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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Recruiting

CT.gov ID

NCT04184674

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 :

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 :

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

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome	Other: Pneumotachograph Other: Esophageal catheter Other: Transthoracic and / or transesophageal cardiac ultrasound Other: Electrical impedance tomography (EIT) for pediatric patients	N/A

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 :

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 Design

Study Type:

Interventional

Anticipated Enrollment :

62 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Impact of the Transpulmonary Pressure on Right Ventricle Function in Acute Respiratory Distress Syndrome

Actual Study Start Date :

Jun 11, 2020

Anticipated Primary Completion Date :

Aug 11, 2022

Anticipated Study Completion Date :

Aug 11, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Right ventricle failure [Three days]
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).

Secondary Outcome Measures

Airways pressure [Three days]
Airways pressure (Paw) will be measured in cmH2O thanks to a pneumotachograph connected to the ventilator.
Oesophageal pressure [Three days]
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.
Transpulmonary pressure calculation [Three days]
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.
Vaso-Active Inotrope Score (VIS) [Three days]
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.
Duration of treatment with vasoactive or inotropic drugs [3 months after hospitalization in Intensive Care Unit]
Number of days under vaso-active or inotropic drugs
Pediatric logistic organ dysfunction score [Three days]
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).
Sepsis-related Organ Function Assessement score [Three days]
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).
Invasive and non invasive ventilation free days [3 months after hospitalization in Intensive Care Unit]
Number of invasive and non invasive ventilation free days
Lung and Chest Wall compliance [Three days]
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).
Length of hospitalization [3 months after hospitalization in Intensive Care Unit]
Length of hospitalization in Intensive Care Unit and in hospital in days.
Mortality at 28 days [28 days]
Death in Intensive Care Unit and at 28 days of hospitalization.
Mortality in Intensive Care Unit [3 months after hospitalization in Intensive Care Unit]
Death in Intensive Care Unit.
Eletrical impedance tomography [3 days]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Ambroise Paré	Boulogne-Billancourt		France	92100
2	Hôpital Necker-Enfants Malades	Paris		France	75015

Sponsors and Collaborators

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