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-ICU1)

Inclusion Criteria:

• Adults ≥18 years of age;
• Patients who are anticipated to require >12 hours of invasive mechanical ventilationand 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 >72hours;
• Severe neurological condition before ICU admission that causes the patient to lackability 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 percussiveventilation (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 ordependencies, including alcohol withdrawal
• Neuromuscular disease that impairs spontaneous ventilation (eg, C5 or higher spinalcord injury, amyotrophic lateral sclerosis, etc);
• Concurrent enrollment in another study that, in the Investigator's opinion, wouldimpact the patient's safety or assessments of this study;
• Participation in other study involving investigational drug(s) or devices(s) within 30days prior to Randomization;
• Anticipated requirement of treatment with continuous infusion of a neuromuscularblocking agent for >4 hours;
• Female patients who are pregnant or breast-feeding;
• Imperative need for continuous active humidification through mechanical ventilationcircuit;
• Attending physician's refusal to include the patient; or
• Inability to obtain informed consent.