1. IAFP Conference McCall, Idaho May 20, 2017 Ann Lima, MD MPH
Sepsis Update
IAFP Conference
McCall, Idaho
May 20, 2017
Ann Lima, MD MPH

2. Objectives Understand history of sepsis definitions and guidelines
Familiarize with most recent literature regarding sepsis
Recognize different tools used for screening and monitoring of sepsis
Familiarize with Sepsis 3 recommendations and Surviving Sepsis 2016 guidelines
Identify areas for clinical improvement and future research

3. Sepsis Timeline SIRS criteria 1991 1991 Sepsis Task Force (1)
Rivers et al 2001
2001 Sepsis Task Force (2)
Surviving Sepsis Campaign 2002
ProCESS, ARISE, ProMISe
2016 Sepsis Task Force (3)

4. Sepsis Identification
SIRS – Systemic Inflammatory Response Syndrome
LODS – Logistic Organ Dysfunction Score
SOFA – Sequential (Sepsis-related) Organ Dysfunction Assessment
qSOFA – Quick Sequential (Sepsis-related) Organ Dysfunction Assessment
NEWS – National Early Warning Score
MEWS – Modified Early Warning Score
RFS – Red Flag Sepsis

5. Surviving Sepsis Campaign
Started in 2002 at European Society of Intensive Care Medicine annual meeting
2012 guidelines came out
Sepsis care bundles
Within 3 hours of presentation
Lactate measurement
Blood cultures prior to administration of antibiotics
Administer broad spectrum antibiotics
Administer 30ml/kg crystalloid for hypotension or lactate >4
Within 6 hours
Measure CVP, MAP, urine output, ScvO2

6. Surviving Sepsis Campaign
Update in April 2015 (after ProCESS, ARISE, ProMISe)
Within 3 hours of presentation (no change)
Lactate measurement
Blood cultures prior to administration of antibiotics
Administer broad spectrum antibiotics
Administer 30ml//kg crystalloid for hypotension or lactate >4

7. Surviving Sepsis Campaign
Update in April 2015 (after trials)
Within 3 hours of presentation (no change)
Within 6 hours
Vasopressors for hypotension, that does not respond to initial fluid resuscitation, to maintain a mean arterial pressure (MAP) > 65mmHg
If persistent hypotension after initial fluid administration, or if initial lactate was >4mmol/L, reassess volume status and tissue perfusion
Re-measure lactate if initial lactate elevated

8. Sepsis 3.0 Sepsis is not simply infection + two or more SIRS criteria
The host response is of key importance
Sepsis represents bad infection where
bad = infection leading to organ dysfunction
“Severe sepsis” is not helpful and should be eliminated

9. Sepsis 3.0
Redefined sepsis as life-threatening organ dysfunction caused by a dysregulated response to infection
Organ dysfunction identified by change in SOFA score >2 points due to the infection.
GCS
P:F ratio (PaO2:FiO2)
BP (MAP and/or pressors)
Platelets
Total Bilirubin
Creatinine

10. Sepsis 3.0 Screening for sepsis, recommend qSOFA >2
Altered mental status
SBP <100mmHG
RR >22/min
Not suggesting not treating until this threshold reached, but offering alternative to SIRS

11. Sepsis 3.0 Lactate? Marker of cellular and/or metabolic stress
Not necessarily tissue hypoperfusion
Independent predictor of mortality
Additional tool
Septic shock is more than hypotension alone

12. Sepsis 3.0 Conclusions Definition Clinical criteria
Septic shock is defined as a subset of sepsis in which underlying circulatory, cellular and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone
Clinical criteria
Hypotension requiring use of vasopressors to maintain MAP ≥65 mmHg and having a serum lactate >2 mmol/l persisting despite adequate fluid resuscitation

13. Sepsis 3.0

14. Response to Sepsis 3.0
Churpek et al sought to compare qSOFA with other scores – SIRS, MEWS, NEWS
Retrospective
30,677 patients
NEWS > MEWS > qSOFA > SIRS
Predicting death and ICU transfer in non-ICU patients
Using the highest non-ICU score of patients (combined outcome of death, ICU transfer):
sensitivity of 91% and specificity of 13% for ≥2 SIRS
54% and 67% for qSOFA ≥2,
59% and 70% for MEWS ≥5,
67% and 66% for NEWS ≥8.
Most patients met ≥2 SIRS criteria 17 hours before the combined outcome compared with 5 hours for ≥2 and 17 hours for ≥1 qSOFA criteria.

15. Response to Sepsis 3.0

16. Response to Sepsis 3.0
Price and Sivayoham aimed to identify the most sensitive sepsis screening tool
Retrospective
178 patients
SIRS > RFS > qSOFA for identification of septic patients at triage (in ED)
RFS > SIRS > qSOFA for mortality sensitivity
qSOFA > RFS > SIRS for mortality specificity
Red Flag Sepsis

17. Response to Sepsis 3.0
Red Flag Sepsis (RFS)

18. Response to Sepsis 3.0
UK Sepsis Trust, advised waiting until qSOFA validated, continue RFS and NEWS
Moskowitz et al 2016
Cortes-Puch et al 2016
American College of Chest Physicians
Multiple emergency medicine and critical care blogs have criticized qSOFA and Sepsis 3.0

19. Response to Sepsis 3.0 Freund et al, JAMA Jan 2017
Prospectively validate qSOFA as mortality predictor
1088 patients
qSOFA had greater prognostic accuracy for in- hospital mortality than SIRS or severe sepsis

20. Response to Sepsis 3.0 Forward et al, Intensive Care Med, March 2017
161 hospitalized (non-ICU) patients
Higher specificity for sepsis, in-hospital mortality, ICU admission and blood culture positivity with qSOFA, than SIRS or Sepsis Kills (SK) criteria
Similar sensitivity for sepsis

21. Response to Sepsis 3.0 Finkelsztein et al 2017 Kim et al 2017
Prospective
152 patients
qSOFA more accurate than SIRS for predicting mortality and ICU-free days
Kim et al 2017
615 patients
qSOFA with low sensitivity and high specificity for sepsis, 28-day mortality and ICU admission

22. Surviving Sepsis Campaign Update
No comment on sepsis criteria (qSOFA), but did use much of sepsis 3 recommendations
No more EGDT
Use crystalloid, can consider albumin if using large amounts of crystalloid
Dynamic reassessment, eg passive leg raise
Use norepi first, then epi, then vasopressin (no more dopamine)

23. Surviving Sepsis Campaign Update
Start resuscitation early with source control, ivf, and antibiotics
Guide resuscitation to normalize lactate in patients with elevated lactate levels
Hospitals have a performance improvement program for sepsis including sepsis screening for acutely ill, high-risk patients.

24. Surviving Sepsis Campaign Update
Routine microbiologic cultures, including 2 sets of blood cultures, be obtained before starting antimicrobial therapy in patients with suspected sepsis and septic shock if doing so results in no substantial delay in the start of antimicrobial therapy.
For the initial management of septic shock, use at least two antibiotics of different antimicrobial classes aimed at the most likely bacterial pathogen for empiric combination therapy.

25. Surviving Sepsis Campaign Update
Combination therapy (ie double-covering pseudomonas or acinetobacter) not to be used:
Ongoing treatment of most other serious infections, including bacteremia and sepsis without shock.
Routine treatment of neutropenic sepsis/bacteremia.
Daily assessment of de-escalation of antimicrobial therapy
Narrow antimicrobial therapy once pathogen identification and/or clinical improvement

26. Surviving Sepsis Campaign Update
Goals of care and prognosis be discussed with patients and families.
Goals of care be incorporated into treatment and end-of-life care planning, utilizing palliative care principles where appropriate.
7-10 days is adequate for most serious infections associated with sepsis and septic shock
Procalcitonin levels can be used to support shortening duration of antimicrobial therapy in sepsis

27. Surviving Sepsis Campaign Update
More guidelines
Steroids
Mechanical ventilation
Nutrition
Glucose Control
Renal replacement therapy

28. Screening, Monitoring Tools
SIRS
SOFA
qSOFA
NEWS
MEWS
RFS
Temperature X
Heart Rate
Blood Pressure
Respiratory Rate
Oxygen Saturation
Use of supplemental oxygen
PaO2:FiO2
Mental status
Leukocyte count
Urine output
Lactate
Purpuric rash
Platelets
Creatinine
Bilirubin

29. Objectives Understand history of sepsis definitions and guidelines
Familiarize with most recent literature regarding sepsis
Recognize different tools used for screening and monitoring of sepsis
Familiarize with Sepsis 3 recommendations and Surviving Sepsis 2016 guidelines
Identify areas for clinical improvement and future research

30. References
Bone RC, Balk RA, Cerra FB, et al. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20(6):864–874.
Dellinger  RP, Levy  MM, Rhodes  A,  et al; Surviving Sepsis Campaign Guidelines Committee Including the Pediatric Subgroup.  Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012.  Crit Care Med. 2013;41(2):
Levy  MM, Fink  MP, Marshall  JC,  et al; International Sepsis Definitions Conference.  2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.  Intensive Care Med. 2003;29(4):
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M et al. Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA 2016; 315:
Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M, Sepsis Definitions Task Force. Developing a new definition and assessing new clinical criteria for septic shock: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA ;315:775–87.
ProCESS Investigators, Yealy DM, Kellum JA, Juang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370(18):
The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371:
Mouncey PR, Osborn TM, Power GS, et al for the ProMISe trial investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015: DOI: /NEJMoa
Churpek MM, Zadravecz FJ, Winslow C, Howell MD, Edelson DP. Incidence and prognostic value of the systemic inflammatory response syndrome and organ dysfunctions in ward patients. Am J Respir Crit Care Med. 2015;192:958–64.
Freund, Lemachatti, Krastinova et al. Prognostic accuracy of sepsis-3 criteria for in0hospital mortality among patients with suspected infection presenting to the emergency department. JAMA Jan 17;317(3):
Kim, Ahn, Kim et al. Predictive performance of the quick sequential organ failur assessment score as a screening tool for sepsis, mortality, and intensive care unit admission in patients with febrile neutropenia. Support Care Cacner May;25 (5):
Finkelsztein, Jones, Ma et al. Comparison of qSOFA and SIRS for predicting adverse outcomes of patients with suspicion of sepsis outside the intensive care unit. Cit Care Mar 26;21(1):73.
Forward, Konency, , Bursont, et al. Predictive validity of the qSOFA criteria for speis in non-ICU inpatients. Intensive Care Med.

31. References
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