Clinical trial NCT03447288: Incidence of Dyssynchronies in Early ARDS
Official title: Incidence of Dyssynchronous Spontaneous Breathing Effort, Breath-stacking and Reverse Triggering in Early ARDS
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: ARDS
Acute Hypoxemic Respiratory Failure
Keywords: Dyssynchrony
Breath-stacking
Asynchrony
Reverse Triggering
Mechanical Ventilation
Sedation
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
First posted: 2018-02-27
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with moderate to severe acute hypoxemic respiratory failure (ARDS and non-ARDS) under sedation and mechanical ventilation.

Brief summary: Patients sedated under mechanical ventilation with acute hypoxemic respiratory failure with a PaO2/FiO2 equal or less than 200mmHg (Acute Respiratory Distress Syndrome, ARDS and non-ARDS) will be included in the study early in the course of the disease (first week of mechanical ventilation). At enrollment, data on the clinical condition of the patient will be recorded together with ventilation settings: ventilation mode, the fraction of inspired oxygen (FiO2), PEEP, tidal volume, set pressure, respiratory rate, time of the respiratory cycle, recent blood gas parameters.

Airway pressure, flow, and esophageal pressure (or alternatively electrical activity of the diaphragm, Eadi) will be recorded 3 times a day for 7 days:

1. Period 1 (morning): duration 20-30 minutes
2. Period 2 (afternoon): duration 20-30 minutes
3. Period 3 (evening / night): duration 20-30 minutes

Registration will be ended at extubation, death or at eight days from the first recording.

Monitoring of vital parameters (hemodynamic and respiratory) will be continuous throughout the duration of the study, as per normal clinical practice. All drugs used during the day of the measurements will be recorded. The patient will then be followed until discharge from the ICU and after 60 days of discharge to evaluate mortality.

As an ancillary study, in a subgroup of patients continuous simplified measurement of respiratory recordings together with hourly clinical data on sedation and extended simplified polysomnography recordings will be performed within the first 7 days from inclusion.

The analysis of the recorded waveforms will be performed in a single center by a centralized system that will quantify dyssynchrony and its intensity, calculate pressure time product, collect clinical and physiological data and outcome, and investigate possible correlations.

Detailed description: Measurements

Physiological measurements Airway pressure, esophageal pressure, electrical activity of the diaphragm and flow

1. Flow and airway pressure signal will be recorded from the ventilators by connecting the ventilator to a laptop computer if possible. Recording these data simultaneously with esophageal pressure or electrical activity of the diaphragm (see later in protocol for details) could be technically unfeasible. In this case, a flow sensor and an additional port for pressure measurement will be connected to the endotracheal tube proximal to the Y connector (without interfering with patient's breathing). Both, flow sensor and pressure port will be connected to differential pressure transducers respectively. Signals will be acquired with at least 100 Hz sampling.
2. In centers used to perform esophageal pressure measurements, an esophageal catheter will be inserted as per usual clinical practice, checked for accuracy with an occlusion test, and connected to a 3 ways stopcock and a pressure transducer. The occlusion test will be recorded and performed before any new recordings. Any ventilator can be used if an esophageal pressure is used.
3. If available, in centers used to record or monitor the electrical activity of the diaphragm, instead of an esophageal catheter, the electrical activity of the diaphragm will be provided by a catheter dedicated to the monitoring of the electrical activity of the diaphragm, or EaDi, on a Servo-I or Servo-U ventilator (Maquet©, Lund, Sweden). This catheter is formally designed to be used for a specific mode of ventilation called Neurally Adjusted Ventilatory Assist (NAVA) but here will be used for monitoring purposes only (NAVA catheter). In such cases a specific software (Servotracker, Maquet) may be used to record all signals from the ventilator.
4. In case the patient has been enrolled but the esophageal catheter cannot be placed or is contraindicated, the recordings will be limited to airway pressure and flow. Each centre should have a minimum of 5 patients with esophageal catheter or electrical activity recording.
5. As an ancillary study, in a subgroup of patients, simplified recordings will be obtained only flow and airway pressure signals will be performed continuously directly taken from the ventilator by connecting the ventilator to a laptop computer equipped with a special software for off line analysis (Better Care ©, Sabadell, Spain).
6. Occlusion pressure (or pressure at 0.1 sec, P0.1) as an index of respiratory drive. In patients triggering the ventilator, the P0.1 will be analyzed from the tracings. The only condition to have reliable measurements is to use a pressure triggering, not a flow triggering.

