Assessing Lung Inhomogeneity During Ventilation for Acute Hypoxemic Respiratory Failure

Not Applicable

Completed

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

• Registration Number: NCT03589482
• Lead Sponsor: University Health Network, Toronto

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-04-06
• Study First Submitted QC: 2018-07-17
• Study First Posted: 2018-07-18
• Study Start: 2019-03-01
• Status Verified: 2020-08
• Primary Completion: 2021-03-31
• Study Completion: 2021-08-31
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ExPRESS algorithm	ExPRESS-derived PEEP level	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.
EIT algorithm	Electrical Impedance Tomography	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Health Network; 🇨🇦 Toronto, Ontario, Canada