Clinical trial NCT06140056: Two Modes of Mechanical Ventilation for Intensive Care Patients With Low Blood Oxygen Due to Breathing Difficulties
Official title: Transpulmonary Pressure During Volume Controlled Mechanical Ventilation Versus Airway Pressure Release Ventilation for Hypoxic Respiratory Failure - a Randomized Feasibility Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hypoxic Respiratory Failure
Ventilators, Mechanical
Keywords: Transpulmonary pressure
Airway pressure release ventilation
Volumen controlled mechanical ventilation
Esophageal pressure
Esophageal manometry
Lead sponsor: University Hospital Bispebjerg and Frederiksberg
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The study examines individuals admitted to the intensive care unit due to breathing difficulties resulting in not getting enough oxygen into their bodies. These patient will receive mechanical ventilation and this study aims to determine how the pressure inside the lungs changes when using two different modes of mechanical ventilation. The goal is to improve management and care of breathing difficulties by gaining insight into changes in lung pressure during mechanical ventilation, as well as comparing the effectiveness of the two ventilator modes.

Detailed description: As hypoxic respiratory failure is an acute condition, this trial will enrol temporarily incompetent patients and obtain consent from the patient's next of kin and an independent medical doctor (trial guardian) as soon as possible after enrolment.

When included in the study, patients will be randomized 1:1 centrally in the RedCap system, using a computer-generated concealed assignment sequence, with permuted blocks of varying sizes, to start with either the intervention (APRV) followed by control (volume controlled mechanical ventilation) or control followed by intervention.

Esophageal manometry will be used as a surrogate to measure the transpulmonary pressure. Arterial blood gasses, blood samples and lung ultrasound will be used to investigate oxygenation, ventilation and aeration.

Treatment targets for both groups during the study are pH \>7.20, saturation ≥ 88% and PaO2 ≥ 8.0 kPa, with FiO2 titrated as low as possible while complying to the oxygenation targets (PaO2 and saturation).

Both arms start with an 'adjustment phase' where the ventilator is adjusted so the respiratory values are within the targets. The intervention adjustment phase is at least 30 minutes. The adjustments will follow standardized protocols.

When the respiratory values are within range, the 'observation period begins' and no changes are made to the ventilator for 3 hours, unless it is necessary to achieve ventilatory treatment targets or deemed necessary by the treating physician. During the trial, the patient must be positioned in a supine position with the headboard elevated 0-30 degrees.

After the first 'observation period', the patient is switched to the opposite ventilation mode and will go through an 'adjustment phase' and 'observation period' again.

Once a patient regains competence, they will be provided with both written and oral information regarding the trial

By comparing volume controlled mechanical ventilation and APRV and their transpulmonary pressures, valuable insight can be gained regarding optimal ventilation strategy for patients with hypoxic respiratory failure. Understanding how various ventilation modes influence transpulmonary pressure and their potential effects on respiratory mechanics can potentially inform designs of trials with individualized respiratory care.

Eligibility criteria: Inclusion Criteria:

* Admitted to the ICU
* Invasive mechanical ventilation with FiO2 ≥ 50% OR PaO2-to-FiO2 ratio \<20 kPa, including PEEP 3 5 cmH20 for at least 6 hours

Exclusion Criteria:

* Meeting inclusion criteria for more than 24 hours
* Severe bronchospasm, defined as warranting treatment aimed at reversing this i.e. inhalation of anticholinergic or bronchodilator beyond what the patient normally use
* Emphysema where treating physician judges the patient at increased risk for pneumothorax from APRV
* Restrictive lung disease defined as a pre-admission diagnosis of restrictive lung disease
* Undrained pneumothorax
* Hemodynamic instability defined as more than 0.20 microgram/kg/min of norepinephrine or any dose of adrenaline infusion to maintain MAP ≥ 65 mmHg
* Age \< 18 years
* Patients who have received APRV previously during the current ICU admission
* Patients in prone position within the last 24 hours

Primary outcomes:
measure: Median peak transpulmonary pressure
timeFrame: During the observation period; 1-6 hours after randomization
Secondary outcomes:
measure: Proportion of patients with peak transpulmonary pressure > 12 cmH2O
timeFrame: During observation period; 1-6 hours after randomization
measure: Change in peak transpulmonary pressure in cmH20
timeFrame: During observation period; 1-6 hours after randomization
measure: Fluctuations in transpulmonary pressure in cmH20
timeFrame: During observation period; 1-6 hours after randomization
measure: Change in fluctuations of transpulmonary pressure in cmH20
timeFrame: During observation period; 1-6 hours after randomization
measure: Nadir PaO2-to-FiO2 ratio
timeFrame: During observation period; 1-6 hours after randomization
measure: Peak FiO2 in %
timeFrame: During observation period; 1-6 hours after randomization
measure: Peak PaCO2 in kPa
timeFrame: During observation period; 1-6 hours after randomization
measure: Nadir pH
timeFrame: During observation period; 1-6 hours after randomization
measure: Lung ultrasound aeration according to LUS
timeFrame: During observation period; 1-6 hours after randomization
Other outcomes:
measure: Proportion of patients unable to tolerate observation period without increasing ventilator settings
timeFrame: During observation period; 1-6 hours after randomization
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: København
country: Denmark
facility: Bispebjerg Hospital
Study officials:
affiliation: University Hospital Bispebjerg and Frederiksberg
name: Theis S Itenov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: