Sepsis

Question 1

Define sepsis

Answer 1

Surviving sepsis campaign 2021 update.
Sepsis: “Life-threatening organ dysfunction caused by a dysregulated host response to infection”

Septic shock:

• sepsis with requirement for vasopressors to maintain MAP >65mmHg
• serum lactate >2mmol/L in absence of hypovolaemia

Question 1

Define sepsis

Answer 1

Surviving sepsis campaign 2021 update.
Sepsis: “Life-threatening organ dysfunction caused by a dysregulated host response to infection”

Septic shock:

• sepsis with requirement for vasopressors to maintain MAP >65mmHg
• serum lactate >2mmol/L in absence of hypovolaemia

Various screen scores have been suggested including:

• SOFA score
• qSOFA
• SIRS
• NEWS

Question 2

What host defence mechanisms exist to protect against infection?

Answer 2

1. Natural barriers:
   - skin
   - mucus
   - ciliary clearance
   - stomach acid
   - healthy flora/microbiome
2. Innate immunity
   - neutrophils, mast cells, dendritic cells, NK cells
3. Adaptive immunity
   - T helper (CD4 cells)
   - B cells

Question 3

What is the pathophysiology of sepsis?

Answer 3

Several pathophysiological processes ultimately lead to tissue hypoxia

1. Vasodilatation:
   - inducible NO synthase from NK activation leads to endothelial NO production
   - distributive shock
2. Loss of endothelial integrity:
   - tight and gap junction impairment in basal membrane
   - glycocalyx disruption
   - bacterial translocation
   - capillary leak
   - ARDS
3. Reduced myocardial contractility
4. Coagulation cascade activation:
   - Inflammatory mediators (IL-1, IL-6, TNFa) cause microthrombi
5. Mitochondrial dysfunction

1-4. Decreased DO2
5. Decreased VO2 and tissue oxygen utilisation

Question 3

What is the pathophysiology of sepsis?

Answer 3

Several pathophysiological processes ultimately lead to tissue hypoxia

1. Vasodilatation:
   - inducible NO synthase from NK activation leads to endothelial NO production
   - distributive shock
2. Loss of endothelial integrity:
   - tight and gap junction impairment in basal membrane
   - glycocalyx disruption
   - bacterial translocation
   - capillary leak
   - ARDS
3. Reduced myocardial contractility
4. Coagulation cascade activation:
   - Inflammatory mediators (IL-1, IL-6, TNFa) cause microthrombi
5. Mitochondrial dysfunction

1-4. Decreased DO2
5. Decreased VO2 and tissue oxygen utilisation

Question 4

What are exotoxins/endotoxins?

Answer 4

Exotoxins are polypeptides from Gram +ve bacteria
- staph, strep. pyogenes, bacillus, clostridia

Endotoxins are in gram -Negative bacterial cell walls (E.coli, salmonella, shigella, vibrio)

Question 5

How should a patient with sepsis be managed?

Answer 5

Resuscitate in A-E approach

Surviving sepsis bundles

3-hour:

• measure lactate
• obtain blood cultures
• administer broad spectrum Abx
• 30ml/kg crystalloid for hypotension or lactate >4

6-hour:

• Vasopressors if MAP <65 after fluid resus
• Repeat lactate if initially raised
• Reassess volume status

Question 6

What is early goal-directed therapy?

Answer 6

2001 NEJM Rivers recommended targeting physiological parameters.
Included fairly standard and non-standard assessments (e.g. early vasopressors, ScvO2 <70%, dobutamine).

Larger RCTs in US (ProCESS), UK (PROMISE) and Australia (ARISE) failed to show similar mortality reduction compared to standard care.

Non-standard care mortality in Rivers much higher.

Question 7

What vasopressors can be used in septic shock?

Answer 7

Noradrenaline is usually first line.
Multiple subsequent studies have failed to convincingly display superiority.

VASST showed non-inferiority comparing vasopressin with NA.

LeoPARDS showed no benefit from levosimendan vs placebo in septic shock

VANISH compared incidence of AKI with NA vs Vasopressin and found no difference in outcome

Question 8

What is the evidence for use of steroids in septic shock?

Answer 8

CORTICUS:

• reduced duration of vasopressor dependence
• No better 28 day mortality

ADRENAL:

• reduced time to resolution of shock
• no improved 90 day mortality

Question 9

What is neutropenic sepsis?

Answer 9

Potentially life-threatening complication of neutropenia.

Defined as:

• temperature >38 or symptoms/signs of sepsis
• In a patient with neutrophils <0.5

Question 10

How is neutropenia graded?

Answer 10

Absolute neutrophil count (ANC)

Mild = 1.0 to 1.5
Moderate = 0.5 to 1.0
Severe = 0.2 to 0.5
Very severe = <0.2

Question 11

What can cause neutropenia?

Answer 11

1. Decreased production
   - Drugs: immunosuppressive therapy, cytotoxic chemo
   - Marrow compromise: Stem cell transplantation, leukaemia, lymphoma, sepsis, radiotherapy
   - Viral infection
   - B12 deficiency
   - aplastic anaemia
2. Increased utilisation/destruction
   - sepsis
   - hypersplenism
   - autoimmune disorders

Question 12

What is the management of neutropenic sepsis?

Answer 12

Resuscitate using ABCDE approach correcting abnormalities as you find them.

Specific features include:

• implementing sepsis six management.
• Broad spectrum abx therapy with anti-pseudomonas cover (Tazocin) +/- amino glycoside following Micro advice.
• Investigate for atypical infection: Fungal cultures, PCP, BAL, galactomannan, CMV titres etc.
• MDT approach with involvement of Microbiology and Haematology.