Ventilator-induced Right Ventricular Injury During EIT-based PEEP Titration in Patients With ARDS

Acute Respiratory Distress Syndrome Clinical Trial

— RIGHTENARDS  

Official title:

Ventilator-induced Right Ventricular Injury During Electrical Impedance Tomography-based Positive End-expiratory Pressure Titration in Patients With Acute Respiratory Distress Syndrome: a Pilot Physiological Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05583461
• Other study ID #: 5546/AO/22
• Status: Recruiting
• Phase: N/A
• Start date: October 26, 2022
• Est. completion date: October 2024

Study information

• Verified date: July 2023
• Source: University of Padova
• Contact: Tommaso Pettenuzzo, MD
• Phone: 00390498213090
• Email: tommaso.pettenuzzo[@]aopd.veneto.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Right ventricular failure may be associated with mortality in patients with acute respiratory distress syndrome (ARDS). Mechanical ventilation may promote right ventricular failure by inducing alveolar overdistention and atelectasis. Electrical impedance tomography (EIT) is a bedside non-invasive technique assessing the regional distribution of lung ventilation, thus helping titrating positive end-expiratory pressure (PEEP) to target the minimum levels of alveolar overdistension and atelectasis. The aim of this physiologic randomized crossover trial is to assess right ventricular size and function with transthoracic echocardiography with different levels of PEEP in adult patients with moderate-to-severe ARDS undergoing controlled invasive mechanical ventilation: the level of PEEP determined according to the ARDS Network low PEEP-FiO2 table, the PEEP value that minimizes the risk of alveolar overdistension and atelectasis (as determined by EIT), the highest PEEP value minimizing the risk of alveolar overdistension (as determined by EIT), and the lowest PEEP level that minimizes the risk of alveolar atelectasis (as determined by EIT). Our findings may offer valuable insights into the level of PEEP favoring right ventricular protection during mechanical ventilation in patients with ARDS.

Description:

Acute respiratory distress syndrome (ARDS) is a diffuse pulmonary inflammatory disease with multifactorial etiology that is very common in patients admitted to the intensive care unit (ICU) and is associated with unsatisfactory short- and long-term prognosis. Patients with ARDS can develop right ventricular (RV) failure, which occurs in 22-50% of patients despite lung protective ventilation and is associated with increased mortality. Despite being required to ensure survival of patients with ARDS, mechanical ventilation itself may have injurious effects on RV function. First, high transpulmonary pressure, secondary to the use of high tidal volume, plateau pressure or positive end-expiratory pressure (PEEP), can cause alveolar overdistension, especially in the aerated parenchymal regions, and collapse of alveolar vessels. The consequent increase in pulmonary arterial pressure may lead to excessively high RV afterload and reduced systolic function. Second, the development of parenchymal atelectasis potentially secondary to the application of low tidal volumes and/or PEEP may increase pulmonary vascular resistance because of extra-alveolar vascular collapse. Finally, mechanical ventilation can have indirect effects on pulmonary circulation and RV function, mediated by alveolar oxygenation, acidosis, and hypercapnia.

The application of PEEP can prevent cyclic opening and closing of the alveoli (i.e., atelectrauma) and improve oxygenation. Ideally, PEEP should maintain lung recruitment and optimize oxygenation and dead space, while at the same time avoiding alveolar overdistension and hemodynamic complications. However, the PEEP titration strategy in patients with ARDS is still widely debated, due to the variability of the effects of PEEP in different patients and different lung parenchymal regions in the same patient. Depending on the extent of potentially recruitable lung parenchyma and the distribution of lung damage, the application of PEEP can cause alveolar overdistension and promote RV failure and/or favor alveolar recruitment and improve RV function. Therefore, it is stil unclear what level of PEEP is associated with the optimization of RV function in patients with ARDS. We may hypothesize that the level of PEEP able to reduce alveolar collapse without increasing overdistension may improve RV function.

Several strategies have been suggested to assess lung recruitability and PEEP responsiveness in patients with ARDS. Electrical impedance tomography (EIT) is a bedside non-invasive technique that monitors the regional distribution of lung ventilation. The choice of the PEEP value that minimizes the extent of overdistension and atelectasis, as assessed with EIT, was associated with better respiratory mechanics and survival in patients with severe ARDS in some pilot studies.

The aim of this prospective pathophysiological interventional study is to evaluate the variation of RV size and function with transthoracic echocardiography in adult patients requiring invasive controlled mechanical ventilation for moderate-to-severe ARDS with four different PEEP values applied according to a randomized sequence in each patient:

• The level of PEEP determined according to the ARDS Network low PEEP-fraction of inspired oxygen (FiO2) table;

• The PEEP value that minimizes the risk of overdistension and atelectasis, as determined by EIT;

• The highest PEEP value that minimizes the risk of overdistension, as determined by EIT;

• The lowest PEEP level that minimizes the risk of atelectasis, as determined by EIT.

The primary hypothesis of the study is that the level of PEEP that simultaneously minimizes alveolar overdistension and collapse is associated with better RV function than the PEEP level selected based on the low PEEP-FiO2 table and PEEP levels that minimize overdistension and collapse, separately. The secondary hypotheses of the study are that: 1) the level of PEEP that minimizes overdistension is associated with better RV function than the level of PEEP that minimizes collapse; 2) the PEEP level that minimizes alveolar collapse is associated with greater pulmonary air content, as assessed by lung ultrasound, compared to the PEEP levels chosen based on the low PEEP-FiO2 table, the PEEP level that minimizes overdistension and collapse simultaneously, and the PEEP level that minimizes overdistension.

