning-induced cardiac dysfunction: where are we today? Intensive Care Med. 2014 Aug;40(8):1069-79. doi: 10.1007/s00134-014-3334-4. Epub 2014 May 27.
• Lemaire F, Teboul JL, Cinotti L, Giotto G, Abrouk F, Steg G, Macquin-Mavier I, Zapol WM. Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation. Anesthesiology. 1988 Aug;69(2):171-9. doi: 10.1097/00000542-198808000-00004.
• Liu J, Shen F, Teboul JL, Anguel N, Beurton A, Bezaz N, Richard C, Monnet X. Cardiac dysfunction induced by weaning from mechanical ventilation: incidence, risk factors, and effects of fluid removal. Crit Care. 2016 Nov 12;20(1):369. doi: 10.1186/s13054-016-1533-9. Erratum In: Crit Care. 2017 Mar 8;21(1):50.
• Lamia B, Maizel J, Ochagavia A, Chemla D, Osman D, Richard C, Teboul JL. Echocardiographic diagnosis of pulmonary artery occlusion pressure elevation during weaning from mechanical ventilation. Crit Care Med. 2009 May;37(5):1696-701. doi: 10.1097/CCM.0b013e31819f13d0. Erratum In: Crit Care Med. 2009 Jul;37(7):2331.
• Grasso S, Leone A, De Michele M, Anaclerio R, Cafarelli A, Ancona G, Stripoli T, Bruno F, Pugliese P, Dambrosio M, Dalfino L, Di Serio F, Fiore T. Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease. Crit Care Med. 2007 Jan;35(1):96-105. doi: 10.1097/01.CCM.0000250391.89780.64.
• Dres M, Teboul JL, Anguel N, Guerin L, Richard C, Monnet X. Extravascular lung water, B-type natriuretic peptide, and blood volume contraction enable diagnosis of weaning-induced pulmonary edema. Crit Care Med. 2014 Aug;42(8):1882-9. doi: 10.1097/CCM.0000000000000295.
• 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.
• Cabello B, Thille AW, Roche-Campo F, Brochard L, Gomez FJ, Mancebo J. Physiological comparison of three spontaneous breathing trials in difficult-to-wean patients. Intensive Care Med. 2010 Jul;36(7):1171-9. doi: 10.1007/s00134-010-1870-0. Epub 2010 Mar 30.
• Dres M, Teboul JL, Anguel N, Guerin L, Richard C, Monnet X. Passive leg raising performed before a spontaneous breathing trial predicts weaning-induced cardiac dysfunction. Intensive Care Med. 2015 Mar;41(3):487-94. doi: 10.1007/s00134-015-3653-0. Epub 2015 Jan 24.
• Caille V, Amiel JB, Charron C, Belliard G, Vieillard-Baron A, Vignon P. Echocardiography: a help in the weaning process. Crit Care. 2010;14(3):R120. doi: 10.1186/cc9076. Epub 2010 Jun 22.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): February 28, 2021
• Study Completion (Actual): June 3, 2022

Study Registration Dates

• First Submitted: March 31, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pulmonary Edema
• Other Study ID Numbers: 2017-A00392-51

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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