The Effect of Inhaled Nitric Oxide on Intrapulmonary Shunt in Acutely Hypoxemic Patients With Severe Obesity
Overview
- Phase
- Not Applicable
- Intervention
- Nitric oxide
- Conditions
- Obesity
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Intrapulmonary shunt
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
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:
- 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.
- 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.
- 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.
Detailed Description
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.
Investigators
Timothy G. Gaulton, MD
Assistant Professor of Anaesthesia
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Acute hypoxemic respiratory failure, defined as persistent hypoxemia (PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 315) and on invasive mechanical ventilation for \< 72 hours
- •Presence of an arterial and central venous catheter (for blood gas measurement)
- •Admitted to a participating MGH ICU
Exclusion Criteria
- •Age \< 18 years
- •Pregnancy or known active breastfeeding
- •Prisoner or Incarceration
- •Inability or unwillingness of subject or legal surrogate/representative to give written informed consent
- •Use of inhaled or oral pulmonary vasodilatory therapy within the 24 hours preceding study enrollment
- •Contraindication to inhaled NO
- •Baseline Methemoglobin ≥ 3%
- •Known left ventricle ejection fraction \< 20%
- •Known history of G6PD deficiency or cytochrome issues
- •Prior adverse reaction to inhaled nitric oxide
Arms & Interventions
Acute hypoxemic respiratory failure
Participants (n = 40) with acute hypoxemic respiratory failure will receive inhaled nitric oxide (20 ppm) for 15 min.
Intervention: Nitric oxide
Outcomes
Primary Outcomes
Intrapulmonary shunt
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.
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.
Secondary Outcomes
- Regional pulmonary perfusion(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.)
- Right ventricular systolic pressure(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.)
- Gas exchange(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.)