Acute Respiratory Distress Syndrome
Conditions
Keywords
Airway Pressure Release Ventilation, spontaneous breathing, electrical impedance tomography, ventilation-perfusion mismatch
Brief summary
This is a single-center, prospective, randomized, three-period crossover physiological study in adult patients with moderate-to-severe acute respiratory distress syndrome (ARDS, PaO₂/FiO₂ ≤150 mmHg). Each enrolled subject will receive all three APRV ventilation conditions in random sequence: low-level spontaneous breathing (spontaneous minute-ventilation proportion 10%-30%), high-level spontaneous breathing (31%-50%), and fully suppressed spontaneous breathing as control. A 30-minute wash-out period is set between each condition to restore unified physiological baseline. Primary outcome is ventilation-perfusion mismatch percentage (mismatch%) measured by Electrical Impedance Tomography (EIT). Secondary outcomes include EIT-derived pulmonary parameters, respiratory mechanics, hemodynamics, diaphragmatic function and safety profiles. Only short-term, reversible ventilator and sedation adjustments will be performed; routine clinical management remains unchanged throughout the trial.
Detailed description
Acute respiratory distress syndrome (ARDS) is a life-threatening critical respiratory illness characterized by heterogeneous pulmonary injury and severe ventilation-perfusion mismatch. Airway Pressure Release Ventilation (APRV) permits spontaneous breathing throughout the whole respiratory cycle, which may improve regional ventilation-perfusion matching and hemodynamic status. Nevertheless, excessive spontaneous breathing effort may trigger pendelluft phenomenon, augment regional lung strain and precipitate patient-self-inflicted lung injury (P-SILI). To date, the safe intensity range of spontaneous breathing during APRV for moderate-to-severe ARDS patients has not been well defined. This single-center, randomized 3-period crossover self-controlled physiological trial enrolls ICU adult patients aged 18-80 years, diagnosed with moderate-to-severe ARDS (PaO₂/FiO₂ ≤ 150 mmHg) within 48-hours of invasive mechanical ventilation. After written informed consent obtained from legal surrogates, subjects will first receive a 60-minute baseline ventilation period following ARDSnet low-tidal-volume pressure-control ventilation strategy under deep sedation without spontaneous breathing. Subsequently, every participant will undergo three APRV intervention states in computer-generated random order: Condition A: APRV with low-intensity spontaneous breathing (spontaneous-contributed minute ventilation 10%-30%); Condition B: APRV with high-intensity spontaneous breathing (31%-50%); Condition C: APRV with fully suppressed spontaneous breathing via deep sedation (RASS -4 to -5). Each intervention maintains target spontaneous-breathing intensity for 30-minute stabilization before data collection. A mandatory 30-minute wash-out phase will be implemented between successive interventions to revert subjects back to baseline pressure-control ventilation and sedation status. Primary endpoint is the comparison of ventilation-perfusion mismatch percentage (mismatch%, calculated as sum of dead-space fraction and shunt fraction) among three states measured by bedside EIT. Secondary endpoints contain multiple EIT quantitative indices, respiratory mechanics parameters (including esophageal-pressure-derived transpulmonary pressure), hemodynamic and right-ventricular function, diaphragmatic ultrasound indices, arterial blood gas variables. Adverse events related to respiratory, circulatory and operational procedures are closely monitored as safety outcomes. Planned sample size is 14-16 enrolled participants to achieve 12 evaluable subjects completing all three intervention sequences considering dropout rate. All ventilator and sedation modifications are short-term and reversible; standard clinical therapeutic regimens will not be altered except for study-related procedures. After finishing all three intervention periods, ventilator and sedation settings will be returned to clinical team's discretion. Linear mixed-effect models will be applied for statistical analysis of crossover-design data.
Interventions
DEVICEAPRV ventilation with low-level spontaneous breathing
APRV ventilation mode, spontaneous-contributed minute-ventilation proportion maintained at 10%-30%. 30-minute stabilization before outcome measurement.
DEVICEAPRV ventilation with high-level spontaneous breathing
APRV ventilation mode, spontaneous-contributed minute-ventilation proportion maintained at 31%-50%. 30-minute stabilization before outcome measurement.
DEVICEAPRV ventilation with fully suppressed spontaneous breathing
APRV ventilation mode, spontaneous breathing fully suppressed by deep sedation (RASS-4 to -5). 30-minute stabilization before outcome measurement.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Each participant receives all three APRV ventilation conditions in random sequence with 30-minute wash-out period between successive conditions. This is a three-period crossover self-controlled physiological study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Age ≥18 and ≤80 years old. 2. Diagnosed with moderate-to-severe ARDS according to the 2023 global ARDS definition. 3\. Within 48 hours of invasive mechanical ventilation. After 1-hour low-tidal-volume pressure-controlled ventilation following ARDSnet strategy, arterial blood gas shows PaO₂/FiO₂ ≤ 150 mmHg. 4\. Written informed consent is obtained from the patient or their legal surrogate decision-maker after full explanation of the study by the principal investigator or authorized study physician.
Exclusion criteria
* 1\. Refractory shock defined as persistent hyperlactatemia and/or prolonged capillary refill time, fluid-resistant, requiring norepinephrine ≥ 0.5 μg/kg/min. 2\. Severe chronic medical conditions severely affecting cardiopulmonary function: severe chronic obstructive pulmonary disease, interstitial lung disease, pulmonary embolism, right-heart failure, pulmonary hypertension, or severe arrhythmia. 3\. Radiologically confirmed bronchopleural fistula, status post lobectomy, or other major thoracic surgery. 4\. Contraindications to electrical impedance tomography (EIT): extensive chest skin injury or infection, implanted cardiac pacemaker or defibrillator, etc. 5\. Contraindications for esophageal manometry placement: esophageal obstruction, perforation, severe esophageal varices, etc. 6\. Diaphragmatic hernia, severe chest wall deformity, or significant pulmonary bullae. 7\. Significant coagulation abnormalities (PT or APTT prolonged ≥2 times upper limit of normal, or INR\>2.0) with active bleeding risk. 8\. Severe intracranial hypertension (\>20 mmHg), severe traumatic brain injury (GCS ≤8), or neuromuscular disorders. 9\. Pregnant or breastfeeding women. 10. Patients already receiving ECMO therapy. 11. Expected survival time \<24 hours judged by attending physician. 12. Body mass index (BMI) \>35 kg/m². 13. Previously enrolled in this study or participating in other interventional clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilation-perfusion mismatch percentage (Mismatch%) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Ventilation-perfusion mismatch percentage (Mismatch%), calculated as the sum of dead-space percentage and shunt percentage measured by electrical impedance tomography (EIT). A composite index reflecting overall ventilation-perfusion mismatch, assessed at baseline and under three APRV experimental conditions. Unit: % |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Esophageal pressure-time product per minute (PTPes/min) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Esophageal pressure-time product per minute (PTPes/min) read directly from the ventilator interface. Unit: cmH₂O·s/min. |
| End-inspiratory transpulmonary pressure (PtpI) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | End-inspiratory transpulmonary pressure (PtpI) derived from airway and esophageal pressure measurements. Unit: cmH₂O. |
| Transpulmonary driving pressure (ΔPtp) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Transpulmonary driving pressure (ΔPtp) derived from airway and esophageal pressure measurements. Unit: cmH₂O. |
| Dynamic transpulmonary driving pressure (ΔPL,dyn) | At the end of each 30-minute APRV experimental condition (after stabilization) | Dynamic transpulmonary driving pressure (ΔPL,dyn) obtained from ventilator measurements; only measured in the presence of spontaneous breathing effort. Unit: cmH₂O. |
| Inspiratory muscle pressure (Pmus) | At the end of each 30-minute APRV experimental condition (after stabilization) | Inspiratory muscle pressure (Pmus) obtained from ventilator measurements; only measured in the presence of spontaneous breathing effort. Unit: cmH₂O |
| End-expiratory occlusion pressure (ΔPocc) | At the end of each 30-minute APRV experimental condition (after stabilization) | End-expiratory occlusion pressure (ΔPocc) obtained from ventilator measurements; only measured in the presence of spontaneous breathing effort. Unit: cmH₂O |
| Airway occlusion pressure (P0.1) | At the end of each 30-minute APRV experimental condition (after stabilization) | Airway occlusion pressure (P0.1) obtained from ventilator measurements; only measured in the presence of spontaneous breathing effort. Unit: cmH₂O |
| Muscular pressure index (PMI) | At the end of each 30-minute APRV experimental condition (after stabilization) | Muscular pressure index (PMI) obtained from ventilator measurements; only measured in the presence of spontaneous breathing effort. Unit: cmH₂O |
