Patients suffering lung failure, possibly from COVID-19 or hypoxic lung failure, will need life-saving support from a breathing machine. Any patient needing this support requires drugs to keep them sleepy, or "sedated" to be comfortable on this machine. Sedation is made possible by using drugs given through a vein. Unfortunately, these drugs are in short supply worldwide due to the high number of COVID-19 patients needing these machines. Another way to provide sleep is by using gases that are breathed in. These are used every day in operating rooms to perform surgery. These gases, also called "inhaled agents" can also be used in intensive care units and may have several important benefits for patients and the hospital. Research shows they may reduce swelling in the lung and increase oxygen levels, which allows patients to recover faster and reduce the time spent on a breathing machine. In turn, this allows the breathing machine to be used again for the next sick patient. These drugs may also increase the number of patients who live through their illness. Inhaled agents are widely available and their use could dramatically lesson the pressure on limited drug supplies. This research is a study being carried out in a number of hospitals that will compare how well patients recover from these illnesses depending on which type of sedation drug they receive. The plan is to evaluate the number who survive, their time spent on a breathing machine and time in the hospital. This study may show immediate benefits and may provide a cost effective and practical solution to the current challenges caring for patients and the hospital space, equipment and drugs to the greatest benefit. Furthermore, the study will be investigating inflammatory profile and neuro-cognitive profiles in ventilated patients. Finally, this trial will be a team of experts in sedation drugs who care for patients with proven or suspected COVID-19 who need lifesaving treatments.
Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective (non-randomized) cohort study conducted in ICUs and ICU enabled environments caring in critically ill COVID-19 and non-COVID hypoxic respiratory failure patients. Participants will be mechanically ventilated and will be variably randomized, within 72 hours of start of sedation treatment, in a 1:1 ratio to either an intravenous or inhaled volatile-based sedation arm depending on availability of sedative drugs for both arms. Stratification will be done by: 1. Age ≥ 65 years 2. participating centre 3. PaO2/FiO2 ratio of 150 Patients who cannot be randomized (due to technical or resource issues in some areas of the hospital) will be entered into the parallel prospective (non-randomized) cohort study and will receive intravenous or inhaled sedation as able in their designated unit. Sedation will be administered according to standard sedation practice and in keeping with current guidelines. Participants will be followed: * daily in ICU until 30 days after enrollment, ICU discharge or death, whichever occurs first; * at 30 days after last dose of drug administration by telephone or through the hospital healthcare database; * at 60 days, 90 days, and 365 days after enrollment by telephone and/or through data linkages with a provincial or hospital or state healthcare database; * Participants will have the option to participate in the neuro-cognitive and / or biomarker assessments
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
800
Isoflurane will be administered using an inhalation device
Sevoflurane will be administered using an inhalation device
University of Alberta Hospital
Edmonton, Alberta, Canada
Grey Nuns Community Hospital
Edmonton, Alberta, Canada
London Health Sciences Centre - University Hospital
London, Ontario, Canada
London Health Sciences Centre - Victoria Hospital
London, Ontario, Canada
The Ottawa Hospital
Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
University Health Network - Toronto General Hospital
Toronto, Ontario, Canada
University Health Network - Toronto Western Hopsital
Toronto, Ontario, Canada
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, Canada
McGill University Health Centre - Royal Victoria Hospital
Montreal, Quebec, Canada
...and 3 more locations
Hospital Mortality
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant hospital mortality as compared to standard intravenous sedation regimen with a 10% difference between groups for 758 participants.
Time frame: 365 days
Ventilator-Free Days
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant ventilation outcomes after 30 days post enrollment, as compared to standard intravenous sedation regimen for 200 participants
Time frame: 30 days
ICU-Free Days
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant time spent in ICU, 30 days post enrollment, as compared to standard intravenous sedation regimen for 128 participants
Time frame: 30 days
Participant Quality of Life at 3 months after discharge
Does the use of inhaled volatile anesthetic-based sedation regimen improve participant quality of life outcomes at 3 months post discharge as compared to standard intravenous sedation regimen for 144 participants. To evaluate the quality of life, the EuroQol-5 Dimensional (EQ5D) survey will be completed at 90 days.
Time frame: 90 days
Delirium and Coma Free Days
To evaluate the days alive and free from delirium and coma while in ICU for 14 days after enrollment
Time frame: 14 days
Median Daily Oxygenation
To evaluate participant median daily oxygenation (PaO2/FiO2) at 3 days post enrollment
Time frame: 3 days
Adjunctive ARDS therapies
To evaluate participant need for adjunctive ARDS therapies (prone, nitric oxide, paralysis, ECMO) during ICU stay
Time frame: 30 days
Hospital-Free Days
To evaluate the number of hospital-free days for participants, 60 days after enrollment
Time frame: 60 days
Disability
To evaluate participant disability at 3 and 12 months post discharge. The World Health Organization Disabiltity Assessment Score (WHODAS 2.0) will be completed at both timepoints. The scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3) and "extreme" (4) - are summed. This method is referred to as simple scoring because the scores from each of the items are simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items.
Time frame: 365 days
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