Sepsis

Question 1

What is sepsis?

Answer 1

Life threatening organ dysfunction from dysregulated immune response to infection.

Question 2

What is used to assess likelihood of patients dying from sepsis?

Answer 2

Sequential Organ Failure Assessment Score (SOFAS)

Question 3

How many people per year enter ICU due to sepsis?

Answer 3

0.77/1000 (total 3 - 4 fold higher)

Question 4

How much does sepsis cost?

Answer 4

39300 per admission

Question 5

What factors make mortality from sepsis more likely?

Answer 5

increased age and neonates

Chronic comorbidities and immunosuppression

Inappropriate antimicrobial therapy (theres a golden time period)

Question 6

What causes sepsis?

Answer 6

Bacteria

Fungi

Viruses

Protozoans (malaria)

Question 7

What steps lead to sepsis?

Answer 7

1) Highly virulent pathogens infect person or immunosuppressed individuals.
2) Body detects pathogen and mounts a local inflammatory response with Toll and NOD receptors and phagocytes.
3) Multi-organ failure
4) Sepsis induced immunosuppression

Question 8

How do you know if someone is infected with a opportunistic bug?

Answer 8

Foci are often evident and bacteria are often antibiotic resistant

Question 9

What are some important microbial factors in the likelihood of progression to sepsis?

Answer 9

Inoculum size

Bacterial structural components forming endotoxins (LPS, peptidoglycan)

Expressed toxins (exotoxins)

Question 10

Why is inoculum size important?

Answer 10

How many bugs initially invading so the higher the inoculum the higher the probability of infection.

Question 11

Which kind of bacteria, gram positive or gram negative, most commonly express exotoxin pathogenicity?

Answer 11

Gram positive infections

Question 12

What are some common toxins produced by bacteria?

Answer 12

Streptokinase

Diphtheria

Clostridia toxins

Staph enterotoxins

Super antigens in the staph and strep toxic shock syndromes

Question 13

How do potential infectious agents enter the body (Primary foci of infection)?

Answer 13

Most enter through the lungs

Intra-abdominal

Blood

Skin

Urine

Question 14

What do Toll and NOD receptors do?

Answer 14

They detect common antigens of pathogens like LPS and release early cytokines and create an early local inflammatory response and then a systemic inflammatory response.

Question 15

When does an infection transition to sepsis?

Answer 15

If there is failure to locally resolve/contain the infection

Question 16

Is sepsis always associated with bacteraemia?

Answer 16

It may or may not be associated with bacteraemia. (20 - 50% of blood cultures come back positive)

Question 17

What changes happen when an infection transitions to sepsis?

Answer 17

Concurrent anti-infective and anti-inflammatory cascades

Microcirculatory dysfunction and coagulopathy

Multi-organ dysfunction without widespread death initially

Hypoxia: Metabolic derangement and mitochondrial dysfunction at tissue

Question 18

What are the symptoms of bacteraemia and sepsis?

Answer 18

Classic signs and symptoms

Abrupt onset

Shaking chills, rigors

Fever or hypothermia

Other signs:

Delirium, stupor, agitation

Dyspnea

Cool or hot

Acute renal failure

Rash (Toxic shock, DIC, purpura fulminans, cellulitis)

Question 19

How is a focus and pathogen looked for?

Answer 19

Clinical assessment

Blood and urine are cultured (as guided by clinical picture: Sputum, pus, CSF)

Imaging (Chest X ray, targeted CT and ultrasound, if CNS based process MRI is taken if patient is stable)

Question 20

Why are blood or urine cultures favoured for diagnosis of sepsis nowover other diagnostic methods?

Answer 20

Because Rapid Molecular diagnostics are increasingly available.

Question 21

What are some examples of the rapid molecular diagnostics now available?

Answer 21

Penumococcal and legionella urinary antigens

Respiratory PCR’s on sputum

Neisseria, legionella, peneumococcal, viral PCRs on CSF

Question 22

What are some modern imagind techniques used for sepsis patients?

Answer 22

CXR

Targeted CT and ultrasound (particularly for the abdomen)

If CNS based process: MRI

Question 23

How is the bug causing sepsis treated?

Answer 23

Antimicrobial therapy (using antibiotics asap due to time critical nature)

Source control (drainage of infected fluid and infected catheter)

Question 24

How is appropriate antimicrobial therapy done?

Answer 24

It must be done within the golden hour

Culture must be taken first so that the correct antibiotics are used

Usually started empirically

Organism is identified

Source control (drainage of infected fluid and infected catheter)

Question 25

How is the host treated in sepsis?

Answer 25

Physiologic support (IV fluids, inotropic support, mechanical ventillation, early nutrition support, glycaemic control, goals directed bundles)

Glucocorticoids (curb inflammation, in refractory septic shock)

Question 26

What has been done so far to investigate treatment of sepsis?

Answer 26

Since 1982: 80 phase 2 and 3 trials of investigational agents and they have all failed.

There are a lack of good animal models.

Question 27

What agents are being investigated to reduce death from sepsis?

Answer 27

Cytokine profiling and targeted immuno modulation

Rapid bacterial diagnostics

Real time antibiotic level monitoring and dosing

Bacterial virulence modulators

Vitamin C

Question 28

How can sepsis be prevented?

Answer 28

Immunizations

Minimizing iatrogenic infections:

Health care bundles for ventilator, intravascular and urinary catheter managent

Hand hygiene

Smart use of antibiotics

Judicial use of catheters

Question 29

What are the long term impacts of people who survive sepsis?

Answer 29

Increased mortality (complex but appears to be causal)

Increased morbidity (mood disorders, chronic fatigue, and accelerated frailty and neurocognitive decline in the elderly)

Question 30

What causes increased mortality in patients who survived sepsis?

Answer 30

Recurrent infection and non-infective death due to sepsis induced immunosuppression and destabilising vascular disease