1. SEPSIS: THE PAST, PRESENT & FUTURE
Bravein Amalakuhan, MD
Pulmonary Medicine
General Critical Care Medicine
Cardiac Surgical Critical Care Medicine

2. OUTLINE OVERVIEW Basics Pathophysiology, Etiology Epidemiology
PART 1
OVERVIEW
Basics
Pathophysiology, Etiology
Epidemiology
DEFINITIONS/DIAGNOSIS
Pre-2016 [Sepsis -1 and -2 Guidelines]
SIRS
Sepsis
Severe Sepsis
Septic Shock
Post-2016 [Sepsis -3 Guidelines]

3. WHAT’S IMPORTANT TO THE GOVERNMENT?
OUTLINE
PART 2
TREATMENT
The Rivers’ Approach
Key Components - Updated
CONTROVERSIES
Code Sepsis & Sepsis Alerts:
Sepsis + Heart Failure:
CMS/JOINT COMMISSION SEPSIS
CORE MEASURES
FUTURE DIRECTIONS
EFFECTIVE?
WHAT DO WE DO?
WHAT’S IMPORTANT TO THE GOVERNMENT?

4. OVERVIEW
PART 1
THE BASICS
PART 1

5. WHAT IS SEPSIS? “To Decay” or “To Rot”
THE BASICS
WHAT IS SEPSIS?
“To Decay” or “To Rot”
“A life-threatening organ dysfunction caused by a dysregulated host response to infection”
HISTORICALLY: GREEK ORIGIN
MODERN TIMES: SCCM / SURVIVING SEPSIS CAMPAIGN
AN UNCONTROLLED INFLAMMATORY RESPONSE

6. PATHOPHYSIOLOGY
Immune cells, Cytokines/Chemokines (IFN’s, TNF’s, IL’s)
A TIDAL WAVE OF INFLAMMATION!!!!

7. INFLAMMATION ON HYPERDRIVE !!!!
PATHOPHYSIOLOGY
INFLAMMATION ON HYPERDRIVE !!!!

9. DISSEMINATED INTRAVASCULAR COAGULATION
DIC
DISSEMINATED INTRAVASCULAR COAGULATION
35% of patients with severe sepsis

10. EPIDEMIOLOGY Mortality: 250,000 Americans die from it each year
1/3rd of in-hospital deaths
Mortality rates: 20-50%
Hospital Admissions:
> 1.5 million cases/year
10% of all ICU admissions
Longer LOS ~4-days compared to other diagnoses
Financial Burden
The single most expensive condition to treat in the hospital
>$20 Billion Dollars/yr

12. OUTLINE

13. WE’RE DOING A BETTER JOB !!!!!’
OUTLINE
WE’RE DOING A BETTER JOB !!!!!’
% MORTALITY
TIME

14. QUESTION Sepsis is a dysregulated and uncontrolled host T or F
response to infection
Sepsis causes vasoconstriction and decreased T or F
permeability
DIC occurs in early stages of sepsis T or F
DIC causes both thrombosis & hemorrhage T or F
Sepsis is no longer a serious health threat T or F

15. DEFINITIONS/ DIAGNOSES
PART 1
THE BASICS
PART 1

16. PRE-2016 SEPSIS-1 & -2 GUIDELINES BP CORRECTS WITH FLUIDS
REQUIRES VASOPRESSORS

17. SIGNS OF ORGAN DAMAGE
SEVERE SEPSIS

18. POST-2016
SEPSIS-3 GUIDELINES

20. OUTLINE

21. QUESTION
75yo male, weighing 50kg’s, with history of DM, HTN, HLD, presents to the local ER with worsening weakness, confusion and SOB. Upon arrival to the ER, patient had the following vitals: BP 60/30, HR 105, temp 102 deg. F, RR of 34, 02 saturation of 85% of room air. Lactate =4, WBC’s 30, Chest X-ray with bilateral infiltrates. He is started on 02 NC. Despite fluids he remains hypotensive.
Q1: What score would you calculate?
Q2: Does he have Sepsis, Severe Sepsis or Septic Shock
Q3: What is the likely source/etiology of the infection?

