Sepsis and Septic Shock Flashcards
What is sepsis?
Systemic illness caused by microbial invasion of normally sterile parts of the body
What are the features of systemic inflammatory response syndrome?
Temperature > 38 or < 36 degrees celsius Heart rate > 90 Respiratory rate > 20 PaCO2 < 32 WBC > 12,000 or < 4,000 or > 10% bands
What are the characteristics of severe sepsis?
Sepsis and end organ damage
What are the characteristics of septic shock?
Severe sepsis and hypotension
When should systemic inflammatory response syndrome (SIRS) be considered to be serious?
If there are signs of infection - SIRS occurs in many situations as a normal physiological response
What is sepsis 3?
The third international consensus definition for sepsis and septic shock
How is sepsis defined by sepsis 3?
Life-threatening organ dysfunction caused by a dysregulated host response to infection
How is organ dysfunction defined?
Acute change in total SOFA score > 2 points, consequent to the infection
What does a SOFA score > 2 reflect?
Overall mortality risk of approximately 10% in a general hospital population with suspected infection
How is septic shock defined by sepsis 3?
Clinical construct of sepsis with persistent hypotension requiring vasopressors to maintain MAP > 65mmHg and having a serum lactate of > 2mmol/l despite adequate volume resuscitation
What is the hospital mortality of patients with septic shock?
40%
What effect does sepsis have on morbidity and mortality?
Both are increased
For each hours delay in administering antibiotics in septic shock, mortality increased by 7.6%
What is the SOFA score?
Sequential Organ Failure Assessment score
When might qSOFA be used?
To promptly identify patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital
Features of qSOFA
Hypotension systolic BP < 100mmHg
Altered mental status
Tachypnoea with respiratory rate > 33/min
What score in the qSOFA suggests a greater risk of poor outcome?
2 or more
What are the bodies defences against sepsis?
Physical barrier - skin, mucosa, epithelial linings
Innate immune system - IgA, dendritic cells, macrophages
Adaptive immune system - lymphocytes, immunoglobulins
Pathogens can’t cause infection without first invading through these defences
Pathophysiology of sepsis
Uncontrolled inflammatory response
Loss of delayed hypersensitivity
Inability to clear infection
What is the change of the sepsis syndrome over time?
Initial increase in inflammatory mediators
Later, shift towards anti-inflammatory immunosuppressive phase
What are the phases in the pathogenesis of sepsis?
Release of bacterial toxins
Release of mediators
Effects of specific mediators
Features of phase 1 of sepsis
Bacterial invasion into the body, source of toxins
Commonly gram negative or gram positive toxins
Features of phase 2 of sepsis
Effects of infections due to endotoxin release
Effects of infections due to exotoxin release
Mediator role on sepsis
Features of exotoxin release in sepsis
Pro-inflammatory response
Small amounts of super-antigens cause a large amount of mediators to be secreted, resulting in a cascade effect
What types of mediators are released in sepsis?
Pro-inflammatory (cause inflammatory response that characterises sepsis)
Compensatory anti-inflammatory (can cause immunoparalysis)
Effects of pro-inflammatory mediators in phase 3 of sepsis
Pro-inflammatory mediators
- promote endothelial cell-leucocyte adhesion
- release arachidonic acid metabolites
- complement activation
- vasodilation of blood vessels by NO
- increased coagulation by release of tissue factors and membrane coagulants
- causes hyperthermia
Effects of anti-inflammatory mediators in phase 3 of sepsis
Inhibit TNF alpha
Augment acute phase reaction
Inhibit activation of coagulation system
Provide negative feedback mechanisms to pro-inflammatory mediators
Clinical features of sepsis and septic shock depend on what factors?
Host
Organism
Environment
Clinical features of organ dysfunction due to sepsis/septic shock
Altered consciousness, confusion, psychosis Tachypnoea (PaO2 < 70mmHg, sats < 90%) Jaundice Decreased platelets Increased PT/APTT Decreased protein C Increased D-dimer Tachycardia Hypotension Oliguria, anuria Increased creatinine
General features of sepsis/septic shock
Fever > 38 - chills, rigors, flushes, cold sweats, night sweats Hypothermia < 36 Tachycardia > 90bpm Tachypnoea > 20/min Altered mental status Hyperglycaemia
Inflammatory variables in sepsis/septic shock
Leucocytosis Leucopenia Normal WCC with > 10% immature forms High CRP High procalcitonin
Haemodynamic variables in sepsis/septic shock
Arterial hypotension
SvO2 > 70%
Organ dysfunction variables in sepsis/septic shock
Arterial hypoxaemia Oliguria Creatinine increased Coagulation abnormalities Thrombocytopenia Hyperbilirubinaemia
Tissue perfusion variables in sepsis/septic shock
High lactate
Skin mottling and reduced capillary perfusion
Host features which can affect sepsis presentation
Age
Co-morbidities
Immunosuppression
Previous surgery
Organism features which can affect sepsis presentation
Gram positive vs gram negative
Virulence factors
Bioburden
Features of environment which can affect sepsis presentation
Occupation e.g. farming, exposed to uncommon infections
Travel e.g. malaria
Hospitalisation
Features of sepsis 6
Air enriched with O2 Antibiotics after blood culture Blood culture Blood gas with lactate Crystalloid Bolus Catheter if severe sepsis or septic shock
Oxygen aim in sepsis
Saturation 94-98%
Blood cultures in sepsis
Make microbiological diagnosis
30-50% positive
2 sets should be taken if there is a spike in temperature
What is lactate a marker of in sepsis?
Generalised hypoperfusion
Severe sepsis
Poor prognosis
What is low urine output a marker of in sepsis?
Renal dysfunction
IV fluids in sepsis
30ml/kg fluid challenge e.g. 2.1L for 70kg patient
When should HDU referral be considered?
Low BP responsive to fluids Lactate > 2 despite fluid resuscitation Elevated creatinine Oliguria Liver dysfunction Bilateral infiltrates Hypoxaemia
When should ITU referral be considered?
Septic shock
Multi-organ failure
If patient requires sedation, intubation and ventilation
Factors to consider regarding antibiotic treatment of sepsis
Working diagnosis from history and examination Local antibiotic guidelines Allergy Previous MRSA, ESBL or CPE Antibiotic toxicity and interaction
What are the commonly released toxins?
Gram positive
- lipopolysaccharides
Gram negative
- Microbial associated molecular pattern (MAMP) - lipoteichoic acid, muramyl dipeptides
- Superantigens - staphylococcal toxic shock syndrome toxin, streptococcal exotoxins
What is the difference between LPS and LTA in endotoxin release?
LPS needs an LPS-binding protein to bind to macrophages, LTA do not need such proteins
