Practice of Ventilation in Critically Ill Patients Without ARDS

Study Overview
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Brief Summary
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The purpose of this international, multicenter study is to determine ventilation practice and outcomes of intubated and ventilated intensive care unit (ICU) patients. Ventilation characteristics and outcomes will be compared between patients without the acute respiratory distress syndrome (ARDS), patients at risk for ARDS, and patients with mild, moderate or severe ARDS. Participating centres worldwide will include adult patients undergoing mechanical ventilation in the ICU during a 7-day period. Patients data will be collected during the first 7 days in the ICU, or until ICU discharge. Follow up is until day 90. Primary endpoint is the tidal volume size used during mechanical ventilation. Secondary endpoints are development of ARDS in patients without ARDS at the onset of mechanical ventilation, worsening of ARDS in patients with ARDS at the onset of mechanical ventilation, pulmonary infection, other pulmonary complications, need for tracheostomy, extra-pulmonary complications, duration of ventilation, length of ICU and hospital stay, and ICU, hospital and 90-day mortality.

Detailed Description
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Research questions: Does ventilation practice, in particular tidal volume size, varies amongst patients without ARDS, patients at risk for ARDS, and patients with mild ARDS? Are tidal volumes used in patients without ARDS higher than those used in patients with ARDS? Are the outcomes in patients without ARDS dependent on the size of tidal volumes? Methods: In this international observational study, consecutive patients in the ICU under mechanical ventilation are eligible for participation. Patients in participating centers will be screened on a daily basis. Patients in mechanical ventilation will be included during a 7-day period, from Monday at 8:00 AM to the next Monday at 7:59 AM (in time zones of the participating centers). The inclusion period will be flexible for participating centers and determined at a later stage together with the study-coordinator. Times points of data collection: Demographic data and baseline data, including severity scores (e.g. APACHE II-scores and SAPS III) and LIPS, are collected from the clinical files on the day of intubation Ventilation settings, gas exchange variables and vital parameters are collected once a daily in the morning, until ventilation is stopped Chest radiography data from available chest X-rays (i.e., no extra chest X-rays are obtained) Predefined complications are recorded from medical chart until discharge from ICU or death, whatever comes first Length of ICU and hospital stay, and ICU, hospital and 90-day mortality Centres: The investigators aim to recruit 40 - 150 centers worldwide. Ethics Approval: National coordinators will be responsible for clarifying the need for ethics approval and applying for this where appropriate according to local policy. Centres will not be permitted to record data unless ethics approval or an equivalent waiver is in place. The investigators expect that in most, if not every participating country, a patient informed consent is not be required. Monitoring: Due to the observational nature of the study, a DSMB is not be necessary. Study Population: Adult patients in the ICU under mechanical ventilation. Data Collection: Data will be collected at inclusion, every day during seven days, day of ICU and hospital discharge and on day 90. Data will be coded by a patient identification number (PIN) of which the code will be kept safe at the local sites. The data will be transcribed by local investigators onto an internet based electronic CRF. Sample Size Calculation: We did not perform a formal sample size calculation, seen the largely descriptive character of this investigation. We expect to collect data from at least 1000 patients, which will be sufficient to test the hypotheses. Statistical Analysis: Patient characteristics will be compared and described by appropriate statistics. Student's t-test or Mann-Whitney U-tests are used to compare continuous variables and chi-squared tests are used for categorical variables. Data are expressed as means (SD), medians (interquartile range) and proportions as appropriate. Comparisons between and within groups are performed using one-way ANOVA and post-hoc analyses for continuous variables. The primary analysis concerns the determination of (variation of) tidal volume size in patients without ARDS. Tidal volume size is compared between predefined patient groups: patients at no risk for ARDS, patients at risk for ARDS, patients with mild ARDS, and patients with moderate or severe ARDS. To identify potential factors associated with outcome like development of ARDS, or worsening of ARDS, development of pulmonary complications, duration of ventilation, or death, univariate analyses are performed. A multivariate logistic regression model is used to identify independent risk factors. A stepwise approach is used to enter new terms into the model, with a limit of p < 0.2 to enter the terms. Time to event variables are analyzed using Cox regression and visualized by Kaplan-Meier. - Organization: The study is conducted by the PROtective VEntilation Network (PROVENet). National co-ordinators will lead the project within individual nations and identify participating hospitals, translate study paperwork, distribute study paperwork and ensure necessary regulatory approvals are in place. They provide assistance to the participating clinical sites in trial management, record keeping and data management. Local coordinators in each site will supervise data collection and ensure adherence to Good Clinical Practice during the trial.

