Critical Illness, Intensive Care Unit Acquired Weakness
Conditions
Brief summary
Background: Patients with critical illness in the intensive care unit (ICU) experience marked skeletal muscle weakness, muscle atrophy and disability in physical function, commonly termed ICU-acquired weakness (ICU-AW). The pathophysiology of ICU-AW is complex, but a key feature of skeletal muscle wasting is disturbed protein metabolism reflected in both increased rate of muscle protein degradation and reduced synthesis. Treatment with 3-OHB seems a promising new anticatabolic treatment in patients with critical illness, preventing ICU-AW. To date, no data exist on the clinical and functional effects of ketone body modulation in patients with critical illness. Objective: The aim to investigate the effect of exogenous 3-OHB administration on muscle protein kinetics and lipolysis in patients with critical illness, aiming towards preventing ICU-AW. Design: A randomized double-blind isocaloric placebo-controlled cross-over study in 10 mechanically ventilated patients with critical illness in the ICU. Methods: Evaluation of whole-body and focal leg protein kinetics using labeled phenylalanine and tyrosine tracers. Assessment of free fatty acid (FFA) turnover using a labeled palmitate tracer. Femoral arterial blood flow (assessed with pulsed-wave Doppler ultrasound) is evaluated once per study period. Blood- and urinary samples are collected routinely throughout the study day. Whenever feasible, muscle and fat biopsies will be taken for analysis of protein and adipocyte metabolic signaling and mitochondrial function. Perspectives: This investigation may grant essential knowledge on ketosis in critical illness. This may lead to larger clinical trials, and hopefully a new and better treatment strategy aimed at preserving muscle mass and function during and improving recovery after critical illness.
Interventions
DIETARY_SUPPLEMENTKetoneAid KE4 Pro Monoester
A dietary supplement containing ketone monoester.
DIETARY_SUPPLEMENTMaltodextrin and fat-based placebo
Dosis isocaloric to the KetoneAid Arm
Sponsors
Aarhus University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
A randomized double-blind isocaloric placebo-controlled cross-over study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Invasive mechanical ventilation via a cuffed endotracheal or tracheotomy tube. * Expected survival of ICU admission. * Adults (≥18 years). * Multi-organ failure (Sequential Organ Failure Assessment Score \[SOFA\] score ≥2 in 2 or more domains).
Exclusion criteria
* Moribund or expected withholding treatment within 48 hours as judged by the investigator. * Palliative goals of care. * Contraindication for enteral nutrition. * Pregnancy. * Known severe musculoskeletal or neurological disability. * Diabetic ketoacidosis. * Phenylketonuria. * BMI ≤17 or deemed malnourished as judged by the investigator. * BMI \>40.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Net leg phenylalanine release | 3 hours | As measured by rate of phenylalanine appearance in relation with the rate of disappearance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in rate of disappearance of phenylalanine over the leg. | 3 hours. | — |
| Whole body palmitate flux | 3 hours. | As measured by rate of appearance of a palmitate-tracer |
| Change in rate of appearance of phenylalanine over the leg. | 3 hours. | — |
| Changes in inflammatory cytokines (IL-1, IL-6, IL-18, TNFa) | 3 hours. | — |
| Changes in intramyocellular protein metabolic signalling pathways. | 3 hours. | The Akt-, mTor-, and ubiquitin-proteasome pathways. |
| Change in arterial pH. | 3 hours. | — |
Countries
Denmark
Contacts
Primary ContactKristoffer Berg-Hansen, MD
Backup ContactNiels Møller, Prof.
Outcome results
None listed