What is systemic inflammatory response syndrome (SIRS)?
Widespread inflammatory response to a variety of clinical insults. This can include things like pancreatitis, burns and trauma
What clinical parameters are assessed to determine if someone has SIRS?
- Heart Rate
- Respiratory rate
- WBC count
When assessing temperature in the criteria for SIRS, what threshold(s) is/are used?
Whan assessing heart rate in the criteria for SIRS, what HR thershold (s) is/are used?
When assessing respiratory rate in the criteria for SIRS, what thershold (s) is/are used?
When assessing the WBC count in the criteria for SIRS, what threshold(s) is/are used?
- >12000 cells/mm3
- <4000 cells/mm3
What is the definition of sepsis?
SIRS plus infection
Life-threatening organ dysfunction caused by dysregulated host repsonse to infection
What is the definition of severe sepsis?
Sepsis plus End organ damage
What is the definiton of septic shock?
Severe sepsis plus Hypotension unresponsive to fluids
Can be identified with a 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 chemical is released in response to vascular endothelial damage caused by infectious organisms?
Nitric oxide - chemical vasodilator
What pathway is activated by bacterial toxins?
Complement pathway - stimulates mast cells
What are the main pro-inflammatory cytokines released by macrophages nad neutrophils in response to bacterial toxin release?
What chemicals do the endothelial cells release in response to being stimulated by TNF and IL-1?
Release of reactive oxygen species and platelet activating factor
What occurs in phase 1 of sepsis pathophysiology?
Release of bacterial toxin
- Endotoxin - LPS
- Exotoxin - superantigen
What occurs in phase 2 of sepsis pathophysiology?
Mediator relsease in response to infection
- Pro-inflammatory cytokines - cause inflammatory response
- Anti-inflammatory sytokines - keeps pro-inflammatory response in check
What chemical does mast cells release in repsonse to activation by the complement pathway?
What is the overall outcome on vascular structure and permeability in response to pro-inflammatory cytokine release?
- Damage and increased permeability
- Net increase in clotting
What are the 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 - release of tissue factors and membrane coagulants
- 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 to pro-inflammatory mediators
What is the difference between septic shock and immunoparalysis in terms of pro-inflammatory and anti-inflammatory cytokines?
- Septic shock - compensatory mechisms are outweighed by pro-inflammatory mechanisms
- Immunoparalysis - Compensatory mechanisms outweigh pro-inflammatory mechanisms
Why is lactate used as a measure of tissue perfusion?
If oxygen supply is inadequate, mitochondria are unable to continue ATP synthesis at a rate sufficient to supply cells with ATP. To compensate, glycolysis is increased, and excess pyruvate is converted to lactate by lactate dehydrogenase, and is released into the blood stream
How is lactate used once it is produced?
- Oxidation back to pyruvate by well-oxygenated muscle cells, heart cells, and brain cells
- Conversion to glucose via gluconeogenesis in the liver and release back into circulation
What is the definiton of septicaemia?
Was used to denote the presence of multiplying bacteria in the circulation, but has been replaced with other terms e.g. sepsis, severe sepsis, septic shock
What are symptoms of sepsis?
- Specific sysmptoms indicative of cause
What are signs that someone has sepsis?
- Increased/decreased temperature
- Decreased urine output
- Warm perfused peripheries
- Bounding pulse
- Low oxygen saturations
- Mottled skin
- Sign of specific source of infection
What could a bounding pulse with warm peripheries indicate?
What are risk factors for the development of sepsis?
- Underlying malignancy
- Age > 65
- Recent surgery/breached skin integrity
Vascular - indwelling devices/IVDU
What organ dysfunction variables would you look at to assess for sepsis?
- Arterial hypoaemia (<50mmHg)
- Oliguria (<0.5ml/kg/h)
- Increased creatinine
- Coagulation abnormalities (PT>1.5, APTT > 60s)
What variables could you use to assess tissue perfusion?
- Skin mottling
- Reduced capillary perfusion
What changes in blood sugar can occur in sepsis?
What investigations would you do if you suspected someone had sepsis as part of the sepsis 6 protocol?
- Blood lactate and FBC
- Blood cultures
- Urine output
What investigations would you do to assess a source of infection in suspected sepsis?
