To study the metabolic fate of amino acids derived from muscle protein breakdown in septic patients.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Protein and amino acid metabolism disorders NEC
- Musculoskeletal and connective tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters will be protein breakdown and glutamine release from the
leg (assessed by a two-pool model using AV leg gradients), albumin synthesis
assessed by 2H5 phenylalanine incorporation. In addition we will study the
incorporation of 13C in urea, glucose and citrate cycle intermediates such
as citrate, fumarate, malate in peripheral leukocytes as a marker of glutamine
utilization by the immune system. Moreover we will measure 13CO2 enrichment in
exhaled air as a measure of total glutamine oxidation. Finally we will quantify
muscle loss using repeated ultrasound measurements
Secondary outcome
nvt
Background summary
Skeletal muscle wasting is a common and major problem in the intensive care
unit. The resulting ICU-acquired weakness is associated with increased
mortality/morbidity, prolonged weaning from ventilator support and prolonged
functional impairment lasting far beyond the time of ICU discharge. It is
conceived by many that muscle protein breakdown during critical illness is a
phylogenetic phenomenon resulting in enhanced release of amino acids into the
circulation to serve as substrate for central protein synthesis (acute phase
response) or rapidly dividing cells including immune cells. However, the actual
metabolic fate of amino acids released during muscle breakdown has been poorly
characterized in critically ill patients. By tracing amino acids derived from
protein breakdown, we aim to better characterize changes in AA kinetics in ICU
patients and gain insight in the (patho)physiology and drivers of protein
catabolism in sepsis.
Study objective
To study the metabolic fate of amino acids derived from muscle protein
breakdown in septic patients.
Study design
non-therapeutic interventional cohort study.
Intervention
Patients participating in this study will receive a primed continuous
intravenous infusion with non-radioactive stable isotope tracers after a 6 hour
fast. 2H5 phenylalanine, 2H2 tyrosine and 13C glutamine will be infused for 6.5
hours. Both arterial and femoral venous blood samples will be collected through
indwelling catheters and analyzed for tracer enrichments. repeated ultrasound
measurements of the leg will be made to quantify muscle loss over time.
Study burden and risks
Stable isotopes are non-radioactive molecules, which have been extensively used
in both healthy and critically ill patients. Phenylalanine, tyrosine and
glutamine are amino acids that are part of normal nutritional formulas used in
the ICU and will not pose any risk to the participants. In addition, the
intravenous infusion will be performed using a tracer dosage, ensuring
visualization but no metabolic alteration of the substrate metabolites. Both
infusion and sampling will take place through indwelling catheters, meaning no
additional punctures or line placements are required. If patient is eligible,
but no femoral line is in place a temporary catheter can be placed. Except for
minimal discomfort due to a single puncture, the risk of accidental puncture of
the artery is <1.5% and can be amended by applying local pressure for 10
minutes. The total amount of blood sampled will be approximately 56 ml (~1.0%
of total circulating volume). This amount of blood sampling has been proven
safe in previous studies in ICU patients and is unlikely to pose any risk or
burden to the participant.
Universiteitssingel 50
Maastricht 6200MD
NL
Universiteitssingel 50
Maastricht 6200MD
NL
Listed location countries
Age
Inclusion criteria
1) Age >18 <75
2) Sepsis on admission (as defined by the Sepsis-3 criteria*)
3) Sepsis still persistent but stabilized as defined by continued need of
vasopressive drugs
- norepinephrine dose, > 0.05-0.25 ug/kg/min
4) Receiving enteral or parenteral nutrition
5) Intubated and Mechanically ventilated
- PaO2/FiO2 ratio of >100 and <300;
6) Femoral venous catheter in place OR eligible for femoral CVL placement
7) Arterial and peripheral venous line (any location) in situ
8) Expected ICU stay > 48 hours, * Sepsis as defined by the third international
consensus definitions for sepsis and septic shock [17]:
- Suspected infection
- SOFA score >= 2
Exclusion criteria
1) Patients who are moribund (not expected to be in ICU for more than 48 hours
due to imminent death)
2) A lack of commitment to full aggressive care during the first week due to
severity of illness, comorbidities and potential harm from maximal treatment
(anticipated withholding or withdrawing treatments in the first week)
3) Any trauma with severe injury or fracture of any extremity.
4) Rhabdomyolysis
5) Proven (pre-existing) skeletal muscle weakness (e.g. due to neuromuscular
disorders or immobility)
6) Renal dysfunction defined as a serum creatinine >171 *mol/L or a urine
output of less than 500 ml/last 24 hours
7) Patients requiring chronic veno-venous hemofiltration
8) Patients on any form of extracorporeal life support (ECMO/ELS)
9) Cirrhosis - Child*s class C liver disease
10) Metastatic cancer or Stage IV Lymphoma with life expectancy <6 months
11) Patients with primary admission diagnosis of burns (>30% body surface area)
12) Weight less than 50 kg or greater than 100 kg
13) Pregnant patients or lactating with the intent to breastfeed
14) Previous enrollment in this study
15) Previous participation in a 13C or 2H tracer study within the last year
16) Enrollment in any other interventional study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL63199.000.17 |