Sepsis and Septic Shock Flashcards
What is sepsis?
Systemic illness caused by microbial invasion of normally sterile parts of the body
What is the traditional mode of sepsis?
SIRS
-Hypo/hyperthermic, tachycardia, tachypnoea, high/low WCC
Sepsis
-SIRS + infection
Severe sepsis
-Sepsis + end organ damage
Septic shock
-Severe sepsis + hypotension
Sepsis
A life-threatening organ dysfunction caused by dysregulated host response to infection
How is organ dysfunction identified?
- Organ dysfunction can be identified as an acute change in total SOFA score >2 points consequent to the infection
- SOFA score >2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection
Septic Shock
Clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP >65mmHg and having a serum lactate of >2mmol/l despite adequate volume resuscitation
What does qSOFA identify?
Patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital can be promptly identified with a qSOFA
What are the components of qSOFA?
Score of 2 or more suggest greater risk of poor outcome
- Hypotension systolic BP <100mmGg
- Altered mental status
- Tachypnoea (RR>22)
Why is sepsis so important?
- Common condition
- Becoming more common
- Increased morbidity
- Increased mortality
What defences does the body have against sepsis?
Physical barrier
-Skin, mucosa, epithelial lining
Innate immune system
-IgA in GIT, dendritic cells/macrophages
Adaptive immune system
-Lymphocytes, immunoglobulins
How does sepsis originate?
- Originates from a breach of integrity of host barrier, whether physical or immunological
- Organism enters the bloodstream creating a septic state
Essentially what is sepsis?
An uncontrolled inflammatory response
What features consistent with immunosuppression do patients with sepsis exhibit?
- Loss of delayed hypersensitivity
- Inability to clear infection
- Predisposition to nosocomial infection
What is the shift of the sepsis syndrome that occurs over time?
- Initially there is an increase in inflammatory mediators
- Later, there is a shift toward an anti-inflammatory immunosuppressive phase
- Depends on the health of the individual patient
What are the 3 phases of the pathogenesis of sepsis?
- Release of bacterial toxins
- Release of mediators
- Effects of specific excessive mediators
What commonly release toxins can be responsible for sepsis?
Gram negative
-Lipopolysaccharide
Gram positive
-Microbial associated molecular pattern (MAMP)
-Lipoteichoic acid
-Muramyl dipeptides
Superantigens
-Staphylococcal toxic shock syndrome toxin (TSST)
-Streptococcal exotoxins
What happens in phase 2 of sepsis (release of mediators)?
- Effects of infection due to endotoxin release
- Effects of infections due to exotoxin release
- Mediator role on sepsis
How are endotoxins released?
- LPS (gram negative) require a binding protein to bind to the toll like receptor
- LTA (gram positive) do not require a protein to bind to the toll like receptor
- Binding to toll like receptors on macrophages leads to release of mediators
How are exotoxins released?
Pro-inflammatory response caused by small amounts of super antigens causing a large amount of mediators to be secreted in a cascade effect
What are the 2 types of mediators which can be released in sepsis?
- Pro-inflammatory mediators which cause the inflammatory response that characterises sepsis
- Compensatory anti-inflammatory reaction which can cause immunoparalysis
What is the effect of excessive 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
What is the effect of excessive anti-inflammatory mediators?
- Inhibit TNF alpha
- Augment acute phase reaction
- Inhibit activation of coagulation system
- Provide negative feedback mechanisms to pro-inflammatory mediators
What happens when there is loss of balance between immune responses in favour of pro-inflammatory mediators?
Septic shock with multi-organ failure and death
What happens when there is loss of balance between immune responses in favour of compensatory anti-inflammatory mediators?
Immunparalysis with uncontrolled infection and multi-organ failure
What does the clinical manifestation of sepsis depend on?
- Host
- Organism
- Environment
What organ dysfunction can occur with sepsis: Brain?
- Altered consciousness
- Confusion
- Psychosis
What organ dysfunction can occur with sepsis: Kidney?
