Inflammatory Response, Muscle Loss, Nutrition
Conditions
Keywords
Ketogenic diet, ketogenic fasting, cyclic enteral nutrition
Brief summary
A physiological human nutrition includes circadian feeding and nighttime fasting during sleep. There is increasing evidence, that this natural fasting episode over nighttime majorly contributes to repair processes of the human body. So far, intensive care patients are normally enterally fed continuously, so that there is no circadian nutrition and no nighttime fasting. An enteral nutrition for 12 hours followed by a fasting period of 12 hours supported by exogenous ketone salts potentially improves the reconstitution of ICU patients compared to ICU patients who are continuously enterally fed.
Detailed description
There is increasing evidence that a circadian rhythm of feeding (cyclic feeding) could be beneficial for critical ill patients. Cyclic feeding and fasting are assumed to have positive effects on the gut microbiome resulting in optimization of host responses to gastrointestinal pathogens. Another positive effect of cyclic feeding potentially results from activation of a fasting response, inducing repair pathways such as ketogenesis, mitochondrial biogenesis, anti-inflammatory pathways, antioxidant defenses and autophagy processes. The activation of these repair pathways could diminish cellular stress and promote cellular recovery in critical ill patients. A randomized controlled trial by van Dyck et al. could show that fasting-mimicking intervals of 12 hours are sufficient to generate a metabolic fasting response without risking a caloric deficit. This fasting response can be enhanced by additional supplementation of exogenous ketones. A cyclic enteral nutrition with 12 hours of daytime feeding and 12 hours of ketogenic nighttime fasting compared to a continuous enteral feeding for 24 hours can potentially improve the reconstitution of critically ill Intensive Care patients. This improved reconstitution can be measured by maintenance of muscle mass (measured by ultrasound of the musculus rectus femoris), urea/creatinine ration, length of ventilation, length of ICU and hospital stay, 30-day mortality, ICU mobility scale.
Interventions
OTHERCyclic enteral feeding with nighttime fasting and exogenous ketone salt supplementation (ß-hydroxybutyrate)
12 hours of enteral feeding (as per patients´individual calorimetric requirements measured by indirect calorimetry) followed by a fasting period of 12 hours supported by the supplementation of exogenous ketone salts.
Sponsors
University Hospital of Cologne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Monocentric, prospective, randomized, interventional trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* written informed consent to participate in this study * admission to ICU * enteral nutrition
Exclusion criteria
* Severe liver dysfunction / liver failure (Child Pugh \>7 points / category B) * Severe kidney dysfunction (KDIGO stage 3) * Total pancreatectomy / insulin dependent diabetes mellitus (IDDM) * Pregnancy / lactation * Hemoglobin concentration \< 80g/l * Severe metabolic disorders / severe autoimmune diseases * Refractory metabolic or respiratory acidosis * Dysfunction of mitochondrial transport of fatty acids * Dysfunction of oxidation of fatty acids * Dysfunction of gluconeogenesis, production and reduction of ketones * Intermittent Porphyria * Severe cardiac arrhythmias / cardiomyopathy * Contraindication against enteral nutrition * Lack of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Loss of muscle mass | From date of randomization until the date of ICU discharge up to 1 month | Loss of muscle mass via Ultrasound of M. rectus femoris of a predefined leg |
| Progress of urea / creatinine ratio | From date of randomization until the date of ICU discharge up to 1 month | Urea / creatinine ratio in the patients´ blood |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU mobility scale on discharge | From date of randomization until the date of ICU discharge up to 1 month | ICU mobility scale (lowest score 0, highest score 10) |
| Length of invasive and noninvasive ventilation | From date of randomization until the date of ICU discharge up to 1 month | Length of invasive and noninvasive ventilation |
| Length of ICU and hospital stay | From date of randomization until the date of hospital discharge up to 6 months | Length of ICU and hospital stay |
| 30 day mortality on day 30 | From date of randomization 30 days | 30 day mortality on day 30 |
Countries
Germany
Contacts
Primary ContactSandra E Stoll, MD, assProf.
Backup ContactFabian Dusse, PD, MD
Outcome results
None listed