Open Lung Strategy, Gas Distribution and Right Heart Function in ARDS Patients

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:

Phase A) "PEEPARDSnet": setting PEEP according to the ARDSnet table (low PEEP/ high FiO2)

Phase B) Recruitability assessment sequence:

B.1) 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).

B.2) Electrical impedance tool: a screening recruitment maneuver will be performed to detect
local changes in pixel compliance at the same PEEP level.

Phase C) "PEEPLRM": LRM plus PEEP guided by transpulmonary pressure. C.1) 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.

During each phase, we will collect:

a. Respiratory system mechanics b. Lung volumes c. Gas exchange d. Hemodynamic parameters e.
Electrical Impedance Tomography (EIT) ventilation and perfusion data f. Transthoracic
echocardiographic indices of RH function

4) Follow-up phase

In 24 and 48 hours, if the subject did not present a negative response to "PEEPLRM" as
described above (item C.1), we will repeat Phase C and we will collect:

1. Respiratory system mechanics

2. Lung volumes

3. Gas exchange

4. Hemodynamic parameters

5. EIT ventilation and perfusion data

6. Transthoracic echocardiographic indices of RH function

Inclusion Criteria:

- ARDS diagnosis within 72h after intubation

- Severe to moderate ARDS (PaO2 / FiO2 < 200 mmHg)

- 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