Pathophysiology and Treatment of Sepsis Flashcards
What is the definition of sepsis?
Life-threatening organ dysfunction caused by a dysregulated response to infection
What is the definition of septic shock?
A subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone
Who are most at risk of developing sepsis?
- Very young (>1 year)
- Older adults (>75 years)
- Those with impaired immune systems due to illness or medications
- Those who have had surgery/invasive procedure in last 6 weeks
- Anyone with breach of skin integrity (cuts, burns, blisters, skin infection)
- IV drug users
- People with indwelling lines or catheters
- Woman who are preganant, have given birth or had a termination of pregancy or miscarriage in last 6 weeks
- Neonates
How often is the pathogen causing sepsis in a patient actually identified?
Only around half of cases
What are the key causitive Pathogens for sepsis?
- Neisseria meningitidis
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Staphylococcus aureus (including MRSA)
- Salmonella typhimurium
- Klebsiella pneumoniae
- Gram negative bacilli
- Candida species
What kind of organisms are asplenics highly suseptibal to?
Encapsulated organisms
What can cause breaching of the host?
- Catheters
- Wounds
- Burns
- Thorn pricks
- Insect bites
- Epithelial cell damage
What are the main factors affecting infection?
- Virulence of pathogen (presence or absence of endotoxin)
- Bioburden (CFU)
- Portal of entry
- Host susceptibility
- Temporal evolution
Name some immune molecules / cells / receptors inolved in the first line of defence against pathogenic insult
- Complement
- Mannose-binding lectin (MBL)
- Phagocytes
- Toll-like receptors (TLRs)
- Nucleoside-binding oligomerisation domain receptors (NLRs)
Name some inflammatory markers produced by the host?
- Interleukins (ILs)
- Tumour Necrosis Factor alpha (TNFa)
- Reactive oxygen species (ROS)
What does TLR4 recognise?
LPS (which is present on many gram-negative bacteria)
What are the three stages of the immune and inflammatory pathways?
- Access
- Recognition
- Response
Where is lipoteichoic acid present?
The cell wall of gram-positive bacteria
What is the host molecule that identifies peptidoglycans?
CD14
What host cell molecule identifies lipoteichoic acid?
Macrophage scavenger receptor
What type of host molecule recognises bacterial DNA?
The nucleotide binding oligomerisation domain (NOD-1, NOD-2)
What does a vast increase in cytokines and effector molecules cause in response to infection in the body?
Increased - Intravascular coagulation - Stress hyperglycaemia - Cytopathic dysoxia Decreased - fibrinolysis - Circulatory control - Endothelial integrity Organ failure
What are the effects of TNFa and IL-2 on the body:
Acute phase response
- Fever
- Hypotension
- Increased HR
- Corticosteroid and ACTH release
- Release of neutrophils
What are the effects of IL-1 and TNFa on the CVS?
- Generalised vasodilation (NO)
- Increased vascular permeability (activated leukocytes)
- Intravascular fluid loss
- Myocardial depression (tissue hypoxia)
- Circulatory shock
What happens to albumin levels in the blood during septic shock?
Decrease
When is a patient screened for sepsis?
- Patient presents with unexplained illness
- Clearly looks unwell and has a likely infctive cause
- OR presents with (or deteriorates to) an individual parameter score of 3 or aggregate score of 4 or higher on FEWS chart
Expain the sepsis screening tool (for non-haematology patients)
- FEWS alert 3 or greater Assess for SIRS - Temperature < 36 C or > 38 - HR > 90 bpm - WCC > 12 or <4 x10^9/l - RR > 20 bpm SEPSIS if any evidence of infection or new infection developing
What does SIRS stand for?
Systemic Inflammatory Response Syndrome
When can a patient be classified as having SIRS?
Having at least 2 of the following
- Fever >38 C or hypothermia <36 C
- Tachycardia >90
- Tachypnea >20 breaths/min
- Leucocytosis >12 x10^9 or leucopoenia <4x10^9/l
How quickly should the sepsis 6 be completed in?
1 hour
When is serum lactate produced?
When cells become hypoxic
SEPSIS SIX
- Give supplementary oxygen (aim for SPO2 of >94%)
- Blood cultures
- IV antibiotics
- Fluid resuscitation
- Serum lactate and Hb
- Strict fluid balance
What should the target Hb be?
> 7 g/dL
What should the general prescribing considerations be in sepsis?
- Patient history (underlying disease, immune status, prior antibiotic use, prior infection, or colonization with multidrug-resistant organisms)
- Potential source of infection
- Microbial resistance patterns within the community hospital, or intensive care unit
- Patient organ dysfunction
- Associated drug toxicities (such as nephrotoxicity with aminoglycosides)
If source is respiratory what should be done?
- Cover with broad spectrum, consider pseudomonas and MRSA
If the source is urine what should be done?
Cover for G-ve and pseudomonas
If the source is abdo what should be done?
Cover for G-ve/+ve and anaerobes
If the source is soft tissue/joint what should be done?
Cover for G-ve/+ve/anaerobes
If the source is CNS what should be done?
Cover for meningitis
If BP is low what should be added in?
IV fluids, oxygen and possible vasopressors
What should the recommended initial broad-spectrum therapy to treat sepsis consist of?
1 or more drugs with activity against all likely pathogens (bacterial, fungal, and/or viral)
If fungal infection is likely what therapy should be undertaken?
Empiric antifungal therapy
What should the first-line of antibiotics be in sepsis?
Amoxicillin + Gentamicin
What antibiotics should be administered if MRSA is suspected or for sever sepsis?
Piperacillin + Vancomycin
If the patient has a true penicillin allergy what antibiotics should be administered?
Vancomycin + Ciprofloxacin + Metronidazole
What antibiotics are considered ‘broad spectrum’?
- Amoxicillin
- Piperacillin-tazobactam
- Ciprofloxacin
Amoxicillin properties
- Broad spectrum
- Not so good for Staph aureus/G -ve
Gentamicin properties
- Good against some G+ve
- Good against many G-ve
- By extension good against pseudomonas
- Not useful versus anaerobes
Peperacillin-tazobactam properties
- Broader spectrum
- Anti-pseudomonal
- G+ve (but not versus MRSA)
- G-ve
- Anaerobes
Vancomycin properties
- Good against G+ve including MRSA, some G-ve
Ciprofloxacin properties
Broad spectrum including pseudomonas
Metronidazole properties
Good against anaerobes
How do you test if the antimicrobial is working?
- Frequent observations
- Repeat cultures
- Test levels of different molecules (procalcitonin test)
What antibiotics should be administered if a patient is suspected to have meningococcal infection (meningitis)?
- Community setting - IV?IM Benzylpenicillin or Cefotaxime
- Hospital setting - IV Ceftriaxone
What can be the short-term effects of sepsis?
- Organ dysfunction
- Coagulation disorders
What can be the longterm effects of sepsis?
- Neurological dysfunction
- Increased mortality rate for at least a year
