Lecture 5: Sepsis and Septic Shock

Question 1

definition of sepsis using the Sepsis-3 guidelines

Answer 1

• sepsis is defined as a life-threatening organ dysfunction caused by dyregulated host response to infection
• SIRS + infection

Question 2

definition of septic shock using the sepsis-3 guidelines

Answer 2

• 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.

Question 3

qSOFA factors for patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital

Answer 3

• hypotension systolic BP < 100mmHg
• altered mental status
• tachypnoea RR > 22/min

score of >/= 2 criteria suggests a greater risk of a poor outcome

Question 4

why is sepsis so important?

Answer 4

• common condition
• becoming more common
• increased morbidity and mortality

Question 5

for each hours delay in administering antibiotics in septic shock, mortality increases by?

Answer 5

7.6%

Question 5

the six key steps in the investigation and management of sepsis, often referred to as ‘sepsis six’ include:

take 3 give 3

Answer 5

• 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)

Question 6

which other investigations may be performed for sepsis?

other than sepsis 6

Answer 6

• imaging: CXR, echo, abdominal US)
• viral PCR for diagnosis of influenza
• urinalysis with or without culture
• lumbar puncture

Question 7

list the body’s defence mechanisms against sepsis

Answer 7

• physical barrier: skin, mucosa, epithelial lining
• innate immune system: IgA in GI tract, dendritic cells/macrophages
• adaptive immune system: lymphocytes, immunoglobulins

Question 8

what is the origin of sepsis?

Answer 8

• originates from a breach of intergrity of host barrier, whether physical or immunological
• organism enters bloodstream creating a septic state

Question 9

what are the three phases in the pathogenesis of sepsis?

Answer 9

1. release of bacterial toxins
2. release of mediators: pro-inflammatory mediators cause inflammatory response that characterises sepsis, compensatory anti-inflammatory reaction can cause immunoparalysis
3. effects of specific excessive mediators

Question 10

what are some commonly released bacterial toxins?

Answer 10

• 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.

Question 11

give examples of pro-inflammatory mediators in sepsis

Answer 11

• TNF-alpha
• IL1B, IL-2, IL-8, IL-15
• neutrophil elastase
• IFN-gamma

Question 12

give examples of anti-inflammatory mediators in sepsis

Answer 12

IL-1Ra
IL-4
IL-10
IL-13

Question 13

what are the effects of excessive pro-inflammatory mediators in sepsis?

Answer 13

• 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

Question 14

what are the effects of excessive anti-inflammatory mediators in sepsis?

Answer 14

• inhibit TNF-alpha
• augment acute phase reaction
• inhibit activation of coagulation system
• provide negative feedback mechanisms to pro-inflammatory mediators

Question 15

why is a balance between the pro-inflammatory and anti-inflammatory mediators important?

Answer 15

• Pro-inflammatory imbalance: septic shock with multiorgan failure and death.
• Anti-inflammatory imbalance: immunoparalysis with uncontrolled infection and multiorgan failure

Question 16

general clinical features of sepsis

Answer 16

• 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

Question 17

inflammatory variables in sepsis

i.e. what a blood test might show

Answer 17

• leucocytosis (WCC > 12,000/ml)
• leucopenia (WCC < 4000/ml)
• normal WCC with greater than 10% immature forms)
• high CRP
• high procalcitonin

Question 18

haemodynamic clinical features in sepsis

Answer 18

• arterial hypotension (systolic < 90mmHg or MAP < 70mmHg)
• SvO2 > 70%

Question 19

organ dysfunction lab values/clinical features in sepsis

Answer 19

• 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

Question 20

tissue perfusion variables present in sepsis

Answer 20

• high lactate
• skin mottling and reduced capillary perfusion

Question 21

which antibiotics are used for intra-abdominal sepsis?

Answer 21

• amoxicillin, gentamicin and metronidazole

Question 22

why are lactate levels important to get in sepsis and what are the two types of lactic acidosis?

Answer 22

Of available biomarkers, lactate has the most support to identify adverse outcomes.

Type A: hypoperfusion
Type B: mitochondrial toxins, alcohol, malignancy, metabolism errors.

Question 23

when to consider high dependency unit (HDU) for sepsis?

Answer 23

• low BP responsive to fluids
• lactate > 2 despite fluid resuscitation
• elevated creatinine
• oliguria
• liver dysfunction, Bil, PT, Plt
• bilateral infiltrates, hypoxaemia

Question 24

when to consider intensive therapy unit (ITU) for sepsis?

Answer 24

• septic shock
• multi-organ failure
• requires sedation, intubation and ventilation