Septic Shock

Pathologic Mechanisms of Septic Shock
Kenneth J. Goodrum, Ph.D. OUCOM

Topics
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Definitions: SIRS,sepsis,shock,MODS Morbidity/mortality of Sepsis/Shock Pathogenesis of shock Microbial triggers(endotoxin, TSSTs) Cytokine and non-cytokine mediators of SIRS and shock Pathophysiology of shock Therapy

Systemic Inflammatory Response Syndrome (SIRS)
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Systemic inflammatory response to a variety of severe clinical insults manifested by ≥ 2 of the following conditions Temperature >38ºC or 90 beats/min Respiratory rate >20 breaths/min or PaCO2 ,100 beats/min) Increased cardiac output (hyperdynamic), although contractility is depressed; hypodynamic in late shock Ventricular dilation; decreased ejection fraction Loss of sympathetic responsiveness

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PATHOPHYSIOLOGYCont.
CardiovascularCont.
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Hypovolemia due to vascular leakage; central venous pressure may be decreased or increased depending upon fluid resuscitation Compromised nutrient blood flow to organs; decreased organ oxygen extraction

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PATHOPHYSIOLOGYCont.
Pulmonary & Renal
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Hyperventilation with respiratory alkalosis Pulmonary hypertension and edema Hypoxemia (arterial pO2 < 50 mmHg) Reduced pulmonary compliance; increased work Respiratory muscle failure Renal hypoperfusion; oliguria Acute tubular necrosis and renal failure

PATHOPHYSIOLOGYCont.
Other
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Disseminated intravascular coagulation (DIC) Blood dyscrasias – leukopenia – thrombocytopenia – polycythemia

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Central and peripheral nervous dysfunction Increased lactate occurs early

Therapies of Sepsis/Septic Shock
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Antibiotics (early administration) Hemodynamic support
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Restore tissue perfusion Normalize cellular metabolism Dopamine, norepinephrine, dobutamine

– Vasopressor agents
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Therapies of Sepsis/Septic Shock (cont.)
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Source control
– Surgical debridement of infected, devitalized tissue – Catheter

References: ● ● Immunological therapy of sepsis:experimental therapies. P. Arndt and E. Abraham. Intensive Care med (201)27:S104-115. Immunological therapy in sepsis:currently available. J.Carlet. Intensive Care Med (2001)27:S93-S103.