Personalized Ventilator Settings for Patients on ECMO

Official title

Personalized Ventilator Settings for Patients on ECMO (PEEPECMO)

Overview

While mechanical ventilation can be used to sustain life in those with lung injury, it, can further worsen lung injury or prevent lung healing resulting in high morbidity and mortality as seen in Acute Respiratory Distress Syndrome (ARDS). Using extracorporeal membrane oxygenation (ECMO), the highest level of life support also known as the heart-lung machine, investigators may minimize injury from mechanical ventilation to allow the lungs to heal; however, the optimal ventilator strategies while on ECMO are unknown. This study will evaluate personalized ventilator strategy compared to standard of care ventilation.

Detailed description

While mechanical ventilation can be used to sustain life in those with severe ARDS, it, can further worsen lung injury or prevent lung healing resulting in high morbidity and mortality. Using ECMO, investigators may be able to minimize injury from mechanical ventilation to allow the lungs to to recover from ARDS; however, the optimal ventilator settings and therapies are unknown while on ECMO. This trial will randomize patients to personalized ventilator strategy vs. standard of care.

Current ventilator guidelines while on V-V ECMO for ARDS use a one-size-fits-all approach - respiratory rate 10, driving pressure 10, and a PEEP of 10. Our central hypothesis is that personalized PEEP adjusted by measuring intrathoracic pressures via esophageal manometry (Pes) will decease ventilator induced lung injury (VILI) as assessed by biomarkers of inflammation (main outcomes IL-6 and sRAGE).

To carry out these aims, participants with ARDS on V-V ECMO will be prospectively randomize patients to two groups:

Control Arm: PEEP of 10 cmH2O (ECMO guidelines). Intervention Arm: PEEP guided by esophageal manometry. Both arms will have be on neuromuscular blockade, with a respiratory rate set at 10 breaths/min and a driving pressure of 10 cmH2O.

In addition to biomarkers of VILI, investigators will assess differences in other physiological outcomes including pulmonary mechanics and gas exchange.

Hypothesis: Personalized PEEP will have improvement in biomarkers (primary outcome - IL-6), increased oxygenation, decreased dead space, and increased respiratory compliance.

Interventions

• Device Personalized Positive End-Expiratory Pressure (PEEP)
  The personalized Positive End-Expiratory Pressure (PEEP) will be determined by esophageal manometry or electrical impedance tomography (EIT)

Primary outcome measures

• Biomarker outcome (IL-6) [Time frame: Baseline at enrollment, 24±12 hours post enrollment, 48±12 hours post enrollment.]
• Respiratory gas exchange (dead space, oxygenation). [Time frame: Baseline at enrollment, 24±12 hours post enrollment, 48±12 hours post enrollment.]
• Respiratory mechanics (compliance of the respiratory system) [Time frame: Baseline at enrollment, 24±12 hours post enrollment, 48±12 hours post enrollment.]

Eligibility criteria

• History of Lung or Cardiac Transplantation, or definite bridge to transplantation
• Patient is not committed to full support
• Treating clinician refusal, or unwillingness to commit to controlled therapeutics (Esophageal Pressure Guided Positive End-Expiratory Pressure and neuromuscular blockade)
• Inability to get informed consent from the patient or legally authorized representative (LAR)
• Patients with contraindications to esophageal balloon placement or inability to successfully place an esophageal balloon will have personalized PEEP determined by electrical impedance tomography.

a. Contraindications include recently treated or bleeding varices, esophageal stricture, hematemesis, esophageal trauma, recent esophageal surgery or other contraindication for nasogastric tube placement, or severe coagulopathy.

• Severe barotrauma that requires lower mean airway pressure (i.e., PEEP) per the treating physician.
• Patients who are pregnant or prisoners.
• Has been on V-V ECMO > 72 hours.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• UC San Diego Health Jacobs Medical Center — La Jolla

Publications

• Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372. PMID 20843245
• Dianti J, Tisminetzky M, Ferreyro BL, Englesakis M, Del Sorbo L, Sud S, Talmor D, Ball L, Meade M, Hodgson C, Beitler JR, Sahetya S, Nichol A, Fan E, Rochwerg B, Brochard L, Slutsky AS, Ferguson ND, Serpa Neto A, Adhikari NKJ, Angriman F, Goligher EC. Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A S PMID 35180042
• 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
• Brodie D, Slutsky AS, Combes A. Extracorporeal Life Support for Adults With Respiratory Failure and Related Indications: A Review. JAMA. 2019 Aug 13;322(6):557-568. doi: 10.1001/jama.2019.9302. PMID 31408142
• Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A; EOLIA Trial Group, REVA, and ECMONet. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med PMID 29791822
• Schmidt M, Pham T, Arcadipane A, Agerstrand C, Ohshimo S, Pellegrino V, Vuylsteke A, Guervilly C, McGuinness S, Pierard S, Breeding J, Stewart C, Ching SSW, Camuso JM, Stephens RS, King B, Herr D, Schultz MJ, Neuville M, Zogheib E, Mira JP, Roze H, Pierrot M, Tobin A, Hodgson C, Chevret S, Brodie D, Combes A. Mechanical Ventilation Management during Extracorporeal Membrane Oxygenation for Acute Re PMID 31144997
• Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2 PMID 30776290
• Tonna JE, Abrams D, Brodie D, Greenwood JC, Rubio Mateo-Sidron JA, Usman A, Fan E. Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO J. 2021 Jun 1;67(6):601-610. doi: 10.1097/MAT.0000000000001432. PMID 33965970

Identifiers

NCT: NCT07673250 · 805593 · 1K23HL181397

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