Impact of the Transpulmonary Pressure on Right Ventricle Function in Acute Respiratory Distress Syndrome (VD-SDRA)

Pulmonary distension induced by mechanical ventilation physiologically alters right ventricle pre and after-load, hence might lead to right ventricle failure. The hypothesis is that in Acute Respiratory Distress Syndrome, the occurence of a right ventricle failure under lung protective ventilation might :

i) be correlated to the transpulmonary pressure level, ii) lead to global heart failure, iii) and extremely result in poor outcome and death.

The primary objective is to test the impact of transpulmonary pressure on right ventricular function in Acute Respiratory Distress Syndrome in adults and children.

Secondary objectives are :

i) to compare thresholds of transpulmonary pressure associated with right ventricle failure between children and adults.

ii) to assess if there is an association between transpulmonary pressure and morbidity and mortality.

- For pediatric patients, a specific monitoring with electrical impedance tomography (EIT) will allow:

• To assess if the transpulmonary pressure is associated with the level of regional pulmonary overdistention (or collapse) on electrical impedance tomography.(EIT)
• To assess if there is an association between the occurrence of right ventricular failure, and distribution of ventilation on EIT.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: Pneumotachograph; Other: Esophageal catheter; Other: Transthoracic and / or transesophageal cardiac ultrasound; Other: Electrical impedance tomography (EIT) for pediatric patients

Detailed Description

Acute Respiratory Distress Syndrome (ARDS) is an acute inflammatory lung injury associated with a high pulmonary vascular permeability, leading to acute respiratory failure. Positive pressure mechanical ventilation,improves survival but might lead to ventilator-induced lung injury (VILI) and right ventricular failure. This hemodynamic effect is more important when compliance is decreased, especially in ARDS.

The use of long protective ventilation (with low tidal volumes and low plateau pressures) has improved prognosis of ARDS in adult patients. However, tidal volume and plateau pressures do not always reflect the lung deformation and the stress induced by the ventilation; these variables depend on the characteristics of the patient's respiratory system. Therefore, management focuses on ventilation strategies according to these characteristics.

Among tools used to evaluate respiratory physiological parameters, the esophageal pressure measurement is easily feasible at the bedside, and well estimates pleural pressure and pulmonary distension. During invasive ventilation, transpulmonary pressure (PL) can be obtained with the difference between the airway pressure and the esophageal pressure. Calculation of transpulmonary pressure in ARDS allows optimal ventilator management of adult and children treated for ARDS.

Although individualized ventilation techniques have shown some benefits in ARDS, studies have failed to show that survival could be improved by such strategies. This lack of efficacy could be partly explained by the hemodynamic impact of ventilation-induced pulmonary distension. It therefore seems essential to combine a robust assessment of right ventricular function with measurements of transpulmonary pressure in order to know the real hemodynamic impact of positive pressure ventilation in ARDS in adults and children.

The primary objective is to test the impact of transpulmonary pressure on right ventricular functionin ARDS adults and children.

Secondary objectives are :

i) to compare thresholds of transpulmonary pressure associated to right ventricle failure between children and adults ii) to assess if there is an association between transpulmonary pressure and morbidity and mortality.

- For pediatric patients, a specific monitoring with electrical impedance tomography (EIT) will allow:

• To assess if the transpulmonary pressure is associated with the level of regional pulmonary overdistention (or collapse) on electrical impedance tomography.(EIT)
• To assess if there is an association between the occurrence of right ventricular failure, and distribution of ventilation on EIT.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Meryl Vedrenne-Cloquet, MD; Phone Number: +33 1 71 39 68 43; Email: meryl.vedrenne@aphp.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Hopital Ambroise Pare
  • Paris, France, 75015
    • Hôpital Necker-Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over one month
• Patients with mild to severe ARDS (onset within 48 hours). ARDS definition will follow Berlin guidelines for adults, and Pediatric Acute Lung Injury Consensus Conference (PALICC) guidelines for children
• Signed consent

Exclusion Criteria :

• Neonates less than 28 days-old
• Pregnancy or breastfeeding
• Any contra-indication to esophageal manometry (less than one month esophagus surgery, bronchopleural or esotracheal fistula, latex allergy)
• No social care

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Acute Respiratory Distress Syndrome; Children of more than one month of age and adults hospitalized in Intensive Care Unit for Acute Respiratory Distress Syndrome.

