Clinical trial NCT06769360: A Pilot Trial of Pressure Muscle Index-Targeted PSV Trial
Official title: A Pragmatic Pilot Trial Evaluating Inspiratory Pressure Adjustment Based on Pressure Muscle Index in Patients Undergoing Pressure Support Ventilation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Critical Care
Acute Hypoxic Respiratory Failure
Ventilator Lung
Keywords: pressure support ventilation
pressure muscle index
inspiratory effort
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2025-01-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Pressure support ventilation (PSV) is one of the most frequently used ventilator modes in the intensive care unit (ICU). The successful implementation of PSV depends on matching the patient's inspiratory effort with the ventilator support. In clinical practice, the pressure support level is usually set and adjusted according to tidal volume (VT) and respiratory rate (RR). However, these parameters may not fully represent the patient's effort. Previous studies have shown that pressure muscle index (PMI), which is measured as the difference between the peak and plateau airway pressure during an end-inspiratory airway occlusion, could reliably determine the low and high inspiratory effort during PSV.

However, the comparative effectiveness of these two pressure support level setting strategies remains uncertain. Our aim is to explore clinical and implementation factors relevant to a future definitive randomized controlled trial to evaluate PMI - and VT/RR - pressure support level setting strategies. The Inspiratory effort-targeted pressure support ventilation pragmatic pilot trial will test clinician adherence and to explore clinical outcomes.

Two centers are included in a pragmatic sequential cluster crossover pilot trial. We enrolled all eligible adults with acute respiratory failure requiring mechanical ventilation admitted to ICU. The pressure support level setting strategy was assigned according to the epoch. The first trial epoch will be assigned to VTRR - pressure support level setting strategy for 4 weeks. The washout week between the two epochs will be 4 weeks. Then sequentially, it will be crossed over to PMI - pressure support level setting strategy for 4 weeks.

* In the VT/RR-targeted group, the pressure support is adjusted to obtain a VT between 6 and 8 ml/kg PBW and RR between 20 and 35 breaths/min until day 28 or death or performance of spontaneous breathing trial (SBT).
* In the PMI-targeted group, the pressure support is adjusted according to PMI between 0 and 2 cmH2O until day 28 or death or performance of SBT.

We will also survey clinicians to understand potential facilitators and barriers to conducting a definitive randomized trial.

Detailed description: Steering committee (chief investigators): Feng-Xue Zhu, Li Weng, Jian-Xin Zhou

Aim.

Our aim is to explore clinical and implementation factors relevant to a future definitive randomized controlled trial to evaluate PMI - and VT/RR - pressure support level setting strategies. The Inspiratory effort-targeted pressure support ventilation pragmatic pilot trial will test clinician adherence and to explore clinical outcomes.

Study design and Work plan.

Two centers are included in a pragmatic sequential cluster crossover pilot trial. The pressure support level setting strategy will be assigned according to the epoch. The first trial epoch will be assigned to VTRR - pressure support level setting strategy for 4 weeks, because that is the current standard practice in ICU prior to study initiation. The washout week between the two epochs will be 4 weeks. Then sequentially, it will be crossed over to PMI - pressure support level setting strategy for 4 weeks. Before each epoch, a one-week comprehensive training program will be conducted for all staff in the participating ICUs.

Patients

Mechanically ventilated patients admitted to the ICU with acute hypoxic respiratory failure (AHRF) will be consecutively screened daily at 08:00-10:00 morning rounds. Patients undergoing PSV are eligible for inclusion. The patients will be enrolled only once during the same hospitalization. Written informed consent will be obtained from the patient or their legal representative.

Study Procedures

In both PMI-targeted and VT/RR-targeted groups, standard clinical care for mechanical ventilation is followed according to local routine practice, which is formatted based on international clinical guidelines, except for pressure support adjustment during PSV.

General standard of care for mechanical ventilation

Analgesia is routinely used in mechanically ventilated patients with continuous infusion of fentanyl or remifentanil. Sedation with midazolam, propofol, or dexmedetomidine is used when the patient exhibits agitation and a light sedation level is maintained on RASS of -2 to +1 or Riker's SAS of 3 to 4.

In patients with AHRF, mechanical ventilation is usually initiated on protective control ventilation, such as volume or pressure control mode, with VT 6-8 ml/kg predicted body weight (PBW), RR to control arterial partial pressure of carbon dioxide (PaCO2) and pH, and FiO2 and PEEP to maintain pulse arterial oxygen saturation (SpO2) between 90% and 95%.

