sepsis and septic shock Flashcards
what is sepsis
systemic illness caused by microbial invasion of normally sterile parts of the body
SIRS + infection
traditional model of sepsis
SIRS
sepsis
severe sepsis
septic shock
SIRS
systemic inflammatory response syndrome temp >38 or <36 HR >90 RR >20 or PaCO2 <32 WBC >12 000 or <4000 or >10% bands
severe sepsis
sepsis + end organ damage
septic shock
severe sepsis + hypotension
define sepsis
life threatening organ dysfunction caused by dysregulated host response to infection
organ dysfunction - an acute change in total SOFA score >2 points consequent to the infection
SOFA score >2 reflects an overall mortality risk of ~10% in a general hospital pop w/ suspected infection
define septic shock
sepsis w/ persisting hypotension requiring vasopressors to maintain MAP >65mmHg and serum lactate >2mmol/L despite adequate volume resus
pts w/ septic shock have a hospital mortality of 40%
what does SOFA stand for
sequential (sepsis related) organ failure assessment score
respiration coagulation LFTs BP GCS renal function - creatinine and urine output
qSOFA
pts w/ suspected infection who are likely to have a prolonged ICU stay or die in hospital can be promptly identified w/ qSOFA
score ≥2 suggests greater risk of a poor outcome
what observations are measured in qSOFA
hypotension - systolic BP <100mmHg
altered mental status
tachypnoea - RR >22/min
importance of sepsis
common condition (30% of pts coming through acute medical assessment unit have some form of sepsis)
becoming more common (living longer, more co-morbidities etc)
increased morbidity and mortality
for every hrs delay in administering abx in septic shock, morality increases by …
7.6%
what are the body’s defences to sepsis
physical - skin, mucosa, epithelial lining
innate immune system - IgA in GI tract, dendritic cells/macrophages
adaptive immune system - lymphocytes, immunoglobulins
origin of sepsis
originates from a break of integrity of host barrier (physical or immunological)
organism enters the bloodstream creating a septic state
pathophysiology of sepsis
uncontrolled inflammatory response
pts w/ sepsis have features consistent w/ immunosuppression
probable change of the sepsis syndrome over time
what are the features consistent w/ immunosuppression in sepsis pts
loss of delayed hypersensitivity
inability to clear infection
predisposition to nosocomial infection
what is the change of the sepsis syndrome over time
initial increase in inflammatory mediators
shift towards an anti-inflammatory immunosuppressive phase
depends on the health of the patient
3 phases in pathogenesis of sepsis
release of bacterial toxins
release of mediators
effects of specific excessive mediators
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
toxins released by gram -ve bacteria
lipopolysaccharide (LPS)
toxins released by gram +ve bacteria
microbial associated molecular pattern (MAMP):
lipoteichoic acid
muramyl dipeptides
superantigens:
staphylococcal toxic shock syndrome toxin (TSST)
streptococcal exotoxins
release of mediators in response to infection
effects of infections due to endotoxin and exotoxin release
mediator role on sepsis
endotoxin release
LPS needs an LPS-binding protein to bind to macrophages
LTA don’t require these proteins
exotoxin release
pro-inflammatory response
small amounts of superantigens will cause a large amount of mediators to be secreted: cascade effect
mediator role in sepsis
2 types of mediators can be released:
pro-inflammatory mediators - causes inflammatory response that characterises sepsis (too much of pro-inflammatory response can lead to septic shock and multiorgan failure and death)
compensatory anti-inflammatory reaction - can cause immunoparalysis - uncontrolled infection and multi-organ failure
examples of pro-inflammatory mediators
TNF-alpha
IL1
IFN-gamma
examples of anti-inflammatory mediators
IL-10
transforming growth factor-beta
LPS-binding protein
effects of specific excessive mediators - pro-inflammatory mediators
promote endothelial cell - leukocyte adhesion
released of arachidonic acid metabolites
complement activation
vasodilation of blood vessels by NO
increased coagulation by release of tissue factors and membrane coagulants
cause hyperthermia
effects of specific excessive mediators - anti-inflammatory mediators
inhibit TNF-alpha
augment acute phase reaction
inhibit activation of coagulation system
provide -ve feedback mechanisms to pro-inflammatory mediators
what do the clinical features of sepsis depend on
host
organism
environment
features of organ dysfunction
CNS: altered consciousness, confusion, psychosis
haematology: reduced platelets, increased PT/APTT, reduced protein c, increased D dimer
resp: tachypnoea, PaO2 <70mmHg, sats <90%
CVS: tachycardia, hypotension
liver: increased liver enzymes, reduced albumin, increased PT
kidney: oliguria, anuria, increased creatinine
general features of sepsis
fever >38C - chills, rigor, flushes, cold sweats, night sweats
hypothermia <36C - esp in elderly, very young children and immunosuppressed
tachycardia >90BPM
tachypnoea >20/min
altered mental status - es- elderly
hyperglycaemia >8mmol/L in the absence of diabetes
inflammatory variables in sepsis
leucocytosis (WCC >12 000/ml) leucopenia (WCC <4000/ml) normal WCC w/ >10% immature forms high CRP high procalcitonin
haemodynamic variables in sepsis
artieral hypotension (systolic <90 or MAP <70) SvO2 >70%
organ dysfunction variables in sepsis
arterial hypoxaemia (PaO2/FiO2 <50mmHg)
oliguria (<0.5ml/kg/h)
creatinine increase compared to normal baseline
coagulation abnormalities (PT >1.5 or APTT >60s)
ileus
thrombocytopenia (<150 000/ml)
hyperbilirubinemia
tissue perfusion variables in sepsis
high lactate
skin mottling and reduced capillary perfusion
effect of host on sepsis presentation
age
comorbidities (COPD, DM, CCF, CRF, disseminated malignancy)
immunosuppression
previous surgery - splenectomy
immunosuppression and sepsis presentation
acquired - HIV/AIDS
drug induced - steroids, chemotherapeutic agents, biologics
congenital - agammaglobulinaemia phagocytic defects, defects in terminal complement component
effect of organism on presentation of sepsis
gram +ve/-ve
virulence factors (e.g. MRSA, toxin secretion, ESBL, KPC, NDM-1)
bioburden
effect of environment on presentation of sepsis
occupation
travel
hospitalisation
Sepsis 6
2A2B2C
take 3, give 3
blood cultures
blood lactate
measure urine output
oxygen - aims sats 94-98%
IV abx
IV fluid challenge
why do we carry out blood cultures
blood lactate
measure urine output
blood cultures - make microbiological diagnosis (30-50% +ve), if spike in temp take 2 sets
lactate - marker of generalised hypoperfusion/severe sepsis/poorer prognosis
low urine output - marker of renal dysfunction
how to choose what abx to use
based on working diagnosis from hx and examination
local abx guidelines
consider: allergy, previous MRSA/ESBL/CPE, abx toxicity/interactions
types of lactate
type A - hypoperfusion
type B - mitochondrial toxins, alcohol, malignancy, metabolism errors
IV fluids
30ml/kg fluid challenge
2.1L for 70kg patient
when to consider HDU referral
low BP responsive to fluids lactate >2 despite fluid resus elevated creatinine oliguria liver dysfunction - Bil, PT, Plt bilateral infiltrates, hypoxaemia
when to consider ITU
septic shock
multi-organ failure
requires sedation, intubation and ventilation
