1. Andrew Harding
PGY-2

2. Why is learning about sepsis important?
You will see it often
Severe sepsis/septic shock mortality ~18-46% (by SIRS)
~10% of all pts in ICU
Most common cause of death in ICU

3. Outline/Objectives Learn how to define and identify sepsis
Know how to work up sepsis
Learn how to triage septic patients
Treat sepsis

4. Outline/Objectives Learn how to define and identify sepsis
Know how to work up of sepsis
Learn how to triage septic patients
Treat sepsis

5. 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
Sick not sick?
Does the patient have sepsis?

6. Case 2 Sick or not sick? Septic?
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
Sick or not sick?
Septic?

7. 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
Sick or not sick?
Septic?
Septic shock?

8. How do you define sepsis?
The old way:
SIRS (Systemic Inflammatory Response Syndrome)
Sepsis
Severe sepsis
Septic shock
What are the SIRS criteria?

9. SIRS Criteria - 2 out of 4 **** BP IS NOT A SIRS CRITERIA ****
Temperature
> 38.0 or < 36.0 HR
> 90
Respiratory status
RR >20 or PaCO2 <32
WBC
>12,000 or <4,000 or >10% bands
- 2 out of 4
**** BP IS NOT A SIRS CRITERIA ****

10. 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
IFN-γ

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

12. Severe sepsis
Sepsis with organ dysfunction

13. Septic shock
Sepsis + hypotension despite “adequate” fluid resuscitation
That is the “old” way of thinking about sepsis

14. The New Definition of Sepsis1
Life-threatening organ dysfunction caused by a dysregulated host response to infection.
How does one define organ dysfunction??
Cardiovascular
Pulmonary
Liver
Renal
Hematologic
CNS/other
How do we objectively assess end organ damage to determine if a patient is “septic”?

15. Sequential Organ Failure Assessment

16. SOFA
February 2016, 19 member task force of the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) discuss identifying and classifying sepsis
Higher SOFA score = 74% chance that pt died
Higher SIRS = 64% likelihood chance
-- SOFA has higher predictive value, may provide better identification of sepsis than SIRS
What does the SOFA score include?

17. SOFA

18. SOFA1
Organ dysfunction can be identified as an acute change in total SOFA score ≥2 points consequent to the infection.
The baseline SOFA score can be assumed to be zero in patients not known to have preexisting organ dysfunction.
A SOFA score ≥2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection. Even patients presenting with modest dysfunction can deteriorate further, emphasizing the seriousness of this condition and the need for prompt and appropriate intervention, if not already being instituted.

19. Septic Shock (by SOFA)
Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.
Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation.
With these criteria, hospital mortality is in excess of 40%.3
That takes so long to calculate! How can we use the SOFA score to identify patients with sepsis?

20. qSOFA
What makes up qSOFA?

21. qSOFA Respiratory rate ≥22/min Altered mentation
Systolic blood pressure ≤100 mm Hg
2 or more = suggestive of sepsis, higher mortality
Let’s go back to our cases..

22. 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
qSOFA?
Does this patient have sepsis? No

23. 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
qSOFA
By SIRS:
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?
Does this patient have septic shock?
By qSOFA?
No, has an infection… but not “septic”

24. 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
qSOFA? 3
Does this patient have sepsis?
Yes
Does this patient have severe sepsis?
Does this patient have septic shock?
Possibly- will need to see how her BP responds to IVFs

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

26. Work Up of Sepsis
Source
Severity

27. History? Source Respiratory Blood Urine GI
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

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

29. Labs? Source Lung Blood Urine GI Other
sputum cx, Legionella/Strep urine Ag, flu A+B, respiratory viral panel
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, diagnostic paracentesis
Other
culture of any drainage, LP, ESR, CRP
**** ALWAYS CULTURE BEFORE STARTING ANTIBIOTICS ****

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

31. Imaging Studies? Lung Blood Urine/GI Other (CNS, Skin/Soft tissue)
CXR, CT chest
Blood
TTE
Urine/GI
CT abd
Other (CNS, Skin/Soft tissue)
CT head, MRI (for OM)

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

33. 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  MICU
Septic shock
MICU

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

35. How do you treat sepsis? 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
FLUIDS
CULTURES
ANTIBIOTICS

36. Initial Treatment of Sepsis
Fluids
Cultures/labs (lactate)
Antibiotics
If source is known, cater abx to the source
If source is unknown, use broad spectrum
Vanc/zosyn
Source control: remove potential source (line holiday) within 12 hrs
*** WHEN GIVING FLUIDS, KEEP IN MIND PT’S RENAL FUNCTION AND EF ****

37. Management of severe sepsis/shock
As always, first assess the ABCs
(A/B) Airway/Breathing
Often times severe sepsis is accompanied by increased work of breathing (compensation for metabolic acidosis)
Many times patients (especially the elderly) cannot keep up the necessary respiratory rate required to compensate

38. Management of severe sepsis/shock
(C) Circulation (perfusion)
Assess early and often
May require arterial line for close monitoring
Inadequate perfusion may be present in the absence of obvious hypotension
Cool, vasoconstricted skin due to redirection of blood flow to core organs (although warm, flushed skin may be present in the early phases of sepsis)
obtundation or restlessness
oliguria or anuria
lactic acidosis
What is “adequate fluid resuscitation?

39. “Adequate Fluid Resuscitation” for Hypotension
“Adequate”: 30 cc/kg (in 70 kg person, ~ 2 L)
If still hypotensive think pressors and MICU

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

41. Pressors Norepinephrine (Levophed) is 1st pressor used in sepsis
Others you can add on if necessary:
Vasopressin
Epinephrine
Phenylephrine
Dopamine
Are there any goals of treatment?

42. Goals for treatment MAP >65
CVP 8-12 (not intubated), (intubated)
Normal lactate
UOP > 0.5 ml/kg/hr
Where do these guidelines come from??

43. The Data Early Goal Directed Therapy Surviving Sepsis Campaign
Rivers et al 20014
Surviving Sepsis Campaign
International guidelines last came out in 2012
Last updated in April 2015 to incorporate new studies on sepsis

44. Early Goal Directed Therapy
The Rivers Trial
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

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

46. 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)

47. 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

48. ScvO2
Central venous O2 saturation (a surrogate for venous oxygen sat, which you need a pulmonary artery catheter to obtain)
= 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)
SvO2 = SaO2 – (VO2/(COxHbx1.34))

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

50. 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

52. ProCESS Trial5 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.”

53. 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

54. Surviving Sepsis Campaign Update
How do you re-assess volume status?

56. TAKE HOME POINTS Identify sepsis using qSOFA and SIRS criteria:
AMS, RR ≥ 22, SBP ≤ 100
T> 38.0 or < 36.0, HR> 90, RR >20 or PaCO2 <32, WBC >12,000 or <4,000 or >10% bands
Initial treatment:
FLUIDS, CULTURES, ABX, PRESSORS
GET CULTURES BEFORE ANTIBIOTICS**
If a patient is going in to septic shock, use levophed as first line pressor

57. References
Singer et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):
Ferreira et al. Serial Evaluation of the SOFA Score to Predict Outcome in Critically Ill Patients. JAMA. 2001;286(14):
Gomez, Kellum. Lactate in Sepsis. JAMA. 2015;313(2):
Rivers et al. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. N Engl J Med. 2001;345:
The ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock. N Engl J Med. 2014;370:
The ARISE Investigators et al. Goal-Directed Resuscitation for Patients with Early Septic Shock. N Engl J Med. 2014;371:
Mouncey et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med. 2015;372: