Sepsis and Septic Shock Flashcards
What is SIRS?
Temp high or low
HR >90
RR >20/PaCO2 <32
WBC >12000 or <4000
What is sepsis?
SIRS + Infection
What is severe sepsis?
Sepsis + end organ damage
What is septic shock?
Severe sepsis + Hypotension
How is sepsis defined?
Life-threatening organ dysfunction caused by dysregulated host-response to infection
SOFA score >2
A SOFA score >2 reflects what?
Overall mortality risk of 10%
How is septic shock defined?
Sepsis with persisting hypotension requiring vasopressors to maintain MAP >65mmHg
AND serum lactate >2mmol/l
What is the qSOFA definition of sepsis?
Systolic BP <100mmHg
Altered mental state
Tachypnoea >22/min
Survival in septic shock is inversely proportional to what?
Time taken to give antibiotics
How does septic shock mortality correlate with with delay in administration?
Each hour = 7.6% increase in mortality risk
What are the body’s defences against sepsis?
Physical barrier
Innate immune system
Adaptive immune system
What structures make up the physical barrier against sepsis?
Skin
Mucosa
Epithelial lining
What structures make up the
innate immune system against sepsis?
IgA in GIT
Dendritic cells/macrophages
What structures make up the
adaptive immune system against sepsis?
Lymphocytes
Immunoglobulins
What is the pathophysiology of sepsis?
Uncontrolled inflammatory response
Features consistent with immunosuppression
Probably change to sepsis syndrome
Why is sepsis said to have features consistent with immunosuppression?
Loss of delayed hypersensitivity
Inability to clear infection
Predisposition to nosocomial infection
What is the change of sepsis to sepsis syndrome?
Initial increase in inflammatory mediators
Later shift towards an anti-inflammatory immunosuppressive phase
The change to sepsis syndrome depends on what?
Health of the individual patient
What are the phases of sepsis pathogenesis?
- Release of bacterial toxins
- Release of mediators
- Effects of specific excessive mediators
What is the first phase of sepsis?
Release of bacterial toxins
Bacterial invasion into body tissues
May or may not be cleared by immune system
What are the commonly released toxins of gram -ve bacteria?
Lipopolysaccharide (LPS)
What are the commonly released toxins of gram +ve bacteria?
Microbial-associated molecular pattern (LTA)
(Lipoteichoic acid, Muramyl dipeptides)
Superantigens (TSST, streptococcal exotoxins)
What is the 2nd phase of sepsis?
Release of mediators in response to infection
Endo/exotoxin release effects
What is the effect of endotoxin release in sepsis?
LPS needs an LPS binding protein, LTA do not
These bind to macrophages and trigger mediator release
What is the effect of exotoxin release in sepsis?
Pro-inflammatory response
Small amount of superantigens release large amounts of mediators
What is the cascade effect of exotoxin release?
Small amount of superantigens release large amounts of mediators
Superantigens act on what?
T-lymphocytes
When Superantigens act on T-lymphocytes, they release what?
IL-2
IFN-y
IL-2 effects what?
Macrophage to release mediators
IFN-y effects what?
Macrophage to release mediators
Endothelial cells to release NO
What are the types of mediators released in sepsis?
Pro-inflammatory mediators
Compensatory anti-inflammatory reaction
What can the Compensatory anti-inflammatory reaction cause?
Immunoparalysis
What is stage 3 of sepsis?
Effects of specific excessive mediators (pro- and anti-inflammatory)
What are the effects of pro-inflammatory mediators?
Promote endothelial cell-leukocyte adhesion Release arachidonic acid metabolites Activate complement Vasodilation (NO) Increase coagulation Cause hyperthermia
What are the effects of anti-inflammatory mediators?
Inhibit TNF alpha
Augment acute phase reaction
Inhibit activation of coagulation system
Provide negative feedback mechanisms
What is septic shock?
