Exogenous Ketone Supplementation in ICU Delirium

Inclusion criteria:

1. Adult patients (≥18 years old) admitted to the medical intensive care unit.
2. Current ICU admission with anticipated ICU stay ≥24 hours.
3. Enteral access in place, planned enteral access placement, or PO intake appropriate, and the ability to receive enteral dosing within 24 hours of enrollment.
4. Ability to complete delirium assessments (CAM-ICU feasible) at time of enrollment.

Exclusion criteria:

1. Severe metabolic acidosis at screening: blood gas pH \<7.20 or bicarbonate \< 8 mmol/L.
2. Diabetic ketoacidosis as an ICU admission diagnosis or hyperketonemia from any ketoacidosis state.
3. Hypoglycemia as an ICU admission diagnosis or glucose \<60 mg/dL.
4. Patients with a history of type 1 diabetes mellitus.
5. Hemoglobin \<7.0.
6. Fulminant hepatic failure or International Normalized Ratio (INR) \> 3, when not attributable to therapeutic anticoagulation or another clearly non-hepatic cause.
7. Refractory shock, defined as a sustained norepinephrine requirement ≥30 µg/min, or norepinephrine-equivalent vasopressor dose, despite appropriate resuscitation, or ongoing escalation of vasopressor support at the time of enrollment.
8. Pregnancy (positive urine/serum hCG at screening or known pregnancy) or breastfeeding.
9. Uncontrolled ileus or gastrointestinal condition, such as an upper gastrointestinal bleed, preventing enteral dosing.
10. ADH/ALDH inhibitors (e.g., fomepizole, disulfiram) use in the prior 7 days or planned.
11. Severe dementia or neurodegenerative disease, defined as either impairment that prevents the patient from living independently at baseline or IQCODE \>4.5. This exclusion also pertains to mental illnesses requiring long-term institutionalization, acquired or congenital intellectual disability, severe neuromuscular disorders, Parkinson's disease, and Huntington's disease. It also excludes patients with severe deficits due to structural brain diseases such as stroke, intracranial hemorrhage, cranial trauma, malignancy, anoxic brain injury, or cerebral edema.
12. Benzodiazepine dependency or alcohol dependency based on the medical team's decision to institute a specific treatment plan involving benzodiazepines or barbiturates (either as continuous infusions or intermittent intravenous boluses) for this dependency.
13. Active seizures during this ICU admission being treated with intravenous benzodiazepines.
14. 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 hours of screening).
15. Admission to ICU only for post-operative monitoring or frequent neurologic assessments.
16. Incarcerated status.
17. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Attending physician refusal.
18. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Patient and/or surrogate refusal.
19. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Patient unable to consent and no surrogate available.
20. Current enrollment in a study that does not allow co-enrollment.