Sepsis (adults) September 2015

Objectives Know the spectrum of disease from infection to septic shock (and why this is important) Understand the difficulties in identifying sepsis Understand the importance of treating sepsis early Know how to treat sepsis Understand toxic shock and what treatment this requires

What is sepsis? Immune system’s response to the lipopolisaccharide in Gram Neg organisms or peptidoglycan in Gram Pos organisms’ cell wall Triggers a cascade of pro- and anti-inflammatory reactions responsible for the clinical syndrome Purified lipopolisaccharide infusion is often used to simulate the sespsis syndrome in clinical and genomic studies Gram positive sepsis is less predictable because of multiple bacterial virulence factors

Spectrum of disease SIRS Sepsis Severe sepsis Septic shock

Pitfalls in diagnosing sepsis Early-on in the disease process Severe sepsis/septic shock causes multiple organ dysfunction Elderly patients Medications like beta-blockers Temp <36C Source of infection not obvious

Why the urgency in treatment? Mortality in septic shock with optimal treatment 30% (ProMISe trial) Delay in reversing shock increases mortality (above 30%) Every hour’s delay in administering antibiotics increases mortality by 7% per hour (above 30%)

Treatment: first 10 minutes In all patients with SIRS, assess for the presence of septic shock Focused examination in order to identify the source of sepsis Diagnostic testing

Treatment: first hour Hypotension/hypoperfusion: 20-30ml/kg fluid bolus Balanced crystalloid solution if potassium normal Consider albumin in malnourished or cirrhotic patients Give broad spectrum antibiotics Choice of a/b based on presumed source Enough IV access Plan imaging early if required to ID source

Treatment: first 6 hours Continue fluid resuscitation if this is still indicated (cool peripheries, delayed CRT, responsiveness to fluid boluses) Start vasopressors: norepinephrine first line Aim for MAP >65mmHg / urine output >0.5ml/h / ScvO2 >70% (in early sepsis)

So what about the lactate…? Why is lactate elevated in sepsis? Hypoperfusion/’anaerobic metabolism’ But tissue oxygenation is still adequate even when PaO2 ≈ 6kPa in sepsis Shock causes increased production through aerobic and anaerobic glycolysis Decrease clearance of lactate in shocked state Why should we measure it? Reduction in lactate by 20% per 2h improves outcome

Sepsis 6 Give O2 Take blood cultures/other microbiology and lactate Give antibiotics Fluid bolus Vasopressors Measure urine output

Toxic shock Gram positive sepsis (cellulitis, necrotizing fasciitis, myositis, burns) Patients typically have flushed skin, is profoundly hypotensive with altered mental state Usual septic shock treatment, but give Clindamycin 1.2g IV as first antibiotic in addition to other antibiotics Clindamycin ‘switches off’ exotoxin production

Summary Think sepsis in any patient with SIRS Then, with urgency, treat as sepsis Remember to give Clindamycin in toxic shock