Clinical trial NCT03589482: Assessing Lung Inhomogeneity During Ventilation for Acute Hypoxemic Respiratory Failure
Official title: Assessing Lung Inhomogeneity During Ventilation for Acute Hypoxemic Respiratory Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Mechanical Ventilation Pressure High
Hypoxemic Respiratory Failure
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2018-07-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Intratidal ventilation heterogeneity
timeFrame: Assessed after completion of 3 hours on randomized strategy (EIT vs ExPRESS)
Secondary outcomes:
measure: Difference in the optimal PEEP levels identified by several different PEEP titration strategies
timeFrame: Assessed immediately after completion of decremental PEEP titration procedure
measure: Change in ratio of partial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2) ratio following a standardized increased in PEEP
timeFrame: Assessed 10 minutes after step PEEP increase from 6-8 to 16-18 cm H2O
measure: Respiratory mechanics (transpulmonary driving pressure)
timeFrame: Assessed after completing 3 hours on the randomized PEEP strategy (EIT vs ExPRESS)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Ewan Goligher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.