Other: Pneumotachograph; Measurements will be performed during the first three days of Acute Respiratory Distress Syndrome management : The first measurement will be performed 5 minutes after the initial ventilator settings.; Measurements will be repeated systematically at 24 hours, 48 hours and 72 hours of evolution.; An additional measure will be performed at each positive end-expiratory pressure modification (maximum 5 measures).; Other: Esophageal catheter; Measurements will be performed during the first three days of Acute Respiratory Distress Syndrome management; The first measurement will be performed 5 minutes after the initial ventilator settings.; Measurements will be repeated systematically at 24 hours, 48 hours and 72 hours of evolution.; An additional measure will be performed at each positive end-expiratory pressure modification (maximum 5 measures).; Other: Transthoracic and / or transesophageal cardiac ultrasound; The right ventricle systolic function will be assessed thanks to a transthoracic cardiac ultrasound in children, and a transthoracic of a transesophageal cardiac ultrasound in adults : Measurements will be performed during the first three days of Acute Respiratory Distress Syndrome management : The first measurement will be performed 5 minutes after the initial ventilator settings.; Measurements will be repeated systematically at 24 hours, 48 hours and 72 hours of evolution.; An additional measure will be performed at each positive end-expiratory pressure modification (maximum 5 measures).; Other: Electrical impedance tomography (EIT) for pediatric patients; For pediatric patients: measurements will be performed during the first three days of Acute Respiratory Distress Syndrome management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right ventricle failure	Right ventricle failure is defined, by ultrasound, as a composite criteria associating : end-diastolic right ventricle/left ventricle area ratio > 0.6 and/or Acute Cor Pulmonale (assocation with a septal dyskinesia),; and/or a tricuspid annular plane systolic excursion < 1,6 cm (adults), z-score < -2 (children),; and/or a doppler-derived tricuspid lateral annular systolic velocity (S wave) < 10 cm/s,; and/or a two-dimensional Fractional Area Change (defined as end-diastolic area - end-systolic area)/end-diastolic area x100) < 35%,; and/or a peak right ventricle free wall 2D strain < -30% (adults), z-score < 2 (children).	Three days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airways pressure	Airways pressure (Paw) will be measured in cmH2O thanks to a pneumotachograph connected to the ventilator.	Three days
Oesophageal pressure	Esophageal pressure (Pes) will be measured in cmH2O thanks to an oesophageal balloon catheter introduced in the mid-esophagus of the patient and connected to a manometer.	Three days
Transpulmonary pressure calculation	Measurements will be performed at different moments during the respiratory cycle: after an inspiratory pause to evaluate the tele-inspiratory transpulmonary pressure (PL-insp), and after an expiratory pause to evaluate the tele-expiratory transpulmonary pressure (PL-PEP ). The PL-insp will be calculated using the ratio between the elastance of the chest wall (Ecw) and of the respiratory system (Ers) thanks to this formula PL = Paw - Paw x (Ecw/Ers). The PL-exp will be calculated using the ratio between Paw et Pes (PL = Paw - Pes). Transpulmonary pressure will be expressed in cmH2O.	Three days
Vaso-Active Inotrope Score (VIS)	Correlation between transpulmonary pressure and morbidity. Vaso-Active Inotrope Score is a hemodynamic score taking into account the cumulative doses of inotropic or vassopressive drugs. It is obtained thanks this calculation : VIS = dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 100 x epinephrine dose (µg/kg/min) + 10 x milrinone dose (µg/kg/min) + 10000 x vasopressin dose (µg/kg/min) + 100 x norepinephrine dose (µg/kg/min). Its value ranges from zero, which is associated to a better outcome, to the maximum cumulative dose without any limit.	Three days
Duration of treatment with vasoactive or inotropic drugs	Number of days under vaso-active or inotropic drugs	3 months after hospitalization in Intensive Care Unit
Pediatric logistic organ dysfunction score	Pediatric logistic organ dysfunction score is a specific pediatric multiple organ dysfunction score that includes 10 variables corresponding to 5 organ dysfunctions. Values extend from 0 (best outcome) to 33 (worst outcome).	Three days
Sepsis-related Organ Function Assessement score	Sepsis-related Organ Function Assessement score is a multiple organ dysfunction score that includes several variables corresponding to 6 organ dysfunctions. Values extend from 0 (best outcome) to 24 (worst outcome).	Three days
Invasive and non invasive ventilation free days	Number of invasive and non invasive ventilation free days	3 months after hospitalization in Intensive Care Unit
Lung and Chest Wall compliance	Lung and chest wall compliances (in mL/cmH2O) will be calculated thanks to the respective ratios tidal volume/(PL-insp - PL-PEP) and tidal volume/(Pes insp - Pes-PEP).	Three days
Length of hospitalization	Length of hospitalization in Intensive Care Unit and in hospital in days.	3 months after hospitalization in Intensive Care Unit
Mortality at 28 days	Death in Intensive Care Unit and at 28 days of hospitalization.	28 days
Mortality in Intensive Care Unit	Death in Intensive Care Unit.	3 months after hospitalization in Intensive Care Unit
Eletrical impedance tomography	Electrical impedance tomography will be monitored only in children. Several methods will be used and compared, based on e.g. pixel information of lung aeration, to assess end-expiratory lung volume (ELLV, in mL) and the distribution of ventilation	3 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Meryl Vedrenne-Cloquet, MD, Assistance Publique - Hôpitaux de Paris; Study Director: Brigitte Fauroux, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2020
• Primary Completion (Actual): June 11, 2022
• Study Completion (Actual): June 11, 2022

Study Registration Dates

• First Submitted: November 28, 2019
• First Submitted That Met QC Criteria: November 28, 2019
• First Posted (Actual): December 3, 2019

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Acute Respiratory Distress Syndrome; Mechanical ventilation; Transpulmonary pressure; Right ventricle failure
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: APHP191033; 2019-A02814-53 (Other Identifier: IDRCB number)

Drug and device information, study documents

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