The Effect of Nutrition on Endogenous Energy Substrate Production in the Early and Late Acute Phase of Critical Illness
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Attenuation of glucose production in response to nutrition in early acute phase in ICU.
Study Overview
Brief Summary
The aim of this study is to investigate when critically ill patients transition from a non-suppressible catabolism to a normal response to feeding.
Endogenous production of glucose, fat and protein will be studied on a minimum of two occasions in mechanically ventilated ICU patients, in a fasted state and during parenteral nutrition. Substrate kinetics are estimated by a tracer dilution method using infusions of isotopically labeled glucose, glycerol and phenylalanine. Blood sampling for metabolomics analysis will be performed to elucidate potential biomarkers indicating an anabolic response to nutrition.
Detailed Description
Background and aims
Critical illness is characterized by several metabolic alterations, including an upregulation of catabolic pathways promoting endogenous energy substrate production. In contrast to starvation catabolism, this endogenous energy supply cannot be suppressed by feeding in the early acute phase of critical illness. This observation is one of the reasons that current guidelines recommend hypocaloric nutrition during the first week in ICU [1]. However, it is not known when this anabolic resistance subsides and a transition towards a normal response to feeding occurs.
The aims of this study are two-fold: 1) to investigate the temporal changes in non-suppressible endogenous energy production during critical illness, and 2) identify potential biomarkers indicating a normalized response to exogenous nutrients.
Protocol
For ICU patients, the protocol is first performed within 24-72 hours (early acute phase) from ICU admission. The protocol will be repeated if an enrolled patient is still in the ICU 120-168 hours (late acute phase) and 240-288 hours (late phase) after the first study session.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •For the ICU group:
- •≥18 years old and admitted to the ICU
- •Invasive mechanical ventilation
- •Arterial and central line in situ
- •Expected to remain in ICU >72 hours
- •For the control group:
- •1. ≥18 years old
Exclusion Criteria
- •Lack of informed consent by patient/next of kin
- •Liver transplant
- •Acute or acute on chronic liver failure
- •Known diabetes mellitus
- •Pancreatic surgery
- •Acute or chronic pancreatitis
- •Intubated only for airway protection or neurologic deficit
- •Mitochondrial disease
- •Disorder of amino acid metabolism
- •Familial hypertriglyceridemia
- •Severe acquired hypertriglyceridemia (≥10 mmol/L)
- •Requiring treatment of hypoglycemia in the last 72 hours before inclusion.
- •Requiring ongoing large volume resuscitation of crystalloids or blood products
- •>72 hours in ICU before enrollment
- •Readmission to ICU within 1 week of ICU discharge.
- •Morbidly obese (BMI ≥35)
- •Limitations of treatment to best supportive care
- •Ongoing treatment with insulin/glucose related to hyperkalemia
Arms & Interventions
ICU Patients
Mechanically ventilated patients admitted to the study site ICU.
Intervention: Stable isotope tracers (Other)
ICU Patients
Mechanically ventilated patients admitted to the study site ICU.
Intervention: Parenteral nutrition (Dietary Supplement)
Control group
Non-hospitalized study subjects recruited through public advertising at the study site, age-matched on group level.
Intervention: Stable isotope tracers (Other)
Control group
Non-hospitalized study subjects recruited through public advertising at the study site, age-matched on group level.
Intervention: Parenteral nutrition (Dietary Supplement)
Outcomes
Primary Outcomes
Attenuation of glucose production in response to nutrition in early acute phase in ICU.
Time Frame: Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.
Difference in endogenous rate of appearance of glucose, calculated from enrichment of labelled substrates in plasma of glucose between the fasted and fed state in the early acute phase in ICU.
Attenuation of phenylalanine production in response to nutrition in early acute phase in ICU.
Time Frame: Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.
Difference in endogenous rate of appearance of phenylalanine, calculated from enrichment of labelled substrates in plasma of phenylalanine, between the fasted and fed states in the early acute phase in ICU.
Attenuation of glycerol production in response to nutrition in early acute phase in ICU.
Time Frame: Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.
Difference in endogenous rate of appearance of glycerol, calculated from enrichment of labelled substrates in plasma of glycerol, between the fasted and fed states in the early acute phase in ICU.
Secondary Outcomes
- Attenuation of glucose production in response to nutrition in the late acute phase compared to the early acute phase in the ICU.(The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.)
- Attenuation of glycerol production in response to nutrition in the late acute phase compared to the early acute phase in the ICU.(The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.)
- Attenuation of phenylalanine production in response to nutrition in the late acute phase compared to the early acute phase in the ICU.(The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.)
- Attenuation of glucose production in response to nutrition in the early acute phase in the ICU compared to healthy controls.(Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.)
- Attenuation of glycerol production in response to nutrition in the early acute phase in the ICU compared to healthy controls.(Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.)
- Attenuation of phenylalanine production in response to nutrition in the early acute phase in the ICU compared to healthy controls.(Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.)
- Difference in non-suppressible glucose production in the fed state between ICU patients.(The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.)
- Difference in non-suppressible glycerol production in the fed state between ICU patients.(The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.)
- Difference in non-suppressible phenylalanine production in the fed state between ICU patients.(The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.)
Investigators
Martin Sundstrom Rehal
Principal Investigator
Karolinska University Hospital