1. SEPSIS Intern Bootcamp Scott Denstaedt, PGYIII

2. Sepsis /ˈsɛpsɨs/; from the Greek σῆψις: the state of putrefaction and decay

3. Background local inflammation  systemic inflammatory response  tissue hypoperfusion and multi- organ failure  DEATH – release of specific toxins eg. Gram Negative Bacteria lipid A, Staph. aureus TSST-1 – Host cytokine response eg. TNF-alpha Septic shock with multi-organ failure is most common cause of death in ICU >750000 cases/year, mortality rate of 1 in 4

4. ***Sepsis is a spectrum of illness that requires early intervention to prevent complications and progression***

5. Definitions Systemic Inflammatory Response Syndrome (SIRS) criteria – response to infectious and non-infectious insults – 2 criteria needed to meet SIRS – Temp >38, <36 – HR >90 – RR >20, PaCO2 <32 (differs depending on textbook) – WBC >12k or <4k or 10% bands *NO BLOOD PRESSURE IN SIRS CRITERIA

6. Definitions Sepsis – 2 SIRS criteria + source of infection (you don’t necessarily need concrete evidence – high level of clinical suspicion is enough)

7. Definitions Severe Sepsis – Sepsis with organ dysfunction (don’t memorize the list below) Sepsis-induced hypotension Lactate above upper limits laboratory normal Urine output <0.5 mL kg/h for more than 2 h despite adequate fluid resuscitation Acute lung injury with Pa O2 /Fi O2 <250 in the absence of pneumonia as infection source Acute lung injury with Pa O2 /Fi O2 <200 in the presence of pneumonia as infection source Creatinine[2.0 mg/dL (176.8 lmol/L) Bilirubin[2 mg/dL (34.2 lmol/L) Platelet count <100,000 lL Coagulopathy (INR >1.5)

8. Definitions Septic Shock – Sepsis induced hypotension despite adequate fluid resuscitation Sepsis induced hypotension = SBP <90mmhg or 40mmhg change from baseline

9. Each term describes the the intensity of infectious insult Increase in # of SIRS criteria associated with decreased interval to progression of severe sepsis and septic shock

10. ***CAVEATS*** Elderly, uremic, and patients with end-stage liver disease or those receiving corticosteroids may NOT have fevers. SIRS Criteria are entirely non-specific – EG. Everyone met SIRS criteria on day one of intern year Clinical picture must be taken into account

12. Rivers et. al 2001 Initial 6 hours of resuscitation in ED ~1-1.5 hours to identification of sepsis on avg.

13. Early Goal Directed Therapy Outcomes Severe Sepsis and Septic Shock – Randomized to standard therapy (iv fluids, abx) v. Early Goal Directed Therapy RESULTS (Patients with EGDT): – Elevated CVP, MAP, Scv02 – Decreased Lactate – Improved Mortality (almost 50% reduction in mortality compared to standard therapy!!)

15. Surviving Sepsis Campaign Global initiative to reduce mortality from sepsis Evidence based guidelines for the management of sepsis Evidence graded based on LEVEL OF RECOMMENDATION (strong v. weak) and QUALITY OF EVIDENCE (ABCD) First published 2003, revised 2008, revised again 2012

16. Diagnosis: – 2 sets of blood cultures from separate sites (culture ALL vascular devices unless <48 hours old) BEFORE antibiotics (1C) – Imaging studies promptly performed to confirm potential source (UG) Antimicrobial Therapy: – Administration of effective antimicrobials within 1 hour of recognition of septic shock (1B) or severe sepsis (1C) – Initial empiric therapy against all likely pathogens and that penetrate adequately into tissue presumed to be the source of sepsis (1B) – DAILY reassessment for de-escalation (1B) Source Control: – seek and diagnose a source - if possible remove it within 12 hours (1C)

17. Initial resuscitation: – Protocolized resuscitation (Early Goal Directed therapy) during first 6 hours (1C) – Abnormal lactate should be re-checked, and normalization sought (2B) – Crystalloids initial fluid of choice (1B) – Hydroxyethyl starches for fluid resuscitation should not be used (1B) – Albumin in severe sepsis and septic shock in patients who require substantial amounts of crystalloid (2C) – Initial fluid challenge = 30ml/kg (1C) – Continue fluid challenge technique as along as there is hemodynamic improvement (UG)

