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Septic shock is defined as a subset of sepsis with severe metabolism alterations, leading to organ failure. Septic shock is associated with a high mortality, around 40% according to the SEPSIS 3 definition.
Metabolic alterations are responsible for lactic acidosis, and results in mitochondrial dysfunction.
This study aims at evaluate the impact of exogenous metabolites on restoring mitochondrial function in septic shock patients with lactate acidosis.
Mitochondrial metabolism (quantitative analysis, mitochondrial function) in intact Peripheral Blood Mononuclear Cells (PBMC) will be isolate and analyse from patients at the early phase of septic shock (admission), at day 2 and 4. Participant's medical history will be recorded: renal and liver metabolism, severity scores and outcomes and the need for supportive care in the intensive care unit (ICU) until 28 days after admission.
Furthermore, the investigators will evaluate wether selected metabolites added to the cell culture medium may improve mitochondrial metabolism.
In this prospective study, the investigators will include patients admitted to the medical ICU of Angers University Hospital and meeting the SEPSIS-3 criteria for the definition of septic shock (Sequential Organ Failure Assessment (SOFA) score > 2, hyperlactatemia > 2 mmol/L and sepsis).
Blood samples will be collected during the usual care of initial resuscitation and analyzed in the laboratory INSERM (Institut national de la santé et de la recherche médicale) U1232 (University Hospital of Angers).
Mitochondrial metabolism will be analyzed in freshly isolated PBMC and after culture for 1-3 days, with or without the addition of selected metabolites to the cell culture medium.
The evolution of ketogenesis, mitochondrial function, acidobasic status will be assessed across the time (blood samples at day 2 and 4).
Survival, renal and liver metabolism, severity scores and outcomes and the need for supportive care in the intensive care unit (ICU) until 28 days after admission will be recorded.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Septic shock admitted in Angers' ICU | Patients aged more than 18, admitted in University Hospital of Angers, who meet the full criteria of septic shock |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Whole blood samples | Biological | Whole blood samples at admission, from day one to three after admission |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in mitochondrial metabolism (mitochondrial membrane depolarization and respiration) with the supplementation of metabolite in the cell culture medium | Using Fluorescence-activated cell sorting system to assess the membrane depolarization of the mitochondria and Oroboros system for mitochondrial respiration | Day 0 (whole blood after cells separation), Day 1-3 after cell culture |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival at 28 days | Survival of patients after ICU admission | Day 28 |
| Change in organs failure | Using the Sequential Organ Failure Assessment Score |
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Inclusion Criteria:
Exclusion Criteria:
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All patients aged 18 or more who meet the SEPSIS-3 criteria for septic shock : a presumed sepsis, with persisting hypotension requiring vasopressors to maintain mean arterial pressure > 65 mmHg and having a serum lactate > 2 mmol/L despite adequate fluid expansion, admitted to the medical ICU of Angers University Hospital.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Julien DEMISELLE, MD | Contact | +33 2 41 35 58 65 | Julien.Demiselle@chu-angers.fr | |
| Pierre ASFAR, MD PhD | Contact | +33 2 41 35 58 65 | PiAsfar@chu-angers.fr |
| Name | Affiliation | Role |
|---|---|---|
| Julien DEMISELLE, MD | University Hospital of Angers | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU | Recruiting | Angers | Maine et Loire | 49933 | France |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| D009102 | Multiple Organ Failure |
| D028361 | Mitochondrial Diseases |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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Whole blood sample for mitochondrial metabolic assessment, DNA extraction for biogenesis and autophagy genes implication
| From Day 0 to Day 4 |
| Change and correlation between lactic acidosis, ketogenesis and mitochondrial function evolutions | biochemical analysis of blood samples, assessment of mitochondrial metabolism (quantitative and qualitative analysis). | From Day 1 to Day 3 |
| Need for renal replacement therapy during the ICU stay | Need for renal replacement therapy and its duration | From Day 1 to Day 28 |
| Need for vasopressors during the ICU stay | Need for vasopressors during the ICU stay and its duration | From Day 1 to Day 28 |
| Need for mechanical ventilation during the ICU stay | Need for mechanical ventilation during the ICU stay and its duration | From Day 1 to Day 28 |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |