Circadian Rhythm, Critical Illness, Enteral Nutrition, Intensive Care Unit, Sleep
Conditions
Keywords
Randomized Controlled Trial
Brief summary
Disruption of circadian rhythms is frequently observed in patients in the intensive care unit (ICU) and is associated with worse clinical outcomes. The ICU environment presents weak and conflicting timing cues to the circadian clock, including continuous enteral nutrition. The goal of this clinical trial is to evaluate the effect of timing of enteral nutrition on the circadian rhythm in critically ill patients. Patients admitted to the intensive care unit will be allocated to receive either continuous or cyclic daytime (8am to 8 pm) enteral feeding. Differences in circadian rhythms will be assessed by 24h patterns in core body temperature, heart rate variability, melatonin and peripheral clock gene expression. Secondary outcomes include depth of sleep, glucose variability and incidence of feeding intolerance. This study is expected to contribute to the optimalisation of circadian rhythms in the ICU.
Interventions
OTHERCyclic daytime enteral nutrition
The allocated feeding schedule is followed from the start of enteral nutrition after ICU admission until discharge from the ICU.
Sponsors
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Investigator-Initiated Randomized Controlled Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old * Receiving of or intention to start enteral nutrition via nasogastric or nasoduodenal tube * Arterial line * Expected duration of ICU admission \> 48 hours
Exclusion criteria
* Receiving parenteral nutrition * Prior night-time (20.00h - 8.00h) enteral tube feeding within the same hospitalization before study inclusion * Readmission to ICU with prior study inclusion * Chronic enteral tube feeding prior to current admission * Presence of one or more contraindications of enteral feeding and/or at significant risk for gastrointestinal tolerance according to standard protocol (including but not limited to gastrointestinal haemorrhage, intestinal ischemia or necrosis, impaired digestive tract integrity due to obstruction or perforation, gastrectomy, enterectomy, history of gastroparesis or oesophageal dysmotility or expected surgery within 24 hours) * Patients with glycaemic emergency (including but not limited to hyperglycaemic hyperosmolar nonketotic coma, diabetic ketoacidosis, severe hypoglycaemia resulting in ICU admission) or patients controlling their glucose levels and insulin dosing via continuous glucose monitoring * Expected death within 24 hours * Do-not-resuscitate (DNR) order * Treatment with extracorporeal membrane oxygenation * Severe neurological damage (significant neurological abnormalities such as bleeding, ischemia, neurotrauma or severe encephalopathy with Glasgow Coma Scale ≤ 8) * Suspected or confirmed pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amplitude of 24-h rhythm of core body temperature | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| Acrophase 24-h rhythm of core body temperature | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean daily insulin administration | From start of study intervention (enteral nutrition) to end of study intervention | Mean of number of insulin units used per day |
| Mean daily caloric intake | From start of study intervention (enteral nutrition) to end of study intervention | Mean of percentage of recommended calories that patient receives per day of interest during study period |
| Daily rates of gastric retention | From start of study intervention (enteral nutrition) to end of study intervention | Gastric retention is defined as gastric residual volume \> 200 mL |
| Amplitude of 24-h rhythm of plasma melatonin levels | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| Acrophase of 24-h rhythm of plasma melatonin levels | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| Amplitude of 24-h rhythm in heart rate variability | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| Acrophase of 24-h rhythm in heart rate variability | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| Amplitude of 24-h rhythm in systolic blood pressure | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| Days on mechanical ventilation | From ICU admission to ICU discharge | Days on mechanical ventilation |
| Amplitude of 24-h rhythm in heart rate | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| Acrophase of 24-h rhythm in heart rate | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| Peripheral clock gene expression | Day 3 (12 p.m.) to day 4 (12 a.m.) after start of the study intervention (= start of enteral nutrition) | Time of day-dependent difference in clock gene expression in PBMCs isolated from blood samples collected at 12 p.m. and 12 a.m. |
| Depth of sleep | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Daytime (8 a.m. to 8 p.m.) to nighttime (8 p.m. to 8 a.m.) ratio of gamma to delta spectral power ratio in EEG measured with a sleep headband |
| Mean daily rate of hyperglycaemia/hypoglycaemia | From start of study intervention (enteral nutrition) to end of study intervention | Hypoglycaemia is defined as glucose levels \< 3.5 mmol/L, hyperglycaemia is defined as glucose levels \>10 mmol/L |
| Mean daily glucose variability | From start of study intervention (enteral nutrition) to end of study intervention | Mean of standard deviation of glucose levels per day |
| 28-day mortality | Up to 28 days | 28-day mortality |
| Acrophase of 24-h rhythm in systolic blood pressure | Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition) | Determined by cosinor analysis |
| ICU length of stay | From ICU admission to ICU discharge | ICU length of stay |
Countries
Netherlands
Outcome results
None listed