| Negative inspiratory force (NIF) | At the end of each 30-minute APRV experimental condition (after stabilization) | Negative inspiratory force (NIF) obtained from ventilator measurements; only measured in the presence of spontaneous breathing effort. Unit: cmH₂O |
| Heart rate | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Heart rate from continuous bedside monitoring, assessed at baseline and under three APRV experimental conditions. Unit: beats per minute. |
| Mean arterial pressure (MAP) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Mean arterial pressure (MAP) measured via invasive arterial catheter, assessed at baseline and under three APRV experimental conditions. Unit: mmHg. |
| Vasopressor dosage (μg/kg/min) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Dosage of vasoactive medications, assessed at baseline and under three APRV experimental conditions. Unit: μg/kg/min |
| Central venous pressure (CVP) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Central venous pressure (CVP), assessed at baseline and under three APRV experimental conditions. Unit: mmHg. |
| Right-ventricular fractional area change | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Right-ventricular fractional area change measured by transthoracic echocardiography, assessed at baseline and under three APRV experimental conditions. Unit: %. |
| Velocity-time-integral (VTI) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Velocity-time-integral (VTI) measured by transthoracic echocardiography, assessed at baseline and under three APRV experimental conditions. Unit: cm. |
| Tricuspid annular plane systolic excursion (TAPSE) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Tricuspid annular plane systolic excursion (TAPSE) measured by transthoracic echocardiography, assessed at baseline and under three APRV experimental conditions. Unit: mm. |
| Cardiac output (CO) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Cardiac output (CO) calculated from velocity-time integral (VTI) measured by transthoracic echocardiography, assessed at baseline and under three APRV experimental conditions. Unit: L/min. |
| Stroke volume (SV) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Stroke volume (SV) calculated from velocity-time-integral (VTI) measured by transthoracic echocardiography, assessed at baseline and under three APRV experimental conditions. Unit: mL. |
| Diaphragm displacement | At the end of 30-minute APRV experimental conditions with spontaneous breathing effort (after stabilization) | Diaphragm displacement measured by bedside diaphragm ultrasound, assessed in two out of the three APRV experimental conditions only when spontaneous breathing was present. Unit: mm. |
| Diaphragm thickening fraction | At the end of 30-minute APRV experimental conditions with spontaneous breathing effort (after stabilization) | Diaphragm thickening fraction measured by bedside diaphragm ultrasound, assessed in two out of the three APRV experimental conditions only when spontaneous breathing was present. Unit: %. |
| Lung 12-zone ultrasound score | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Lung ultrasound score based on 12-zone lung ultrasound assessment, assessed at baseline and under three APRV experimental conditions. Unit: unitless. |
| Match percentage(match%) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Match percentage derived from electrical impedance tomography (EIT). Unit: %. |
| Pendelluft amplitude | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Pendelluft amplitude derived from electrical impedance tomography (EIT). Unit: %. |
| Dead-space percentage | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Dead-space percentage derived from electrical impedance tomography (EIT), assessed at baseline and under three APRV experimental conditions. Unit: %. |
| Shunt percentage | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Intrapulmonary shunt percentage derived from electrical impedance tomography (EIT), assessed at baseline and under three APRV experimental conditions. Unit: %. |
| Global inhomogeneity index (GI) | Baseline and at the end of each 30-minute experimental condition during the study intervention period | Global inhomogeneity index (GI) derived from electrical impedance tomography (EIT). Unit: unitless. |
| Center of ventilation (CoV) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Center of ventilation (CoV) derived from electrical impedance tomography (EIT), assessed at baseline and under three APRV experimental conditions. Unit: %. |
| Tidal recruitment-derecruitment | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Tidal recruitment-derecruitment (Tidal R/D) derived from electrical impedance tomography (EIT), assessed at baseline and under three APRV experimental conditions. Unit: %. |
| Ventilation distribution | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Regional ventilation distribution derived from electrical impedance tomography (EIT), assessed at baseline and under three APRV experimental conditions. Unit: %. |
