Septic Shock
Pathologic Mechanisms of Septic Shock
Kenneth J. Goodrum, Ph.D. OUCOM
Topics
● ● ● ● ●
● ●
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)
●
● ● ●
●
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
● ●
● ●
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
● ● ● ● ● ● ●
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
● ●
Disseminated intravascular coagulation (DIC) Blood dyscrasias – leukopenia – thrombocytopenia – polycythemia
● ●
Central and peripheral nervous dysfunction Increased lactate occurs early
Therapies of Sepsis/Septic Shock
● ●
Antibiotics (early administration) Hemodynamic support
– (fluid resuscitation)
● ●
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
Kenneth J. Goodrum, Ph.D. OUCOM
Topics
● ● ● ● ●
● ●
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)
●
● ● ●
●
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
● ●
● ●
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
● ● ● ● ● ● ●
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
● ●
Disseminated intravascular coagulation (DIC) Blood dyscrasias – leukopenia – thrombocytopenia – polycythemia
● ●
Central and peripheral nervous dysfunction Increased lactate occurs early
Therapies of Sepsis/Septic Shock
● ●
Antibiotics (early administration) Hemodynamic support
– (fluid resuscitation)
● ●
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
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.