Inhaled Sedation in Critically Ill Patients
- Conditions
- SedationAirway Extubation
- Interventions
- Registration Number
- NCT07000526
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 620
- Adult patients receiving mechanical ventilation, with an anticipated duration >48 hours after randomization, and requiring deep sedation (target RASS between -3 and -5).
- Contraindication to isoflurane or propofol
- 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
- ECMO
- ECCO2R
- Active humidification strictly required
- Burns
- Lack of informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Study group Isoflurane Inhaled sedation with Isoflurane. Initial dose: 3 mL/h. Gradual dose increase until target RASS is achieved. Do not exceed 14 mL/h. Guided by end tidal isoflurane concentration (EtISO), the recommended maximum dose for prolonged use is 1%. Short periods at up to 1.5% may be considered. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added. Control group Propofol Intravenous sedation with propofol (20 mg/mL). Initial dose: 0.5-1 mg/kg/h. Gradual dose increase until target RASS is achieved. Do not exceed 4 mg/kg/h. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added.
- Primary Outcome Measures
Name Time Method Ventilator-free days at day 28 from randomization From 48 hs after 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 Outcome Measures
Name Time Method Key secondary objective: ICU-free days at day 28 post-randomization From 48 hs after 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 48 hs after randomization until day 28 Mean number of hours from sedation withdrawal to successful extubation.
Administration of rescue sedation From 48 hs after randomization until day 28 Number of patients requiring the addition of one or more hypnotics
Sedation efficacy From 48 hs after 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 48 hs after 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
Trial Locations
- Locations (21)
Hospital Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Rey Juan Carlos
🇪🇸Madrid, Spain
Hospital Reina Sofía
🇪🇸Murcia, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario Joan XXIII
🇪🇸Tarragona, Spain
Hospital Universitario de Toledo
🇪🇸Toledo, Spain
Hospital Vega Baja
🇪🇸Orihuela, Alicante, Spain
Hospital Universitario Doctor José Molina Orosa
🇪🇸Arrecife, Lanzarote-Canary Islands, Spain
Hospital Universitario de Albacete
🇪🇸Albacete, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Corporacio Sanitaria Parc Taulí
🇪🇸Barcelona, Spain
Hospital Universitario de Bellvitge
🇪🇸Barcelona, Spain
Hospital Universitario Valle de Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario Santa Lucía
🇪🇸Cartagena, Spain
Hospital Arnau de Vilanova
🇪🇸Lérida, Spain
Hospital Univeritario Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Universitario de Getafe
🇪🇸Madrid, Spain
Hospital Universitario de la Princesa
🇪🇸Madrid, Spain
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Rio Hortega
🇪🇸Valladolid, Spain