Sepsis and Septic Shock Flashcards
Define sepsis
Life threatening organ dysfunction caused by dysregulated host response to infection
Define 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
(sepsis with low blood pressure and high lactate)
What is the SOFA score
Sequential organ failure assessment score
Used to track a person’s status during the stay in an intensive care unit (ICU) to determine the extent of a person’s organ function or rate of failure
What are the systems involved in the sofa score?
Respiratory (PaO2)
Nervous system (GCS)
Cardiovascular (MAP or administration of vasopressors required)
Liver (bilirubin)
Coagulation (platelets)
Kidneys (creatinine)
What is the qSOFA score?
Quick SOFA Score as an initial way to identify patients at high risk for poor outcome with an infection
Only includes three clinical criteria (low blood pressure, high respiratory rate, any altered mental state)
The presence of 2 or more qSOFA points near the onset of infection was associated with a greater risk of death or prolonged intensive care unit stay. These are outcomes that are more common in infected patients who may be septic than those with uncomplicated infection.
qSOFA basically is a good indicator for who is likely to be septic
What are the components of the bodyes defence against sepsis?
Physical barrier
Innate immune system
Adaptive immune system
- Physical barrier – skin, mucosa, epithelial lining
- Innate immune system – IgA in gastrointestinal tract, dendritic cells / macrophages
- Adaptive immune system – lymphocytes, immunoglobulins
How does sepsis arise?
Failure of host barrier (physical or immunological)
Organism enters the blod stream creating a septic state
Patients with sepsis are said to have features consistent with immunosuppression, what are these features?
- Loss of delayed hypersensitivity
- Inability to clear infection
- Predisposition to nosocomial infection
What is the 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 are comonly 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 is the difference between endotoxins and exotoxins?
Exotoxins are toxic substances secreted by bacteria and released outside the cell. Pro inflammatory response, small amounts of superantigens will cause a large amount of mediators to be secreted: cascade effect
Endotoxins are bacterial toxins consisting of lipids that are located within a cell. (LPS needs a LPS binding protein to bind to macrophages, LTA (Lipoteichoic acid) does not
What are the two types of mediators that can be released in sepsis/?
- Pro-inflammatory mediators – causes inflammatory response that characterises sepsis
- Compensatory anti-inflammatory reaction – can cause immunoparalysis
Name some pro-inflammatory mediators
TNF-alpha
IL1b, IL-2, IL-8, IL-15
Neutrophil elastase
IFN-gamma
Prostaglandins, prostacyclin
Name some anti-inflammatory mediators
IL-1Ra
IL-4
IL-10
IL-13
LPS binding protein
Soluble TNF alpha receptor
Epinephrine phospholipase a2
What are the actions of 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
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 result of unbalanced pro-inflammaotry and inflammatory mediators?
Too much pro-inflammatory = septic shock with multiorgan failure and death
Too much anti-inflammatory = immunoparalysis with uncontrolled infection and multiorgan failure
What are the clincal features of sepsis in terms of organ dysfunction?
General features:
- Fever over 38 degrees, presenting as chills, rigors, flushes, cold sweats, night sweats
- Hypothermia (less than 36 degrees - especially in the elderly and the very young, remember the imunosuppressed)
- Tachycardia (over 90 bpm)
- Tachypnoea (rr over 20/min)
- Altered mental status - especially in the elderly
- Hyperglycaemia (over 8mmol/l in the absence of diabetes)
Altered consciousness
Confusion
Psychosis
Tachypnoea
PaO2 less than 70mmHg
Sats less than 90%
Jaundice
Increase in liver enzymes
Decrease in albumin
Increase in prothrombin time
Decrease in platelets
Increase in activated partial thromboplastin time
Decrease in protein C (a zymogen, the activated form of which plays an important role in regulating anticoagulation, inflammation, cell death, and maintaining the permeability of blood vessel walls in humans and other animals.)
Increase in D-dimer
Tachycardia
Hypotension
Oliguria
Anuria
Increase in creatinine
What are the 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
What are the haemodynamic variables in sepsis?
- Arterial hypotension (systolic <90mmHg or MAP <70mmHg)
- SvO2 >70%
Mixed venous oxygen saturation (SvO2) is the percentage of oxygen bound to hemoglobin in blood returning to the right side of the heart. This refects the amount of oxygen “left over” after the tissues remove what they need.
What are the 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 the tissue perfusion variables in sepsis?
- High lactate
- Skin mottling and reduced capillary perfusion
What can effect the presentation of sepsis?
- 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
The organism:
- Gram positive versus Gram negative
- Virulence factors (example: MRSA, toxin secretion, ESBL, KPC, NDM-1)
- Bioburden
What is the sepsis 6?
Take 3 give 3
Take: Blood cultures, blood lactate, measure urine output
Give: Oxygen aim sats 94-98%, IV antibiotics, IV fluid challenge
Lactate is a mrker of generalised hypoperfusion/severe sepsis/poorer prognosis
Low urine output is a marker of renal dysfunction
What is the difference between type A and type B lactate?
- Type A - Hypoperfusion
- Type B – Mitochondrial toxins, Alcohol, Malignancy, metabolism errors
When do 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 do you consider ITU?
Septic shock
Multi-organ failure
Requires sedation, intubation and ventilation
What is treatment of pneumonia based on the CURB65 score?
Low severity
CURB65 = 0-1 (amoxicillin)
Moderate severity
CURB65 = 2 (amoxicillin and clarithromycin orally. If oral administration is not possible then amoxicillin IV or benzylpenicillin IV plus clarithromycin)
High Severity
CURB65 = 3-5 (IV co-amoxiclav plus IV clairithromycin, if leigonella strongly suspected, consider adding levofloxacin)
Legionella has diarrhoea, high ALT, hyponatraemia
Detected by urinary antigen
