Physiological Study of Minimally Invasive ECCO2R in Exacerbations of COPD Requiring Invasive Mechanical Ventilation

Study Overview
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Brief Summary
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Morbidity and mortality in COPD result largely of acute exacerbations.The optimization of the respiratory management represents a fundamental challenge for improving prognosis and reducing mortality. While the hospital mortality of patients treated with NIV has decreased over years, and is currently less than 10 %, mortality in patients treated with invasive ventilation remains higher than 25%. To improve the prognosis of patients with acute exacerbation of COPD requiring invasive mechanical ventilation is therefore a major challenge in terms of morbidity and mortality. Among the means available to achieve this goal, minimally invasive extracorporeal CO2 removal (ECCO2R) seems to be a very promising approach. The investigators hypothesize that the addition of minimally invasive ECCO2R is likely to limit dynamic hyperinflation in COPD patients requiring invasive mechanical ventilation for an acute exacerbation, while improving gas exchange.

Detailed Description
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Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the U.S. and is expected to become the third leading cause of death in 2020. Morbidity and mortality in COPD result largely of acute exacerbations, which are responsible for 1.5 million ED visits and 750,000 hospitalizations per year in the U.S. The optimization of the respiratory management of acute exacerbations represents a fundamental challenge for improving prognosis and reducing mortality. The value of non-invasive ventilation (NIV) for severe acute exacerbations of COPD was formally demonstrated by randomized clinical trials. In the setting of severe COPD exacerbations, NIV is actually very largely employed, largely ahead from invasive mechanical ventilation. While the hospital mortality of patients treated with NIV has decreased over years, and is currently less than 10 %, mortality in patients treated with invasive ventilation remains as high than 25%. Mortality in patients treated with invasive ventilation after failure of NIV seems to be growing and is actually close to 30%. To improve the prognosis of patients with acute exacerbation of COPD requiring invasive mechanical ventilation is therefore a major challenge in terms of morbidity and mortality. Among the means available to achieve this goal, minimally invasive extracorporeal CO2 removal (ECCO2R) seems to be a very promising approach. The investigators hypothesize that the addition of minimally invasive ECCO2R is likely to limit dynamic hyperinflation in COPD patients requiring invasive ventilation for an acute exacerbation, while improving gas exchange. If confirmed, it could imply a more rapid weaning from invasive ventilation in relation to: less hemodynamic consequences of positive pressure ventilation reduced risk of baro-volo trauma of the lung parenchyma reduction in the use of sedative drugs a chest configuration minimizing diaphragmatic flattening, therefore favoring the generation of higher trans-diaphragmatic pressures a decrease in the work of breathing (WOB), in connection with the previous point and with a decrease in alveolar ventilation required for pulmonary CO2 elimination during the ECCO2R treatment All of these elements are clinically relevant, as a reduction in the duration of invasive ventilation is associated in the literature with a decrease in the incidence of pneumonia associated with mechanical ventilation, as well as with a decrease in the duration of ICU-stay.

Official Title
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Physiological Study of Minimally Invasive Extracorporeal CO2 Removal in Exacerbations of COPD Requiring Invasive Mechanical Ventilation

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Device: extracorporeal CO2 removal (Hemolung device)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinical exacerbation of a known or suspected COPD intubation and invasive mechanical ventilation since less than 72 hrs. ACV or CV mode (VT 8 ml/kg, RR 12/min., PEEP : 0 cmH20) pH < 7.30 and PaCO2 > 55 mm Hg and PEEPi (end-expiratory occlusion) > 5 cmH20 written inform consent (patient, patient's legal surrogate) affiliation to a social security regime Exclusion Criteria: Body Mass Index (BMI) > 35 kg/m2 PaO2/FiO2 < 200 mm Hg history of hemorrhagic stroke heparin-induced thrombocytopenia Severe thrombopenia type II history

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: extracorporeal CO2 removal<br>extracorporeal CO2 removal initiated shortly after intubation, using the veno-venous Hemolung device | Device: extracorporeal CO2 removal (Hemolung device)<br>* ECCO2R in severe exacerbation of COPD patients, requiring invasive mechanical ventilation with persistent respiratory acidosis and dynamic hyperinflation<br>* Other names: ECCO2R;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intrinsic PEEP (PEEPi) | PEEPi at baseline and after ECCO2R by the Hemolung® device and adjustment of ventilator settings, expressed in cmH20 | 12 hours (between measurements at baseline and under ECCO2R) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Residual capacity (FRC) | FRC using the nitrogen washout method, expressed in mL | 12 hours (between measurements at baseline and under ECCO2R) | 
| PaO2 | PaO2 expressed in mmHg | 12 hours (between measurements at baseline and under ECCO2R) | 
| PaCO2 | PaCO2 expressed in mmHg | 12 hours (between measurements at baseline and under ECCO2R) | 
| Arterial O2 saturation | Arterial O2 saturation expressed in % | 12 hours (between measurements at baseline and under ECCO2R) | 
| pH | pH expressed in absolute value | 12 hours (between measurements at baseline and under ECCO2R) | 
| amount of sedative drugs | amount of sedative drugs (per day and cumulative) | Average time period of 6 days | 
| length of intubation | length of intubation (days) | Average time period of 7 days, up to 28 days | 
| length of ICU-stay | length of ICU-stay (days) | Average time period of 8 days, up to 28 days | 
| length of hospital stay | length of hospital stay (days) | Average time period of 9 days, up to 28 days | 
| ICU mortality | Number of in ICU-deceased participants (expressed in absolute number and %) | Average time period of 9 days, up to 28 days | 
| catheter related complications | catheter related complications (thrombosis, bleeding, pneumothorax, infection) expressed in total number of complications, in average number of complications per participant and in number of patients with complications | Average time period of 9 days | 
| Hemolung related complications | Hemolung related complications (thrombosis, bleeding) expressed in total number of complications, in average number of complications per participant and in number of patients with complications | Average time period of 9 days | 
| non catheter-related bleedings | non catheter-related bleedings expressed in total number of bleedings, in average number of bleedings per participant and in number of patients with bleedings | Average time period of 9 days | 
| work of breathing per Liter | work of breathing with and without ECCO2R, expressed in Joules per Liter of ventilation | Average time period of 7 days | 
| work of breathing per minute | work of breathing with and without ECCO2R, expressed in Joules per minute | Average time period of 7 days | 
| work of breathing per breath | work of breathing with and without ECCO2R, expressed in Joules per breath | Average time period of 7 days | 
| Occlusion pressure in 100msec (P0.1) | Occlusion pressure in 100msec in parallel to work breathing measurements with and without ECCO2, expressed in cmH2O | Average time period of 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extracorporeal CO2 removal