Practice of Ventilation in Critically Ill Patients Without ARDS

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

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.

Research questions:

1. Does ventilation practice, in particular tidal volume size, varies amongst patients without ARDS, patients at risk for ARDS, and patients with mild ARDS?

2. Are tidal volumes used in patients without ARDS higher than those used in patients with ARDS?

3. 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:

1. 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

2. Ventilation settings, gas exchange variables and vital parameters are collected once a daily in the morning, until ventilation is stopped

3. Chest radiography data from available chest X-rays (i.e., no extra chest X-rays are obtained)

4. Predefined complications are recorded from medical chart until discharge from ICU or death, whatever comes first

5. 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.

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