Sepsis and septic shock Flashcards
What is sepsis?
Systemic illness caused by microbial invasion of normally sterile parts of the body
What is it that the SOFA score looks at to measure?
- Respiration: PaO2
- Coagulation: Platelets
- Liver: Bilirubin
- Cardiovascular
- Glasgow coma scale
- Renal: Creatinine and urine output
What is the scoring for PaO2 in the SOFA score
- > /= 400 mm Hg (53.3kPa)
- <400 (53.3)
- <300 (40)
- <200 (26.7) with respiratory support
- < 100 (13.3) with respiratory support
What is the scoring for platelets in the SOFA score
- > /= 150 x 10^3 Micro Litres
- < 150
- <100
- <50
- <20
What sore of the qSOFA suggests a greater risk of poor outcome?
2 or more
What is the body’s defence against sepsis?
- Physical barrier: skin, mucosa, epithelial lining
- Innate immune system: IgA in gastrointestinal tract, dendritic cells / macrophages
- Adaptive immune system: lymphocytes, immunoglobulins
What is the origin of sepsis?
- Originates from a breach of integrity of host barrier, whether physical or immunological
- Organism enters the bloodstream creating a septic state
Describe the pathophysiology of sepsis
• Uncontrolled inflammatory response
• Patients with sepsis have features consistent with immunosuppression:
○ Loss of delayed hypersensitivity
○ Inability to clear infection
○ Predisposition to nosocomial infection
• Probable change of the sepsis syndrome 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 three phases of pathogenesis of sepsis?
- Release of bacterial toxins
- Release of mediators
- Effects of specific excessive mediators
What happens in phase one of the pathogenesis 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
• Commonly released toxins:
○ Gram negative
- Lipopolysaccharide (LPS)
○ Gram positive
- Microbial-associated molecular pattern (MAMP)
□ Lipoteichoic acid
□ Muramyl dipeptides
- Superantigens
□ Staphylococcal toxic shock syndrome toxin (TSST)
□ Streptococcal exotoxins
What happens in phase two of the pathogenesis of sepsis?
• Effects of infections due to endotoxin release
○ LPS needs an LPS-binding protein to bind to macrophages
○ LTA do not need such proteins
• Effects of infections due to exotoxin release
○ Pro-inflammatory response
○ Small amounts of superantigens will cause a large amount of mediators to be secreted: cascade effect
• Mediator role on sepsis
○ Two types of mediators can be released
○ Pro-inflammatory mediators – causes inflammatory response that characterises sepsis
○ Compensatory anti-inflammatory reaction – can cause immunoparalysis
What happens in phase three of the pathogenesis of sepsis?
• Pro-inflammatory mediators
○ Promote endothelial cell – leukocyte adhesion
○ Release of arachidonic acid metabolites
○ Complement activation
○ Vasodilation of blood vessels by NO
○ Increase coagulation by release of tissue factors and membrane coagulants
○ Cause hyperthermia
• Anti-inflammatory mediators
○ Inhibit TNF alpha
○ Augment acute phase reaction
○ Inhibit activation of coagulation system
○ Provide negative feedback mechanisms to pro-inflammatory mediators
What are the general features of sepsis?
- Fever >38 degrees C – presenting as chills, rigors, flushes, cold sweats, night sweats, etc.
- Hypothermia <36 degrees C – especially in the elderly and very young children (remember the immunosuppressed)
- Tachycardia >90 beats/min
- Tachypneoa >20 /min
- Altered mental status – especially in the elderly
- Hyperglycemia >8 mmol/l in the absence of diabetes
What are the inflammatory variables of sepsis?
- Leukocytosis (WCC > 12,000/ml)
- Leukopenia(WCC < 4,000/ml)
- Normal WCC with greater than 10% immature forms
- High CRP
- Highprocalcitonin
What are the haemodynamic variables of sepsis?
- Arterial hypotension (systolic <90 mmHg or MAP <70 mmHg)
* SvO2>70%
What are the organ dysfunction variables in sepsis?
- Arterialhypoxaemia(PaO2/FiO2< 50 mmHg)
- Oliguria (<0.5ml/kg/h)
- Creatinine increase compared to baseline
- Coagulation abnormalities (PT >1.5 or APTT >60s)
- Ileus
- Thrombocytopenia (<150,000/ml)
- Hyperbilirubinemia
What are the tissue perfusion variables in sepsis?
- High lactate
* Skin mottling and reduced capillary perfusion
What parts of a host can affect sepsis presentation?
• Age
• Co-morbidities (COPD, DM, CCF, CRF, disseminated malignancy)
• Immunosuppression
○ Acquired – HIV/AIDS
○ Drug-induced – steroids, chemotherapeutic agents, biologics
○ Congenital –agammaglobulinemia, phagocytic defects, defects in terminalcomplement component
• Previous surgery - splenectomy
What parts of the organism can affect the presentation of sepsis?
- Gram positive versus Gram negative
- Virulence factors (example: MRSA, toxin secretion, ESBL, KPC, NDM-1)
- Bioburden
How might the environment affect the presentation of sepsis?
- Occupation
- Travel
- Hospitalisation
What are the sepsis 6?
- Blood cultures
- Blood lactate
- Measure urine output
- Oxygen aim sats 94-98%
- IV antibiotics
- IV fluid challenge
What are you looking for in the measurements of sepsis 6?
• Blood cultures
○ make microbiological diagnosis (30-50% positive)
○ if spike in temperature, take 2 sets
• Lactate – marker of generalisedhypoperfusion/severe sepsis/poorerprognosis
• Low Urine output – marker of renal dysfunction
What should be considered when prescribing antibiotics?
- Based on working diagnosis from History and Examination
- Local antibiotic guidelines
- BUT consider allergy
- BUT consider previous MRSA, ESBL, CPE
- BUT considerAbxtoxicity/interactions
Explain lactate biomarker
- Type A -Hypoperfusion
- Type B – Mitochondrial toxins, Alcohol, Malignancy, metabolismerrors
- Of available biomarkers, lactate has the most support to identifyadverse outcomes
How should IV fluids be prescribed?
- 30ml/kg fluid challenge (expert opinion)
* 2.1L 70 kg patient
When should you consider a HDU referral?
- Low BP responsive to fluids
- Lactate >2 despite fluid resuscitation
- Elevated creatinine
- Oliguria
- Liver dysfunction,Bil, PT,Plt
- Bilateral infiltrates, hypoxaemia
When should you consider ITU?
- Septic shock
- Multi-organ failure
- Requires sedation, intubation and ventilation