18. Vasopressors: – Norepinephrine initial pressor (1B) – Epinephrine added to or as substitute for norepinephrine (2B) – Vasopressin 0.03 added to NE to reach MAP or decrease dosage of NE (UG) – Dopamine only in highly selected patients (due to risk of arrhythmia) (2C) – Pheynlephrine only if arrhythmia with NE or as a salvage therapy (1C) – Low dose dopamine for renal protection should not be used (1A) – All patients on vasopressors should receive arterial catheters (UG)

19. Steroids: – NO STEROIDS if initial resuscitation (fluid/pressors) adequate. If this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day (2C). Blood product administration: – transfuse only when Hgb <7g/dl to target of 7-9 in the absence of extenuating cricumstances (1B) – FFP should not be used to correct coagulopathy in the absence of bleeding or planned procedure (2D) – transfuse prophylactically when platelets 50k if active bleeding, surgery or invasive procedure (2D)

20. Mechanical ventilation (ARDS) – another lecture all together Sedation: – minimize sedation and titrate to sepcific endpoints 1B – Neuromuscular blocking agents avoided if possible if no ARDS 1C Glucose control: – initialize protocolized glucose management when 2 blood glucose levels >180 (insulin gtt), target goal <180 1A DVT prophy and Stress ulcer prophy: – LMWH when possible in severe sepsis 1B, Dalteparin if CrCl <30 – PPI or H2RA in severe sepsis, septic shock 1B Nutrition: – enteral or oral feeding as tolerated in first 48 hours 2C Goals of care: – set goals of care 1B – address as early as feasibile, no later than 72 hours after admission 2C

21. 2008 compared to 2012 Crystalloid initial fluid of choice Epinephrine 2 nd pressor of choice Dopamine no longer recommended Activated protein C no longer recommended Normalization of lactate as an endpoint in sepsis induced hypoperfusion Use of 1,3-B-D Glucan and antigalactomannan antibodies if concern for invasive candidal infection

22. Your Septic Patient: H+P age infectious review of systems: fever/chills, fatigue, myalgias, cognition, HA, sensitivity to light, rhinorrhea, sore throat, neck stiffness, cough, sob, cp, n/v/d, abdominal pain, back pain, dysuria, frequency, skin changes or wounds, recent sick contacts, recent antibiotics medical comorbidities (chronic diseases etc.) medications: immunosuppressants

23. Your Septic Patient: Exam vitals Temp, HR, RR, BP (stable or not) head and neck (meningeal signs, oropharynx, sinuses), cardiac (murmurs!), respiratory (signs of consolidation), back (CVA, spinal/paraspinal) tenderness, abdomen, ascites, skin exam for wounds, feet!

24. Your Septic Patient: Labs WBC - %PMN, %bands Hgb and Plt (important for sepsis and DIC) BUN/Cr Anion Gap LFT (Hyperbilirubinemia in sepsis, also shock liver) INR (to assess for DIC) Lactate if hypotension, anion gap, ill appearing ABG if anion gap, hypoxic, obtunded (pH patient belongs in ICU) U/A, Urine culture Blood cultures from two different sites Culture other sites as necessitated by history and exam

25. Your Septic Patient: Imaging CXR Other imaging depending on your clinical suspicion (usually CT with contrast)

26. Your Septic Patient: Treatment Empiric therapy based on suspected source of infection Supportive Care – Early Goal Directed Therapy – Surviving Sepsis Campaign, update 2012

27. Clinical Method Identify your septic patient (based on the definitions) Triage level of care (Floor v ICU) Work-up and treat their underlying infection Resuscitate according to EGDT and Surviving Sepsis Campaign – Initial fluid resuscitation 30mL/kg as fast as possible, unless CHF/low EF If in MICU place central line, arterial line

29. Clinical Pearls Managing Sepsis on the floor: – Use defined endpoints for fluid resuscitation U/O >0.5cc/kg/hr MAP >65 Normalization of lactate KNOW the patients Ejection Fraction and renal function Fluid resuscitation is the priority!!! Start pressors if MAP <65, even if CVP not yet known Transfer to MICU: – Hypotension resistant to fluid resuscitation (Septic shock) – usually after 4-6L fluid – Severe lactic acidosis (pH 7.2-7.25) – Severe or acutely worsening hypoxia or obtundation

30. Sources Rivers et. al Early Goal Directed Therapy, NEJM 2001 Dellinger et. al Surviving Sepsis Campaign 2012, Intensive Care Med 2013 Current Diagnosis and Treatment: Critical Care, 3 rd Edition http://www.youtube.com/watch?v=MceGURf XdR0 http://www.youtube.com/watch?v=MceGURf XdR0