22. OUTLINE
TREATMENT
PART 2

23. EARLY GOAL DIRECTED THERAPY
Within 6-hrs of presentation to the ER, the following parameters should be achieved via the following interventions:
Parameters:
CVP 8-12
MAP 65-90
Uout >0.5 ml/kg/hr
Scv02 >70%
HCT >30%
Interventions:
Early Mechanical Ventilation
Fluid Resuscitation
Vasoactive agents
Transfusions
Antibiotics
OUTDATED APPROACH

24. THE RIVERS’ APPROACH

25. KEY TRIALS – THE TRILOGY
In each of those last three studies patients received early abx and > 30cc/kg of fluids before randomization

26. CURRENT GUIDELINES: THE NEW STANDARD OF CARE - ’SEPSIS-3’
TREATMENT COMPONENTS
CURRENT GUIDELINES: THE NEW STANDARD OF CARE - ’SEPSIS-3’
Source Control
Early administration of Antibiotics (Goal: <1-hour)
Broad spectrum initially
Early Administration of Fluids (Goal: <3-hrs)
30ml/kg of IV Crystalloids
Target MAP >65
No need to target CVP, Scv02 or urine output
Norepinephrine is the 1st line Vasopressor
Add Vasopressin or Epinephrine

27. TREATMENT COMPONENTS
CURRENT GUIDELINES
Normalize lactate levels with resuscitation efforts
Stop antibiotics early if procalcitonin low (< 0.5 ug/L)
Hydrocortisone 200mg/day if vasopressors and fluid resuscitation are not able to normalize hemodynamics
Blood Glucose Control: (mg/dl)
Nutrition:
Start TPN only after day #7/8
Early enteral nutrition
Do not check gastric residuals

28. ANTIBIOTICS ARE KEY !!!!!

29. QUESTION
75yo male, weighing 50kg’s, with history of DM, HTN, HLD, presents to the local ER with worsening weakness/ confusion/SOB. Vitals upon arrival to ER: BP 60/30, HR 105, temp 102 deg. F, RR of 34, 02 saturation of 85% of room air. Lactate =4, WBC’s 30, Chest X-ray with bilateral infiltrates. He is started on 02 NC. Despite fluids he remains hypotensive.
Q4: How much fluids should he have been given?
Q5: What is your first, second and third line vasopressors?
Q6: He is on moderate doses of 2 vasopressors. Next step?

30. CONTROVERSIES
PART 2

31. CODE SEPSIS / SEPSIS ALERTS
Improves mortality when baseline mortality rates >30% !!!!
Improves PROCESSES and ensures we don’t get complacent
However its criteria are non-specific  SIRS SEPSIS
It should simply prompt a discussion with the involved physicians
IS THERE AN INFECTION?
SHOULD WE GIVE ABX AND FLUIDS?
NO MANDATORY ORDERS! – DISCUSS
Post-op Patients ????

32. SEPSIS AND CHF PATIENTS
Complex
Hard to tease out the predominant contributor to a patient’s hemodynamic instability
Get more info!!!!
MAP, CO (4-6), CI, SVR ( ), Cardiac Echo
Arterial line
Vigeleo, EV1000-FloTrac, LiDCO
Cardiogenic Shock: Low MAP, Low CO, High SVR
Septic Shock: Low MAP, High CO, Low SVR
MORTALITY RATE FROM SEPTIC SHOCK? 50% IN-HOSPITAL MORTALITY
MORTALITY RATE FROM CHF Exacerbation?

33. SEPSIS AND CHF PATIENTS
In-hospital Mortality from Septic Shock: %
In-hospital Mortality from Cardiogenic Shock: %
Frequency: Septic Shock >>>>> Cardiogenic shock
Any difference in treatment in someone with chronic CHF and septic shock?

34. QUESTION
75yo female, weighing 50kg’s, with history of DM, HTN, HLD, CAD s/p stents, EF 30%, presents to the local ER with worsening weakness, confusion and SOB. Upon arrival to the ER, patient had the following vitals: BP 60/30, HR 105, temp 102 deg. F, RR of 34, 02 saturation of 85% of room air. Lactate =4, WBC’s 30, Chest X-ray with bilateral infiltrates. He is started on a 60% venturi mask.
Q1: Do you give fluids or start on vasopressors right away?
Q2: What is the predominant form of shock? And how do you determine it?
Q3: What vasopressor is your first choice?

