1. Sepsis Dr John Green

2. Definitions Infection – An inflammatory response to microorganisms or the presence of microorganisms in normally sterile tissue. SIRS – 2 or more of – Temp >38 <36 – HR >90 – RR >20 or PaCO2 <4.3 – WCC >12 <4 or <10% immature forms

3. Sepsis – SIRS & Presumed infection Severe Sepsis – Organ dysfunction or hypotension. Septic Shock – Severe sepsis persisting despite fluid resuscitation. Hypotension – SBP 40mmHg

5. Pathogenensis of Severe Sepsis - The very basics Over activity of innate immune response. Massive cytokine release. Activation of coagulation system. Positive and negative feedback, interlinked process’. Genetic polymorphism. Multisystem involvement.

6. (Failed) Therapies Demonstrate a Multifactorial and Interconnected Pathogenesis Coagulation – APC, AT-III, TFPI, Heparin Immunomodulation – Anti-TNF, Anti-PAF, Bradykinin antagonists, Steroids, Antioxidants, G-CSF, High dose HF Others – Naloxone, Methylene Blue

7. Describing the Patient With Sepsis - PIRO DomainDescription PredispositionPremorbid state, Patient background InsultWhat is the infection? ResponseSIRS, CRP, WCC etc Organ FailuresSOFA Score, Description

8. Scoring systems Difficult to remember but for exams focus on; – Why and how it was developed ? – What it is best used for ? – Why it can be criticised ? In Sepsis APACHE, SAPS and SOFA the big 3

9. APACHE Designed for research – to define a case mix. Does not take into account the diagnosis, only the insult. APACHE – APACHE 2 – Reduced number of acute physiology variables (34-12) – Simplified chronic health. – ‘And’ became ‘Age’. – Emergency surgery incorporated. APACHE 2 – APACHE 3 – Weightings changed. – Coefficients and weightings (secret) allow some degree of individual patient applicability – but not much better than APACHE 2 when tested.

10. SAPS Simplified APACHE SAPS II – Probability of death based on logistic regression.

11. SOFA 6 organs scored 0 (normal) to 4. Designed for daily assessment. Useful for resource decisions (funding) Designed for simplicity

12. Others Multiple Organ Dysfunction Score Mortality Prediction Model Therapeutic Intervention Scoring System