Sepsis
Conditions
Interventions
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 glut
Sponsors
Maastricht UMC+
Eligibility
Inclusion criteria
Inclusion criteria: 1) Age >18 0.05-0.25 mcg/kg/min 4) Intubated and Mechanically ventilated - PaO2/FiO2 ratio of >100 mm Hg (>13 kPa) 5) Femoral venous and peripheral venous line 6) Arterial line (any location) in situ 7) Expected ICU stay > 48 hours
Exclusion criteria
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 umol/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 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 outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Across the leg phenylalanine and glutamine kinetics (indicator of muscle protein synthesis/breakdown and release of muscle derived glutamine respectively) 2. Glutamine substrate utilization for energy and immune cell funciton (i.e. 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) 3. Correlation between outcome 1 and 2 (i.e. is increased substrate utilization associated with increase muscle breakdown and therefore a driver of muscle wasting in sepsis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Plasma total phenylalanine and tyrosine concentrations (expressed as µmol/L) Total plasma amino acids (AAmax [µmol/L]) Fractional and absolute synthesis rates of albumin 1-13C glucose enrichment 1-13C Urea enrichment 1-13C enrichment in citrate cycle intermediates (such as citrate, fumarate and malate in peripheral leukocytes) M. rectus fermoris cross sectional area (CSA expressed in cm2) Plasma Il-6, IL-1ß and TNF-a concentrations (nmol/L) | — |
Contacts
Public ContactRob van Gassel
Maastricht UMC+
Outcome results
None listed