Clinical trial NCT03612583: Lung and Diaphragm-Protective Ventilation by Means of Assessing Respiratory Work
Official title: Lung and Diaphragm-Protective Ventilation by Means of Assessing Respiratory Work
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diaphragm Injury
Lung Injury
Respiratory Insufficiency
Mechanical Ventilation Complication
Keywords: Diaphragm Dysfunction
Acute Respiratory Failure
Sedation
Mechanical Ventilation
Lung Stress
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2018-08-02
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is designed to test a proposed strategy for lung- and diaphragm-protective ventilation (LDPV) in patients with acute hypoxemic respiratory failure. Ventilation and sedation will be titrated to evaluate whether it is feasible and safe within this patient population.

Detailed description: Lung injury and diaphragm injury incurred by mechanical ventilation have very serious adverse effects on patients with acute respiratory failure. Lung injury results from excessive mechanical stress and strain applied to the lung by the ventilator and/or respiratory muscles, while diaphragm injury results from either insufficient or excessive inspiratory effort.

The objective of this study is to investigate a new LDPV strategy designed to prevent both disuse-mediated and load-induced diaphragm injury, while also preventing excess global and regional mechanical stress and strain in the injured lung. To achieve these goals, the following specific targets to be met are: (1) respiratory muscle effort similar to that of healthy subjects breathing at rest, (2) lung stress within safe limits, and (3) clinically acceptable gas exchange.

Targets are assessed through measurements of global lung stress, tidal recruitment, inspiratory effort, diaphragm contractile effort and adequacy of respiratory muscle and systemic tissue perfusion. Measurements commence at enrollment and continue for 24 hours consecutively.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with acute hypoxemic respiratory failure
* PaO2:FiO2 ratio less than or equal to 300 mm Hg at time of screening
* Oral endotracheal intubation and mechanical ventilation
* Bilateral airspace opacities on chest radiograph or chest CT scan

Exclusion Criteria:

* Liberation from mechanical ventilation is anticipated within 24 hours
* Intubated for traumatic brain injury or stroke
* Contraindication to esophageal catheterization
* Intracranial hypertension

Primary outcomes:
measure: Rate of patients achieving and maintaining LDPV targets
timeFrame: Assessed after achievement of LDPV targets for 24 hours
Secondary outcomes:
measure: Inspiratory effort at lower and higher PEEP levels
timeFrame: Assessed 10 minutes after PEEP and sedation are adjusted
measure: Expiratory diaphragmatic effort at lower and higher PEEP levels
timeFrame: Assessed 10 minutes after PEEP and sedation are adjusted
measure: Lung stress and strain at low and high sweep gas flow rates
timeFrame: Assessed 10 minutes after PEEP and sedation are adjusted
measure: Inspiratory effort at low and high sweep gas flow rates
timeFrame: Assessed 10 minutes after PEEP and sedation are adjusted
measure: Sedative infusion rate at low and high sweep gas flow rates
timeFrame: Assessed 10 minutes after PEEP and sedation are adjusted
measure: Accuracy of artificial intelligence model in predicting patient outcomes
timeFrame: Assessed after completing the 24-hour maintenance period
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: Dianti J, Fard S, Wong J, Chan TCY, Del Sorbo L, Fan E, Amato MBP, Granton J, Burry L, Reid WD, Zhang B, Ratano D, Keshavjee S, Slutsky AS, Brochard LJ, Ferguson ND, Goligher EC. Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial. Crit Care. 2022 Aug 29;26(1):259. doi: 10.1186/s13054-022-04123-9.