Susceptibility for Entrainment: Role of Ventilator Settings on the Occurrence of Reverse Triggering and Its Physiological Consequences - the SEVeRe Study

NCT06293976 | Recruiting

• 1 other identifier: 4506
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Reverse triggering (RT) is a frequent phenomenon observed in sedated patients under a mechanical ventilation mode called assist-control ventilation. RT is when the ventilator would trigger the patient's respiratory effort instead of the correct order of the patient's respiratory effort triggering the ventilator. Reverse triggering can have negative consequences (loss of protective lung ventilation, and causing double breaths - with the ventilator giving two consecutive breaths and not allowing the patient to exhale) but also offer some protective effects (avoid diaphragm disuse atrophy). The balance of its negative vs positive effects depends on its frequency and magnitude of its associated respiratory effort. Respiratory entrainment is the most often referred mechanism involving a change in patient's rate of breathing effort from that of patient's intrinsic rate to the rate of mechanical insufflation. The specific ventilatory settings associated with or responsible for RT remains unknown. Aims: To assess in mechanically ventilated critically ill patients the influence of the set respiratory rate (RR) and tidal volume (Vt) on the presence/development of RT and to describe the pattern of respiratory muscle activity during Reverse Triggering (RT). Methods. 30 adult patients (15 in each group), sedated and under assist-controlled ventilation will be included. Ventilator settings will be modified to modulate the frequency and magnitude of reverse triggering. Initially, with the ventilator on a mode called volume control, which means the ventilator controls the amount of air (tidal volume) and the number of breaths the patients gets every minute (respiratory rate \[RR\]). The tidal volume will be set at the current standard clinical practice setting (6 ml/kg of predicted body weight). The presence of an intrinsic respiratory rate will be assessed with an end-expiratory occlusion maneuver. Next, the number of breaths the ventilator gives per minute (RR) will be changed from 6 breaths less to 6 breaths more, in steps of 2 breaths every minute. The protocol will be repeated again changing the amount of air the patients gets (tidal volume) from 4, 5, 7 and 8 ml/kg. Continuous recordings of airway pressure, flow, esophageal pressure, electrical activity of the diaphragm, main accessory muscles and frontal electroencephalography will be obtained during the protocol and baseline clinical and physiological characteristics and outcomes will be recorded. A validated software will be used to detect RT and measure the intensity and timing of each muscle electrical activity and the magnitude of the inspiratory effort during RT.

Conditions

Respiration, Artificial; Reverse Triggering

Keywords

Hypnotics and Sedatives; Respiratory Muscles

Outcome Measures

Primary Outcomes (2)

• The rate of of reverse triggered breaths occurring after each change in the ventilator respiratory rate and tidal volume.

  The rate of reverse triggered breaths occurring after each change in the ventilator respiratory rate and tidal volume.

  1 minutes

• The magnitude of the effort, measured by the drop in the esophageal pressure in cmH2O, associated with the reverse triggered breaths after each change in the ventilator respiratory rate and tidal volume

  The magnitude of the effort, measured by the drop in the esophageal pressure in cmH2O, associated with the reverse triggered breaths after each change in the ventilator respiratory rate and tidal volume

  1 minute

Study Arms (1)

Patients under mechanical ventilation

EXPERIMENTAL

Patients intubated for more than 12 hours, on assist-control ventilation, not triggering the ventilator with or without reverse triggering, exposed to sedation for at least 6 hours, with a sedation-agitation score ≤ 4.

Other: Changes in the ventilator respiratory rate and tidal volume

Interventions

Changes in the ventilator respiratory rate and tidal volume OTHER

With the ventilator on volume control and Vt at 6 ml/kg of predicted body weight (PBW) (standard clinical practice), an end-expiratory occlusion of 30 seconds on the ventilator will be performed to search for intrinsic respiratory rate (RR). The set RR will be modified from 6 breaths per minute (bpm) below up to 6 bpm above the clinical RR in steps of 2 bpm every 1 minute (random order). The changes in RR described above will be repeated with Vt set at 5, 7 and 8 ml/kg PBW (random order). The steps described above will be aborted at any point if SpO2 drops below 85% for at least two minutes, mean arterial pressure drops below 60 mmHg, or plateau pressure \>35 cmH2O. If an intrinsic respiratory rate ≥8 bpm is present and P/F ratio is ≥150, it will be propose to the clinician to place the patient in pressure support at a level preferred by clinicians for 5 minutes. If the patient tolerates well, it will be propose to the clinician to maintain the patient in pressure support ventilation,

Patients under mechanical ventilation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients intubated for more than 12 hours
• On assist-control ventilation, not triggering the ventilator
• Exposed to sedation for at least 6 hours
• With a sedation-agitation score ≤ 4.

You may not qualify if:

• primary severe neurological disorders
• previous lung transplant
• contraindications for esophageal catheter insertion
• current use of continuous neuromuscular blocking agents at the time of the study procedure
• severe metabolic acidosis (pH \< 7.25) at the time of study procedure.

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

Unity Health Toronto - St. Michael's Hospital

Toronto, Ontario, M5B 1T8, Canada

RECRUITING

MeSH Terms

Conditions

Respiratory Aspiration

Interventions

Tidal Volume

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Inspiratory Capacity; Vital Capacity; Total Lung Capacity; Lung Volume Measurements; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Laurent Brochard

  Unity Health Toronto - St. Michael's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antenor Rodrigues

CONTACT

416-864-5686; Antenor.Rodrigues@unityhealth.to

Irene Telias

CONTACT

irene.telias@unityhealth.to

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2024
• First Posted: March 5, 2024
• Study Start: January 30, 2025
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: May 20, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)