The physiological data obtained from this study may offer valuable insights into the right ventricular-protective level of PEEP in patients with ARDS and support future large randomized studies investigating PEEP levels associated with improved patient survival.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Moderate to severe acute respiratory distress syndrome

2. Inclusion within 72 hours of acute respiratory distress syndrome diagnosis

3. Endotracheal intubation or tracheostomy

Exclusion criteria:

1. Age lower than 18 years old

2. Pregnancy

3. Absence of informed consent

4. Thoracic surgery or lung transplant during the admission

5. Contraindications to recruitment maneuvers (mean arterial pressure lower than 65 mmHg despite administration of fluids or vasopressors, active air leaks through a chest tube, pneumothorax or subcutaneous or mediastinal emphysema in absence of chest drainage)

6. Contraindications to electrical impedance tomography (contraindication to recruitment maneuvers, presence of pacemakers or other electronic devices in the chest, injuries or burns in the electrode placement area)

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Right Ventricular Dysfunction
• Syndrome
• Ventricular Dysfunction
• Ventricular Dysfunction, Right

Intervention

Procedure:
• Positive end-expiratory pressure titration
Positive end-expiratory pressure level

Locations

Country	Name	City	State
Italy	University Hospital of Padua	Padua

Sponsors (1)

Lead Sponsor	Collaborator
University of Padova

Country where clinical trial is conducted

Italy, 

References & Publications (43)

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* Note: There are 43 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Right ventricle diameter 1	Maximal transversal dimension in the basal one third of right ventricular inflow at end-diastole in the right ventricle-focused apical four-chamber view	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Right ventricle diameter 2	Transversal right ventricular diameter in the middle third of right ventricular inflow, approximately halfway between the maximal basal diameter and the apex, at the level of papillary muscles at end-diastole.	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Right ventricle fractional area change	Ratio of the difference between end-diastolic area and end-systolic area to end-diastolic area, which are determined after manual tracing of right ventricular endocardial border from the lateral tricuspid annulus along the free wall to the apex and back to medial tricuspid annulus, along the interventricular septum at end-diastole and at end-systole, in the right ventricle-focused apical four-chamber view	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Eccentricity index	Ratio between two left ventricular axes, one parallel to the interventricular septum and one perpendicular to this, in the mid-papillary parasternal short axis view	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Tricuspid annular plane systolic excursion	Tricuspid annular longitudinal excursion by M-mode, measured between end-diastole and peak systole in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Systolic velocity of the lateral tricuspid annulus derived from tissue Doppler imaging	Peak systolic velocity of lateral tricuspid annulus by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Right ventricular index of myocardial performance	The ratio of the sum between isovolumic contraction and relaxation times to ejection time measured by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Right ventricle systolic pressure	Calculated from the velocity of tricuspid regurgitation jet, measured in the view allowing the highest value, by applying simplified Bernoulli equation and adding right atrial pressure estimated from central venous pressure	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Myocardial isovolumic acceleration	Ratio of lateral tricuspid annulus peak velocity during isovolumic contraction to acceleration time by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Right ventricle stroke index	Ratio of right ventricular stroke volume, calculated as product between velocity-time integral at the level of pulmonary valve and transverse area of right ventricular outflow tract in the aortic valve-level parasternal short axis view during systole, and body surface area	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Right ventricle stroke work index	Product between right ventricle stroke index and right ventricle systolic pressure	Measured after 20 minutes from the application of each of the four levels of PEEP
Primary	Right ventricular free wall longitudinal strain	Peak value of longitudinal speckle-tracking-derived strain, averaged over the three segments of the right ventricular free wall, after manual tracing of right ventricular endocardial border from the lateral tricuspid annulus along the free wall to the apex and back to medial tricuspid annulus in right ventricle-focused apical four-chamber view	Measured after 20 minutes from the application of each of the four levels of PEEP
Secondary	Ventilator settings	Tidal volume, respiratory rate, fraction of inspired oxygen, inspiratory to expiratory time	Measured after 20 minutes from the application of each of the four levels of PEEP
Secondary	Respiratory mechanics	Plateau pressure, total positive end-expiratory pressure, driving pressure, mechanical power	Measured after 20 minutes from the application of each of the four levels of PEEP
Secondary	Arterial blood gas analysis	pH, arterial partial pressure of carbon dioxide, arterial partial pressure of oxygen, arterial oxygen saturation, bicarbonate, lactate	Measured after 20 minutes from the application of each of the four levels of PEEP
Secondary	Dead space	Estimated from the Bohr-Enghoff equation (ratio of the difference between arterial partial pressure of carbon dioxide and end-tidal carbon dioxide to arterial partial pressure of carbon dioxide)	Measured after 20 minutes from the application of each of the four levels of PEEP
Secondary	Ventilatory ratio	Product between minute ventilation and arterial partial pressure of carbon dioxide, divided by predicted body weight x 100 x 37.5	Measured after 20 minutes from the application of each of the four levels of PEEP
Secondary	Shunt	Calculated as (1 - arterial oxygen saturation) divided by (1 - central venous oxygen saturation)	Measured after 20 minutes from the application of the intervention
Secondary	Hemodynamics	Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, central venous pressure, dosage of vasoactive agents	Measured after 20 minutes from the application of the intervention
Secondary	Pleural and lung ultrasound	Lung ultrasound score, lung reaeration score	Measured after 20 minutes from the application of the intervention
Secondary	Renal ultrasound	Renal resistive index, renal venous stasis index	Measured after 20 minutes from the application of the intervention
Secondary	Ultrasound image quality	Quality assessed according to the 2018 American College of Emergency Physicians Guidelines	Measured after 20 minutes from the application of the intervention