35. SEPSIS AND CHF PATIENTS
CMS Core Measures
SEPSIS AND CHF PATIENTS
PART 2
Septic patients with pre-existing systolic or diastolic dysfunction have increased mortality!!!
Robust Data
Fluids have not been shown to adversely impact Pa02/Fi02 ratios or intubations rates
Uoellette et al. Critical Care 2014
Really difficult to get pulmonary edema in a truly septic patient even if pre-existing LV dysfunction with just 2L of crystalloids!!!!

36. CMS CORE MEASURES
Mandatory Reporting of Sepsis Bundle Compliance (2015)
Goal: 100%/”All or Nothing” Score
Complete the following within 3-hrs of presentation:
Measure lactate
Obtain blood cultures
Administer broad spectrum antibiotics
Admin 30cc/kg of crystalloids for low BP or lactate>4
Complete the following within 6-hrs of presentation:
Re-measure lactate
Start vasopressors if warranted

37. SEVERE SEPSIS

38. SEPTIC SHOCK

39. FUTURE DIRECTIONS IN SEPSIS TREATMENT SEPSIS AND CHF PATIENTS
PART 2
Septic patients with pre-existing systolic or diastolic dysfunction have increased mortality!!!
Robust Data
Fluids have not been shown to adversely impact Pa02/Fi02 ratios or intubations rates
Uoellette et al. Critical Care 2014
Really difficult to get pulmonary edema in a truly septic patient even if pre-existing LV dysfunction with just 2L of crystalloids!!!!

40. MORE EFFECTIVE ANTIBIOTICS
Novel Antibiotics
Increasing incidence and prevalence of multi-drug resistant organisms
Research into the development of antibiotics with novel mechanisms of action
MORE EFFECTIVE ANTIBIOTICS

41. IMMUNE THERAPY
Sepsis is a balance between “Hyperinflammation” (SIRS) and “Antinflammation” (CARS) at the cellular level
Targeting specific inflammatory/immune mediators associated with poor outcomes
Blocking vs. Promoting certain Biomarkers
Eg. HLA-DR, IL-10, IL-6, IL-3, CCL4, GM-CSF
CHEST 2017: Vitamin C + Thiamine + Hydrocortisone ?
IMMUNOMODULATION

42. REFERENCES
Singer, M., Deutschman, C.S., Seymour, C.W. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315: 801–810
Seymour, C.W., Liu, V.X., and Iwashyna, T.J. Assessment of clinical criteria for sepsis for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315: 762–774
Levy, M.M., Rhodes, A., Phillips, G.S. et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015; 43: 3–12
Kaukonen, K.-M., Bailey, M., Pilcher, D., Cooper, D.J., and Bellomo, R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015; 372: 1629–1638
Rhodes, A., Phillips, G., Beale, R. et al. The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intens Care Med. 2015; 41: 1620–1628
Rhee, C., Seymour, C.W., Iwashyna, T.J. et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, JAMA. 2017; 318: 1241–1249
Sprung, C.L. and Trahtemberg, U. What definition should we use for sepsis and septic shock?. Crit Care Med. 2017; 45: 1564–1567
Liu, V.X., Fielding-Singh, V., Greene, J.D. et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med. 2017; 196: 856–863
Rhodes, A., Evans, L.E., Alhazzani, W. et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: Intensive Care Med. 2017; 43: 1–74
Dellinger RP, Levy MM, Rhodes A, et al: Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: Crit Care Med 2013; 41:580–637
Centers for Medicare & Medicaid Services: CMS to Improve Quality of Care during Hospital Inpatient Stays Available at:
sheets/2014-Fact-sheets-items/ html.
Poutsiaka DD, Porto M, Perry W, et al. Comparison of the Sepsis-2 and Sepsis-3 Definitions of Sepsis and Their Ability to Predict Mortality in a Prospective Intensive Care Unit Cohort. Open Forum Infect Dis. 2017; 4(Suppl 1): S602. Published 2017 Oct 4. doi: /ofid/ofx