Transition of control modes to PSV

During the morning rounds, the responsible ICU physicians check the ventilator mode for each patient. The ventilator mode is recommended to transit from controlled modes to PSV if all the following criteria are met:

1. The patient is able to trigger ventilator breaths;
2. PaO2/FiO2 above 100 mmHg;
3. PEEP below 15 cmH2O;
4. Stable hemodynamic status (none or stable doses of vasopressors);
5. No sedation or light sedation (\[RASS\] of -2 to +1 or \[SAS\] of 3 to 4).

PSV setting strategy

In both the PMI-targeted and VT/RR-targeted groups, the same principle PSV settings are followed except for the adjustment of pressure support level:

1. The inspiratory trigger sensitivity is set as 1-2 L/min for the flow-trigger or 1.5-3 cmH2O for the pressure-trigger;
2. Inspiration-to-expiration cycle-off is set as 25% of the peak inspiratory flow. Responsible physicians can adjust this parameter in case of suspected cycle-off patient-ventilator asynchrony;
3. FiO2 and PEEP are set to maintain SpO2 between 90% and 95%. Specifically, if SpO2 is lower than 90%, PEEP and then FiO2 will be increased by 2 cmH2O and 0.1, respectively; whereas if SpO2 is higher than 95%, FiO2 and then PEEP will be decreased by 0.1 and 2 cmH2O, respectively.

In the VT/RR-targeted group, the pressure support is adjusted to obtain a VT between 6 and 8 ml/kg PBW, RR between 20 and 35 breaths/min, and no signs of respiratory distress, such as prominent use of the accessory respiratory muscles, nose flaring, retractions, etc.

In the PMI-targeted group, the pressure support is adjusted according to the PMI between 0 and 2 cmH2O. During PSV, after an end-inspiratory airway occlusion, Paw will reach a plateau. PMI can be measured on the ventilator screen as plateau Paw minus peak Paw by using a sliding marking line when the screen frozen function is initiated. According to our previous studies, a PMI value of 0 to 2 cmH2O will be used as the target for pressure support adjustment. This PMI range represents a well-accepted normal inspiratory effort.

During the study period in the two groups, pressure support adjustment will be performed at least twice daily.

Rescue backup of controlled ventilation

In both groups, PSV can be switched to protective controlled modes when predefined criteria are met, which include at least one of the following conditions:

1. Pressure support level above 20 cmH2O;
2. PEEP above 15 cmH2O;
3. pH \< 7.30;
4. PaO2/FiO2 ≤ 100 mmHg;
5. Strong inspiratory effort which cannot be controlled by sedation;
6. Unstable hemodynamic status (systolic blood pressure below 90 mmHg with vasopressors or systolic blood pressure above 180 mmHg);
7. Active cardiac ischemia;
8. Unconsciousness (RASS \< -3 or SAS \< 2);
9. Dangerous agitation that cannot be controlled by sedation (RASS \> +2 or SAS \> 6).

Data will be documented in patients whose mechanical ventilation is switched to controlled modes. The patients will be reassessed at least every 12 hours and transited back to PSV as soon as possible according to the abovementioned criteria. The patients will be visited daily until 28 days after randomization. Data will be documented and reported for those patients whose controlled ventilation is not transited back to PSV during the follow-up.

Weaning and extubation

The weaning and extubation process follows clinical guidelines recommended by the American Thoracic Society and the American College of Chest Physicians.

The attending physicians assess readiness to initiate the weaning process during daily morning rounds. If all the following aspects are satisfied, an SBT will be performed:

1. Improvement of the cause of intubation and mechanical ventilation;
2. Hemodynamic stability when the dose of norepinephrine is less than 0.1 μg/kg/min or equivalent and lasts for 6 hours at stable or reduced doses;
3. No agitation or coma;
4. SpO2 higher than 90% with FiO2 less than 0.4 and PEEP less than 5 cmH2O.

SBT is conducted by respiratory therapists using the low-level PSV with pressure support of 5 cmH2O and PEEP of 5 cmH2O. The SBT will last at least 30 min, and criteria for failure of SBT include:

1. RR of greater than 35 breaths/min for more than 5 min;
2. SpO2 of less than 90%;
3. Elevated PaCO2 and/or pH of less than 7.3;
4. Heart rate (HR) of greater than 140 beats/min or a sustained change in HR of more than 20%;
5. Systolic blood pressure greater than 180 mmHg or less than 90 mmHg;
6. Signs of cardiac ischemia indicated by dynamic ST changes on ICU monitor or electrocardiogram;
7. Abrupt unconsciousness with RASS below -3 or SAS below 2;
8. Signs of anxiety, agitation, or diaphoresis. Patients with a failure SBT will be mechanically ventilated with PSV following settings and adjustments according to the original grouping.

