Acute Respiratory Distress Syndrome Clinical Trial
Official title:
Regional Vascular Recruitment With Inhaled Nitric Oxide in Patients With ARDS
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).
Status | Recruiting |
Enrollment | 70 |
Est. completion date | May 30, 2026 |
Est. primary completion date | April 30, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility | 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) |
Country | Name | City | State |
---|---|---|---|
United States | Massachusetts General Hospital | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Massachusetts General Hospital |
United States,
ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. — View Citation
Borges JB, Suarez-Sipmann F, Bohm SH, Tusman G, Melo A, Maripuu E, Sandstrom M, Park M, Costa EL, Hedenstierna G, Amato M. Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse. J Appl Physiol (1985). 2012 Jan;112(1):225-36. doi: 10.1152/japplphysiol.01090.2010. Epub 2011 Sep 29. — View Citation
Cressoni M, Caironi P, Polli F, Carlesso E, Chiumello D, Cadringher P, Quintel M, Ranieri VM, Bugedo G, Gattinoni L. Anatomical and functional intrapulmonary shunt in acute respiratory distress syndrome. Crit Care Med. 2008 Mar;36(3):669-75. doi: 10.1097/01.CCM.0000300276.12074.E1. — View Citation
De Santis Santiago R, Teggia Droghi M, Fumagalli J, Marrazzo F, Florio G, Grassi LG, Gomes S, Morais CCA, Ramos OPS, Bottiroli M, Pinciroli R, Imber DA, Bagchi A, Shelton K, Sonny A, Bittner EA, Amato MBP, Kacmarek RM, Berra L; Lung Rescue Team Investigat — View Citation
Greene R, Zapol WM, Snider MT, Reid L, Snow R, O'Connell RS, Novelline RA. Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. Am Rev Respir Dis. 1981 Nov;124(5):593-601. doi: 10.1164/arrd.1981.124.5.593. No abstract available. — View Citation
Johnson TR. Dual-energy CT: general principles. AJR Am J Roentgenol. 2012 Nov;199(5 Suppl):S3-8. doi: 10.2214/AJR.12.9116. — View Citation
Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG, Calfee CS. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019 Mar 14;5(1):18. doi: 10.1038/s41572-019-0069-0. — View Citation
Morais CCA, Safaee Fakhr B, De Santis Santiago RR, Di Fenza R, Marutani E, Gianni S, Pinciroli R, Kacmarek RM, Berra L. Bedside Electrical Impedance Tomography Unveils Respiratory "Chimera" in COVID-19. Am J Respir Crit Care Med. 2021 Jan 1;203(1):120-121 — View Citation
Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med. 1993 Feb 11;328(6):399-405. doi: 10.1056/NEJM199302113280605. — View Citation
Safaee Fakhr B, Araujo Morais CC, De Santis Santiago RR, Di Fenza R, Gibson LE, Restrepo PA, Chang MG, Bittner EA, Pinciroli R, Fintelmann FJ, Kacmarek RM, Berra L. Bedside monitoring of lung perfusion by electrical impedance tomography in the time of COV — View Citation
Tomashefski JF Jr, Davies P, Boggis C, Greene R, Zapol WM, Reid LM. The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol. 1983 Jul;112(1):112-26. — View Citation
Zapol WM, Kobayashi K, Snider MT, Greene R, Laver MB. Vascular obstruction causes pulmonary hypertension in severe acute respiratory failure. Chest. 1977 Feb;71(2 suppl):306-7. doi: 10.1378/chest.71.2_supplement.306. No abstract available. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Age | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes.
Age (years) |
Day 1 | |
Other | Gender | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1 | |
Other | Height | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1 | |
Other | Weight | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1 | |
Other | Race | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1 | |
Other | Ethnicity | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1 | |
Other | Comorbidities | Presence in the past medical history of conditions such as hypertension, diabetes,obesity, COPD, liver disease, and heart failure, among others.
