Airway Extubation, Sedation
Conditions
Keywords
Inhaled sedation, Mechanical ventilation, Delirium
Brief summary
The proposal of this study is to compare inhaled sedation with isoflurane administered via the Sedaconda ACD-S system with intravenous sedation with propofol. Patients will be randomized 1:1 to receive either inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous propofol. The primary endpoint is the number of ventilator-free days at 28 days after randomization.
Detailed description
Justification: Isoflurane has recently emerged as an attractive alternative for intensive care unit (ICU) sedation. Due to their favorable pharmaco-kinetic and dynamic profile, this agent has been progressively introduced into clinical practice. Isoflurane has proven to be non-inferior to propofol in terms of efficacy and safety and it has been suggested that it may facilitate ventilator weaning. However, no differences in length of mechanical ventilation were found. These studies have focused on short sedation durations. In fact, long-term effects and outcomes associated with isoflurane for ICU sedation are not yet fully understood. Hypothesis: Inhaled sedation with isoflurane administered via the Sedaconda ACD-S system in critically ill patients leads to a shorter duration of mechanical ventilation at 28 days and a reduced length of ICU stay compared to intravenous sedation with propofol. Main objective: To compare the number of ventilator-free days at day 28 post-randomization between critically ill patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol in critically ill patients expected to require more than 48 hours of invasive mechanical ventilation. Key secondary objective: To compare the number of ICU-free days at day 28 post-randomization in both treatment arms. Secondary objectives: To compare time to extubation after sedation withdrawal, efficacy in maintaining a target level of sedation, compare the percentage of patients requiring one or more additional hypnotics, compare the incidence and duration of delirium at day 28, assess mental, cognitive, and quality of life status at 90 days post-hospital discharge between both treatment groups. Methodology: Phase IV, low-intervention, open-label, multicenter, randomized controlled trial with intention-to-treat analysis including mechanically ventilated patients expected to require a minimum of 48 hours of mechanical ventilation with a RASS score between -3 and -5. Patients will be randomized 1:1 to receive inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous sedation with propofol. A total of 620 patients will be included from a pool of 22 participating centers.
Interventions
DRUGIsoflurane
Inhaled sedation with isoflurane via Sedaconda ACD-S
DRUGPropofol
Intravenous sedation with Propofol 20 mg/ml
Sponsors
Instituto de Investigación Hospital Universitario La Paz
Instituto de Salud Carlos III
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
\- Adult patients receiving mechanical ventilation, with an anticipated duration \>48 hours after randomization, and requiring deep sedation (target RASS between -3 and -5).
Exclusion criteria
* Contraindication to isoflurane or propofol * Patients with maternal ancestry from Venezuela, due to the potential presence of an mt-ND4 gene mutation associated with neurological injury after exposure to certain volatile anaesthetic agents * Significant air leak, defined as a leak exceeding 30% of the delivered minute ventilation * Allergy to isoflurane or propofol * Cardiopulmonary arrest * History of ventricular tachycardia or long QT syndrome * Tidal volume \< 300 mL or PaCO₂ \> 50 mmHg at the time of randomization. * Invasive mechanical ventilation for more than 48 hours at the time of randomization. * Pregnancy * Breast feeding * Acute neurological condition * Patients expected to require repeated surgical interventions during their ICU stay. * ECMO * ECCO2R * Active humidification strictly required * Neuromuscular disease or high spinal cord injury likely to prevent discontinuation of mechanical ventilation due to baseline condition * Requirement for benzodiazepine use for a specific indication * Burns * Life expectancy less than 48 hours, or patients with such a level of severity that death during the ICU stay is considered highly likely. * Any condition (e.g., blindness, deafness, dementia) or language barrier that prevents the administration of delirium or cognitive assessment scales. * Lack of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free days at day 28 from randomization | From randomization until day 28 | Number of days between randomization and day 28 during which the patient is alive and free from invasive mechanical ventilation. Patients who die before day 28, or who remain on mechanical ventilation at day 28, are assigned zero ventilator-free days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Key secondary objective: ICU-free days at day 28 post-randomization | From randomization until day 28 | Number of days between randomization and day 28 during which the patient is alive and free from the ICU. Patients who die before day 28, or remain in the ICU on day 28, are assigned zero ICU-free days. |
| Time to extubation | From randomization until day 28 | Mean number of hours from sedation withdrawal to successful extubation. |
| Administration of rescue sedation | From randomization until day 28 | Number of patients requiring the addition of one or more hypnotics |
| Sedation efficacy | From randomization until extubation or day 28 | Difference between the target sedation level and the actual measured level using Richmond Agitation Sedation Scale (RASS). Possible RASS score ranges from -5 (unarousable) to +4 (combative) |
| Number of Participants With Delirium | From randomization until extubation or day 28 | Number of patients with delirium using the Confusion Assessment Method in ICU (CAM-ICU) |
| Mortality | From randomization to day 60 | All cause mortality at 60 days from randomization |
| Number of Participants With Psychological disorders | at 90 days of hospital discharge | Psychological status assessed using: 1.- Hospital Anxiety and Depression Scale (HADS). score of 8 or greater on the anxiety or depression subscale is used to identify symptoms of clinically significant anxiety or depression. 2.- Impact of Event Scale - Revised (IES-R), a self-report measure designed to assess the severity of post-traumatic stress disorder. Optimal screening threshold established as 1.6 (Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness. Crit Care Med 2020) |
| Number of Participants With Cognitive Disorders | at 90 days of hospital discharge | Cognitive status assessed using Montreal Cognitive Assessment (MoCA) test. Total score ranges from zero to 30. Mild cognitive impairment: 18-25, moderate: 10-17, and severe: less than 10 (Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness. Crit Care Med 2020) |
| Number of Participants With Treatment-Related Adverse Events | From randomization to day 28 | Number of participants who experience at least one adverse event of special interest, deemed by the investigators to be related to the administered hypnotic, including events of mild, moderate, severe intensity, as well as serious adverse events |
Countries
Spain
Contacts
CONTACTJosé M. Añón, MD, PhD
PRINCIPAL_INVESTIGATORJosé M. Añón, MD, PhD
Hospital Universitario La Paz. IdiPAZ
Outcome results
None listed