Muscle-derived Amino Acids in Sepsis

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 21

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 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

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 <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

Study & Design

Study Type: Observational non invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Across the leg phenylalanine and glutamine kinetics (indicator of muscle protein synthesis/breakdown and release of muscle derived glutamine respectively)<br>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)<br>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 Outcome Measures

Name	Time	Method
Plasma total phenylalanine and tyrosine concentrations (expressed as µmol/L)<br>Total plasma amino acids (AAmax [µmol/L])<br>Fractional and absolute synthesis rates of albumin<br>1-13C glucose enrichment<br>1-13C Urea enrichment<br>1-13C enrichment in citrate cycle intermediates (such as citrate, fumarate and malate in peripheral leukocytes)<br>M. rectus fermoris cross sectional area (CSA expressed in cm2)<br>Plasma Il-6, IL-1ß and TNF-a concentrations (nmol/L)<br>