Alveolar Edema, ARDS, Human, Lung Injury, Acute, Mechanical Ventilation Complication, Respiratory Distress Syndrome, Right Heart Failure, Right Ventricular Dysfunction
Conditions
Keywords
ARDS, PEEP titration, Open Lung Strategy, Right heart function, Lung recruitment maneuver, Esophageal Pressure, Respiratory system compliance
Brief summary
The goal of this interventional crossover study, in intubated and mechanically ventilated Acute Respiratory Distress Syndrome (ARDS) patients, is to compare two positive end-expiratory pressure (PEEP) titration techniques regarding: respiratory mechanics, gas exchange, changes in aeration, ventilation/perfusion matching its impact on cardiac function, especially the right heart (RH). The PEEP titration techniques are: PEEP selection based on low PEEP/high FiO2 table (PEEPARDSnet) and lung recruitment maneuver (LRM) plus PEEPdec titration based on the best compliance of the respiratory system(PEEPLRM).
Detailed description
A recent large observational study published on JAMA showed that Acute Respiratory Distress Syndrome (ARDS) is associated with high mortality and developed in 10.4% of 29,144 patients admitted to the intensive care unit from 50 countries across 5 continents. Mechanical ventilation is the cornerstone for lung treatment during ARDS. Lung protective ventilation improved ARDS outcome significantly. However, it is still unclear what method should be used to select levels of positive end-expiratory pressure (PEEP). In the current study proposal, the investigators hypothesized that, when ARDS lungs are recruitable, a lung recruitment maneuver (LRM) and PEEP titration (PEEPLRM) improve ventilation/perfusion matching and decreased right heart workload when compared to the actual standard of care PEEP selection based on low PEEP/high FiO2 table (PEEPARDSnet). The investigators will test this hypothesis in an interventional crossover study. 50 patients with ARDS will be enrolled in a physiological and lung and heart imaging study. The protocol is divided in the following phases: A) PEEPARDSnet: setting PEEP according to the ARDSnet table (low PEEP/ high FiO2) B) Recruitability assessment sequence: P-V curve tool (Hamilton ventilator): evaluate patient recruitability, among three criteria, two must be positive to consider a subject recruitable: (1) Presence of a lower inflection point (2) Linear compliance measured more than 2 times higher than the dynamic compliance (3) Increase in volume of more than 300mL during the descendant limb of the PV curve at a same given pressure (20 cmH2O)(Hysteresis property). C)PEEPLRM: LRM plus PEEP decremental trial guided by best compliance. Lung and heart response to PEEPLRM: we will compare the driving pressure (DP) value (DP = Plateau pressure - PEEP) and transthoracic echocardiography (TTE) with the values at PEEPARDSnet. In the advent of an increased DP and/or new onset of abnormal values at the TTE, we will resume the PEEPARDSnet settings during the 48h follow-up phase. Before and after the lung recruitment maneuver and decremental PEEP trial, we will collect: 1. Respiratory system mechanics 2. Lung volumes 3. Gas exchange 4. Hemodynamic parameters 5. Electrical Impedance Tomography (EIT) ventilation and perfusion data 6. Transthoracic echocardiographic indices of RH function Follow-up phase: In 24 and 48 hours, if the subject did not present a negative response to PEEPLRM as described above , we will repeat the recruitment maneuver and the decremental PEEP trial and and we will collect: 1. Respiratory system mechanics (i.e. driving pressure) 2. Lung volumes 3. Gas exchange 4. Hemodynamic parameters 5. EIT ventilation and perfusion data 6. Transthoracic echocardiographic indices of RH function before and after the aforementioned intervention.
Interventions
PROCEDUREPEEP ARDSnet
PEEP settings based on the low PEEP/high FiO2 table
PROCEDUREPEEP LRM
A lung recruitment maneuver (LRM) followed by PEEP guided by transpulmonary pressure.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Physiologic crossover study. There is no randomization.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* ARDS diagnosis within 72h after intubation * Severe to moderate ARDS (PaO2 / FiO2 \< 200 mmHg) with PEEP\>5 cmH2O * Presence of an arterial line * Between 18 and 85 years old
Exclusion criteria
* Persistent systolic blood pressure \< 90 mmHg and/or \>180 mmHg despite the use of vasopressor or vasodilators * Increment in vasopressors over the past two hour just before enrollment of: more than 15 mcg/min for norepinephrine and dopamine, more than 10 mcg/min in epinephrine; and more than 50 mcg/ min for phenylephrine. * Advanced lung disease confirmed by computed tomography findings * Presence or history of pneumothorax * Severe coagulopathy (INR ≥ 4) * Severe thrombocytopenia (Platelets count ≤ 5,000/mm3) * Usage of any devices with electric current generation such as pacemaker or internal cardiac defibrillator * Recent esophageal trauma or surgery * Known presence of esophageal varices * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Driving Pressure (cmH2O) | 1h (Phase A: PEEP ARDSnet) and 2h (Phase C: PEEP LRM) after the beginning of the study procedures | The primary endpoint of this study is to describe the airways driving pressures (defined as Plateau Pressure minus PEEP) during PEEP ARDSnet and PEEP LRM. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dead space (%) | 1h (Phase A: PEEP ARDSnet), 2h (Phase C: PEEP LRM), 24h and 48h after the beginning of the study procedures | This exploratory outcome is the volume (as a percent) of a breath that does not participate in gas exchange.The measure will be made using infrared absorption technology by a mainstream analyzer positioned distally to the Y piece and connected to a capnogram. |
| Right heart function (Transthoracic Echocardiography) | 1h (Phase A: PEEP ARDSnet), 2h (Phase C: PEEP LRM), 24h and 48h after the beginning of the study procedures | Exploratory outcome |
| Gas distribution, gas content, end-expiratory lung volume (using Electrical Impedance Tomography) | 1h (Phase A: PEEP ARDSnet), 2h (Phase C: PEEP LRM), 24h and 48h after the beginning of the study procedures | Exploratory outcome |
| Ventilation/perfusion matching (using Electrical Impedance Tomography) | 1h (Phase A: PEEP ARDSnet), 2h (Phase C: PEEP LRM), 24h and 48h after the beginning of the study procedures | Exploratory outcome |
| Chest wall and lung elastances (cmH2O/L) | 1h (Phase A: PEEP ARDSnet), 2h (Phase C: PEEP LRM), 24h and 48h after the beginning of the study procedures | This exploratory outcome represents the respiratory system elastance. The respiratory system elastance (ERS = EL + ECW) is the sum of lung elastance (EL) and chest wall (ECW) elastance. In order to measure ERS, we will need airway pressure (measured by connecting the endotracheal tube with a pressure transducer) and pleural pressure (measured by placing an esophageal balloon connected to a pressure transducer, the esophageal pressure is a surrogate of the pleural pressure). |
| Days free of mechanical ventilation | 28 days | Exploratory outcome |
| ICU length of stay | 28 days | Exploratory outcome |
| Hospital length of stay | 28 days | Exploratory outcome |
| Mortality | 28 days | Exploratory outcome |
| Blood arterial and central venous pressures | 1h (Phase A: PEEP ARDSnet), 2h (Phase C: PEEP LRM), 24h and 48h after the beginning of the study procedures | Exploratory outcome |
Countries
United States
Outcome results
None listed