Sepsis + Septic Shock

Question 1

What is the definition of sepsis?

Answer 1

systemic illness caused by microbial invasion of normally sterile parts of the body OR
life threatening organising dysfunction due to dysregulated host response to infection

Question 2

What is the definition of septic shock?

Answer 2

Sepsis + persisting hypotension (requiring vasopressors to maintain MAP > 65mmHg + serum lactate > 2 mol/L)

Question 3

What is SIRS + causes of it?

Answer 3

systemic inflammatory response syndrome

causes by trauma, burns, pancreatitis, haemorrhage, ischaemia

Question 4

What are the clinical features of SIRS?

Answer 4

Temp > 38
HR > 90
RR > 20
PaCO2 < 32
WBCs high

Question 5

What scoring criteria is used to assess sepsis?

What is the significance for this criteria?

Answer 5

qSOFA: 3 criteria =
Hypotension (SBP < 100 mmHg)
Altered mental status (GCS < 15)
RR high (> 22 breaths per min)

score 2 or more = greater risk of poor outcome

Question 6

What are the body’s defence mechanisms against infection?

Answer 6

physical barrier: skin, mucosa, epithelial lining
innate immune system: IgA in GI tract, macrophages
adaptive immune system: lymphocytes, immunoglobulins

Question 7

What is the importance of sepsis?

Answer 7

common condition causing increased morbidity, increased mortality (hospital mortality of 40%)

Question 8

What is the origin of sepsis?

Answer 8

There is a breach of host barrier (can be physical or immunological) + organisms enter the bloodstream creating a septic state

Question 9

What features of immunosuppression do patients with sepsis have?

Answer 9

• Inability to clear infection
• loss of delayed hypersensitivity
• predisposition to hospital acquired infection (HAI)

Question 10

Briefly describe the change of the mediators in sepsis over time?

Answer 10

Initially = increase in inflammatory mediators
Later = increase in anti-inflammatory mediators

Question 11

What are the 3 phases of sepsis?

Answer 11

1. release of bacterial toxins
2. release of mediators
3. effects of specific excessive mediators

Question 12

Describe what happens in the first phase of sepsis?

Answer 12

Bacterial invasion into body tissues

This may/ may not be cleared by existing immune system

Question 13

What are the commonly released toxins in the first stage?

release of bacterial toxins

Answer 13

Gram negative: Lipopolysacchride (LPS)
Gram positive: microbial-associated molecular pattern (MAMP)
Superantigens: staphylococcal toxic shock syndrome toxin, streptococcal exotoxins

Question 14

Describe what happens in the second phase of sepsis?

release of mediators

Answer 14

Endotoxin release: LPS + LPS binding protein bind to macrophages

Exotoxin release: causes pro-inflammatory response + small amount super antigens cause a large amount of mediators to be secreted (cascade effect)

Mediator role: Pro-inflammatory mediators cause characteristic inflammatory response of sepsis
Compensatory anti-inflammatory mediators can cause immunoparalysis

Question 15

Describe the third phase of sepsis?

effects pro-inflammatory + anti-inflammatory mediators

Answer 15

Pro-Inflammatory mediators effects:

• promote endothelial cell to leukocyte adhesion
• complement activation
• release of prostaglandins
• vasodilation of blood vessels
• increase coagulation by release of tissue factors + membrane coagulants
• cause hyperthermia

Anti-Inflammatory mediators effects:

• inhibit TNF alpha (cytokine in systemic inflammation)
• halt acute phase reaction
• inhibit activation of coagulation system
• provide negative feedback mechanisms to pro-inflammatory mediators

Question 16

What happens if the pro-inflammatory mediators outweigh the compensatory anti-inflammatory mediators?

Answer 16

Immunoparalysis + uncontrolled infection + multi organ failure

Question 17

What happens if the compensatory anti-inflammatory mediators outweighs the pro-inflammatory mediators?

Answer 17

Septic shock + multi organ failure –> death

Question 18

What are the clinical features of sepsis?

Answer 18

Fever > 38 C (chills, rigors, night sweats)
Hypothermia < 36 C
Tachycardia > 90 beats/min
Tachypnoea > 20/ min
Altered mental status
Hyperglycaemia > 8 mmol/l in the absence of diabetes

Question 19

What are the inflammatory variables in sepsis?

Answer 19

Leucocytosis = WCC high
Leucopenia = WCC low
High CRP
High procalcitonin

Question 20

What are the haemodynamic variables in sepsis?

Answer 20

Arterial hypotension (systolic < 90 mmHg or MAP < 70 mmHg)
O2 Sat (SvO2) < 70%

Question 21

What are the dysfunction variables in sepsis?

Answer 21

Arterial hypoxaemia
Oliguria
Creatinine high
Coagulation abnormalities
Ileus
Thrombocytopenia
Hyperbilirubinaemia

Question 22

What are the tissue perfusion variables in sepsis?

Answer 22

High lactate
Skin mottling
Reduced capillary perfusion

Question 23

What are the host factors which affect the presentation of sepsis?

Answer 23

Age
Co-morbidities (COPD, DM, malignancy)
Immunosuppression- HIV, steroids, chemo drugs
Previous surgery

Question 24

What are the effects of the organism on sepsis presentation?

Answer 24

• Gram positive versus Gram negative
• Virulence factors (example: MRSA, toxin secretion, ESBL, KPC, NDM-1)
• Bioburden

Question 25

Effect of environment on presentation of sepsis?

Answer 25

Occupation
Travel
Hospitalisation

Question 26

What is the purpose of SEPSIS 6?

Answer 26

to reduce mortality and cost

Question 27

Outline the steps of SEPSIS 6

Answer 27

1. Give high flow oxygen
2. Obtain IV/IO access and take blood
3. Give IV or IO antibiotics
4. Consider fluid resuscitation
5. Involve senior clinicians early
6. Consider inotropic support early (–>ICU)