- Oliguria
- Anuria
- Increased creatinine
What organ dysfunction can occur with sepsis: Lung?
- Tachypnoea
- PaO2 <70mmHg
- Sats <90%
What organ dysfunction can occur with sepsis: Heart?
- Tachycardia
- Hypotension
What organ dysfunction can occur with sepsis: Blood?
- Decreased platelets
- Decreased protein C
- Increased D-dimer
- Increased PT/APTT
What organ dysfunction can occur with sepsis: Liver?
- Jaundice
- Increased liver enzymes
- Increased PT
- Decreased albumin
What are the general features of sepsis?
- Fever >38C: presenting as chills, rigors, flushes, cold sweats, night sweats, etc
- Hypothermia <36C : 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
What inflammatory variables are there is sepsis?
- Leucocytosis (WCC > 12,000/ml)
- Leucopenia (WCC < 4,000/ml)
- Normal WCC with greater than 10% immature forms
- High CRP
- High procalcitonin
What haemodynamic variables are there in sepsis?
- Arterial hypotension (systolic <90mmHg or MAP <70mmHg)
- SvO2 >70%
What organ dysfunction variables are there in sepsis?
- Arterial hypoxaemia (PaO2/FiO2 < 50mmHg)
- Oliguria (<0.5ml/kg/h)
- Creatinine increase compared to baseline
- Coagulation abnormalities (PT >1.5 or APTT >60s)
- Ileus (paralytic)
- Thrombocytopenia (<150,000/ml)
- Hyperbilirubinaemia
What tissue perfusion variables are there in sepsis?
- High lactate
- Skin mottling and reduced capillary perfusion
What host factors can affect a host’s presentation of sepsis?
- Age
- Co-morbidities (COPD, DM, CCF ,CRF disseminated malignancy)
- Immunosuppression
- Previous surgery including splenectomy
Give examples of reasons why someone might be immunosuppressed.
Acquired
-HIV/AIDs
Congenital
-Agammaglobulinemic, phagocytic defects, defects in terminal complement component
Drug induced
-Steroids, chemotherapeutic agents, biologics
What organism factors can effect the presentation of sepsi?
- Gram positive versus Gram negative (rule of thumb: + act on diaphragm up and - on diaphragm down)
- Virulence factors (example: MRSA, toxin secretion, ESBL, KPC, NDM-1)
- Bioburden
What environment factors can influence presentation of sepsis?
- Occupation
- Travel
- Previous hospitalisations
What algorithm should be used in the treatment of sepsis?
Sepsis 6
- Take 3: give 3
- 2As, 2Bs, 2Cs
What are the components of sepsis management?
Take
- Blood cultures
- Blood lactate
- Urine output
Give
- Oxygen (94-98%)
- IV antibiotics
- IV fluid challenge
Why do we take blood cultures in sepsis?
- Make microbiological diagnosis (30-50% positive)
- If spike in temperature, take 2 sets
Why do we check lactate in sepsis?
Marker of generalised hypoperfusion, severe sepsis and poorer prognosis
Why do we measure urine output in sepsis?
It is a marker of renal dysfunction
How do you decide what antibiotics to give?
- Based on working diagnosis from History and Examination
- Local antibiotic guidelines
- BUT consider allergy
- BUT consider previous MRSA, ESBL, CPE
- BUT consider Abx toxicity/interactions
What is type A lactic acidosis associated with?
Hypoperfusion of tissues
What is type b lactic acidosis associated with?
- Mitochondrial toxins
- Alcohol
- Malignancy
- Metabolism errors
What is the fluid challenge required in sepsis?
30ml per kg
When should a HDU referral be considered in sepsis?
- Low BP responsive to fluids
- Lactate >2 despite fluid resuscitation
- Elevated creatinine
- Oliguria
- Liver dysfunction, Bil, PT, Plt
- Bilateral infiltrates, hypoxaemia
When should an ICU referral be considered in sepsis?
- Septic shock
- Multi-organ failure
- Requires sedation, intubation and ventilation