Official Title
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Practice of Ventilation in Critically Ill Patients Without Acute Respiratory Distress Syndrome - An International Observational Study

Conditions
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Mechanical Ventilation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to a participating ICU Intubated in the participating ICU, or in the emergency room or operation room before the present ICU admission Exclusion Criteria: Age < 18 years Receiving only non-invasive ventilation Patients under invasive mechanical ventilation previous to the 7-day period of inclusion Patients transferred from another hospital under invasive mechanical ventilation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mechanical Ventilation<br>Patients under mechanical ventilation in the ICU | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tidal Volume Size | Tidal volume size in milliliters per kilogram of predicted body weight | During mechanical ventilation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other Ventilation Parameters | Plateau and peak pressure, positive end-expiratory pressure, driving pressure, respiratory rate, inspired oxygen fraction, inspiration to expiration ratio, and minute volume | During mechanical ventilation | 
| Development of ARDS | Patients are defined as having ARDS if they met the Berlin criteria for ARDS. | From date of inclusion until the date of first documented ARDS or date of hospital discharge or death from any cause, whichever came first, assessed up to three months | 
| Worsening of ARDS | Defined as any worse in the degree of severity according to Berlin criteria. | From date of inclusion until the date of first documented worsening of ARDS or date of hospital discharge or death from any cause, whichever came first, assessed up to three months | 
| Other Pulmonary Complications | Atelectasis, barotrauma, pleural effusion | From date of inclusion until the date of first documented pulmonary complication or date of hospital discharge or death from any cause, whichever came first, assessed up to three months | 
| Pulmonary Infection | Defined as need of new antibiotics plus at least one of the following criteria: 1) new or changed sputum; 2) new or changed lung opacities on chest X-ray; 3) temperature > 38.3 ºC; or 4) WBC count > 12,000. | From date of inclusion until the date of first documented pulmonary infection or date of hospital discharge or death from any cause, whichever came first, assessed up to three months | 
| Need for Tracheostomy | Need for tracheostomy during hospital stay | From date of inclusion until the date of first documented tracheostomy or date of hospital discharge or death from any cause, whichever came first, assessed up to three months | 
| Extra-Pulmonary Complications | Acute kidney injury, circulatory failure, gastrointestinal failure, acute or exacerbation of chronic heart failure, liver failure, and delirium. | From date of inclusion until the date of first documented extra-pulmonary complication or date of hospital discharge or death from any cause, whichever came first, assessed up to three months | 
| Duration of Mechanical Ventilation | Time between orotracheal intubation and successful extubation; note: in case of intermittent MV via a tracheostomy, every day a patient needs MV counts as one extra day of MV, irrespective of duration of MV that specific day; in case of non-invasive MV, every day a patient needs non-invasive MV counts as one extra day of MV, irrespective of duration of non-invasive MV that specific day. | During mechanical ventilation | 
| Length of Stay in ICU on Day 90 | Time between admission and discharge or death | Until day 90 | 
| Length of Stay in Hospital on Day 90 | Time between admission and discharge or death | Until day 90 | 
| All-cause ICU Mortality | Any death during ICU stay | Until day 90 | 
| All-cause Hospital Mortality | Any death during hospital stay | Until day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanical ventilation, Acute respiratory failure, Acute respiratory distress syndrome