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

Mechanical Ventilation Complication Clinical Trial

Official title:

Open Lung Strategy, Gas Distribution and Right Heart Function in ARDS Patients: an Open Lung is a Better Heart

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03202641
• Other study ID #: OLA-HEART
• Status: Recruiting
• Phase: N/A
• Start date: June 19, 2019
• Est. completion date: August 2024

Study information

• Verified date: November 2022
• Source: Massachusetts General Hospital
• Contact: Lorenzo Berra, MD
• Phone: 6176437733
• Email: lberra[@]partners.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this interventional crossover study, in intubated and mechanically ventilated Acute Respiratory Distress Syndrome (ARDS) patients, is to compare two positive end-expiratory pressure (PEEP) titration techniques regarding: respiratory mechanics, gas exchange, changes in aeration, ventilation/perfusion matching its impact on cardiac function, especially the right heart (RH). The PEEP titration techniques are: PEEP selection based on low PEEP/high FiO2 table ("PEEPARDSnet") and lung recruitment maneuver (LRM) plus PEEPdec titration based on the best compliance of the respiratory system("PEEPLRM").

Description:

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:

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

B) Recruitability assessment sequence:

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).

C)"PEEPLRM": LRM plus PEEP decremental trial guided by best compliance. 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.

Before and after the lung recruitment maneuver and decremental PEEP trial, we will collect:

1. Respiratory system mechanics

2. Lung volumes

3. Gas exchange

4. Hemodynamic parameters

5. Electrical Impedance Tomography (EIT) ventilation and perfusion data

6. Transthoracic echocardiographic indices of RH function

Follow-up phase:

In 24 and 48 hours, if the subject did not present a negative response to "PEEPLRM" as described above , we will repeat the recruitment maneuver and the decremental PEEP trial and and we will collect:

1. Respiratory system mechanics (i.e. driving pressure)

2. Lung volumes

3. Gas exchange

4. Hemodynamic parameters

5. EIT ventilation and perfusion data

6. Transthoracic echocardiographic indices of RH function

before and after the aforementioned intervention.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 2024
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• ARDS diagnosis within 72h after intubation

• Severe to moderate ARDS (PaO2 / FiO2 < 200 mmHg) with PEEP>5 cmH2O

• 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

Related Conditions & MeSH terms

• Acute Lung Injury
• Alveolar Edema
• ARDS, Human
• Lung Injury
• Lung Injury, Acute
• Mechanical Ventilation Complication
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Right Heart Failure
• Right Ventricular Dysfunction
• Ventricular Dysfunction
• Ventricular Dysfunction, Right

Intervention

Procedure:
• PEEP ARDSnet
PEEP settings based on the low PEEP/high FiO2 table
• PEEP LRM
A lung recruitment maneuver (LRM) followed by PEEP guided by transpulmonary pressure.

Locations

Country	Name	City	State
United States	Massachussets General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (19)

Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. — View Citation

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

Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967 Aug 12;2(7511):319-23. — View Citation

Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. Erratum in: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350. — View Citation

Borges JB, Okamoto VN, Matos GF, Caramez MP, Arantes PR, Barros F, Souza CE, Victorino JA, Kacmarek RM, Barbas CS, Carvalho CR, Amato MB. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006 Aug 1;174(3):268-78. Epub 2006 May 11. — View Citation

Costa EL, Lima RG, Amato MB. Electrical impedance tomography. Curr Opin Crit Care. 2009 Feb;15(1):18-24. Review. — View Citation

de Matos GF, Stanzani F, Passos RH, Fontana MF, Albaladejo R, Caserta RE, Santos DC, Borges JB, Amato MB, Barbas CS. How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography. Crit Care. 2012 Jan 8;16(1):R4. doi: 10.1186/cc10602. — View Citation

Demory D, Arnal JM, Wysocki M, Donati S, Granier I, Corno G, Durand-Gasselin J. Recruitability of the lung estimated by the pressure volume curve hysteresis in ARDS patients. Intensive Care Med. 2008 Nov;34(11):2019-25. doi: 10.1007/s00134-008-1167-8. Epub 2008 Jun 25. — View Citation

Frerichs I, Amato MB, van Kaam AH, Tingay DG, Zhao Z, Grychtol B, Bodenstein M, Gagnon H, Böhm SH, Teschner E, Stenqvist O, Mauri T, Torsani V, Camporota L, Schibler A, Wolf GK, Gommers D, Leonhardt S, Adler A; TREND study group. Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group. Thorax. 2017 Jan;72(1):83-93. doi: 10.1136/thoraxjnl-2016-208357. Epub 2016 Sep 5. Review. — View Citation

