Sepsis and Septic Shock

Question 1

What is sepsis?

Answer 1

Systemic illness caused by microbial invasion of normally sterile parts of the body

Question 2

What are the features of systemic inflammatory response syndrome?

Answer 2

Temperature > 38 or < 36 degrees celsius 
Heart rate > 90 
Respiratory rate > 20 
PaCO2 < 32 
WBC > 12,000 or < 4,000 or > 10% bands

Question 3

What are the characteristics of severe sepsis?

Answer 3

Sepsis and end organ damage

Question 4

What are the characteristics of septic shock?

Answer 4

Severe sepsis and hypotension

Question 5

When should systemic inflammatory response syndrome (SIRS) be considered to be serious?

Answer 5

If there are signs of infection - SIRS occurs in many situations as a normal physiological response

Question 6

What is sepsis 3?

Answer 6

The third international consensus definition for sepsis and septic shock

Question 7

How is sepsis defined by sepsis 3?

Answer 7

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

Question 8

How is organ dysfunction defined?

Answer 8

Acute change in total SOFA score > 2 points, consequent to the infection

Question 9

What does a SOFA score > 2 reflect?

Answer 9

Overall mortality risk of approximately 10% in a general hospital population with suspected infection

Question 10

How is septic shock defined by sepsis 3?

Answer 10

Clinical construct of sepsis with persistent hypotension requiring vasopressors to maintain MAP > 65mmHg and having a serum lactate of > 2mmol/l despite adequate volume resuscitation

Question 11

What is the hospital mortality of patients with septic shock?

Answer 11

40%

Question 12

What effect does sepsis have on morbidity and mortality?

Answer 12

Both are increased

For each hours delay in administering antibiotics in septic shock, mortality increased by 7.6%

Question 13

What is the SOFA score?

Answer 13

Sequential Organ Failure Assessment score

Question 14

When might qSOFA be used?

Answer 14

To promptly identify patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital

Question 15

Features of qSOFA

Answer 15

Hypotension systolic BP < 100mmHg
Altered mental status
Tachypnoea with respiratory rate > 33/min

Question 16

What score in the qSOFA suggests a greater risk of poor outcome?

Answer 16

2 or more

Question 17

What are the bodies defences against sepsis?

Answer 17

Physical barrier - skin, mucosa, epithelial linings
Innate immune system - IgA, dendritic cells, macrophages
Adaptive immune system - lymphocytes, immunoglobulins

Pathogens can’t cause infection without first invading through these defences

Question 18

Pathophysiology of sepsis

Answer 18

Uncontrolled inflammatory response
Loss of delayed hypersensitivity
Inability to clear infection

Question 19

What is the change of the sepsis syndrome over time?

Answer 19

Initial increase in inflammatory mediators

Later, shift towards anti-inflammatory immunosuppressive phase

Question 20

What are the phases in the pathogenesis of sepsis?

Answer 20

Release of bacterial toxins
Release of mediators
Effects of specific mediators

Question 21

Features of phase 1 of sepsis

Answer 21

Bacterial invasion into the body, source of toxins

Commonly gram negative or gram positive toxins

Question 22

Features of phase 2 of sepsis

Answer 22

Effects of infections due to endotoxin release
Effects of infections due to exotoxin release
Mediator role on sepsis

Question 23

Features of exotoxin release in sepsis

Answer 23

Pro-inflammatory response

Small amounts of super-antigens cause a large amount of mediators to be secreted, resulting in a cascade effect

Question 24

What types of mediators are released in sepsis?

Answer 24

Pro-inflammatory (cause inflammatory response that characterises sepsis)
Compensatory anti-inflammatory (can cause immunoparalysis)

Question 25

Effects of pro-inflammatory mediators in phase 3 of sepsis

Answer 25

Pro-inflammatory mediators - promote endothelial cell-leucocyte adhesion - release arachidonic acid metabolites - complement activation - vasodilation of blood vessels by NO - increased coagulation by release of tissue factors and membrane coagulants - causes hyperthermia

Question 26

Effects of anti-inflammatory mediators in phase 3 of sepsis

Answer 26

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

Question 27

Clinical features of sepsis and septic shock depend on what factors?

