Sepsis and septic shock

what is sepsis

systematic illness caused by microbial invasion of normally sterile parts of the body

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

septic shock

sepsis with persisting hypotension requiring vasopressors to maintain MAP >65mmHg and having a serum lactate of >2mmol/l despite adequate volume resuscitation

SIRS

temp >38C or <36C

HR >90

RR>20 or PaCO2 <32

WBCs > 12,00 or <4,000 or >10% bands

what do they use in intensive care for sepsis

SOFA

sequential organ failure assessment score

qSOFA

hypotension - systolic BP < 100mmHg

altered mental status

tachypnea, RR>22/min

-score of >2 suggests greater risk of a poor outcome

what do you use for patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital

qSOFA

body’s physical barrier against sepsis

skin

mucosa

epithelial lining

body’s innate immune system against sepsis

Iga in GI tract, dendritic cells/macrophages

adaptive immune system against sepsis

lymphocytes

immunoglobulins

how does sepsis originate

breach of integrity of host barrier, physical or immunological

organisms enter the bloodstream creating a septic state

pathophysiology of sepsis and 3 phases in the pathogenesis of sepsis

uncontrolled inflammatory response

1. release of bacterial toxins

2. release of mediators

3. effects of specific excessive mediators

patients with sepsis have features consistent with what?

immunosuppression

•Loss of delayed hypersensitivity

•Inability to clear infection

•Predisposition to nosocomial infection

how does sepsis syndrome change over time

initially increase in inflammatory mediators

Later, there is a shift toward an anti-inflammatory immunosuppressive phase

what are the two types of toxins released

endotoxins

exotoxins

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

commonly 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

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

endotoxin release

LPS needs an LPS-binding protein to bind to macrophages

LTA binds to macrophages and taken up by toll-like receptors

-both release mediators from macrophage

exotoxin release

Pro-inflammatory response

Small amounts of superantigens will cause a large amount of mediators to be secreted: cascade effect

pro inflammatory mediators

causes inflammatory response that characterises sepsis

Th1

compensatory anti inflammatory reaction

can cause immunoparalysis

Th2

effects of specific excessive mediators - pro-inflammatory mediators

•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

effects of specific excessive mediators - anti-inflammatory mediators

•Inhibit TNF alpha

•Augment acute phase reaction

•Inhibit activation of coagulation system

•Provide negative feedback mechanisms to pro-inflammatory mediators

if compensatory anti-inflammatory > pro-inflammatory

septic shock with multiorgan failure and death

-need balance

if pro-inflammatory > compensatory anti-inflammatory

immunoparalysis with uncontrolled infection and multiorgan failure

-need balance

general features of sepsis

•Fever >38^oC – presenting as chills, rigors, flushes, cold sweats, night sweats, etc

•Hypothermia <36^oC – 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

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%

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

tissue perfusion variables in sepsis

•High lactate

•Skin mottling and reduced capillary perfusion

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

effect of organism on presentation of sepsis

•Gram positive versus Gram negative

•Virulence factors (example: MRSA, toxin secretion, ESBL, KPC, NDM-1)

•Bioburden

effect of environment on presentation of sepsis

occupation

travel

hospitilisation

sepsis 6

take 3

• blood cultures

• blood lactate

• measure urine output

give 3

• oxygen aim sats 94-98%

• IV antibiotics

• IV fluid challenge

OR

2As, 2Bs, 2Cs

Air enriched with O2

Antibiotics after blood culture

Blood culture

Blood gas with lactate

Crystalloid bolus

Catheter (urinary) if severe sepsis or septic shock

what is the use of blood cultures

makes microbiological diagnosis

what is the purpose of lactate

marker of generalised hypoperfusion/severe sepsis/poorer prognosis

what is the purpose of low urine output

marker of renal dysfunction

what to consider when giving antibiotics

allergy

previous MRSA, ESBL, CPE

antibiotic toxicity/interactions

lactate type A

hypoperfusion

lactate type B

mitochondrial toxins

alcohol

malignancy

metabolism erros

IV fluids

30ml/kg fluid challenge

2.1L 70kg patients

when to consider high dependency unit referral

•Low BP responsive to fluids

•Lactate >2 despite fluid resuscitation

•Elevated creatinine

•Oliguria

•Liver dysfunction, Bil, PT, Plt

•Bilateral infiltrates, hypoxaemia

when to consider intensive therapy unit

•Septic shock

•Multi-organ failure

•Requires sedation, intubation and ventilation