| Perfusion distribution | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Regional pulmonary perfusion distribution derived from electrical impedance tomography (EIT), assessed at baseline and under three APRV experimental conditions. Unit: %. |
| Peak airway pressure (Ppeak) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Airway peak pressure (Ppeak) measured by mechanical ventilator, assessed at baseline and under three APRV experimental conditions. Unit: cmH₂O |
| Plateau pressure (Pplat) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Airway plateau pressure (Pplat) obtained from end-inspiratory hold maneuver, assessed at baseline and under three APRV experimental conditions. Unit: cmH₂O. |
| Driving pressure (ΔP) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Driving pressure (ΔP) derived from mechanical ventilator measurements. Unit: cmH₂O. |
| Static respiratory system compliance (Cstat) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Static respiratory system compliance (Cstat), assessed at baseline and under three APRV experimental conditions. Unit: mL/cmH₂O. |
| End-inspiratory esophageal pressure (PesI) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | End-inspiratory esophageal pressure (PesI) measured by esophageal manometry, assessed at baseline and under three APRV experimental conditions. Unit: cmH₂O. |
| End-expiratory esophageal pressure (PesE) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | End-expiratory esophageal pressure (PesE) measured by esophageal manometry, assessed at baseline and under three APRV experimental conditions. Unit: cmH₂O |
| Esophageal pressure swing (ΔPes) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Esophageal pressure swing (ΔPes) measured by esophageal manometry, assessed at baseline and under three APRV experimental conditions. Unit: cmH₂O. |
| Overdistension (OD) pixel count | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Pixel count of lung overdistension (OD), exported directly from electrical impedance tomography (EIT) software basic module, averaged over complete respiratory cycles within selected time interval, measured at baseline (prior to intervention, after stabilization) and at the end of each 30-minute APRV experimental condition (after stabilization). Unit: pixels. |
| Overdistension (OD) proportion | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Proportion of lung overdistension (OD) relative to total lung-region pixels, exported directly from electrical impedance tomography (EIT) software basic module, averaged over complete respiratory cycles within selected time interval, measured at baseline (prior to intervention, after stabilization) and at the end of each 30-minute APRV experimental condition (after stabilization). Unit: %. |
| Recruitment (CR) pixel count | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Pixel count of lung recruitment (CR), exported directly from electrical impedance tomography (EIT) software basic module, averaged over complete respiratory cycles within selected time interval, measured at baseline (prior to intervention, after stabilization) and at the end of each 30-minute APRV experimental condition (after stabilization). Unit: pixels. |
| Recruitment (CR) proportion | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Proportion of lung recruitment (CR) relative to total lung-region pixels, exported directly from electrical impedance tomography (EIT) software basic module, averaged over complete respiratory cycles within selected time interval, measured at baseline (prior to intervention, after stabilization) and at the end of each 30-minute APRV experimental condition (after stabilization). Unit: %. |
| Atelectasis (AT) pixel count | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Pixel count of lung atelectasis (AT), exported directly from electrical impedance tomography (EIT) software basic module, averaged over complete respiratory cycles within selected time interval, measured at baseline (prior to intervention, after stabilization) and at the end of each 30-minute APRV experimental condition (after stabilization). Unit: pixels. |
| End-expiratory transpulmonary pressure (PtpE) | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | End-expiratory transpulmonary pressure (PtpE) derived from airway and esophageal pressure, assessed at baseline and under three APRV experimental conditions. Unit: cmH₂O. |
| Atelectasis (AT) proportion | Baseline and at the end of each 30-minute experimental condition during the study intervention period. | Proportion of lung atelectasis (AT) relative to total lung-region pixels, exported directly from electrical impedance tomography (EIT) software basic module, averaged over complete respiratory cycles within selected time interval, measured at baseline (prior to intervention, after stabilization) and at the end of each 30-minute APRV experimental condition (after stabilization). Unit: %. |
Countries
China
Contacts
CONTACTXiaojing Zou
PRINCIPAL_INVESTIGATORxiaojing zou, MD
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed