Sepsis and Septic Shock Flashcards
what is the definition of sepsis?
- Sepsis derives from the Greek work “sepo” meaning decay or decomposition
- Systemic illness caused by microbial invasion of normally sterile parts of the body
what are the different types of sepsis?
systemic inflammatory response syndrome - SIRS is a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of cytokine storm, in which there is abnormal regulation of various cytokines. SIRS is also closely related to sepsis, in which patients satisfy criteria for SIRS and have a suspected or proven infection
can you have infection and SIRS?
You can have infection, SIRS or both
what is the proper definition of sepsis?
Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host response to infection
- 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
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. Not used to diagnose but used to say what patients are likely to have a poorer outcome and higher mortality
what is septic shock?
Septic shock 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
Patients with septic shock have a hospital mortality of 40%
why is sepsis so important?
- Common condition
- Becoming more common
- Increased morbidity
- Increased mortality
what is the length of stay like in a patient with sepsis compared to other conditions?
what is the survival in septic shock based on?
Survival in septic shock based on antimicrobial delay
For each hours delay in administering antibiotics in septic shock, mortality increases by 7.6%
can we make a difference?
- There are interventions proven to reduce mortality and cost
- However, these interventions are not routinely done in all settings
- Myocardial infarction: Time is muscle
- Stroke: Time is brain
- Sepsis: Time is ____
life
what are the bodys defences 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
what is 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 (originating in hospital)
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 in the pathogenesis of sepsis?
- Release of bacterial toxins
- Release of mediators
- Effects of specific excessive mediators
WHat happens in Phase 1: Release of bacterial toxins?
- Bacterial invasion into body tissues is a source of dangerous toxins
- May or may not be neutralised and cleared by existing immune system
Gram negative and positive release different toxins
what toxins are released by gram negative?
Lipopolysaccharide (LPS)
what toxins are released by 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: Release of mediators in response to infection?
- Effects of infections due to endotoxin release
- Effects of infections due to exotoxin release
- Mediator role on sepsis
what is involved in endotoxin release?
- LPS needs an LPS-binding protein to bind to macrophages
- LTA do not need such proteins
what is involved in exotoxin release?
- Pro-inflammatory response
- Small amounts of superantigens will cause a large amount of mediators to be secreted: cascade effect
What is the mediator role in sepsis (Th1 vs Th2)?
- Two types of mediators can be released
- Pro-inflammatory mediators - causes inflammatory response that characterises sepsis
- Compensatory anti-inflammatory reaction - can cause immunoparalysis
Phase 3: Effects of specific excessive mediators
What do pro-inflammatory mediators cause?
- 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
Phase 3: Effects of specific excessive mediators
What do anti-inflammatory mediators cause?
- Inhibit TNF alpha
- Augment acute phase reaction
- Inhibit activation of coagulation system
- Provide negative feedback mechanisms to pro-inflammatory mediators
what do you need to happen between the 2 different immune responses?
Balance between the various immune responses
What happens if there is more of a pro-inflammatory repsonse than an anti-inflammatory repsonse?
Septic shock with multiorgan failure and death
What happens if there is more of an anti-inflammatory repsonse than a pro-inflammatory response?
Immunoparalysis with uncontrolled infection and multiorgan failure
How does the bodies immune system react in sepsis?
Healthy – as soon as infected their body produces an inflammatory response
What do the clinical features of sepsis depend upon?
Depends on a number of factors:
- Host
- Organism
- Environment
what organ dysfunction can sepsis cause?
what are the general features of sepsis?
- Fever >38oC - presenting as chills, rigors, flushes, cold sweats, night sweats, etc
- Hypothermia <36oC - 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 are some inflammatory variables in sepsis
- Leucocytosis (WCC > 12,000/ml)
- Leucopenia (WCC < 4,000/ml)
- Normal WCC with greater than 10% immature forms
- High CRP
- High procalcitonin
Haemodynamic variables in sepsis
- Arterial hypotension (systolic <90mmHg or MAP <70mmHg)
- SvO2 >70%
What are Organ dysfunction variables 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
- Thrombocytopenia (<150,000/ml)
- Hyperbilirubinaemia
What are Tissue perfusion variables in sepsis?
- High lactate
- Skin mottling and reduced capillary perfusion
What is the effect of host on sepsis presentation?
- Age
- Co-morbidities (COPD, DM, CCF, CRF, disseminated malignancy)
- Immunosuppression:
- Acquired – HIV/AIDS
- Drug-induced – steroids, chemotherapeutic agents, biologics
- Congenital – agammaglobulinaemia, phagocytic defects, defects in terminal complement component
• Previous surgery - splenectomy
What is the effect of organism on presentation of sepsis?
- Gram positive versus Gram negative
- Virulence factors (example: MRSA, toxin secretion, ESBL, KPC, NDM-1)
- Bioburden
What is the effect of environment on presentation of sepsis
- Occupation
- Travel
- Hospitalisation
Case 1:
- 55 year old gentleman
- History of DM, smoker and IHD
- Admitted through Emergency Department with fever, nausea, vomiting and abdominal pain x 4 hours
Examinations:
- Temp: 38.3oC
- Resp rate: 24/ min
- Pulse: 120 bpm - tachycardia
- BP: 160/85
- HS: normal
- Chest: Clear
- Abdomen: Tenderness in epigastrium, no rebound, BS present
Investigations:
- WCC: 15,600/ml - high
- Platelets: 240,000/ml
- INR: 1.2
- U&E: Normal
- LFT: Bil 80; AAT 20; ALP 35; GGT 40
- Lactate 2.2mmol/l - high
- Glucose: 8.8mmol/l
- CXR and AXR: normal
Treated in A&E:
- Sepsis 6
- Started on Amoxicillin, Gentamicin and Metronidazole for intra-abdominal sepsis
- 6 hours later patient failed to improve
Why is this?
- Admitted with SIRS
- On post-take round another blood test was carried out
- Serum amylase 1450
- Diagnosed as Acute pancreatitis
- Antibiotics stopped and patient transferred to surgery for further management
what is the management process of suspeted sepsis
what are the 2 different sepsis 6?
Take 3: Give 3
2 As, 2 Bs, 2 Cs
what is sepsis 6 Take 3: Give 3?
- Blood cultures
- Blood lactate
- Measure urine output
- Oxygen aim sats 94-98%
- IV Antibiotics
- IV fluid challenge
what is sepsis 6 2 As, 2 Bs, 2 Cs?
what take blood cultures?
make microbiological diagnosis (30-50% positive)
if spike in temperature, take 2 sets
why measure lactate?
marker of generalised hypoperfusion/severe sepsis/poorer prognosis
why measure urine outpu?
Low Urine output – marker of renal dysfunction
What antibiotics should be used?
- 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 are the types of lactate and what do they indictae?
- Type A - Hypoperfusion
- Type B – Mitochondrial toxins, Alcohol, Malignancy, metabolism errors
- Of available biomarkers, lactate has the most support to identify adverse outcomes
how much IV fluids are required?
- 30ml/kg fluid challenge (expert opinion)
- 2.1L 70kg patient
When should you consider 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
Case 2:
- 68 year old woman admitted with worsening shortness of breath
- History of IHD, CVA and bed bound
- On examination: Alert, Temp 38oC, Resp rate 26/min, pulse 120/min irreg, BP 85/60, Chest dullness right base
- qSOFA =
2
Case 2:
- What is your working diagnosis?
- How would you make a diagnosis?
- What score will you use?
What should be done in the next 60 minutes?
- Oxygen
- IV fluid challenge
- Blood cultures
- Blood lactate
- IV Antibiotics
- Monitor urine output
