Sepsis and septic shock Flashcards
Define sepsis
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
What is SIRS?
Systemic inflammatory response syndrome
Characterised by high or low temp, tachycardia/tachypnoea, high or low WCC
Sepsis is defined as a combination of what?
SIRS and infection
Severe sepsis is defined as a combination of what?
Sepsis and end organ damage
Septic shock is defined as a combination of what?
severe sepsis and hypotension
Look
Remember you can have:
Infection presenting with SIRS
Infection without SIRS
SIRS without infection – burns, surgery, major trauma
What is qSOFA?
A scoring system for sepsis.
It is used to predict mortality and is not diagnostic.
What are the 3 criteria for qSOFA?
- Altered mental status GCS <15
- Respiratory rate ≥22
- Systolic BP ≤100
= 1 point for each
What does a SOFA score of ≥2 mean?
Greater risk of a poor outcome in patients with suspected infection.
These patients should be more thoroughly assessed for evidence of organ dysfunction.
Look
Time = life
For each hour’s delay in administering antibiotics in septic shock, mortality increases by 7.6%
What are the body’s defence mechanisms against sepsis? (3)
Physical barrier - skin, mucosa, epithelial lining
Innate immune system - IgA in GI tract, dendritic cells / macrophages
Adaptive immune system - lymphocytes, immunoglobulins
How does sepsis start?
Breach of the host barrier, whether physical or immunological.
Organism can then enter the bloodstream creating a septic state
Which features do patients with sepsis share with immunosuppressed patients?
Loss of delayed hypersensitivity
Inability to clear infection
Predisposition to health-care associated infections
Timeline: How does sepsis develop?
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
3 phases in the pathogenesis of sepsis
- Release of bacterial toxins
- Release of mediators
- Effects of specific excessive mediators
Phase 1 of sepsis
Bacterial invasion into body tissues is a source of dangerous toxins
May or may not be neutralised and cleared by existing immune system
What is a common toxin released by Gram negative bacteria?
Lipopolysaccharide
What are commonly released toxins by Gram positive bacteria? (2)
Microbial-associated molecular pattern (MAMP) - LTA, Muramyl dipeptides
Superantigens - TSST, streptococcal exotoxins
Phase 2 of sepsis
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
Superantigens bind directly to what? What does this produce?
T cells
Small amounts of superantigens will cause a large amount of mediators to be secreted: cascade effect
What are the 2 types of mediators that can be released in response to infection?
Th1
Th2
Describe the Th1 response
Pro-inflammatory mediators – causes inflammatory response that characterises sepsis
Describe the Th2 response
Compensatory anti-inflammatory reaction – can cause immunoparalysis
Most important pro-inflammatory mediators
IL–1
TNF alpha
IFN gamma
Most important anti-inflammatory mediators
IL-10
Transforming growth factor beta
Effects of pro-inflammatory mediators
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)
Effects of anti-inflammatory mediators
Inhibit TNF alpha
Augment acute phase reaction
Inhibit activation of coagulation system
Provide negative feedback mechanisms to pro-inflammatory mediators
Look
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.
What happens if you have a bigger compensatory anti-inflammatory response?
Immunoparalysis with uncontrolled infection and multi-organ failure
What happens if you have a bigger pro-inflammatory response?
Septic shock with multi-organ failure and death
General features of sepsis (8)
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%
Look
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
Inflammatory variables in sepsis
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
Effect of host on sepsis presentation
Age
Co-morbidities
Immunosuppression
Previous surgery - splenectomy
Describe how the sepsis 6
Take 3: Give 3 method works
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
Why is Lactate so important?
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
When might a patient need referred to a high dependency unit?
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
When might a patient need referred to intensive treatment unit?
Septic shock
Multi-organ failure
Requires sedation, intubation and ventilation
