The goal of this clinical trial is to learn about the effects of inhaled nitric oxide on oxygenation and lung perfusion in participants with severe obesity who have acute hypoxemic respiratory failure and are on mechanical ventilation The main questions it aims to answer are: 1. In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on oxygenation in participants with severe obesity compared to participants with normal body weight. 2. In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on lung perfusion and heart function in participants with severe obesity compared to participants with normal body weight. 3. In acute hypoxemic respiratory failure, does severe obesity impact nitric oxide signaling pathways? Participants with acute hypoxemic respiratory failure will be exposed to inhaled nitric oxide (20 ppm) while being clinically monitored.
The study is a single-center, open-label clinical trial in mechanically ventilated participants with acute hypoxemic respiratory failure. The primary aim is to assess changes in intrapulmonary shunt (primary study outcome) to inhaled nitric oxide in participants with severe obesity and those with normal body weight. The secondary aims are to determine differences in regional lung perfusion (measured by electrical impedance tomography), right ventricular pressure (measured by transthoracic echocardiography), and biomarkers of nitric oxide signaling dysfunction (nitric oxide activity, pro-inflammatory cytokines, endothelial glycocalyx fragments) The primary study intervention involves inhaled nitric oxide at 20 ppm for 15 minutes. The investigators will compare inhaled nitric oxide response in participants with severe obesity (defined by body mass index greater than or equal to 40) to participants with normal body weight (defined by body mass index 18.5-24.9). 40 participants with acute hypoxemic respiratory failure will be enrolled (20 with severe obesity and 20 with normal body weight). The investigators will enroll a separate cohort of mechanically ventilated participants who do not have acute hypoxemic respiratory failure (10 with severe obesity and 10 with normal body weight). In this cohort, investigators will collect additional blood at a single time point to compare levels of nitric oxide signaling pathways between patients with and without acute hypoxemia across body weight.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
60
20ppm for 15 minutes delivered by INO max(Nitric Oxide) Company : INO therapeutics, Inc.
Massachusetts General Hospital
Boston, Massachusetts, United States
Intrapulmonary shunt
Intrapulmonary shunt will be defined as the difference in intrapulmonary shunt (%) to inhaled nitric oxide. Intrapulmonary shunt will be defined using the modified Berggren equation based on central venous and arterial oxygen concentrations from a central venous and peripheral arterial catheter.
Time frame: Intrapulmonary shunt will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation.
Regional pulmonary perfusion
In participants who are already receiving neuromuscular blocking agents, regional pulmonary perfusion will be measured and defined as the % change to inhaled nitric oxide in 4 lung regions of interest (right upper, right lower, left upper, left lower)
Time frame: Regional pulmonary perfusion will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation.
Gas exchange
Measures of gas exchange be defined by Pa02/Fi02 and dead space fraction in response to inhaled nitric oxide
Time frame: Gas exchange will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation.
Right ventricular systolic pressure
The investigators will measure right ventricular systolic pressure, an ultrasound surrogate of pulmonary arterial pressure, in response to inhaled nitric oxide
Time frame: Right ventricular systolic pressure will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation.
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