Septic Shock

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  • Topic: Shock, Blood, Systemic inflammatory response syndrome
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  • Published : April 23, 2012
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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.


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



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
– (fluid resuscitation)
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Restore tissue perfusion Normalize cellular metabolism Dopamine, norepinephrine, dobutamine

– Vasopressor agents


Therapies of Sepsis/Septic Shock (cont.)


Source control
– Surgical debridement of infected, devitalized tissue – Catheter replacement





Supplemental oxygen (treatment of acute respiratory distress syndrome,ARDS) Nutritional support

Controversial Current Therapies for Septic Shock


Anti-inflammatory agents
– – – – Cortocosteroids Ibuprofen Prostaglandin E1 Pentoxifylline



Oxygen Scavengers
– N-acetylcysteine – selenium

Controversial Current Therapies for Septic Shock(cont.)


Drugs modifying coagulation
– Anti-thrombin III



Drugs enhancing host defenses
– – – – Intravenous immunoglobulin (IVIG) Interferon-gamma GM-CSF immunonutrition

Controversial Current Therapies for Septic Shock(cont.)


Other drugs
– Growth hormone, antibiotics, fresh frozen plasma, anesthetic sedative and analgesic agents, catecholamines



Hemofiltration, plasma filtration, plasma exchange

Experimental Therapies of Sepsis/Septic Shock


Anti-endotoxin therapies
– IVIG, BPI protein

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IL-1Ra Anti-TNF-alpha, soluble TNFR PLA2 inhibitors, PAF inhibitors iNOS inhibitors Anti-coagulants (APC)

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.

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