Effects of Large Tidal Volumes Despite Minimal Inspiratory Support in Spontaneously Ventilated Intubated Resuscitation Patients. Pathophysiological Exploratory Study. (InLarge)

Some ICU ventilated patients might present with large tidal volume despite very low or inexistant presser support. Patient-Self Inflicted Lung Injury (P-SILI) might appear related with large alveolar stretch an distension. Two clinical presentations are observed: patients with or without respiratory distress signs such as supra-clavicular depression and thoracic-abdominal asynchronies.

The aim of this study is to compare the pulmonary physio(-patho)logical parameters of these two types of patients (eupneic or with respiratory distress signs), and presenting important TV in spite of a minimal adjustment of the ventilatory support, except for Acute Respiratory Distress Syndrome (ARDS).

Study Overview

• Status: Recruiting
• Conditions: Ventilator-Induced Lung Injury; Intensive Care Unit; Encephalopathy; Invasive Mechanical Ventilation; Tidal Volume; Patient-Self Inflicted Lung Injury
• Intervention / Treatment: Other: Multiparametric mesurements

Detailed Description

The use of invasive mechanical ventilation is one of the most frequent therapies in the intensive care unit. There are several types of indication, depending on the failure: mainly neurological, hemodynamic or respiratory. In recent years, the concept of Ventilator Induced Lung Injury (VILI) has led to changes in ventilator settings in both intensive care units and operative rooms. Thus, tidal volume (TV) reduction to 6-8 mL.kg-1 of predicted body weight, the use of an individualized positive end-expiratory pressure (PEEP) and the possible use of therapies to optimize pulmonary aeration (alveolar recruitment maneuvers, prone positioning sessions...) have become mandatory. More recently, some authors have described the existence of Patient-Self Inflicted Lung Injury (P-SILI). In certain situations (delirium, encephalopathies, pulmonary receptor stimulation, metabolic acidosis...), some patients may present, in spite of an "optimized" ventilator setting, very important VT, which may exceed 10 mL.kg-1 of theoretical ideal weight. Two circumstances of observation of these large VT needs despite low pressure supports can be observed. The first corresponds to a patient with signs of respiratory distress (signs of respiratory distress: supra-clavicular, thoraco-abdominal asynchronies...) who presents with significant inspiratory efforts. The second is a patient with no sign of respiratory distress (eupnea). In both cases, the "trigger" comes from a (hyper)-stimulation (drive) of respiratory brainstem centers.

It is currently uncertain whether these two types of patients are comparable in terms of P-SILI. It is possible that in the second case, lesions are non-existent (or minimal) due to low trans-pulmonary pressure (stress) and low levels of pulmonary alveolar distension (strain). Indeed, the most likely determinant of alveolar injury is trans-pulmonary pressure, defined as the difference between upper airway pressure and pleural pressure (Ptp = Paw - Ppl). Thus, in case of a negative pathophysiological parameter, it would be preferable to sedate the patient more deeply and to temporarily consider controlled mechanical ventilation to limit the alveolar stretch and lesions. However, we know that excessive sedation of resuscitation patients increases their morbidity and mortality, by exposing them to increased duration of mechanical ventilation, and thus to the risk of pneumonia acquired under mechanical ventilation. In this context, daily sedation release tests are recommended. Physicians must therefore find the right balance between an optimal level of sedation compatible with the least deleterious ventilatory support possible.

The aim of this study is to compare the pulmonary physio(-patho)logical parameters of these two types of patients (eupneic or with respiratory distress signs), and presenting important TV in spite of a minimal adjustment of the ventilatory support, except for Acute Respiratory Distress Syndrome (ARDS).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • Recruiting
    • CHU

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients over 18 years old
• Patients admitted to the adult intensive care unit at Estaing Hospital, Clermont-Ferrand
• Patients under invasive mechanical ventilation (intubation or tracheostomy)
• Patients with a tidal volume greater than 10 mL.kg-1 of predicted body weight despite a minimal pressure support (< 5 cmH2O)
• Patients with sedation compatible with spontaneous ventilation with inspiratory support and positive end-expiratory pressure
• Patient calm (RASS between -2 and 0)
• Consent to participate in the study from the patient or authorization to carry out the research collected from the designated trusted person (failing that, a family member or a close relative who has a close and stable relationship with the patient) in accordance with the procedures described in Title II of the First Book of the Public Health Code. If no relative is present, the patient may be included on the advice of the investigator (article L. 1111-6). A consent form for the continuation of the study and the use of the data will then be signed by the patient if and when he/she is conscious and lucid again, or if the patient is unable to express his/her consent, an authorization to continue the research will be obtained from the designated trusted person
• Patient benefiting from a Social Security system

Exclusion Criteria:

• Refusal to participate in the proposed study
• Protected adults

• Contraindication to the placement of a nasogastric tube:

  • Severe uncorrected blood flow disorder
  • Known naso-sinusal lesion
  • Recently ligated esophageal varices (< 48h)

• Contraindication to the use of the tomographic electroimpedancemetry technique

  • Thoracic lesions
  • Thoracic dressings
  • Pace-maker/implantable defibrillator
• Known injury to central respiratory centers, including neurocompromised patients
• Patients with Acute Respiratory Distress Syndrome (according to Berlin criteria)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Large tidal volumes without respiratory distress symptoms; Large tidal volumes (> 10 mL.kg-1 of predicted body weight) despite low pressure support, without respiratory distress symptoms	Other: Multiparametric mesurements; Multiparametric assessments will necessitate the use of a plastic belt to record electro-impedancemetry tomography data; and a nano-gatsric tube fitted with esophageal and gastric low pressure balloons; Other Names: Oesophageal pressure; Gastric pressure; P0,1; Tomography electro-impedancemetry
Other: Large tidal volumes with respiratory distress symptoms; Large tidal volumes (> 10 mL.kg-1 of predicted body weight) despite low pressure support, with respiratory distress symptoms (for example, supra-clavicular and thoracic-abdominal asynchronies...)	Other: Multiparametric mesurements; Multiparametric assessments will necessitate the use of a plastic belt to record electro-impedancemetry tomography data; and a nano-gatsric tube fitted with esophageal and gastric low pressure balloons; Other Names: Oesophageal pressure; Gastric pressure; P0,1; Tomography electro-impedancemetry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transpulmonary driving pressure	Comparison of transpulmonary motor pressure levels during spontaneous invasive mechanical ventilation of patients with large tidal volumes (>10 mL.kg-1 theoretical ideal weight) despite minimal pressure support (inspiratory support <5 cmH20). Transpulmonary motor pressure is defined as follows: ΔPtp = (Pplateau - Inspiratory Poeso) - (PEEP - Expiratory Poeso)	During 1 hour starting from inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transpulmonary pressure (alveolar stress)	Maximum transpulmonary pressure (alveolar stress) defined as follows: Ptp = Pplateau - Inspiratory Poeso	At inclusion and after 1 hour
Pressure of respiratory occlusion (P0,1)	Pressure of respiratory occlusion (P01) representative of respiratory drive, automatically delivered by the ventilator	At inclusion and after 1 hour
Driving pressure	Driving pressure	At inclusion and after 1 hour
Work of breathing	Work of breathing as defined as follows: WOB = ΔP x ΔV during inspiration	At inclusion and after 1 hour
Alveolar strain	Alveolar strain defined as follows: Strain = TV / FRC	At inclusion and after 1 hour
Energy transmitted to the patient's lungs by the ventilator	Energy transmitted to the patient's lungs by the ventilator as defined by Gattinoni et al. (Intensive Care Medicine 2016)	At inclusion and after 1 hour

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2020
• Primary Completion (Anticipated): June 25, 2023
• Study Completion (Anticipated): June 25, 2023

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 27, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: ICU; Mechanical Ventilation; Ventilator-Induced Lung Injury; Tidal volume; Patient-Self Inflicted lung Injury
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Thoracic Injuries; Wounds and Injuries; Brain Diseases; Lung Injury; Ventilator-Induced Lung Injury
• Other Study ID Numbers: InLarge (RBHP 2018 Godet 2)

Drug and device information, study documents

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