Lecture 5: Sepsis and Septic Shock Flashcards
definition of sepsis using the Sepsis-3 guidelines
- sepsis is defined as a life-threatening organ dysfunction caused by dyregulated host response to infection
- SIRS + infection
definition of septic shock using the sepsis-3 guidelines
- septic shock can be identified as sepsis with persisting hypotension requiring vasopressors to maintain MAP > 65mmHg and having a serum lactate of > 2mmol/l despite adequate volume resuscitation.
qSOFA factors for patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital
- hypotension systolic BP < 100mmHg
- altered mental status
- tachypnoea RR > 22/min
score of >/= 2 criteria suggests a greater risk of a poor outcome
why is sepsis so important?
- common condition
- becoming more common
- increased morbidity and mortality
for each hours delay in administering antibiotics in septic shock, mortality increases by?
7.6%
the six key steps in the investigation and management of sepsis, often referred to as ‘sepsis six’ include:
take 3 give 3
- take bloods (FBC, U&E, LFT, CRP, lactate)
- take blood cultures
- monitor urine output
- administer oxygen if required
- administer IV antibiotics
- administer IV fluid resuscitation (30ml/kg)
which other investigations may be performed for sepsis?
other than sepsis 6
- imaging: CXR, echo, abdominal US)
- viral PCR for diagnosis of influenza
- urinalysis with or without culture
- lumbar puncture
list the body’s defence mechanisms against sepsis
- physical barrier: skin, mucosa, epithelial lining
- innate immune system: IgA in GI tract, dendritic cells/macrophages
- adaptive immune system: lymphocytes, immunoglobulins
what is the origin of sepsis?
- originates from a breach of intergrity of host barrier, whether physical or immunological
- organism enters bloodstream creating a septic state
what are the three phases in the pathogenesis of sepsis?
- release of bacterial toxins
- release of mediators: pro-inflammatory mediators cause inflammatory response that characterises sepsis, compensatory anti-inflammatory reaction can cause immunoparalysis
- effects of specific excessive mediators
what are some commonly released bacterial toxins?
- Gram negative: lipopolysaccharide (LPS)
- Gram positive: microbial-associated molecular pattern (MAMP) e.g. lipoteichoic acid (LTA), muramyl dipeptides. Superantigens e.g. staphylococcal toxic shock syndrome toxin (TSST) and streptococcal exotoxins.
give examples of pro-inflammatory mediators in sepsis
- TNF-alpha
- IL1B, IL-2, IL-8, IL-15
- neutrophil elastase
- IFN-gamma
give examples of anti-inflammatory mediators in sepsis
IL-1Ra
IL-4
IL-10
IL-13
what are the effects of excessive pro-inflammatory mediators in sepsis?
- promote endothelial cell - leukocyte adhesion
- release of rachidonic acid metabolites
- complement activation
- vasodilation of blood vessels by NO
- increased coagulation by release of tissue factors and membrane coagulants
- cause hyperthermia
what are the effects of excessive anti-inflammatory mediators in sepsis?
- inhibit TNF-alpha
- augment acute phase reaction
- inhibit activation of coagulation system
- provide negative feedback mechanisms to pro-inflammatory mediators
why is a balance between the pro-inflammatory and anti-inflammatory mediators important?
- Pro-inflammatory imbalance: septic shock with multiorgan failure and death.
- Anti-inflammatory imbalance: immunoparalysis with uncontrolled infection and multiorgan failure
general clinical features of sepsis
- fever > 38C: chills, rigors, flushes, cold sweats, night sweats etc.
- hypothermia < 36C: especially in elderly and very young children
- tachycardia > 90bpm
- tachypnoea > 20/min
- altered mental status
- hyperglycaemia > 8mmol/l in absence of diabetes
inflammatory variables in sepsis
i.e. what a blood test might show
- leucocytosis (WCC > 12,000/ml)
- leucopenia (WCC < 4000/ml)
- normal WCC with greater than 10% immature forms)
- high CRP
- high procalcitonin
haemodynamic clinical features in sepsis
- arterial hypotension (systolic < 90mmHg or MAP < 70mmHg)
- SvO2 > 70%
organ dysfunction lab values/clinical features in sepsis
- arterial hypoxaemia < 50mmHg PaO2)
- oliguria (< 0.5ml/kg/hr)
- creatinine increase compared to baseline
- coagulation abnormalities (PT > 1.5 or APTT > 60secs)
- ileus
- thrombocytopenia (< 150,000/ml)
- hyperbilirubinaemia
tissue perfusion variables present in sepsis
- high lactate
- skin mottling and reduced capillary perfusion
which antibiotics are used for intra-abdominal sepsis?
- amoxicillin, gentamicin and metronidazole
why are lactate levels important to get in sepsis and what are the two types of lactic acidosis?
Of available biomarkers, lactate has the most support to identify adverse outcomes.
Type A: hypoperfusion
Type B: mitochondrial toxins, alcohol, malignancy, metabolism errors.
when to consider high dependency unit (HDU) for sepsis?
- low BP responsive to fluids
- lactate > 2 despite fluid resuscitation
- elevated creatinine
- oliguria
- liver dysfunction, Bil, PT, Plt
- bilateral infiltrates, hypoxaemia
