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.