- Examination - anywounds/surgery
- Swab sample - prosthetic, epidural
- Lumbar puncture
- Echo - vegitations
- Pleural fluid culture
- Peritoneal fluid culture
What bloods would you do if you suspected someone had sepsis?
- FBC with differential white count
- U+E's, serum creatinine
- Blood cultures
How much does the risk of mortality increase by per hour of delay of antibiotic adminstration to someone who is septic?
7.6% per hour
Why would you do U+Es in someone with suspected sepsis?
Electrolytes frequently deranged
Why would you do FBC with differential white count in sepsis?
- Low platelets
Deranged white cells (can be one of following):
- WBC count >12×10^9/L (12,000/microlitre) (leukocytosis)
- WBC count <4×10^9/L (4000/microlitre) (leukopenia)
- Normal WBC count with >10% immature forms
Why would you do LFTs in sepsis investigation?
Determine liver function
- Elevated bilirubin
- Elevated ALT/AST, Alk phos and gamma-T
Why would you ask for a serum lactate in someone with suspected sepsis?
To evaluate tissue perfusion - Persistently elevated lactate levels may parallel the degree of malperfusion or organ failure.
- Levels >2 mmol/L (>18 mg/dL) associated with adverse prognosis
- Even worse prognosis with levels >4 mmol/L (>36 mg/dL)
Why would you perform an ABG in someone with suspected sepsis?
ABG evaluation facilitates optimisation of oxygenation, and is indicative of metabolic status (acid-base balance).
Lactate levels are most reliably assessed using an ABG sample. However, in practice, a venous blood gas (VBG) sample is often used
Most patients do not undergo ABG sampling unless there is a respiratory component.
PaCO2 <4.3 kPa (32 mmHg) is one of the diagnostic criteria for SIRS
What is the best way to obtain a serum lactate?
Why would you take a serum glucose in someone that is septic?
Marker for stress
May be elevated, with or without known history of diabetes, due to the stress response and to altered glucose metabolism.
Can be low - acute liver failure
Why would you take a serum creatinine in someone that is septic?
To assess renal dysfunction
What is important to remember about the white cell count when used to assess sepsis?
It is sensitive but not specific for sepsis. Can also be changed by non-infectious injury, cancer, and immunosuppressive agents
Why would you take a CRP in someone that is septic?
Baseline marker for inflammation - can map its progress through treatment
When taking blood cultures, what is important to remember?
Take BEFORE administration of antibiotics
What are the three aspects of the sepsis 6 that are to do with management of a patient with sepsis?
- IV antibiotics - within 1 hour
- Oxygen - aim 94-98%
- IV fluid - minimum 500ml
If a septic patient was not responding to fluid challenge, how would you maintain their BP, and what threshold would you aim for?
Vasopressors - >65mmHg
When would you consider moving to HDU?
If evidence of severe sepsis:
- Low BP responsive to fluids
- Lactate >2
- Elevated creatinine
- Liver dysfunction, Bil, PT, Plt
- Bilateral infiltates, hypoxaemia
When would you consider moving to ITU?
Evidence of Septic shock
- Multi-organ failure
- Requires sedation, intubation and ventilation
What can cause SIRS?
What is the SOFA?
Sequential organ failure assessment
What are the different criteria assessed in the qSOFA?
- BP <100
- RR >22
- GCS < 15
What severity of sepsis would someone have if their lactate was raised but was < 2 mmol/L?
What severity of sepsis would someone have if they haed a lactate between 2-4 mmol/L?
What severity of sepsis would someone have if their lactate was > 4 mmol/L?
What features would indicate that someone is at high risk of severe illness/death from sepsis?
- Altered mental state
- RR >/= 25
- HR > 130
- SBP = 90/>40 below normal
- UO < 0.5 ml/kg/hr
- Mottled skin
- Non-blanching rash
What respiratory conditions can occur due to end organ damamge due to sepsis?
What are features of ARDS?
- Impaired oxygenation
- INfiltrates on CXR
What cardiovascular conditions can occur due to end organ damage due to sepsis?
- Myocardial dysfunction/failure
- Septic Shock
What renal cponditions can occur due to end organ damage caused by sepsis?
What haematological disorders can occur as a result of end organ daamge caused by sepsis?
What CNS conditions can occur due to end organ damage from sepsis?
What are features of DIC/coagulopathy?