Intervention: Propofol
Trial phase: Phase 3
ATC code: N01AX10
SMILES: CC(C)c1cccc(C(C)C)c1O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 438
Group description: Route and Concentration. The study drug will be administered intravenously (IV) by continuous infusion at concentrations of 10 mg/mL propofol. Patients will only receive study drug while in the ICU and on mechanical ventilation, and thus will be monitored with continuous telemetry as per usual ICU practice.

Dosing Range. Study drug dose will be titrated in a double-blind manner according to clinical effect to achieve a "goal" or "target" Richmond Agitation Sedation Score set by the managing clinical team. For patients in the propofol group, dose will range from 5-50 mcg/kg/min.

Propofol: For patients in the propofol group, dose will range from 5-50 mcg/kg/min. For example, a 70 kg patient would receive 10.5 mL of study drug per hour, which would provide 25 mcg/kg/min of propofol. This dose range has been selected after literature review and discussions with critical care practitioners, investigational pharmacists, and the MENDS2 study steering committee.
Eligibility criteria:
Inclusion Criteria:

Consecutive patients will be eligible for inclusion in the MENDS2 study if they are: [1] adult patients (≥18 years old) [2] in a medical and/or surgical ICU and [3] on MV and requiring sedation and [4] have suspected or known infection

Exclusion Criteria:

Patients will be excluded (i.e., not consented) for any of the following reasons:

Rapidly resolving organ failure, indicated by planned immediate discontinuation of MV, at time of screening for study enrollment
Pregnant or breastfeeding
Severe dementia or neurodegenerative disease, defined as either impairment that prevents the patient from living independently at baseline or IQCODE >4.5, measured using a patient's qualified surrogate. This exclusion also pertains to mental illnesses requiring long-term institutionalization, acquired or congenital mental retardation, severe neuromuscular disorders, Parkinson's disease, and Huntington's disease. It also excludes patients in coma or with severe deficits due to structural brain diseases such as stroke, intracranial hemorrhage, cranial trauma, malignancy, anoxic brain injury, or cerebral edema.
History of 2nd or 3rd degree heart block, bradycardia < 50 beats/minute, pacemaker for bradyarrythmias or uncompensated shock.If patient has a pacemaker for bradyarrythmias, then patient does not meet this exclusion criterion and may be enrolled.
Benzodiazepine dependency or history of alcohol dependency based on the medical team's decision to institute a specific treatment plan involving benzodiazepines (either as continuous infusions or intermittent intravenous boluses) for this dependency.
Active seizures during this ICU admission being treated with intravenous benzodiazepines.
Expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family/medical team (e.g., likely to withdraw life support measures within 24 hrs of screening)
Inability to understand English or deafness or vision loss that will preclude delirium evaluation. The inability to understand English (for example in Spanish-only or Mandarin-only speaking patients) will not result in exclusion at centers where the research staff is proficient and/or translation services are actively available in that particular language; these patients will not be followed in the long-term follow-up phase of the trial since the testing materials are primarily available only in English. Patients with laryngectomies and those with hearing deficits are eligible for enrollment if their medical condition permits them to communicate with research staff.

Inability to obtain informed consent from an authorized representative within 48 hours of meeting all inclusion criteria, i.e., developing sepsis and qualifying organ dysfunction criteria for the following reasons:

Attending physician refusal.
Patient and/or surrogate refusal.
Patient unable to consent and no surrogate available.
48-hour period of eligibility was exceeded before the patient was screened.
Prisoners.
Medical team following patient unwilling to use the sedation regimens.
Documented allergy to propofol or dexmedetomidine.
Current enrollment in a study that does not allow co-enrollment or that uses delirium as a primary outcome.
Patients who are on muscle relaxant infusions at time of screening with plans to maintain paralysis >48 hours.
Greater than 96 hours on mechanical ventilation prior to meeting all inclusion criteria.