Sepsis
Conditions
Keywords
bacterial lipopolysaccharides, hyperlactatemia, muscle lactate
Brief summary
Sepsis is characterized by hyperlactatemia, the severity of which is proportionate with sepsis severity. The pathophysiological mechanisms (increased lactate production vs decreased lactate utilization; tissues involved in sepsis-induced lactate production) remain largely unknown. In this study, the investigators will assess whole body and regional metabolism in healthy young male subjects on two occasions, once after administration of an intravenous bacterial endotoxin challenge, and once without intervention. In one group of subjects, whole body lactate metabolism will be measured over 10 hours after the endotoxin challenge * Energy expenditure and net substrate oxidation rates (indirect calorimetry) * Lactate kinetics (measured by means of a continuous, exogenous sodium lactate infusion) * Glucose kinetics (measured with 6,6 d2 glucose) * Hemodynamic parameters and body temperature * Blood clinical chemistry In one group of subjects, whole body lactate metabolism will be measured over 10 hours after the endotoxin challenge * Energy expenditure and net substrate oxidation rates (indirect calorimetry) * Lactate kinetics (measured by means of a continuous, exogenous sodium lactate infusion) * Glucose kinetics (measured with 6,6 d2 glucose) * Hemodynamic parameters and body temperature * Blood clinical chemistry In a second group of subjects, regional muscle lactate metabolism will be measured over 10 hours after the endotoxin challenge by means of muscle microdialysis
Interventions
OTHERbacterial endotoxin challenge
iv administration of 2ng/kg bacterial endotoxin
Sponsors
Centre Hospitalier Universitaire Vaudois
University of Lausanne
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* gender male * body mass index (BMI) \< 25 kg/m2 * absence of known disease
Exclusion criteria
* any known pathology * abnormal cardio-pulmonary and hemodynamic status * electrocardiographic alterations * history of allergy * current medications * drug abuse * consumption of more than 20g/day alcohol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Whole body lactate production | single bacterial endotoxin administration; measurements over 6.5 hours following administration | Whole body lactate clearance will be measured by measuring the increase in blood lactate at steady state during a conrtinuous exogenous sodium lactate infusion. Lactate production will be calculated as the product of lactate clearance times per-infusion blood lactate concentration |
| skeletal muscle lactate concentration | single bacterial endotoxin administration; measurements over 6.5 hours following administration | interstitial muscle measured by means of in vivo microdialysis ; calculation of muscle-blood lactate gradient |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| whole body energy expenditure | single bacterial endotoxin administration; measurements over 6.5 hours following administration | open circuit indirect calorimetry (hood) |
| body temperature | single bacterial endotoxin administration; measurements over 6.5 hours following administration | — |
Countries
Switzerland
Outcome results
None listed