This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. |
Day 1 | |
Other | Hours Elapsed since intubation | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1 | |
Other | Apache II score | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Within 24 hours of intensive care admission | |
Other | Intensive care unit survival at 28 days | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 28 | |
Other | Hospital survival at 28 days | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 28 | |
Other | Ventilation-free days | This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | From day 1 to day 28 | |
Other | PaO2 | The PaO2 will be measured with an arterial blood sample. This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1, arterial blood gas samples will be taken at two time points: before and 1 hour after iNO. Subsequent days up to 28 days will be determined by the critical care staff | |
Other | PaCO2 | The PaCO2 will be measured with an arterial blood sample. This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1, arterial blood gas samples will be taken at two time points: before and 1 hour after iNO. Subsequent days up to 28 days will be determined by the critical care staff | |
Other | Ph | The Ph will be measured with an arterial blood sample. This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1, arterial blood gas samples will be taken at two time points: before and 1 hour after iNO. Subsequent days up to 28 days will be determined by the critical care staff | |
Other | Methemoglobin (MetHb) | The MetHb will be measured with an arterial blood sample. This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1, arterial blood gas samples will be taken at two time points: before and 1 hour after iNO. Subsequent days up to 28 days will be determined by the critical care staff | |
Other | HCO3 (bicarbonate) | The HCO3 will be measured with an arterial blood sample. This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | Day 1, arterial blood gas samples will be taken at two time points: before and 1 hour after iNO. Subsequent days up to 28 days will be determined by the critical care staff | |
Other | Tidal Volume | Ventilator Parameter. This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. | From day 1 to day 28 | |
Other | Plateau, peak and positive end-expiratory pressures | Ventilator Parameters are measured during tidal ventilation, inspiratory and expiratory holds.
This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. |
From day 1 to day 28 | |
Other | Respiratory rate | Ventilator Parameters are measured during tidal ventilation, inspiratory and expiratory holds.
This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. |
From day 1 to day 28 | |
Other | Flow | Ventilator Parameters are measured during tidal ventilation, inspiratory and expiratory holds.
This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. |
From day 1 to day 28 | |
Other | Vasopressors requirements (dopamine, dobutamine, epinephrine, levosimendan, milrinone, vasopressin, norepinephrine) | We will calculate the Vasoactive-inotropic score (VIS). The VIS compares different vasoactive-inotropic drugs and doses among the patients.
VIS = dopamine dose (mg/kg/min)+ dobutamine [mg/kg/min) +100 x epinephrine dose (mg/ kg/min) +50 x levosimendan dose [mg/kg/min) + 10 x milrinone dose [mg/kg/min)+ 10,000 x vasopressin [units/kg/min) + 100x norepinephrine dose [mg/kg/min) using the maximum dosing rates of vasoactive and inotropic medications. Ref: Koponen et al. British Journal of Anaesthesia, 122 (4): 428e436 (2019). This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. |
From day 1 to day 28 | |
Other | Arterial blood pressure, central venous pressure, pulmonary artery pressure | Hemodynamic parameters. The pulmonary artery pressure will be measured if the subject have a pulmonary artery pressure placed by the ICU staff with clinical purposes.
This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. |
From day 1 to day 28 | |
Other | Life sustaining therapies | Other life-sustaining therapies than mechanical ventilation and vasopressors administration: Antibiotics, Renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO), chemotherapy, and artificial nutrition.
This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. |
From day 1 to day 28 | |
Other | CRP, MCP-1, TNF-alpha, IL-6, IL-8, IL-10, Ang-2, VEGF | Blood samples will be collected and Systemic markers of inflammation and plasma cytokines: CRP, MCP-1, TNF-alpha, IL-6, IL-8, IL-10, Ang-2, VEGF will be measured.
This exploratory outcome plans to utilize electrical impedance tomography as an image marker and combine them with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS sub-phenotypes. |
From day 1 to day 28 | |
Primary | Change in regional lung perfusion after the delivery of inhaled nitric oxide | The primary outcome is to detect changes in regional perfusion distribution with the administration of inhaled nitric oxide with electrical impedance tomography by measuring changes in impedance. | Day 1 | |
Secondary | Compare methods to detect change in regional lung perfusion after the delivery of inhaled nitric oxide | The secondary outcome is to To compare electrical impedance tomography measurements against the gold standard dual-energy computed tomography (DECT) | Day 1 |
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