Answer 27

Host Organism Environment

Question 28

Clinical features of organ dysfunction due to sepsis/septic shock

Answer 28

``` Altered consciousness, confusion, psychosis Tachypnoea (PaO2 < 70mmHg, sats < 90%) Jaundice Decreased platelets Increased PT/APTT Decreased protein C Increased D-dimer Tachycardia Hypotension Oliguria, anuria Increased creatinine ```

Question 29

General features of sepsis/septic shock

Answer 29

``` Fever > 38 - chills, rigors, flushes, cold sweats, night sweats Hypothermia < 36 Tachycardia > 90bpm Tachypnoea > 20/min Altered mental status Hyperglycaemia ```

Question 30

Inflammatory variables in sepsis/septic shock

Answer 30

``` Leucocytosis Leucopenia Normal WCC with > 10% immature forms High CRP High procalcitonin ```

Question 31

Haemodynamic variables in sepsis/septic shock

Answer 31

Arterial hypotension | SvO2 > 70%

Question 32

Organ dysfunction variables in sepsis/septic shock

Answer 32

``` Arterial hypoxaemia Oliguria Creatinine increased Coagulation abnormalities Thrombocytopenia Hyperbilirubinaemia ```

Question 33

Tissue perfusion variables in sepsis/septic shock

Answer 33

High lactate | Skin mottling and reduced capillary perfusion

Question 34

Host features which can affect sepsis presentation

Answer 34

Age Co-morbidities Immunosuppression Previous surgery

Question 35

Organism features which can affect sepsis presentation

Answer 35

Gram positive vs gram negative Virulence factors Bioburden

Question 36

Features of environment which can affect sepsis presentation

Answer 36

Occupation e.g. farming, exposed to uncommon infections Travel e.g. malaria Hospitalisation

Question 37

Features of sepsis 6

Answer 37

``` Air enriched with O2 Antibiotics after blood culture Blood culture Blood gas with lactate Crystalloid Bolus Catheter if severe sepsis or septic shock ```

Question 38

Oxygen aim in sepsis

Answer 38

Saturation 94-98%

Question 39

Blood cultures in sepsis

Answer 39

Make microbiological diagnosis 30-50% positive 2 sets should be taken if there is a spike in temperature

Question 40

What is lactate a marker of in sepsis?

Answer 40

Generalised hypoperfusion Severe sepsis Poor prognosis

Question 41

What is low urine output a marker of in sepsis?

Answer 41

Renal dysfunction

Question 42

IV fluids in sepsis

Answer 42

30ml/kg fluid challenge e.g. 2.1L for 70kg patient

Question 43

When should HDU referral be considered?

Answer 43

``` Low BP responsive to fluids Lactate > 2 despite fluid resuscitation Elevated creatinine Oliguria Liver dysfunction Bilateral infiltrates Hypoxaemia ```

Question 44

When should ITU referral be considered?

Answer 44

Septic shock Multi-organ failure If patient requires sedation, intubation and ventilation

Question 45

Factors to consider regarding antibiotic treatment of sepsis

Answer 45

``` Working diagnosis from history and examination Local antibiotic guidelines Allergy Previous MRSA, ESBL or CPE Antibiotic toxicity and interaction ```

Question 46

What are the commonly released toxins?

Answer 46

Gram positive - lipopolysaccharides Gram negative - Microbial associated molecular pattern (MAMP) - lipoteichoic acid, muramyl dipeptides - Superantigens - staphylococcal toxic shock syndrome toxin, streptococcal exotoxins

Question 47

What is the difference between LPS and LTA in endotoxin release?

Answer 47

LPS needs an LPS-binding protein to bind to macrophages, LTA do not need such proteins