Efficacy and Safety of Inhaled Isoflurane Delivered Via the Sedaconda ACD-S Compared to Intravenous Propofol for Sedation of Mechanically Ventilated Intensive Care Unit Adult Patients (INSPiRE-ICU2)

Inclusion Criteria:

   - Adults ≥18 years of age;

   - Patients who are anticipated to require >12 hours of invasive mechanical ventilation
   and continuous sedation in the ICU; and

   - Receipt of continuous sedation due to clinical need for sedation to RASS <0.

Exclusion Criteria:

   - Need for RASS -5;

   - Sedation for invasive mechanical ventilation immediately prior to Baseline for >72
   hours;

   - Severe neurological condition before ICU admission that causes the patient to lack
   ability to participate in the study (ie, unable to be assessed for RASS and CPOT);

   - Ventilator tidal volume <200 or >1000 mL at Baseline;

   - Need for extracorporeal membrane oxygenation (ECMO), extracorporeal CO2 removal
   (ECCO2R), high frequency oscillation ventilation (HFOV), or high frequency percussive
   ventilation (HFPV) at Screening;

   - Comfort care only (end of life care);

   - Contraindication to propofol or isoflurane;

   - Known or family history of MH;

   - Severe hemodynamic compromise, defined as the need for norepinephrine ≥0.3 mcg/kg/min
   (or equivalent vasopressor dose) to maintain blood pressure within acceptable range,
   assumed to be mean arterial pressure ≥65 mmHg unless prescribed clinically;

   - Allergy to isoflurane or propofol, or have propofol infusion syndrome.

   - History of ventricular tachycardia/Long QT Syndrome;

   - Requirement of IV benzodiazepine or barbiturate administration for seizures or
   dependencies, including alcohol withdrawal

   - Neuromuscular disease that impairs spontaneous ventilation (eg, C5 or higher spinal
   cord injury, amyotrophic lateral sclerosis, etc);

   - Concurrent enrollment in another study that, in the Investigator's opinion, would
   impact the patient's safety or assessments of this study;

   - Participation in other study involving investigational drug(s) or devices(s) within 30
   days prior to Randomization;

   - Anticipated requirement of treatment with continuous infusion of a neuromuscular
   blocking agent for >4 hours;

   - Female patients who are pregnant or breast-feeding;

   - Imperative need for continuous active humidification through mechanical ventilation
   circuit;

   - Attending physician's refusal to include the patient; or

   - Inability to obtain informed consent.