Sepsis

Question 1

What is the significance of sepsis?

Answer 1

• 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

Question 2

What are the factors contributing to the increasing incidence of sepsis?

Answer 2

• 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

Question 3

What is the mortality/morbidity of sepsis?

Answer 3

• 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%

Question 4

What is bacteremia?

Answer 4

• 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

Question 5

What is sepsis?

Answer 5

-confirmed or clinical evidence of infection plus evidence of a systemic response

Question 6

What is severe sepsis?

Answer 6

-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)

Question 7

What is septic shock?

Answer 7

-sepsis-associated hypotension that is associated with lactic acidosis or organ hypoperfusion and cannot be reversed by the administration of IV fluids

Question 8

What is SIRS?

Answer 8

• 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

Question 9

What is a cytokine storm?

Answer 9

-SIRS can be considered a subset of cytokine storm, a general term for cytokine dysregulation

Question 10

What is the disease continuium of sepsis?

Answer 10

-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

Question 11

What are the clinical features of sepsis?

Answer 11

• 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

Question 12

What is TLRs role in SIRS?

Answer 12

• 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

Question 13

What is gram negative shock?

Answer 13

• 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

Question 14

What is inflammation-activated coagulation?

Answer 14

• 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

Question 15

What is the role of activated protein C?

Answer 15

• 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

Question 16

What is transient bacteremia?

Answer 16

• chewing
• teeth brushing
• manipulation of infected tissue
• surgery involving non-sterile sites
• in a patient with a working reticuolo-endothelial system (functioning liver and spleen), such bacteremia is of little clinical consequence

Question 17

What is intermittent bacteremia?

Answer 17

• most often associated due to an extravascular infection which provides a portal of entry for the bacteria (e.g UTI, abscess
• also seen during the early course of some diseases- meningitis, pyogenic arthritis, osteomyelitis

Question 18

What is continuous bacteremia?

Answer 18

• bacterial endocarditis and other endovascular infections

- during early stages of specific infections: typhoid dever, brucellosis, leptospirosis

Question 19

What is intravascular vs extravascular?

Answer 19

• intravascular- within the cardiovascular system

- extravascular- bacteria enter the bloodstream through the lymphatic system from another site of infection

Question 20

What are examples of intravascular infections?

Answer 20

• infective endocarditis
• mycotic aneurysm
• thrombophlebitis
• IV catheter associated bacteremia

Question 21

What is infective endocarditis?

Answer 21

• denotes infection of the endocardial surface of the heart and implies the physical presence of microorganism in the lesion
• in the past, the disease has been classified as cute or subacute
• the acute form follows a fulminant course, usually with high fever, systemic toxicity, and leukocytosis; death occurs in several days to less than 6 weeks
• the subacute form death occurs in 6 weeks to 3 months
• the chronic form death occuring later than 3 months

Question 22

What is the pathogenesis of infective endocarditis?

Answer 22

• damage to the cardiac endothelium
• leads to deposition of platelets and fibrin
• then organisms gain access to bloodstream and stick leading to colonization
• protective layer of fibrin and platelets matrix
• bacterial multiplication
• vegetation formation

Question 23

What do infective endocarditis lesions look like?

Answer 23

• the primary pathology of IE involves vegetations which consist primarily of fibrin, platelet aggregates, and bacterial masses
• lesions may be single or multiple and vary in size from a few millimeters up to several centimeters in size
• the valve surface must first be altered to produce a suitable site for bacterial attachment and colonization

Question 24

What is a mycotic aneurysm?

Answer 24

• intravascular infection
• results from damage to endothelial cells lining the arteries leading to seeding of the organism- the infection causes inflammatory damage and weakening of arterial wall

Question 25

What is suppurative thrombophlebitis?

Answer 25

• intravascular infection
• results from damage to the endothelial cells lining a vein
• results in clot formation and seeding of the clot by organisms

Question 26

What are Catheter-Related Bloodstream Infections?

Answer 26

• catheter-related septicemia is estimated to occur in 400,000 of the 5 million Americans who are catheterized each year (8%)
• the treatment for 1 episode of catheter-related septicemia in the critically ill patient will add an average of 6.5 additional hospital days in ICU and will cost and additional $29,000
• most of the cases of nosocomial bacteremia are related to the use of intravascular devices

Question 27

What are the factors associated with catheter-related bloodstream infections>

Answer 27

• prolonged catheterization
• frequent manipulations
• occlusive plastic dressings
• contaminated skin solutions
• poor aseptic technique
• catheter material
• location of catheter

Question 28

What are the 5 potential sources for catheter colonization and catheter-related sepsis?

Answer 28

• the insertion site
• the catheter hub
• hematogenous seeding of the catheter
• contamination of the infusate
• hands of the health care personnel

Question 29

Which organisms cause catheter related infections?

Answer 29

• Commonly: coagulase-neg staph, Staph aureus, Candida species
• Other: Bacillus species, Corynebacterium JK, Acinetobacter species, Pseudomonas species, Xanthomonas maltophilia

Question 30

What are secondary BSIs?

Answer 30

• extravascular
• represents most cases of clinically significant bacteremia
• pathogensis: local site of infection to lymphatics
• spread to bloodstream
• empirical therapy for BSI can be based on primary site of infection

Question 31

What are the organisms associated with neoplasms?

Answer 31

• clostridium septicum
• other relatively uncommon Clostria species
• Streptococcus bovis
• Aeromonas hydrophilia
• Plesiomonas shigelloides
• campylobacter species

Question 32

How do you diagnose BSIs?

Answer 32

• blood cultures
• important in diagnosis for a febrile patient
• to establish the presence of infection (thereby excluding the presence of infection (thereby excluding a non-infectious cause of fever)
• to reassure the clinician about the chosen empirical therapy
• to streamline antibiotic treatment after assessment of the antibiotic sensitivity of the isolate

Question 33

Why take a blood culture?

Answer 33

• Adults- low number of CFUs/,: (most times <1 organism per mL)
• direct relationship between blood volume and yield- yield is increased by 3.2% for each mL of blood cultured
• Children- take what you can get, bacteremic load 10 to 100 times higher than adults
• number of blood culture sets: optimally 3 sets in a 24 period, each set represents 20mL of blood, Yield 1 bottle 38%, 1 set 80%, 2 sets 90%, 3 sets 99%

Question 34

How do you prepare for a blood culture>

Answer 34

• after vessel site selected a 5 cm areas of skin should be disinfected by swabbing concentrically with 70% alcohol, from the venipuncture site outward
• the site should be cleansed once again, this time with 10% povidone-iodine or 2% tincture of iodine again in a circular motion
• allow the iodine to dry completely before performing venipuncture. This should take 1-2 minutes

Question 35

How do you differentiate infectious SIRS from noninfectious SIRS?

Answer 35

-procalcitonin level is elevated in infectious SIRS

Question 36

What is procalcitonin?

Answer 36

• PCT is a marker of inflammatory response and is stimulated by bacterial products (endotoxins/LPS) and cytokines (IL-1, IL-2, IL-6, TNFalpha)
• evidence suggests that it can be used as a biomarker for bacterial pneumonia and bacterial sepsis
• levels increase 3-6 hours of stimulus, higher levels associated with poorer prognosis
• elevated values are highly suggestive of an infection, typically bacterial with systemic response
• levels may also be used to indicated appropriate therapy- a PCT that is rising or not declining by at least 10% a day is a poor prognostic indicator and suggests infection is not controlled

Question 37

How are PCT associated with sepsis risk?

Answer 37

• less than 0.5 ng/mL- low risk for progressive to severe sepsis and/or septic shock
• between 0.5- 2 ng/mL- sepsis should be considered
• greater than 2 ng/mL- high risk for progression to severe sepsis and/or septic shock