Safety of prolonged, intermittent supplementation of enteral ketone esters in critically ill adult patients Other
Conditions
Interventions
Ten critically ill patients will all receive 3-hydroxybutyrate via a gastric tube every 2 hours, for a total of 7 doses per day. This will be followed by a 12-hour therapy-free interval after the last
Sponsors
Universitair Ziekenhuis Leuven
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained 2. At least 18 years of age at the time of signing the Informed Consent Form (ICF) 3. Patient expected to stay at the ICU for at least 6 days after start of the first 3HHB administration 4. The presence of a gastric feeding tube
Exclusion criteria
Exclusion criteria: 1. Therapy restriction code 2. Patients refusing blood transfusion upon ICU admission will be considered as having a therapy restriction upon admission and will not be included 3. Expected to die within 48 hours after screening (= moribund patients) 4. No arterial and central venous line, or expected to have one of these lines removed before the end of the study period (= not critically ill enough to be representative for the future target population, and no possibility to take blood samples without additional venapuncture) 5. Contraindication for enteral drug administration 6. Readmission to the ICU after previous inclusion in the RCT 7. Inborn metabolic disease 8. Clinical need for a ketogenic diet in ICU 9. Underweight (BMI< 18.5 kg/m²) or admitted with complications due to anorexia nervosa 10. Known to be pregnant or lactating 11. ICU admission with diabetic ketoacidosis or hyperosmolar hyperglycemic state 12. Acute or acute on chronic liver failure 13. High intravenous glucose need to prevent spontaneous hypoglycemia 14. Metabolic acidosis (pH <7.30 and bicarbonate <18 mmol/l)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of plasma 3-hydroxybutyrate concentrations above 1 mmol/L during the 16-hour treatment interval (from first bolus to the expected complete clearance of 3HB, 4h post last bolus), measured by LC-MS/MS | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Plasma 3-hydroxybutyrate levels during the 6 day intervention window (E), measured by LC-MS/MS 2. Plasma levels of 3HHB and metabolite 1,3-butanediol during the 6 day intervention window (E), measured by LC-MS/MS 3. Urine levels of 3HHB, 3-hydroxybutyrate and 1,3-butanediol during the 6 day intervention window (E), measured by LC-MS/MS 4. Blood glucose concentrations during the 6 day intervention window (E), measured by blood-gas-analyzer on ICU 5. Incidence of severe (<40 mg/dl) hypoglycemia during the 6 day intervention window (S), measured by blood-gas-analyzer on ICU 6. Incidence of ketoacidosis during the 6 day intervention window, defined as a new onset metabolic acidosis with arterial pH less than 7.25 and serum bicarbonate less than 15 mmol/L occurring simultaneously with a 3HB level of at least 10 mmol/L (S), measured by blood-gas-analyzer on ICU 7. Incidence of 3HB levels exceeding 10 mmol/L at any time, without concomitant acidosis, during the 6 day intervention window (S), measured with a ketone stick test on arterial blood in the ICU 8. Incidence of accumulation (pre-administration trough levels exceeding 5 mmol/L) without ketoacidosis during the 6 day intervention window (S), measured with a ketone stick test on arterial blood in the ICU 9. Plasma levels of cholesterol (HDL, LDL, total), triglycerides, free fatty acids over time during the 6 day intervention window (E), measured by commercial kits 10. Plasma levels of bilirubine, gamma-glutamyltransferase, aspartate transaminase and alanine transaminase over time during the 6 day intervention window (S), measured by commercial kits | — |
Countries
Belgium
Contacts
Public ContactHelena Wintmolders
Outcome results
None listed