BEARDS: Incidence of Dyssynchronies in Early ARDS

Sponsor

Unity Health Toronto (Other)

Overall Status

Recruiting

CT.gov ID

NCT03447288

Collaborator

(none)

300

Enrollment

Locations

66.5

Anticipated Duration (Months)

21.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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:

Period 1 (morning): duration 20-30 minutes
Period 2 (afternoon): duration 20-30 minutes
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.

Condition or Disease	Intervention/Treatment	Phase
ARDS Acute Hypoxemic Respiratory Failure

Detailed Description

Measurements

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

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.
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.
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.
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.
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).
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.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Incidence of Dyssynchronous Spontaneous Breathing Effort, Breath-stacking and Reverse Triggering in Early ARDS

Actual Study Start Date :

Jan 15, 2017

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Outcome Measures

Primary Outcome Measures

Prevalence of dyssynchrony [Within 1 Year]
For each patients, the number of dyssynchrony (reverse triggering, breath stacking, short cycles) will be counted over the recorded period. An asynchrony index, (number of dyssynchrony divided by the total number of breaths) as well as the number of dyssynchrony per minute will be calculated globally and for each dyssynchrony type. Patients with ARDS will be compared to patients with AHRF. Patients with severe ARDS or severe AHRF (<120) will be compared to less severe patients.

Secondary Outcome Measures

Intensity of dyssynchrony [Within 1 Year]
Assessement of the frequency and magnitude of effort assessed by esophageal pressure or electrical activity of he diaphragm for each type of dyssynchrony
Correlation of clinical outcome with intensity of dyssynchrony [Within 1 Year]
Outcomes will be the duration of mechanical ventilation (in days); the number of ventilator-free days at day 28 (number of days alive without mechanical ventilation in 28 days; death equals 0 ventilator-free days); ICU survival and hospital survival. For each type of dyssynchrony, the outcomes will be correlated with the intensity of dyssynchrony. Intensity of dyssynchrony will be based on the dyssynchrony index above a minimal level of effort for each dyssynchrony. The outcomes above several thresholds of dyssynchrony index (10%, 30%, 50%) will be compared.
Impact of reverse triggering on breathing effort [Within 1 Year]
The breathing effort (pressure-time product) will be calculated and its value will be compared for breaths with and without reverse triggering.
Quantification of spontaneous breathing efforts associated with dyssynchronies. [Within 1 Year]
For each dyssynchrony found, the effort measured by the pressure-time product using esophageal pressure will be calculated. And the clinically relevant dyssynchronies will be determined based on a minimal amount of effort.
Association between pH and Dyssynchrony [Within 1 Year]
Arterial pH will be compared at different values of dyssynchrony index above a minimal level (10%, 30% and 50%).
Association between sedation and Dyssynchrony [Within 1 Year]
Level of sedation (assessed either Sedation Agitation Score "SAS" or the Richmond Agitation and Sedation Scale "RASS") by the will be compared at different values of dyssynchrony index above a minimal level (10%, 30% and 50%).
Association between sedatives and Dyssynchrony [Within 1 Year]
Values of dyssynchrony index above a minimal level will be compared between patients receiving primarily propofol versus benzodiazepines.
Clusters of dyssynchronies [Within 1 Year]
Timing of detection of dyssynchrony
Sleep depth measured with EEG [Within 1 Year]
As part of an ancillary exploratory study, various measures of brain activity, using EEG derived parameters including distribution of sleep depth using an automated scoring system named Odds Ratio Product (ORP) will be studied. ORP score ranges from 0 (corresponding to deep sleep) to 2.5 (corresponding to full wakefulness).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St Michael's hospital	Toronto	Ontario	Canada	M5B 1W8
2	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
3	Beijing Tiantan Hospital, Capital Medical University	Beijing		China	100050
4	Centre Hospitalier Universitaire - CHU Angers	Angers		France	49933
5	Universitätsklinikum Schleswig-Holstein	Kiel		Germany	24105
6	University Hospital of Heraklion	Heraklion		Greece	711 10
7	University of Ferrara	Ferrara		Italy
8	Azienda Ospedaliero - Universitaria OORR Ospedali Riuniti di Foggia	Foggia		Italy	71122
9	ASST Santi Paolo e Carlo	Milano		Italy
10	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano		Italy
11	VU University Medical Centre Amsterdam	Amsterdam		Netherlands	1007 MB
12	Vall d'Hebron University Hospital	Barcelona		Spain
13	National Cheng-Kung University and Hospital	Tainan City		Taiwan	704
14	Siriraj Hospital	Bangkok		Thailand	10700