Clinical Sepsis

Question 1

On the disease continuum, what is the difference between SIRS and sepsis? What distinguishes severe sepsis?

Answer 1

SIRS is a non-specific clinical response that can be caused by infection as well as trauma, burns and other insults, but sepsis is SIRS with a confirmed infectious process. In severe sepsis there are signs of organ dysfunction in at least one organ. ‘Infection suspected and SOFA score 2+’

Question 2

What distinguishes septic shock from severe sepsis?

Answer 2

Septic shock is severe sepsis with hypotension refractory to adequate volume resuscitation.

Question 3

What is the mortality in sepsis and in septic shock?

Answer 3

Sepsis 10%

Septic shock 40%

Question 4

What is the difference between the SOFA score and the qSOFA score?

Answer 4

SOFA required assessment of most systems, with GCS, bilirubin, creatinine, MAP and other tests of organ function. This was too complicated and SOFA scores were missing on many patients, so the quick SOFA (qSOFA) was introduced, and involves measuring just SBP (<100) and respiratory rate (>22) and altered mentation.

Question 5

What is the toxic component of LPS?

Answer 5

Lipid A (highly preserved)

Question 6

What is the relationship between endotoxin and Gram-negative sepsis?

Answer 6

Endotoxin directly triggers coagulation and fibrinolytic pathways, and indirectly (endothelial activation) initiates the cytokine cascade producing an inflammatory response. The greater the plasma levels of endotoxin (i.e. LPS), the worse the chances of survival.

Question 7

What must you measure within 3 hours of identifying a case of potential sepsis?

Answer 7

Lactate

Question 8

Some sepsis patients have better survival. What protein can account for this?

Answer 8

Antiendotoxin

Question 9

What group of pathogens are often implicated in sepsis? What other pathogens can be involved? Which of these has a mortality of 50%?

Answer 9

The ESCAPE pathogens (nosocomial infection).

Can also have viral sepsis, or candida. Candidaemia sepsis has a high mortality if 50%.

Question 10

Give a short summary of sepsis pathophysiology

Answer 10

Infection, maladaptive response with systemic NFkB->TNFa->vasorelaxation, permeability, hypercoagulation->hypotension and hypovolaemia->shock->mitochondrial dysfunction->hypoxia->multiple organ failure->death.

Microvascular coagulation->tissue injury->organ dysfunction->death.

Question 11

How do genetic factors influence susceptibility to sepsis?

Answer 11

There can be mediators over expression leading to an inflammatory tendency, such that there is systemic instead of localised inflammation. And thus, instead of regaining homeostasis, you develop sepsis.

Question 12

Why is there hypotension in sepsis?

Answer 12

There is hypovolaemia due to capillary leak, and there is also reduced vascular time and myocardial depression.

Question 13

What are the 3 primary features of cardiovascular failure in sepsis?

Answer 13

Hypovolaemia
Hypotension
Shock

Question 14

Summarise the immediate (<6 hours) and subsequent management of sepsis.

Answer 14

Within 6 hours: aims are resuscitation, early antibiotics and source control. Sepsis 6: administer high-flow O2, take blood cultured and consider infective source, administer IV antibiotics, IV fluid resuscitation, check haemoglobin and lactate, commence hourly urine output measurement.

Subsequent management: care bundles with thromboprophylaxis, etc. Renal support (dialysis if required).