Sepsis

Question 1

Definition of SIRS

Answer 1

Systemic Inflammatory Response (SIRS)
• Temperature > 38 or 90
• RR>20
• PaCO2 12000

Question 2

Consequences of SIRS/Sepsis

Answer 2

Organ dysfunction:
o	Low PaO2
o	Oliguria
o	Rise in Serum Cr
o	Coagulation abnormalities
o	Paralytic ileus
o	Thrombocytopenia
o	Hyperbilirubinemia
Hypoperfusion (low BP):
o	Hyperlactatemia
o	Decreased capillary refill or mottling

Question 3

What is the progression of SIRS to death?

Answer 3

Can progress to severe sepsis, shock, and MODS (Multiple Organ Dysfunction Syndrome)

Question 4

How does LPS induce sepsis?

Answer 4

LPS binds TLR → increase NFkB transcription factor which upregulates expression of pro-inflammatory mediators to cause
• Vasodilation and endothelial cell activation
• Leukocyte recruitment and activation
• Coagulation and NET formation

Question 5

What are the primary chemical mediators of sepsis?

Answer 5

Primary sepsis mediators:

IL-1, TNF-alpha, ROS, RNS, lipids

Question 6

What are the secondary chemical mediators of sepsis?

Answer 6

Secondary mediators:

NO, PAF, PG, LT, IL, kinins

Question 7

What is the pathophysiology of sepsis?

Answer 7

o	LPS and other bacterial components elicit immune response of Endothelial cells, PMNs, and monocytes→ release pro-inflammatory mediators
o	Vicious cycle of hypoperfusion, ischemia, microcirulatory shunts and acidosis
o	MODS (Multiple Organ Dysfunction Syndrome)
o	Death

Question 8

What are the three patterns of response commonly seen in sepsis patients?

Answer 8

o	Classic (healthy young adults):  Hyperimmune response in first 2-3 days, followed by transient immune suppression and resolution
o	Elderly malnourished: Hyperimmune for first 1.5 d followed by sepsis-induced immunosuppression for ~ 1 week that then resolves
o	DM, ESRF, CAP: hyperimmune response is much less profound and shorter, followed by sepsis-induced immunosuppression that does not resolve

Question 9

How do the pathology of deaths differ between those who die early in sepsis vs those who die later in the course?

Answer 9

• Early death is from cytokine storm (hyperinflammatory response) → from Th1 cytokines and chemokines
• Late death usually from primary infection or development of secondary infection (hypoinflammatory response) → from Th2, and immune cell depletion

Question 10

What is the treatment for sepsis?

Answer 10

Treatment is most effective when bundled (Note that guidelines have changed a lot even in the last decade)

6 hr Resuscitation Bundle 
•	Routine sepsis screen 
•	Normalize serum lactate
•	Blood and respiratory culture
•	Broad spectrum antibiotics within 1 hr
•	IV N/S (fluids) 30 ml/kg in first 2 hrs
•	Vasopressor
•	EGDT (in shock, lactate> 4)
•	Avoid HYPOglycemia

24 hr Management Bundle
• Glycemic control but avoid HYPOglycemia
• Lung protective ventilation