Two Modes of Mechanical Ventilation for Intensive Care Patients With Low Blood Oxygen Due to Breathing Difficulties

Transpulmonary Pressure During Volume Controlled Mechanical Ventilation Versus Airway Pressure Release Ventilation for Hypoxic Respiratory Failure - a Randomized Feasibility Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypoxic Respiratory Failure; Ventilators, Mechanical
• Intervention / Treatment: Other: Volumen controlled mechanical ventilation; Other: Airway pressure release ventilation

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Theis Itenov, MD, PhD; Phone Number: +4551341945; Email: theis.skovsgaard.itenov@regionh.dk

Study Locations

• Denmark
  • København, Denmark, 2400
    • Bispebjerg Hospital
    • Contact: Theis Itenov, MD, PhD; Phone Number: +4551341945; Email: theis.skovsgaard.itenov@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Duration: 3 hours	Other: Volumen controlled mechanical ventilation; Mechanical ventilation mode
Experimental: Intervention; Duration: 3 hours	Other: Airway pressure release ventilation; Mechanical ventilation mode

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median peak transpulmonary pressure	Measured with esophageal manometry in cmH20.	During the observation period; 1-6 hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with peak transpulmonary pressure > 12 cmH2O	Measured with esophageal manometry	During observation period; 1-6 hours after randomization
Change in peak transpulmonary pressure in cmH20	Measured with esophageal manometry. Calculated as beginning - end of observation period	During observation period; 1-6 hours after randomization
Fluctuations in transpulmonary pressure in cmH20	Measured with esophageal manometry. Difference between peak and nadir transpulmonary pressure during respiratory cycle	During observation period; 1-6 hours after randomization
Change in fluctuations of transpulmonary pressure in cmH20	Measured with esophageal manometry. Calculated as beginning - end of observation period.	During observation period; 1-6 hours after randomization
Nadir PaO2-to-FiO2 ratio	Calculated by PaO2/FiO2. PaO2 from arterial blood gasses and FiO2 from ventilator setting	During observation period; 1-6 hours after randomization
Peak FiO2 in %	FiO2 from ventilator settings	During observation period; 1-6 hours after randomization
Peak PaCO2 in kPa	PaCO2 from arterial blood gasses	During observation period; 1-6 hours after randomization
Nadir pH	pH from arterial blood gasses	During observation period; 1-6 hours after randomization
Lung ultrasound aeration according to LUS	Evaluating lung aeration by Lung Ultrasound Score	During observation period; 1-6 hours after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients unable to tolerate observation period without increasing ventilator settings	Defined as measures aimed at increasing either oxygenation or ventilation	During observation period; 1-6 hours after randomization

Collaborators and Investigators

• Sponsor: University Hospital Bispebjerg and Frederiksberg
• Investigators: Principal Investigator: Theis S Itenov, MD, PhD, Bispebjerg Frederiksberg Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Estimated): November 20, 2023

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Esophageal manometry; Transpulmonary pressure; Esophageal pressure; Airway pressure release ventilation; Volumen controlled mechanical ventilation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hypoxia
• Other Study ID Numbers: H-23050947

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data will be owned by the steering committee. De-identified data will be made available 1 year after the primary publication of the outcome data. The statistical code will be submitted as an appendix to primary publication.
• IPD Sharing Time Frame: A year after publication of the primary outcome data
• IPD Sharing Access Criteria: By written request to the steering committee. The sharing of data must be subject to a written agreement between the Capital Region of Denmark and receiver, and in accordance with data regulations. The steering committe will ensure that this.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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