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.