Extubation will be performed in endotracheal intubated patients who pass the SBT, and mechanical ventilation will be discontinued in patients with tracheostomy. PSV will be restored to maintain the grouping in patients with reintubation or reapplication of mechanical ventilation via tracheostomy within seven days. The decision to reintubate and restore mechanical ventilation will be at the discretion of the ICU physician team according to the local standard of care. The duration of mechanical ventilation will be added to the total duration.

Data Collection

An electronic case report form (eCRF) is designed and available online via Electronic Data Capture System (Yiduoyun medical health corporation, suzhou, china).

Data collected at the study entry

At baseline, demographics, comorbidities, diagnosis for ICU admission, recent medical history, reasons for mechanical ventilation, duration of ventilation before enrolment, conditions of gas exchange, and mechanical ventilation settings will be documented, as will the Acute Physiological and Chronic Health Evaluation II (APACHE II) score at the ICU admission.

Data collection during daily visits

All patients will be visited daily between 08:00 and 12:00 until successful weaning or separation of mechanical ventilation, death, hospital discharge, or until 28 days after randomization. Successful weaning or separation of mechanical ventilation is defined as extubation without reintubation or death within the next seven days, whether post-extubation noninvasive ventilation is used or not, or ICU discharge without invasive mechanical ventilation within seven days, whichever comes first.

Data collected include:

1. Gas exchange: SpO2 and arterial blood gas analysis;
2. Hemodynamics: blood pressure, HR, vasoactive agents, and cumulative fluid balance during the last day;
3. Analgesia and sedation: RASS or SAS score, visual analog scale or critical care pain observation tool, the use of analgesics and sedatives;
4. Sequential Organ Failure Assessment (SOFA) score;
5. Switch to controlled ventilation: whether switching to controlled mode during the last 24 hours, reasons, and settings;
6. PSV: pressure support level, PEEP, FiO2, VT, and RR;
7. Respiratory drive: the negative airway pressure generated during the first 100 ms against an end-expiratory airway occlusion (airway occlusion pressure, P0.1) (29);
8. SBT: whether performing an SBT during the last 24 hours, methods, and results;
9. Extubation or discontinuation of mechanical ventilation: whether performed during the last 24 hours;
10. Re-intubation or restoration of mechanical ventilation: whether performed during the last 24 hours and reasons;
11. Tracheostomy: whether performed during the last 24 hours;
12. Self-extubation: whether occurring during the last 24 hours;
13. 28-day follow-up: duration of mechanical ventilation, length of stay in the ICU and hospital, and death.

After the study, a questionnaire survey will be conducted involving all staff members in the participating ICUs. The survey mainly includes Likert scales to assess the PMI - pressure support level setting strategy acceptability and also assessed feasibility of conducting a full RCT. Additionally, we also have open-ended questions to understand the difficulties in implementation and ways to improve compliance.

Eligibility criteria: Inclusion Criteria:

1. PSV initiated during the last 24 hours, whether transition from controlled modes or primary initiation;
2. Mechanical ventilation expected to be required for at least 24-48 hours by responsible physicians;
3. The partial pressure of oxygen in arterial blood (PaO2)/inspired oxygen fraction (FiO2) ≤ 300 mmHg (measuring at clinical FiO2 and positive end-expiratory pressure \[PEEP\]);
4. No sedation or stable sedation with Richmond Agitation Sedation Scale (RASS) of -2 to +1 or Riker's Sedation-Agitation Scale (SAS) of 3 to 4.

Exclusion Criteria:

1. Age younger than 18 years old;
2. Initiation of PSV before ICU admission;
3. Duration of mechanical ventilation longer than 7 days before enrollment;
4. History of neuromuscular diseases;
5. Clinical suspicion of increased intracranial pressure;
6. Presentation with pneumothorax and/or bronchopleural fistula;
7. Extracorporeal support;
8. Moribund conditions;
9. Refusal by the ICU physicians or the patient.

Primary outcomes:
measure: Feasibility of PMI target pressure support level setting strategy
timeFrame: 1 year
Secondary outcomes:
measure: Feasibility of VT/RR target pressure support level setting strategy
timeFrame: 1 year
measure: Ventilator-free days (VFDs)
timeFrame: 1 year
measure: Duration of mechanical ventilation before enrollment
timeFrame: 1 year
measure: Total duration of mechanical ventilation
timeFrame: 1 year
measure: The time before the first SBT
timeFrame: 1 year
measure: Weaning time
timeFrame: 1 year
measure: Frequency of prolonged weaning
timeFrame: 1 year
measure: Frequency of self-extubation, re-intubation, tracheotomy, and mechanical ventilation longer than 21 days
timeFrame: 1 year
measure: Length of stay in the ICU and hospital
timeFrame: 1 year
measure: ICU mortality, hospital mortality, and 28-day mortality
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
Study officials:
affiliation: Beijing Shijitan Hospital, Capital Medical University
name: Jian-Xin Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References: