Sepsis Flashcards
What is the significance of sepsis?
- major cause of morbidity and mortality worldwide
- leading cause of death in nonocornary ICU
- 11th leading cause of death overall
- more than 750,00 cases of severe sepsis in US annually
- in the US, more than 500 patients die of severe sepsis daily
What are the factors contributing to the increasing incidence of sepsis?
- increasingly aggressive oncological chemo and radiation
- widespread use of corticosteroid and immunosuppressive therapies for organ transplantation and/or inflammatory diseases
- increasing survival of patients predisposed to sepsis, such as neonates, elderly and those with diabetes, ancer, major organ failure or granulocytopenia
- the increased use of invasive devices such as surgical prostheses, inhalation equipment, and IV and urinary cathters
- the indiscriminate use of antimicrobial drugs that create conditions for oevergrowth, colonization, and subsequent infection by aggressive, antimicrobial-resistant pathogens
What is the mortality/morbidity of sepsis?
- varies according to the degree of pathologic derangment and the presence of a documented infection- SIRS up to 7%, sepsis 16-28%, septic shock 45-65%
- complications from sepsis: CNS dysfunction 19%, ARDS 2-8%, liver failure 12%, Acute renal failure 9-23%, DIC 8-18%
- complications from septic shock: ARDS 18%, DIC 38%, Acute renal failure 50%
What is bacteremia?
- presence of viable bacteria within the liquid component of the blood
- bacteremia may be transcient, as it commonly is after injury to muscoal surface (septicemia is bacteremia + clinical manifestations)
- may be primary (without an identifiable source of focus of infection) or more often, secondary with an intravascular or extravascular focus of infection
What is sepsis?
-confirmed or clinical evidence of infection plus evidence of a systemic response
What is severe sepsis?
-sepsis with associated organ dysfunction with one or more of the following: hypotension, confusion, oliguria, hypoxia (not explained by primary respiratory disease), metabolic lactic acidosis, DIC, hepatic dysfunction (not explained by primary liver disease)
What is septic shock?
-sepsis-associated hypotension that is associated with lactic acidosis or organ hypoperfusion and cannot be reversed by the administration of IV fluids
What is SIRS?
- systemic inflammatory response syndrome
- an inflammatory state of the whole body without a proven source of infection
- SIRS with a confirmed infection proven through a positive culture positive for pathogenic organisms is called sepsis
- complications- SIRS can result in multiple organ dysfunction syndrome
- other causes- severe trauma, complication of surgery, burns, acute pancreatitis, immunodeficiency
What is a cytokine storm?
-SIRS can be considered a subset of cytokine storm, a general term for cytokine dysregulation
What is the disease continuium of sepsis?
-the spectrum range from initially as SIRS to sepsis (bacteremia with SIRS) then to severe sepsis (sepsis with signs of organ system failure) then to septic shock (sepsis induced hypothension despite adequate fluid resuscitation leading to multiple organ dysfunction syndrome
What are the clinical features of sepsis?
- symptoms of sepsis usually are nonspecific and include: fever and shaking chills or alternatively, a very low body temperature, decreased urination, rapid pulse and breathing, nausea and vomiting, diarrhea, confusion
- early recognition of sepsis is critical for effective intervention and improved outcomes-once triggered, the combination of systematic inflammation, coagulation, and impaired fibrinolysis can lead to acute organ dysfunction (severe sepsis) and death even when the underlying infectious process is controlled
What is TLRs role in SIRS?
- TLR4 plays the most critical role in mediating SIRS
- TLR4- lipopolysaccharide
- TLR2- peptidoglycan and lipoteichoic acid
- engagement of TLR4 leads to the release of proinflammatory mediators TNF-alpha, IL-1 and IL-6
What is gram negative shock?
- excessive release of cytokines often triggered by LPS of gram negative bacteria can lead to diffuse intravascular coagulation with consequent defective clotting, changes in vascular permeability, loss of fluid into the tissues, a fall in blood pressure, circulatory collapse, and hemorrhagic necrosis
- to the cytokines TNF and IL-1 cause endothelial cells to express cell adhesions molecules and tissue thromboplastic- these promote adhesion of circulating cells and deposition of fibrin, platelet activating factor (PAF) enhances these effects
What is inflammation-activated coagulation?
- severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging changes to severe DIC
- these blood clots can reduce or block blood flow through the blood vessels which can damage the body’s organs
What is the role of activated protein C?
- sepsis leads to organ failure and death via a cascade of inflammation and coagulation
- activated protein C (naturally occuring modulator of coagulation and inflammation as well as antithrombin) blocks the cascade at several points
- a formulation of recombinant human APC has been approved for treating sepsis
