Dr Z B Banoo Inkosi Albert Luthuli Central Hospital Paediatric ...
Dr Z B Banoo Inkosi Albert Luthuli Central Hospital Paediatric ...
Dr Z B Banoo Inkosi Albert Luthuli Central Hospital Paediatric ...
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<strong>Dr</strong> Z B <strong>Banoo</strong><br />
<strong>Inkosi</strong> <strong>Albert</strong> <strong>Luthuli</strong> <strong>Central</strong> <strong>Hospital</strong><br />
<strong>Paediatric</strong> Intensive Care Unit
Unwanted<br />
Persistent<br />
Ubiquitous<br />
Mysterious<br />
Leading cause of death
Pathophysiology<br />
Definition dilemmas<br />
Diagnostic Tools<br />
Clinical to Cultures<br />
Biomarkers to genomics<br />
Summary
Derived from the Greek word ŋΨις<br />
Decomposition of animal and vegetable<br />
organic matter<br />
100 years ago link between bacteria<br />
and sepsis<br />
sepsis synonymous with severe infection
Precise definition of the disease process<br />
in question<br />
Complex process, multiple sites, multiple<br />
organisms<br />
Multitude of symptoms & signs, varying<br />
over time, severity from mild to fatal<br />
Complexity and variation- single<br />
definition impossible
Microbiological markers<br />
Blood cultures<br />
Tracheal Aspirates<br />
Urine MCS<br />
Cerebral Spinal Fluid<br />
Pus Swabs
Clinical<br />
Manifestation<br />
Acute Phase<br />
Proteins<br />
Cytokines<br />
Cytokines<br />
Inflammatory<br />
Cells<br />
Inflammatory<br />
cells<br />
Orgs<br />
Organisms
Indicator of a biological state<br />
Measurable substance in an organism<br />
Molecular marker or signature molecule<br />
Diagnostic and/or prognostic utility<br />
Surrogate endpoint
Leucocytosis<br />
Leucopenia<br />
White Blood<br />
Count<br />
Insensitive<br />
Non-specific<br />
Marker of<br />
Inflammation<br />
Bandemia
Inflammatory stimuli marginalization,<br />
extravasation and activation of<br />
granulocytes and monocytes<br />
Release of pro-inflammatory cytokines<br />
TNF<br />
IL-1<br />
IL-6<br />
Production of acute phase proteins
Late<br />
Biomarker<br />
Serial<br />
Measurements<br />
C- reactive protein<br />
Low<br />
sensitivity<br />
and<br />
specificity<br />
Peak 2-3 days
APP produced in response to proinflammatory<br />
cytokines<br />
Direct measure of the cytokines earlier<br />
indication of infection<br />
IL-1, IL-6, TNF, sIL2R<br />
Initial reports of high sensitivity and<br />
specificity have not been borne out in<br />
clinical trials
Soluble triggering receptor expressed on<br />
myeloid cells<br />
Upregulated in neutrophils and<br />
monocytes during bacterial infection<br />
Limited value in neutropenia
Identification of resistant genes by<br />
molecular techniques<br />
Genomics – identification of genes<br />
upregulated in infection eg IL8 AND<br />
MCP-1 Mrna<br />
Proteonomics – mass spectrometry<br />
profiling technology to identify host<br />
response proteins<br />
Gelsolin, Copeptin, Endothelial-1…..
Sepsis – homogenous disease process<br />
inadequate<br />
Clinical variables – too sensitive,<br />
nonspecific<br />
Synthesis of clinical, physiological and<br />
laboratory features
Gut<br />
instinct<br />
Clinical<br />
features<br />
Sepsis<br />
Special<br />
Investigations<br />
Biomarkers