1. Intern Boot Camp: Sepsis Cassie Kovach PGY-3

2. Outline/Objectives Identification of sepsis Work up of sepsis Triaging sepsis Treatment of sepsis

3. Outline/Objectives Identification of sepsis Work up of sepsis Triaging sepsis Treatment of sepsis

4. Sepsis is a continuum SIRS (Systemic Inflammatory Response Syndrome) Sepsis Severe sepsis Septic shock

5. SIRS Physiology Inflammatory state affecting the whole body Release of cytokines  acute phase reaction  fever, leukocytosis  vasodilation/vascular leak  hypotension, tachy, edema, hypoxemia, tissue hypoperfusion Non-specific

6. SIRS Criteria Temperature > 38.0 or < 36.0 HR > 90 Respiratory status RR >20 or PaCO2 <32 WBC >12,000 or 10% bands **** BP IS NOT A SIRS CRITERIA ****

7. Sepsis 2/4 SIRS criteria + identified or suspected infection

8. Severe sepsis Sepsis with organ dysfunction – Cardiovascular Sepsis-induced hypotension: SBP 40 or <2 SD below normal for age in absence of other causes Elevated lactate UOP < 0.5 mg/kg/hr for 2 hrs despite adequate hydration – Pulmonary ALI with PaO 2 /FiO2<250 in the absence of PNA ALI with PaO 2 /FiO2<200 in the presence of PNA – Liver Bili > 4.0 – Renal Cr >2.0 (incr >0.5) – Hematologic Plt < 100,000 INR > 1.5

9. Septic shock Sepsis + hypotension despite “adequate” fluid resuscitation

10. Sick or not sick? Severe sepsis/septic shock mortality ~18-46% ~10% of all pts in ICU Most common cause of death in ICU

11. Case 1 38 yo F just finished running marathon, goes to medical tent because of lightheadedness – VS: 37.4, 130, 88/60, 24, 97% RA – Labs not available How many SIRS criteria? 2 Does this patient have sepsis? No

12. Case 2 65 yo M presents with productive cough, fever, chills. – VS: 38.1, 92, 120/80, 16, 90% RA – Labs: WBC 3.8, Hb 9, plt 180 RFP WNL, HFP WNL, lactate WNL, coags WNL How many SIRS criteria? 3 Does this patient have sepsis? Yes Would it make a difference in diagnosis of sepsis if had CXR which showed LLL infiltrate? No Does this patient have severe sepsis? No Does this patient have septic shock? No

13. Case 3 89 yo F sent from NH with confusion, diarrhea – VS: 35.8, 98, 22, 85/45, 97% RA – Labs: WBC 10,000 with 12% bands, Hb 10, plt 160 bicarb 15, Cr 1.3 (baseline 0.7), lactate 4.1 ABG: 7.29/25/89 How many SIRS criteria? 4 Does this patient have sepsis? Yes Does this patient have severe sepsis? Yes Does this patient have septic shock? Possibly- will need to see how her BP responds to IVFs

14. SIRS Criteria Temperature > 38.0 or < 36.0 HR > 90 Respiratory status RR >20 or PaCO2 <32 WBC >12,000 or 10% bands **** BP IS NOT A SIRS CRITERIA ****

15. Outline/Objectives Identification of sepsis Work up of sepsis Triaging sepsis Treatment of sepsis

16. History? Source Severity

17. History? Source – Lung Cough, sore throat, rhinorrhea Sick contacts – Blood Fatigue, lines in place, IVDU – Urine Dysuria, hematuria, flank pain – GI Diarrhea, nausea, vomiting, abd pain Recent abx or hospitalization, recent travel, sick contacts – Other: Skin/soft tissue, bone/joint, ascites, CNS, heart Skin changes, rash, joint pain, HA, confusion, back pain, neck stiffness, photophobia

18. History? Severity – Fevers/chills, appetite, po intake – Progression – Onset

19. Labs? Source Severity

20. Labs? Source – Lung sputum cx – Blood Bcx: 2 peripheral + 1 from each line the pt has (central lines, HD lines, art lines, etc) – Urine UA + Ucx – GI C diff, fecal leuks, stool cx – Other culture of any drainage, diagnostic paracentesis, LP, ESR, CRP **** ALWAYS CULTURE BEFORE STARTING ANTIBIOTICS ****

21. Labs? Severity – Does patient have evidence of any organ damage?  Need to evaluate organ systems to determine CBC RFP HFP Lactate Coagulation screen ABG ScvO2

22. Studies? Source Severity

23. Studies? Source/Severity – Lung CXR, CT chest – Blood TTE – Urine/GI CT abd – Other CT head, MRI (for OM)

24. Outline/Objectives Identification of sepsis Work up of sepsis Triaging sepsis Treatment of sepsis

25. When to transfer to MICU Sepsis – Usually can treat on the floor Severe sepsis – Floor or MICU depending on how severe the organ dysfunction is Severe lactic acidosis  MICU Respiratory distress requiring intubation  MICU Septic shock – MICU

26. Outline/Objectives Identification of sepsis Work up of sepsis Triaging sepsis Treatment of sepsis

27. Treatment Early Goal Directed Therapy – Rivers et al 2001 Surviving Sepsis Campaign – International guidelines last came out in 2012 – Recently updated in April 2015 to incorporate new studies on sepsis

28. Early Goal Directed Therapy Single center, 263 enrolled patients Purpose: evaluate efficacy of 6 hrs of EGDT prior to admission to ICU Results: – 30.5% mortality in EGDT group compared to 46.5% mortality in standard therapy (p=0.009) – During interval from 7-72 hrs, pts in EGDT had higher mean ScvO2, lower lactate, higher pH than standard therapy We typically follow a version of the algorithm from this trial in the ICU

29. CVP > 8 MAP >65 ScvO2 >70% Early Goal Directed Therapy algorithm EARLY Initial 6 hrs of resuscitation in the ED GOAL DIRECTED

30. CVP?? Approximation of R atrial pressure Gives an idea of volume status Measured by the nurses off of a central line (terminates in the SVC… near the R atrium) Mechanical ventilation increases CVP (because of PEEP)

31. MAP?? Mean arterial pressure Approximates average blood pressure throughout the cardiac cycle MAP = 2/3 DBP + 1/3 SBP Automatically calculated in our EMR and on BP monitor

32. ScvO2?? Central venous O2 saturation = the oxygen saturation of blood that is returning to the R atrium (lowest O2sat in the body before going to lungs) Drawn from a central line Indication of tissue hypoxia (more tissue hypoxia  more oxygen extraction at tissue level  decreased O2 saturation of blood returning to heart)

33. CVP > 8 MAP >65 ScvO2 >70% Early Goal Directed Therapy algorithm EARLY Initial 6 hrs of resuscitation in the ED GOAL DIRECTED

34. ProCESS Trial Published in NEJM May 1, 2014 Multicenter, 1341 patients enrolled Purpose: to determine if EGDT is generalizable and if all aspects of protocol are necessary Results: – At 60 days: no sig difference between EGDT and either protocol- based standard therapy group or usual-care group – No sig difference in 90 day mortality, 1 yr mortality, or need for organ support Conclusion: “protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes.”

35. ARISE Trial, ProMISE Trial Published in NEJM in Oct 2014 and April 2015 Also multicenter, large trials (ARISE: Australia, New Zealand, ProMISE: England) General conclusion from both: Strict EGDT protocol did not improve outcome

36. Surviving Sepsis Campaign Takes several studies into account when developing international guidelines for treating sepsis Splits care in to 2 “bundles”: one to be completed within 3 hrs and the other within 6 – Note: all groups in ProCESS trial essentially followed the 3 hr bundle – Updated in April 2015 to take into account the 3 new trials evaluating EGDT

38. Surviving Sepsis Campaign Update

40. Initial Treatment Antibiotics – If source is known, cater abx to the source – If source is unknown, use broad spectrum Vanc/zosyn Fluids Remove potential source (line holiday) within 12 hrs Obtain labs to help determine severity (lactate) *** WHEN GIVING FLUIDS, KEEP IN MIND PT’S RENAL FUNCTION AND EF ****

41. Hypotension If not responsive to “adequate” hydration, will need pressors in the MICU – “Adequate”: 30 cc/kg (in 70 kg person, ~ 2 L)

42. Pressors Need central line – Aggressive fluid resuscitation – Administration of pressors – Measure CVP Need arterial line – More accurate BP monitoring – Know second-to-second changes in BP

43. Pressors Norepinephrine (Levophed) is 1 st pressor used in sepsis Others you can add on if necessary: – Vasopressin – Epinephrine – Phenylephrine – Dopamine

44. Goals for treatment MAP >65 CVP 8-12 (not intubated), 12-15 (intubated) ScvO2 >70% Normal lactate UOP > 0.5 ml/kg/hr

45. Tools for treatment Fluids Antibiotics Pressors Blood products- if Hb <7, plt <10,000 (Albumin) Steroids- only if fluids/pressors not adequate Mechanical ventilation Central lines/arterial lines Nutrition- in first 48 hrs DVT/stress ulcer ppx

46. Summary SIRS criteria: T> 38.0 or 90, RR >20 or PaCO2 12,000 or 10% bands Sepsis workup should focus on identifying source and severity Initial treatment: cx, abx, fluids Patients with septic shock and some with severe sepsis require MICU