12.4: Sepsis

Question 1

What component for gram negative organisms can cause shock?

Answer 1

• Lipid polysaccharide

- It is actually the host response to to this and infection that cause shock

Question 2

What is SIRS? Criteria?

Answer 2

“Systemic inflammatory response syndrome”
- Massive inflammatory rxn from systemic cytokine release
Must include 2 of the following:
1. Temp > 38 or 90
3. RR > 20 or PaCO212k or 10% immature

Question 3

What is Sepsis?

Answer 3

• SIRS + documented cultured infection

Question 4

What is severe sepsis?

Answer 4

• Sepsis + organ dysfunction or hypoperfusion

Question 5

Signs of severe sepsis?

Answer 5

1. Lactic acidosis
2. Oliguria: insul to kidney
3. Hypoxemia
4. Acute change in mental status
5. Edema
6. HYPERglycemia
7. Tachycardia / tachypnea

Question 6

What is septic shock?

Answer 6

• Refractory hypotension plus hypoperfusion organ abnormalities
• BP cannot be brought up

Question 7

What is ileus?

Answer 7

• Absent normal bowl sounds from inability of intestine to contract normally and move waste out of body

Question 8

Causes of SIRS?

Answer 8

1. Bacteremia
2. Burn
3. Trauma
4. Acute pancreatitis
5. Acute adrenal insufficiency
6. Ischemic tissue injury

Question 9

Percent of septic ptns with positive cultures?

Answer 9

• 50%

- Close to 50/50 split between gram +/- and some fungi

Question 10

What is gram negative LPS?

Answer 10

“Lipopolysaccharide”

• Found in all gram negative orgs
• On the outer membrane of molecule
• LIPID A is core unit it which biologic activity resides

Question 11

Where does bioactive capability of LPS reside?

Answer 11

• Lipid A

- Long chain fatty acids in outer membrane

Question 12

Can organisms without LPS cause sepsis? Examples?

Answer 12

Yes

1. Gram positives
2. Fungi
3. Parasites
   * **Exotoxins and other components of cell wall can cause

Question 13

What are TLRs?

Answer 13

“Toll like receptors”

- Recognizing PAMPs and DAMPs on molecules

Question 14

What does TLR2 recognize?

Answer 14

• Peptidoglycan of gram positives

Question 15

What does TLR4 recognize?

Answer 15

• LPS from gram negatives

Question 16

What does binding to TLR cause?

Answer 16

• Intracellular signalling leading to transcription of proinflammatory cytokines

Question 17

What is LPB?

Answer 17

“LPS binding protein”

• Acute phase reactant that binds to LPS
• Complex binds CD4 receptor on inflammatory cells activating inflammatory genes
• Can also complex with endothelial cells causing adhesion and cytokine release

Question 18

What are the proinflammatory cytokines?

Answer 18

1. TNF Alpha
2. IL-1
3. Il-2
4. IL-6
5. IL-8
6. IL-10

Question 19

Which two cytokines are major players in sepsis

Answer 19

1. TNF Alpha

2. IL-1

Question 20

What are the anti inflammatory cytokines?

Answer 20

1. IL4

2. IL 10

Question 21

How is coagulation cascade activated in sepsis?

Answer 21

• TNF alpha increases expression of tissue factor on macs

- Intrinsic factor XII can be activated as well

Question 22

What does TNF activate?

Answer 22

• Coagulation cascade via TF on macs
• Plasminogen
• Leads to DIC with microthrombi

Question 23

Mediators of dilation in sepsis?

Answer 23

1. Kinin system: activated by factor XII
2. NO: activated by TNF IL1 and LPS
3. Impaired ADH secretion

Question 24

Main cause of cellular injury in sepsis?

Answer 24

1. Ischemia from adherance and microcirculatory lesions

- Direct cytotoxicity and apoptosis issues as well

Question 25

Which part of host immune system activated in sepsis?

Answer 25

- Innate via TLR leading to inflammatory cytokine release

Question 26

Other systems activated in sepsis?

Answer 26

1. Coagulation/Fibrinolytic = DIC 2. Complement 3. Kinin 4. NO

Question 27

3 major clinical components of clinical shock?

Answer 27

1. Systemic arterial hypotension 2. Clinical signs of hypoperfusion 3. Hyperlactatemia: > 1.5mmol/L

Question 28

Definition of systemic arterial hypotension in sepsis?

Answer 28

Systolic

Question 29

What are the 3 windows into HYPOperfusion in sepsis?

Answer 29

1. Skin – cold, clammy, vasoconstriction, cyanosis | 2. Renal – UOP

Question 30

Clinical studies in SIRS?

Answer 30

``` • WBC >12,000 or 10% immature forms) • Elevated CRP • Elevated Procalcitonin • Glucose >140 in absence of diabetes – SEPSIS • Decreased O2 saturation or PaO2 • Elevated creatinine • Elevated bilirubin, other liver tests • Thrombocytopenia, elevated INR Elevated lactate ```

Question 31

Fluid management in sepsis?

Answer 31

1. Replace .5L in first 30 min - Crystalloid fluids are preferred 2. Central venous catheter: want CVP 8-12

Question 32

Target for MAP in septic ptn.?

Answer 32

> 65

Question 33

When should antibiotics be administered in sepsis?

Answer 33

- Empirical broad spectrum IV within first hour | - Not waiting for culture results

Question 34

Next volume step after fluids?

Answer 34

- Vasopressors: NE

Question 35

Bundle to be completed in first 3 hours of sepsis?

Answer 35

1. Measure lactate 2. Culture blood 3. Broad spectrum antibiotics 4. 30ml/kg crystalloid fluids

Question 36

Bundle to be completed in first 6 hours of sepsis?

Answer 36

1. Vasopressors for refractory hypotension: MAP>65 | 2. Remeasure lactate

Question 37

Steroids effective in controlling septic shock?

Answer 37

Hydrocortisone (200 mg/day) in patients in whom hypotension persists despite adequate fluid resuscitation and vasopressor therapy

Question 38

Are there host modifying drugs for sepsis?

Answer 38

No