Imbalance between pro-inflammatory mediators and anti-inflammatory mediators (too much pro-)
What is immunoparalysis with uncontrolled infection?
Imbalance between pro-inflammatory mediators and anti-inflammatory mediators (too much anti-)
The clinical manifestation of sepsis depends on what?
Host
Organism
Environment
What are the neurological effects of sepsis-induced organ dysfunction?
Altered consciousness
Confusion
Psychosis
What are the respiratory effects of sepsis-induced organ dysfunction?
Tachypnoea
Low PaO2
Reduced O2 saturation
What are the hepatic effects of sepsis-induced organ dysfunction?
Jaundice
Increased liver enzymes
Low albumin
Increased INR
What are the haematological effects of sepsis-induced organ dysfunction?
Decreased platelets
Decreased protein C
Increased D-dimer
What are the cardiac effects of sepsis-induced organ dysfunction?
Tachycardia
Hypotension
What are the renal effects of sepsis-induced organ dysfunction?
Oliguria
Anuria
Increased creatinine
What are the general features of sepsis?
Fever - chills/rigors/flushes Hypothermia Tachycardia Tachypnoea Altered mental state - esp. elderly Hyperglycaemia
Hypothermia is a more common sepsis symptom in who?
Elderly
Very young
Immunosuppressed
What inflammatory markers are changed in sepsis?
↑ or ↓ WCC (may be normal)
↑ CRP
↑ Procalcitonin
What are the tissue perfusion variables in sepsis?
High lactate
Skin mottling
Reduced capillary perfusion
What factors in the host can effect the presentation of sepsis?
Age
Co-morbidities
Immunosuppression
Previous surgery i.e splenectomy
What are the main forms of immunosuppression?
Acquired
Drug induced
Congenital
What are the common causes of Drug induced immunosuppression?
Steroids
Chemotherapeutic agents
Biologics
What are the common causes of Congenital immunosuppression?
Agammaglobulinaemia
Phagocytic defects
Defects in complement
What factors in the pathogen can effect the presentation of sepsis?
Gram +ve vs -ve
Virulence factors
Bioburden
What are the Sepsis 6?
Take 3:Give 3
2As, 2Bs, 2Cs
Air enriched with O2 Antibiotics after blood culture Blood culture Blood gas + lactate Crystalloid bolus (fluids) Catheter if severe
What is the diagnostic criteria for sepsis?
Infection - documented and suspected plus some of: General variables Fever or Hypothermia Tachycardia Tachypnea Altered mental status Significant edema or positive fluid balance Hyperglycemia (in the absence of diabetes) Inflammatory variables Leukocytosis Leukopenia Normal WBC count with greater than 10% immature forms Elevated plasma CRP Elevated procalcitonin Hemodynamic variables Arterial hypotension Organ dysfunction variables Arterial hypoxemia Acute oliguria Creatinine increase Coagulation abnormalities Ileus Thrombocytopenia Elevated biliruben Tissue perfusion variables Hyperlactatemia Decreased capillary refill Mottling
What does lactate tell us?
Marker of generalised hypoperfusion/severe sepsis
What does oliguria tell us?
Renal dysfunction
What do blood cultures tell us?
Microbiological diagnosis
How should blood cultures be taken if theres a spike in temperature?
Take 2 sets
What must be considered when giving antibiotics for sepsis?
Working Dx Guidelines Allergy Previous infection Consider toxicity/interactions
What is type A lactate?
Hypoperfusion
What is type B lactate?
Mitochondrial toxins
Alcohol
Malignancy
Metabolism errors
What does lactate tell us about sepsis?
Prognostic indicator
How should fluids be given in sepsis?
30ml/kg
When should you consider a HDU referral?
Low BP response to fluids Lactate >2 despite fluids Elevated creatinine Oliguria Liver dysfunction (Bilirubin, PT, Platelets) Hypoxaemia
When should you consider ITU?
Septic shock
Multi-organ failure
Requires sedation, intubation and ventilation