As an ancillary study, in a subgroup of patients, a simplified extended polysomnography recording will be performed during the first 7 days after inclusion using a home polysomnography device (Prodigy, CerebraHealth ©, Canada) equipped with 2 frontal EEG a reference electrode to the mastoid, EMG, and electrooculogram.

Data collection

At the beginning of the recordings, ventilatory settings will be collected: ventilator brand, mode of ventilation and settings including: FiO2, PEEP, set and real tidal volume (or pressure), set and real respiratory rate, maximum inspiratory flow, inspiratory time, Glasgow coma scale and Richmond Agitation Sedation Scale (RASS) or Riker Sedation Agitation Scale (SAS). Any medications used at the day of the measurement and before will be collected especially neuromuscular blocking agents, sedatives (brands and doses), opiates and vasopressors including dose, duration of the treatment and date of last use. Investigators will also collect clinical characteristics of the patients (SAPS and SOFA at ICU admission and at the day of the recording, main ARDS or AHRF etiology and risk factors, age, gender, weight, height, days of mechanical ventilation, patient's position -supine vs prone-, kidney and liver function). Other comorbidities will be recorded, with special emphasis in the ones that could affect the incidence of the studied phenomenon, such as: COPD, lung transplant or any neuromuscular condition that could affect the respiratory drive or respiratory muscle function.

Patients will be followed up to get the total duration of mechanical ventilation, ICU length of stay, day of the first weaning attempt, day of tracheotomy if any, status at ICU discharge (alive or death) and at hospital discharge and at day 60.

Eligibility criteria: Inclusion Criteria:

* Moderate and severe ARDS and AHRF, according to the Berlin definition. The absence of the Chest X-Ray criterion (e.g. unilateral disease) or the presence of primary cardiac dysfunction will define AHRF.
* Continuous intravenous sedation
* Deep sedation: Richmond Agitation Sedation Scale (RASS) ≤ -3 or Riker Sedation-Agitation Scale (SAS) ≤ 3

Exclusion Criteria:

* \<18 years
* Patients with a significant bronchopleural fistula
* Pure COPD exacerbation
* Patients on chronic home ventilation

Primary outcomes:
measure: Prevalence of dyssynchrony
timeFrame: Within 1 Year
Secondary outcomes:
measure: Intensity of dyssynchrony
timeFrame: Within 1 Year
measure: Correlation of clinical outcome with intensity of dyssynchrony
timeFrame: Within 1 Year
measure: Impact of reverse triggering on breathing effort
timeFrame: Within 1 Year
measure: Quantification of spontaneous breathing efforts associated with dyssynchronies.
timeFrame: Within 1 Year
measure: Association between pH and Dyssynchrony
timeFrame: Within 1 Year
measure: Association between sedation and Dyssynchrony
timeFrame: Within 1 Year
measure: Association between sedatives and Dyssynchrony
timeFrame: Within 1 Year
measure: Clusters of dyssynchronies
timeFrame: Within 1 Year
measure: Sleep depth measured with EEG
timeFrame: Within 1 Year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St Michael's hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
city: Angers
country: France
facility: Centre Hospitalier Universitaire - CHU Angers
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Heraklion
country: Greece
facility: University Hospital of Heraklion
city: Ferrara
country: Italy
facility: University of Ferrara
city: Foggia
country: Italy
facility: Azienda Ospedaliero - Universitaria OORR Ospedali Riuniti di Foggia
city: Milano
country: Italy
facility: ASST Santi Paolo e Carlo
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Amsterdam
country: Netherlands
facility: VU University Medical Centre Amsterdam
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Tainan City
country: Taiwan
facility: National Cheng-Kung University and Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
Study officials:
affiliation: Unity Health Toronto
name: Laurent Brochard, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bianchi I, Grassi A, Pham T, Telias I, Teggia Droghi M, Vieira F, Jonkman A, Brochard L, Bellani G. Reliability of plateau pressure during patient-triggered assisted ventilation. Analysis of a multicentre database. J Crit Care. 2022 Apr;68:96-103. doi: 10.1016/j.jcrc.2021.12.002. Epub 2021 Dec 21.
citation: Pham T, Montanya J, Telias I, Piraino T, Magrans R, Coudroy R, Damiani LF, Mellado Artigas R, Madorno M, Blanch L, Brochard L; BEARDS study investigators. Automated detection and quantification of reverse triggering effort under mechanical ventilation. Crit Care. 2021 Feb 15;25(1):60. doi: 10.1186/s13054-020-03387-3.