Assessing Lung Inhomogeneity During Ventilation for Acute Hypoxemic Respiratory Failure (ALIVE)

Mechanical ventilation can cause damage by overstretching the lungs, especially when the lungs are collapsed or edematous. Raising ventilator pressures can reduce lung collapse and this can prevent overstretching from mechanical ventilation. It remains uncertain how much pressure (PEEP - positive end-expiratory pressure) should be used on the ventilator and how to identify patients who will benefit from higher ventilator pressures vs. lower ventilator pressures. The investigators are using a unique new imaging technology, electrical impedance tomography (EIT), to study this problem and to determine the safest and most effective ventilator pressure level. The results of this study will inform future trials of higher vs. lower PEEP strategies in mechanically ventilated patients.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome; Hypoxemic Respiratory Failure; Mechanical Ventilation Pressure High
• Intervention / Treatment: Device: Electrical Impedance Tomography; Other: ExPRESS-derived PEEP level

Detailed Description

Patients participating in this physiological cross-over randomized trial will undergo a series of PEEP maneuvers designed to assess lung recruitability, PEEP responsiveness, and optimal PEEP. EIT imaging and esophageal manometry will be employed throughout the protocol to quantify the effect of PEEP on lung function. Patients will be randomized to be ventilated at PEEP levels supplied by the ExPRESS strategy or by the EIT hyperdistention/collapse algorithm. The biological response will be assessed by measuring serum cytokines.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute (≤7 days) hypoxemia with PaO2:FiO2 ratio less than or equal to 200 mm Hg
• Oral endotracheal intubation and mechanical ventilation
• Bilateral airspace opacities on chest radiograph or CT

Exclusion Criteria:

• Contraindication to EIT electrode placement (burns, chest wall bandaging limiting electrode placement)
• Contraindication to esophageal catheter placement (recent upper GI surgery, actively bleeding esophageal varices)
• Respiratory failure predominantly due to cardiogenic cause or fluid overload
• Ongoing hemodynamic instability (requiring 2 vasopressor agents by continuous infusion AND rising vasopressor infusion rate requirements in the previous 8 hours)
• Ongoing ventilatory instability (P/F < 70 mm Hg, pH < 7.2; ventilator driving pressures, PEEP, or FiO2 increasing by more than 25% in previous 30 minutes)
• Intracranial hypertension (suspected or diagnosed by medical team)
• Known or suspected pneumothorax recognized within previous 72 hours
• Bronchopleural fistula
• Bridge to lung transplant
• Recent lung transplantation (within previous 6 weeks)
• Attending physician deems the transient application of high airway pressures (>40 cm H2O) to be unsafe

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EIT algorithm; Patients randomized to this arm will be ventilated at the PEEP level selected by the EIT algorithm, which selects a PEEP at which both collapse and hyperdistention are minimized.	Device: Electrical Impedance Tomography; Electrical impedance tomography (EIT) is a new technique that enables real-time visualization of the distribution of ventilation at the bedside. This technique allows clinicians and investigators to immediately determine how applying higher or lower PEEP levels affect stress and strain in the lung. The investigators propose to apply this new technique to test a strategy for finding the optimal level of PEEP that prevents lung injury and improves outcomes in critically ill patients.
Active Comparator: ExPRESS algorithm; Patients randomized to this arm will be ventilated at the PEEP level selected by the ExPRESS algorithm, which is a method that targets a tidal volume of 6 ml/kg predicted body weight and then titrates PEEP until plateau airway pressure reaches 28 cm H2O.	Other: ExPRESS-derived PEEP level; The ExPRESS algorithm is a traditional approach to selecting PEEP based on respiratory mechanics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intratidal ventilation heterogeneity	A measure of variation in the distribution of ventilation throughout the lung as detected by electrical impedance tomography	Assessed after completion of 3 hours on randomized strategy (EIT vs ExPRESS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the optimal PEEP levels identified by several different PEEP titration strategies	Compare the relative degree of agreement or disparity between PEEP levels recommended by different PEEP titration strategies	Assessed immediately after completion of decremental PEEP titration procedure
Change in ratio of partial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2) ratio following a standardized increased in PEEP	Measurement of changes in oxygenation by PaO2/FiO2 ratio due to PEEP	Assessed 10 minutes after step PEEP increase from 6-8 to 16-18 cm H2O
Respiratory mechanics (transpulmonary driving pressure)	The swing in transpulmonary pressure during inspiration, a measure of dynamic lung stress	Assessed after completing 3 hours on the randomized PEEP strategy (EIT vs ExPRESS)

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Ewan Goligher, MD, PhD, University Health Network, Toronto

Publications and helpful links

General Publications

• Santa Cruz R, Villarejo F, Irrazabal C, Ciapponi A. High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD009098. doi: 10.1002/14651858.CD009098.pub3.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: April 6, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 18, 2018

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 18-6091; 17-6226 (Other Identifier: UHN CAPCR Related ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No