Fumagalli J, Berra L, Zhang C, Pirrone M, Santiago RRS, Gomes S, Magni F, Dos Santos GAB, Bennett D, Torsani V, Fisher D, Morais C, Amato MBP, Kacmarek RM. Transpulmonary Pressure Describes Lung Morphology During Decremental Positive End-Expiratory Pressure Trials in Obesity. Crit Care Med. 2017 Aug;45(8):1374-1381. doi: 10.1097/CCM.0000000000002460. — View Citation

Kacmarek RM, Villar J, Sulemanji D, Montiel R, Ferrando C, Blanco J, Koh Y, Soler JA, Martínez D, Hernández M, Tucci M, Borges JB, Lubillo S, Santos A, Araujo JB, Amato MB, Suárez-Sipmann F; Open Lung Approach Network. Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial. Crit Care Med. 2016 Jan;44(1):32-42. doi: 10.1097/CCM.0000000000001383. — View Citation

Lachmann B. Open Lung in ARDS. Minerva Anestesiol. 2002 Sep;68(9):637-42; discussion 640, 643. Review. — View Citation

Lansdorp B, Hofhuizen C, van Lavieren M, van Swieten H, Lemson J, van Putten MJ, van der Hoeven JG, Pickkers P. Mechanical ventilation-induced intrathoracic pressure distribution and heart-lung interactions*. Crit Care Med. 2014 Sep;42(9):1983-90. doi: 10.1097/CCM.0000000000000345. — View Citation

Maggiore SM, Jonson B, Richard JC, Jaber S, Lemaire F, Brochard L. Alveolar derecruitment at decremental positive end-expiratory pressure levels in acute lung injury: comparison with the lower inflection point, oxygenation, and compliance. Am J Respir Crit Care Med. 2001 Sep 1;164(5):795-801. — View Citation

Matamis D, Lemaire F, Harf A, Brun-Buisson C, Ansquer JC, Atlan G. Total respiratory pressure-volume curves in the adult respiratory distress syndrome. Chest. 1984 Jul;86(1):58-66. — View Citation

Pinsky MR. My paper 20 years later: Effect of positive end-expiratory pressure on right ventricular function in humans. Intensive Care Med. 2014 Jul;40(7):935-41. doi: 10.1007/s00134-014-3294-8. Epub 2014 Apr 24. — View Citation

Pirrone M, Fisher D, Chipman D, Imber DA, Corona J, Mietto C, Kacmarek RM, Berra L. Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients. Crit Care Med. 2016 Feb;44(2):300-7. doi: 10.1097/CCM.0000000000001387. — View Citation

Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2014 Mar 6;370(10):980. doi: 10.1056/NEJMc1400293. — View Citation

Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008 Nov 13;359(20):2095-104. doi: 10.1056/NEJMoa0708638. Epub 2008 Nov 11. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Chest wall and lung elastances (cmH2O/L)	This exploratory outcome represents the respiratory system elastance. The respiratory system elastance (ERS = EL + ECW) is the sum of lung elastance (EL) and chest wall (ECW) elastance. In order to measure ERS, we will need airway pressure (measured by connecting the endotracheal tube with a pressure transducer) and pleural pressure (measured by placing an esophageal balloon connected to a pressure transducer, the esophageal pressure is a surrogate of the pleural pressure).	1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Other	Dead space (%)	This exploratory outcome is the volume (as a percent) of a breath that does not participate in gas exchange.The measure will be made using infrared absorption technology by a mainstream analyzer positioned distally to the Y piece and connected to a capnogram.	1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Other	Right heart function (Transthoracic Echocardiography)	Exploratory outcome	1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Other	Gas distribution, gas content, end-expiratory lung volume (using Electrical Impedance Tomography)	Exploratory outcome	1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Other	Ventilation/perfusion matching (using Electrical Impedance Tomography)	Exploratory outcome	1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Other	Blood arterial and central venous pressures	Exploratory outcome	1h (Phase A: "PEEP ARDSnet"), 2h (Phase C: "PEEP LRM"), 24h and 48h after the beginning of the study procedures
Other	Days free of mechanical ventilation	Exploratory outcome	28 days
Other	ICU length of stay	Exploratory outcome	28 days
Other	Hospital length of stay	Exploratory outcome	28 days
Other	Mortality	Exploratory outcome	28 days
Primary	Driving Pressure (cmH2O)	The primary endpoint of this study is to describe the airways driving pressures (defined as Plateau Pressure minus PEEP) during "PEEP ARDSnet" and "PEEP LRM".	1h (Phase A: "PEEP ARDSnet") and 2h (Phase C: "PEEP LRM") after the beginning of the study procedures