Inhaled isoflurane versus IV propofol for sedation of ventilated ICU patients

Inhaled Sedation in Critically Ill Patients: a Multicentre Randomized Clinical Trial

This trial will test whether inhaled isoflurane delivered through the Sedaconda ACD‑S shortens time on the ventilator compared with intravenous propofol in adults needing deep sedation and expected to require mechanical ventilation for more than 48 hours.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 620 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Instituto de Investigación Hospital Universitario La Paz (Academic / other)
• Locations: 22 sites (Orihuela, Alicante and 21 other locations)
• Trial ID: NCT07000526 on ClinicalTrials.gov

What this trial studies

This randomized, phase 4 trial assigns adult ICU patients 1:1 to inhaled isoflurane via the Sedaconda ACD‑S device or to standard intravenous propofol for deep sedation. The primary outcome is ventilator-free days at 28 days after randomization, with key secondary outcomes including ICU-free days, time to extubation after sedation withdrawal, and adequacy of sedation. Eligible patients are adults on invasive mechanical ventilation expected to need more than 48 hours of ventilation with a target RASS between -3 and -5 and without contraindications such as ECMO, pregnancy, or severe respiratory derangements. The trial emphasizes longer sedation periods to address gaps left by earlier short-duration studies of inhaled ICU sedation.

Who should consider this trial

Good fit: Adults on invasive mechanical ventilation who require deep sedation (RASS -3 to -5), are expected to need ventilation for more than 48 hours, and have no contraindications to isoflurane or propofol are the intended participants.

Not a fit: Patients with contraindications to either drug, those already ventilated for more than 48 hours, patients on ECMO or ECCO2R, pregnant or breastfeeding individuals, or those with acute neurological conditions or severe respiratory derangements are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, inhaled isoflurane could reduce duration of mechanical ventilation and ICU stay, lowering complication risk and speeding patient recovery.

How similar studies have performed: Prior short-duration ICU studies have shown isoflurane to be non-inferior to propofol and have suggested it may facilitate weaning, but long-term outcomes after prolonged inhaled sedation remain largely untested.

Eligibility criteria

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
* 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

Where this trial is running

Orihuela, Alicante and 21 other locations

• Hospital Vega Baja — Orihuela, Alicante, Spain (Recruiting)
• Hospital Universitario Doctor José Molina Orosa — Arrecife, Lanzarote-Canary Islands, Spain (Not_yet_recruiting)
• Hospital Universitario de Albacete — Albacete, Spain (Not_yet_recruiting)
• Hospital Germans Trias i Pujol — Badalona, Spain (Not_yet_recruiting)
• Corporacio Sanitaria Parc Taulí — Barcelona, Spain (Not_yet_recruiting)
• Hospital Universitario de Bellvitge — Barcelona, Spain (Not_yet_recruiting)
• Hospital Universitario Valle de Hebron — Barcelona, Spain (Recruiting)
• Hospital General Universitario Santa Lucía — Cartagena, Spain (Not_yet_recruiting)
• Hospital Arnau de Vilanova — Lleida, Spain (Not_yet_recruiting)
• Hospital Universitario La Paz — Madrid, Spain (Recruiting)
• Hospital Univeritario Puerta de Hierro — Madrid, Spain (Not_yet_recruiting)
• Hospital Universitario de Getafe — Madrid, Spain (Not_yet_recruiting)
• Hospital Universitario de la Princesa — Madrid, Spain (Recruiting)
• Hospital Universitario Gregorio Marañon — Madrid, Spain (Not_yet_recruiting)
• Hospital Universitario Infanta Leonor — Madrid, Spain (Recruiting)
• Hospital Universitario Rey Juan Carlos — Madrid, Spain (Recruiting)
• Hospital Reina Sofía — Murcia, Spain (Not_yet_recruiting)
• Hospital Universitario Virgen de la Arrixaca — Murcia, Spain (Not_yet_recruiting)
• Hospital Universitario Joan XXIII — Tarragona, Spain (Not_yet_recruiting)
• Hospital Universitario de Toledo — Toledo, Spain (Not_yet_recruiting)
• Hospital Clínico Universitario de Valencia — Valencia, Spain (Recruiting)
• Hospital Universitario Rio Hortega — Valladolid, Spain (Recruiting)

Study contacts

• Principal investigator: José M. Añón, MD, PhD — Hospital Universitario La Paz. IdiPAZ
• Study coordinator: José M. Añón, MD, PhD

Conditions Sedation; Airway Extubation; Inhaled sedation; Mechanical ventilation; Delirium