Sepsis and septic shock

Question 1

Define sepsis

Answer 1

Life-threatening organ dysfunction caused by dysregulated host response to infection

Organ dysfunction can be identified as an acute change in total SOFA score >2 points consequent to the infection

Question 2

What is SIRS?

Answer 2

Systemic inflammatory response syndrome

Characterised by high or low temp, tachycardia/tachypnoea, high or low WCC

Question 3

Sepsis is defined as a combination of what?

Answer 3

SIRS and infection

Question 4

Severe sepsis is defined as a combination of what?

Answer 4

Sepsis and end organ damage

Question 5

Septic shock is defined as a combination of what?

Answer 5

severe sepsis and hypotension

Question 6

Look

Answer 6

Remember you can have:

Infection presenting with SIRS

Infection without SIRS

SIRS without infection – burns, surgery, major trauma

Question 7

What is qSOFA?

Answer 7

A scoring system for sepsis.

It is used to predict mortality and is not diagnostic.

Question 8

What are the 3 criteria for qSOFA?

Answer 8

• Altered mental status GCS <15
• Respiratory rate ≥22
• Systolic BP ≤100

= 1 point for each

Question 9

What does a SOFA score of ≥2 mean?

Answer 9

Greater risk of a poor outcome in patients with suspected infection.

These patients should be more thoroughly assessed for evidence of organ dysfunction.

Question 10

Look

Answer 10

Time = life

For each hour’s delay in administering antibiotics in septic shock, mortality increases by 7.6%

Question 11

What are the body’s defence mechanisms against sepsis? (3)

Answer 11

Physical barrier - skin, mucosa, epithelial lining

Innate immune system - IgA in GI tract, dendritic cells / macrophages

Adaptive immune system - lymphocytes, immunoglobulins

Question 12

How does sepsis start?

Answer 12

Breach of the host barrier, whether physical or immunological.

Organism can then enter the bloodstream creating a septic state

Question 13

Which features do patients with sepsis share with immunosuppressed patients?

Answer 13

Loss of delayed hypersensitivity

Inability to clear infection

Predisposition to health-care associated infections

Question 14

Timeline: How does sepsis develop?

Answer 14

Initially there is an increase in inflammatory mediators

Later, there is a shift toward an anti-inflammatory immunosuppressive phase

But this all depends on the health of the individual patient

Question 15

3 phases in the pathogenesis of sepsis

Answer 15

1. Release of bacterial toxins
2. Release of mediators
3. Effects of specific excessive mediators

Question 16

Phase 1 of sepsis

Answer 16

Bacterial invasion into body tissues is a source of dangerous toxins

May or may not be neutralised and cleared by existing immune system

Question 17

What is a common toxin released by Gram negative bacteria?

Answer 17

Lipopolysaccharide

Question 18

What are commonly released toxins by Gram positive bacteria? (2)

Answer 18

Microbial-associated molecular pattern (MAMP) - LTA, Muramyl dipeptides

Superantigens - TSST, streptococcal exotoxins

Question 19

Phase 2 of sepsis

Answer 19

Body responds to infection (release of toxins) by releasing mediators

Effects of infection due to endotoxin/exotoxin release kick in

Bacteria can be taken up by any of the antigen presenting cells and in turn they will be able to activated CD4 t cell to produce either TH1 or TH2 response

Question 20

Superantigens bind directly to what? What does this produce?

Answer 20

T cells

Small amounts of superantigens will cause a large amount of mediators to be secreted: cascade effect

Question 21

What are the 2 types of mediators that can be released in response to infection?

Answer 21

Th1

Th2

Question 22

Describe the Th1 response

Answer 22

Pro-inflammatory mediators – causes inflammatory response that characterises sepsis

Question 23

Describe the Th2 response

Answer 23

Compensatory anti-inflammatory reaction – can cause immunoparalysis

Question 24

Most important pro-inflammatory mediators

Answer 24

IL–1
TNF alpha
IFN gamma

Question 25

Most important anti-inflammatory mediators

Answer 25

IL-10 | Transforming growth factor beta

Question 26

Effects of pro-inflammatory mediators

Answer 26

Promote endothelial cell – leukocyte adhesion Release of arachidonic acid metabolites Complement activation Vasodilatation of blood vessels by NO Increase coagulation by release of tissue factors and membrane coagulants Cause hyperthermia – TNF alpha (pro-inflammatory mediator)

Question 27

Effects of anti-inflammatory mediators

Answer 27

Inhibit TNF alpha Augment acute phase reaction Inhibit activation of coagulation system Provide negative feedback mechanisms to pro-inflammatory mediators

Question 28

Look

Answer 28

There needs to be a balance between the Th1 and Th2 responses to an infection because if you go more towards one way or the other you’re going to have problems.

Question 29

What happens if you have a bigger compensatory anti-inflammatory response?

Answer 29

Immunoparalysis with uncontrolled infection and multi-organ failure

Question 30

What happens if you have a bigger pro-inflammatory response?

Answer 30

Septic shock with multi-organ failure and death

Question 31

General features of sepsis (8)

Answer 31

Fever >38oC – presenting as chills, rigors, flushes, cold sweats, night sweats, etc Hypothermia <36oC – especially in the elderly and very young children (remember the immunosuppressed) Tachycardia >90 beats/min Tachypnoea >20 /min Altered mental status – especially in the elderly Hyperglycaemia >8mmol/l in the absence of diabetes Arterial hypotension (systolic <90mmHg or MAP <70mmHg) SvO2 >70%

Question 32

Look

Answer 32

Remember that immunocompromised patients may not be able to produce an immune response so may not have a fever but still present with symptoms of sepsis

Question 33

Inflammatory variables in sepsis

Answer 33

Leucocytosis (WCC > 12,000/ml) = high Leucopenia (WCC < 4,000/ml) Normal WCC with greater than 10% immature forms - an immature neutrophil is called a band; bands are increased in number by bacterial infection High CRP High procalcitonin

Question 34

Effect of host on sepsis presentation

Answer 34

Age Co-morbidities Immunosuppression Previous surgery - splenectomy

Question 35

Describe how the sepsis 6 | Take 3: Give 3 method works

Answer 35

Take 3 samples/tests: Blood cultures Blood lactate Measure urine output - marker of renal dysfunction Give 3: Oxygen aim sats 94-98% IV Antibiotics IV fluid challenge - for hypotension

Question 36

Why is Lactate so important?

Answer 36

It is a marker of generalised hypoperfusion/severe sepsis/poorer prognosis 2 types: Type A and B Poorly perfused tissue beds result in global tissue hypoxia, which is often found in association with an elevated serum lactate level. A serum lactate value greater than 4 mmol/L (36 mg/dL) is correlated with increased severity of illness and poorer outcomes even if hypotension is not yet present - require IV fluids

Question 37

When might a patient need referred to a high dependency unit?

Answer 37

Low BP responsive to fluids Lactate >2 despite fluid resuscitation Elevated creatinine Oliguria - small urine output despite fluid resuscitation Liver dysfunction, Bil, PT, Plt Bilateral infiltrates, hypoxaemia

Question 38

When might a patient need referred to intensive treatment unit?

Answer 38

Septic shock Multi-organ failure Requires sedation, intubation and ventilation