Esophageal Pressure-Guided Optimal PEEP/mPaw in CMV and HFOV: The EPOCH Study

NCT02342756 | Unknown

• 1 other identifier: 14-8253
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The use of positive end-expiratory pressure (PEEP) has been shown to prevent the cycling end-expiratory collapse during mechanical ventilation and to maintain alveolar recruitment, keeping lung portions open, increasing the resting end-expiratory volume. On the other hand PEEP may also overdistend the already open lung, increasing stress and strain. Theoretically high frequency oscillatory ventilation (HFOV) could be considered an ideal strategy in patients with ARDS for the small tidal volumes, but the expected benefits have not been shown yet. PEEP and HFOV should be tailored on individual physiology. Assuming that the esophageal pressure is a good estimation of pleural pressure, transpulmonary pressure can be estimated by the difference between airway pressure and esophageal pressure (PL= Paw - Pes). A PL of 0 cmH2O at end-expiration should keep the airways open (even if distal zones are not certainly recruited) and a PL of 15 cmH2O should produce an overall increase of lung recruitment. The investigators want to determine whether the prevention of atelectrauma by setting PEEP and mPaw to obtain 0 cmH2O of transpulmonary pressure at end expiratory volume is less injurious than lung recruitment limiting tidal overdistension by setting PEEP and mPaw at a threshold of 15 cmH2O of transpulmonary pressure. The comparison between conventional ventilation with tidal volume of 6 ml/Kg and HFOV enables us to understand the role of different tidal volumes on preventing atelectrauma and inducing lung recruitment. The use of non-invasive bedside techniques such as lung ultrasound, electrical impedance tomography, and transthoracic echocardiography are becoming necessary in ICU and may allow us to distinguish between lung recruitment and tidal overdistension at different PEEP/mPaw settings, in order to limit pulmonary and hemodynamic complications during CMV and HFOV.

Conditions

Respiratory Distress Syndrome, Adult; Ventilator-Induced Lung Injury

Keywords

ARDS, HFOV

Outcome Measures

Primary Outcomes (1)

• Ventilator-induced lung injury (VILI) in patients with ARDS as measured by serum cytokines

  IL-6, TNF, IL-10, IL-1β, and IL-1ra and other cytokines will be detected in EDTA plasma with commercially available enzyme-linked immunosorbent assays (ELISA)

  1 hour after initiation of each experimental ventilation strategy

Secondary Outcomes (2)

• Assessment of lung recruitment and tidal overdistension

  1 hour after initiation of each experimental ventilation strategy

• Impact of transpulmonary pressure on right ventricular function (RV)

  1 hour after initiation of each experimental ventilation strategy

Study Arms (2)

Group 1: CMV - HFOV

EXPERIMENTAL

Patients in group 1 will start with conventional mechanical ventilation with different values of PEEP (A-PEEP so that PLEEO = 0 cmH2O, B- PEEP so that PLEIO = 15 cmH2O, C- PEEP so that PLEEO = 0 cmH2O) and then will be ventilated with high frequency oscillatory ventilation (D- mPaw so that PL = 0 cmH2O, E- mPaw so that PL = 15 cmH2O, F- mPaw so that PL = 0 cmH2O) Intervention: Device: Targeting transpulmonary pressure to avoid VILI

Device: Targeting transpulmonary pressure to avoid VILI

Group 2: HFOV - CMV

EXPERIMENTAL

Patients in group 2 will start with high frequency oscillatory ventilation (D- mPaw so that PL = 0 cmH2O, E- mPaw so that PL = 15 cmH2O, F- mPaw so that PL = 0 cmH2O) and then will be ventilated with conventional mechanical ventilation with different values of PEEP (A-PEEP so that PLEEO = 0 cmH2O, B- PEEP so that PLEIO = 15 cmH2O, C- PEEP so that PLEEO = 0 cmH2O). Intervention: Device: Targeting transpulmonary pressure to avoid VILI

Device: Targeting transpulmonary pressure to avoid VILI

Interventions

Targeting transpulmonary pressure to avoid VILI DEVICE

Set different values of PEEP (CMV) and mPaw (HFOV) to obtain determined values of transpulmonary pressure (0 and 15 centimeters of water) and to determine the impact of ventilation on VILI

Group 1: CMV - HFOV; Group 2: HFOV - CMV

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Moderate or severe ARDS, defined according to the Berlin definition (2);
• Endotracheal intubation or tracheostomy

You may not qualify if:

• Severe heart failure/cardiogenic shock;
• Pulmonary arterial hypertension requiring systemic vasodilators;
• Contraindications to esophageal balloon: esophageal pathology (stricture, perforation, high grade of varices), recent history of esophageal or gastric surgery, upper GI tract bleeding, severe coagulopathy and nasal trauma;
• Contraindications to Electrical Impedance Tomography (EIT): a temporary or permanent pacemaker, or implantable cardioverter-defibrillator (ICD);
• Age \< 16 years.

Sponsors & Collaborators

• University of Toronto: lead
• University Health Network, Toronto: collaborator
• Nihon Kohden: collaborator

Study Sites (2)

Intensive Care Unit (ICU) of Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Medical Surgical ICU - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (14)

• Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest. 1997 Mar 1;99(5):944-52. doi: 10.1172/JCI119259.

  PMID: 9062352 BACKGROUND

• Fan E, Needham DM, Stewart TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA. 2005 Dec 14;294(22):2889-96. doi: 10.1001/jama.294.22.2889.

  PMID: 16352797 BACKGROUND

• Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lapinsky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE; Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008 Feb 13;299(6):637-45. doi: 10.1001/jama.299.6.637.

  PMID: 18270352 BACKGROUND

• 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.

  PMID: 19001507 BACKGROUND

• Akoumianaki E, Maggiore SM, Valenza F, Bellani G, Jubran A, Loring SH, Pelosi P, Talmor D, Grasso S, Chiumello D, Guerin C, Patroniti N, Ranieri VM, Gattinoni L, Nava S, Terragni PP, Pesenti A, Tobin M, Mancebo J, Brochard L; PLUG Working Group (Acute Respiratory Failure Section of the European Society of Intensive Care Medicine). The application of esophageal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med. 2014 Mar 1;189(5):520-31. doi: 10.1164/rccm.201312-2193CI.

  PMID: 24467647 BACKGROUND

• Bouhemad B, Brisson H, Le-Guen M, Arbelot C, Lu Q, Rouby JJ. Bedside ultrasound assessment of positive end-expiratory pressure-induced lung recruitment. Am J Respir Crit Care Med. 2011 Feb 1;183(3):341-7. doi: 10.1164/rccm.201003-0369OC. Epub 2010 Sep 17.

  PMID: 20851923 BACKGROUND

• Volpicelli G, Elbarbary M, Blaivas M, Lichtenstein DA, Mathis G, Kirkpatrick AW, Melniker L, Gargani L, Noble VE, Via G, Dean A, Tsung JW, Soldati G, Copetti R, Bouhemad B, Reissig A, Agricola E, Rouby JJ, Arbelot C, Liteplo A, Sargsyan A, Silva F, Hoppmann R, Breitkreutz R, Seibel A, Neri L, Storti E, Petrovic T; International Liaison Committee on Lung Ultrasound (ILC-LUS) for International Consensus Conference on Lung Ultrasound (ICC-LUS). International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med. 2012 Apr;38(4):577-91. doi: 10.1007/s00134-012-2513-4. Epub 2012 Mar 6.

  PMID: 22392031 BACKGROUND

• Repesse X, Charron C, Vieillard-Baron A. Right ventricular failure in acute lung injury and acute respiratory distress syndrome. Minerva Anestesiol. 2012 Aug;78(8):941-8. Epub 2012 Jun 7.

  PMID: 22672932 BACKGROUND

• Fichet J, Moreau L, Genee O, Legras A, Mercier E, Garot D, Dequin PF, Perrotin D. Feasibility of right ventricular longitudinal systolic function evaluation with transthoracic echocardiographic indices derived from tricuspid annular motion: a preliminary study in acute respiratory distress syndrome. Echocardiography. 2012 May;29(5):513-21. doi: 10.1111/j.1540-8175.2011.01650.x. Epub 2012 Feb 13.

  PMID: 22324535 BACKGROUND

• Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, Zhou Q, Matte A, Walter SD, Lamontagne F, Granton JT, Arabi YM, Arroliga AC, Stewart TE, Slutsky AS, Meade MO; OSCILLATE Trial Investigators; Canadian Critical Care Trials Group. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med. 2013 Feb 28;368(9):795-805. doi: 10.1056/NEJMoa1215554. Epub 2013 Jan 22.

  PMID: 23339639 BACKGROUND

• Young D, Lamb SE, Shah S, MacKenzie I, Tunnicliffe W, Lall R, Rowan K, Cuthbertson BH; OSCAR Study Group. High-frequency oscillation for acute respiratory distress syndrome. N Engl J Med. 2013 Feb 28;368(9):806-13. doi: 10.1056/NEJMoa1215716. Epub 2013 Jan 22.

  PMID: 23339638 BACKGROUND

• Terragni PP, Rosboch G, Tealdi A, Corno E, Menaldo E, Davini O, Gandini G, Herrmann P, Mascia L, Quintel M, Slutsky AS, Gattinoni L, Ranieri VM. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2007 Jan 15;175(2):160-6. doi: 10.1164/rccm.200607-915OC. Epub 2006 Oct 12.

  PMID: 17038660 BACKGROUND

• Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967 Aug 12;2(7511):319-23. doi: 10.1016/s0140-6736(67)90168-7. No abstract available.

  PMID: 4143721 RESULT

• 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.

  PMID: 22797452 RESULT

MeSH Terms

Conditions

Respiratory Distress Syndrome; Ventilator-Induced Lung Injury

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Injury

Study Officials

• Eddy Fan, MD, PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Francesca Facchin, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Eddy Fan, MD, PhD, Assistant Professor of Medicine, Interdepartmental Division of Critical Care Medicine

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: January 21, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: January 30, 2015

Record last verified: 2015-01

Locations

CA (2)