Vascular ARDS Recruitment After Inhaled Nitric Oxide

Acute respiratory distress syndrome (ARDS) is when a person's lungs become inflamed, which can be caused by infection, trauma, surgery, blood transfusion, or burn. ARDS often leads to a situation where the person cannot breathe independently and needs machines' help. Once the lungs are inflamed, the small air sacs responsible for exchanging gases (i.e., ventilation) and the blood flow in the lungs (i.e., perfusion) can be affected. In the past, most research focused on studying ventilation physiology and how to help people breathe with machines. Less was done on perfusion because it requires imaging techniques such as computed tomography with intravenous contrast and radiation. One treatment option for low oxygen levels is inhaled nitric oxide (iNO), a gas that can dilate the lung blood vessels and improve oxygenation; however, it is not always clear whether this treatment will work. Electrical Impedance Tomography (EIT) is a bedside and accessible imaging technique that is radiation-free and non-invasive and can potentially detect changes in lung perfusion. EIT can perform multiple measurements; it is portable and accessible. This prospective interventional study aims to assess changes in regional blood perfusion in the lungs of patients with ARDS in response to iNO utilizing EIT. The main questions it aims to answer are:

1. If EIT can measure lung regional perfusion response to an iNO challenge of 20ppm for 15 minutes.
2. If EIT is comparable to dual-energy computed tomography (DECT), the gold-standard method to detect changes in regional lung perfusion.
3. If EIT can be an imaging marker to identify ARDS severity

Participants will be divided into two cohorts:

1. Cohort 1 (n=60): Participants will be asked to be monitored by EIT before, during, and after the administration of iNO (20 ppm) for 15 minutes (OFF-ON-OFF)
2. Cohort 2 (N=10): Participants will be asked to be monitored by EIT and DECT before and during the administration of iNO (20 ppm) for 15 minutes (OFF-ON).

The investigators will screen patients with ARDS diagnosis daily at MGH intensive care units and work in the consenting process with the ICU team and surrogates. The enrollment period will be limited to the time subjects will undergo the study procedures. Subjects will exit the study as soon as the study procedures are completed. No further procedures are planned; therefore, subjects will not be asked to return to the hospital exclusively for research-related purposes.

The enrolled subjects will be divided into two cohorts. Cohort 1 (n=60) will be monitored with EIT before, during, and after the administration of iNO. Cohort 2 (n=10) will be monitored with EIT and DECT before and during the administration of iNO.

Methods to answer question 1 (To measure the topographic perfusion response to an iNO challenge with EIT):

- The EIT monitoring will be composed of ventilation and perfusion distributions. First, the ventilation is recorded; at this point, no additional maneuver is needed; the subjects need to wear the electrode belt connected to the device, and their ventilation will be recorded. Secondly, for the perfusion distribution, after a pause in the ventilation, EIT measures the distribution of blood perfusion in the lungs during the injection of a 10 mL bolus of 11.7% hypertonic saline solution through a central venous catheter. Cohort 1 (n=60) will receive 20ppm of iNO for 15 minutes. Cohort 1 will be monitored with EIT before, during, and after the iNO delivery in an OFF-ON-OFF fashion.

Methods to answer question 2 (To compare EIT measurements against the gold standard DECT):

- Cohort 2 (n=10) will be monitored with EIT and DECT. They will receive 20ppm of iNO for 15 minutes. The subjects will be transported to the computed tomography (CT) room, and the first DECT (DECT OFF) will be performed before the iNO delivery. After the DECT OFF, the EIT belt will be placed, and ventilation/perfusion will be measured before the iNO delivery (EIT OFF). Then, the iNO delivery will start, and after 15 minutes, the EIT ON will be recorded. The EIT belts will be removed, and the second DECT (DECT ON) will be performed. Of note, the EIT belt needs to be removed before the DECT acquisitions because the electrodes generate artifacts that would compromise the image quality.

Methods to answer question 3 (To determine ARDS phenotypes based on regional perfusion imaging):

- The investigators will explore the vascular response measured by EIT and categorize subjects accordingly. The investigators plan to apply EIT patterns as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes.

Finally,

* Blood MetHb levels will be continuously monitored before, during, and after each iNO administration of the day. At the end of each iNO administration, MetHb will continue to be monitored until values return to the level recorded before the current treatment and
* The NO, nitrogen dioxide (NO2) will be continuously monitored by INOmax DSIR (Mallinckrodt) deliver system.

Eligibility Criteria:
Inclusion Criteria:

* Adult intubated and mechanically ventilated patients (≥ 18 years old) admitted to the intensive care unit (ICU)
* ARDS diagnosis with mild to moderate severity by Berlin criteria1 (100 mmHg \< PaO2/FiO2 \<= 300 mmHg)
* Presence of an arterial line for blood gas measurement and blood pressure monitoring and of a central line for hypertonic saline injection

Exclusion Criteria:

* Suspected pregnancy, pregnancy or less than six weeks postpartum
* Younger than 18 years or older than 80 years
* Baseline methemoglobin ≥ 5%
* Subjects enrolled in another interventional research study
* Presence of pneumothorax
* Usage of any devices with electric current generation, such as a pacemaker or internal cardiac defibrillator
* Preexisting chronic lung disease or pulmonary hypertension
* Past medical history of lung malignancy or pneumonectomy, or lung transplant
* Left ventricle ejection fraction \<20%
* Hemodynamic instability is defined as:

  * Persistent systolic blood pressure \<90 mmHg and/or \>180 mmHg despite the use of vasopressor or vasodilators, or
  * Requiring an increment in inotropic vasopressors over the past two hours just before enrollment: more than 15 mcg/min for norepinephrine and dopamine, more than 10 mcg/min in epinephrine, and more than 50 mcg/ min for phenylephrine.
* Hypernatremia (serum sodium \> 150 mEq/L)
* Patients cannot be enrolled for DECT if they have:

  * History of allergic reaction to intravenous contrast
  * Renal dysfunction on the day of the study (serum creatinine \> 1.5 mg/dL)