Sepsis Flashcards
What is sepsis?
Life threatening organ dysfunction from dysregulated immune response to infection.
What is used to assess likelihood of patients dying from sepsis?
Sequential Organ Failure Assessment Score (SOFAS)
How many people per year enter ICU due to sepsis?
0.77/1000 (total 3 - 4 fold higher)
How much does sepsis cost?
39300 per admission
What factors make mortality from sepsis more likely?
increased age and neonates
Chronic comorbidities and immunosuppression
Inappropriate antimicrobial therapy (theres a golden time period)
What causes sepsis?
Bacteria
Fungi
Viruses
Protozoans (malaria)
What steps lead to sepsis?
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
How do you know if someone is infected with a opportunistic bug?
Foci are often evident and bacteria are often antibiotic resistant
What are some important microbial factors in the likelihood of progression to sepsis?
Inoculum size
Bacterial structural components forming endotoxins (LPS, peptidoglycan)
Expressed toxins (exotoxins)
Why is inoculum size important?
How many bugs initially invading so the higher the inoculum the higher the probability of infection.
Which kind of bacteria, gram positive or gram negative, most commonly express exotoxin pathogenicity?
Gram positive infections
What are some common toxins produced by bacteria?
Streptokinase
Diphtheria
Clostridia toxins
Staph enterotoxins
Super antigens in the staph and strep toxic shock syndromes
How do potential infectious agents enter the body (Primary foci of infection)?
Most enter through the lungs
Intra-abdominal
Blood
Skin
Urine
What do Toll and NOD receptors do?
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.
When does an infection transition to sepsis?
If there is failure to locally resolve/contain the infection
Is sepsis always associated with bacteraemia?
It may or may not be associated with bacteraemia. (20 - 50% of blood cultures come back positive)
What changes happen when an infection transitions to sepsis?
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
What are the symptoms of bacteraemia and sepsis?
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)
How is a focus and pathogen looked for?
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)
Why are blood or urine cultures favoured for diagnosis of sepsis nowover other diagnostic methods?
Because Rapid Molecular diagnostics are increasingly available.
What are some examples of the rapid molecular diagnostics now available?
Penumococcal and legionella urinary antigens
Respiratory PCR’s on sputum
Neisseria, legionella, peneumococcal, viral PCRs on CSF
What are some modern imagind techniques used for sepsis patients?
CXR
Targeted CT and ultrasound (particularly for the abdomen)
If CNS based process: MRI
How is the bug causing sepsis treated?
Antimicrobial therapy (using antibiotics asap due to time critical nature)
Source control (drainage of infected fluid and infected catheter)
How is appropriate antimicrobial therapy done?
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)
How is the host treated in sepsis?
Physiologic support (IV fluids, inotropic support, mechanical ventillation, early nutrition support, glycaemic control, goals directed bundles)
Glucocorticoids (curb inflammation, in refractory septic shock)
What has been done so far to investigate treatment of sepsis?
Since 1982: 80 phase 2 and 3 trials of investigational agents and they have all failed.
There are a lack of good animal models.
What agents are being investigated to reduce death from sepsis?
Cytokine profiling and targeted immuno modulation
Rapid bacterial diagnostics
Real time antibiotic level monitoring and dosing
Bacterial virulence modulators
Vitamin C
How can sepsis be prevented?
Immunizations
Minimizing iatrogenic infections:
Health care bundles for ventilator, intravascular and urinary catheter managent
Hand hygiene
Smart use of antibiotics
Judicial use of catheters
What are the long term impacts of people who survive sepsis?
Increased mortality (complex but appears to be causal)
Increased morbidity (mood disorders, chronic fatigue, and accelerated frailty and neurocognitive decline in the elderly)
What causes increased mortality in patients who survived sepsis?
Recurrent infection and non-infective death due to sepsis induced immunosuppression and destabilising vascular disease
