1. Sepsis Management in the Emergency Department Bryon K. Frost, MD, FACEP September 13, 2010 Medical Staff Meeting

2. 1) We will discuss and define Cryptic Shock. 2) Relevant literature review on Early Goal Directed Therapy in the Emergency Department. Lecture Agenda

3. MAP = SVR X CO P<0.001 Outcomes of Patients with a Baseline MAP > 100, Lactate >36 CONTROL n = 25 and Treatment n = 23 Cryptic Shock Cryptic Shock: Inadequate tissue perfusion without hypotension.

4. A clinical response arising from a nonspecific insult, including  2 of the following: –Temperature  38 o C or  36 o C –HR  90 beats/min –WBC count  12,000/mm 3 or  4,000/mm 3 SIRS = systemic inflammatory response syndrome. The critical factor in saving lives of patients in shock is early recognition!!! SIRS with a presumed or confirmed infectious process Sepsis SIRS Infection/ Trauma Severe Sepsis Sepsis + > 1 system organ failure. Persistent hypotension ↓ Septic Shock Death Cryptic Shock Sepsis A: Disease Continuum ↓

5. “You should already suspect that shock could appear if the underlying disease is left undiagnosed and untreated”. STAGE 1Local Infection onlyAnticipation STAGE 1: Local Infection only (Anticipation)

6. Cryptic Shock “The absence of shock is due to the fact that compensatory mechanisms are at play”( SVR gives rise to Cryptic Shock) STAGE 2Systemic InfectionPre-Shock STAGE 2: Systemic Infection (Pre-Shock)

7. Many physicians fail to recognize this stage: “Pt does not look right"... and "I don't know what is going on, but the blood pressure is not too bad"... Stage 3Compensated Shock- Normotensive, “Cryptic Shock” Stage 3: Compensated Shock- Normotensive, “Cryptic Shock”

8. “B.P. can only be restored with intravenous fluid and vasopressors. If you have not diagnosed the cause of shock by now, it will be very difficult to treat pt.” Stage 4Decompensated Shock-Reversible Stage 4: Decompensated Shock- Reversible

9. Death Stage 5Decompensated Shock-Irreversible Stage 5: Decompensated Shock- Irreversible

10. Early Goal Directed Therapy (EGDT) Literature Review:

11. MortalityAcute 28 Day 60 Day EGDT30.5%33.3%44.3% Standard (p)46.5% (0.009)49% (0.01)56.9% (<0.001) Rivers E. N Eng J Med. 2001; Nov8;345:1368-77 * P < 0.01 Early Goal Directed Therapy Dr. River’s Data:

12. * p < 0.02 BIG NEWS !!! ICUHosp Decreased Days 3.57.2 Decreased Resource Utilization - Days EGDT vs.. Control: Survivors Resource Utilization of Survivors Dr. River’s Study : Health Care Resource Use - Days

13. “Duration of hypotension before initiation of antimicrobial therapy is the critical determinant of survival in human septic shock” Kumer et al, Crit Care Med 2006 Early Goal Directed Therapy Dr. Kumer’s Data:

14. Rivers E P Chest 2010;138:476-480 Literature Review of EGDT Effectiveness:

15. The “BAD”: 1.“Community- acquired septic shock: early management and outcome in a nationwide study in Finland” - VARPULA 2. “Failure to implement evidence- based guidelines for sepsis at the ED” - José The GOOD: 1.“The Surviving Sepsis Campaign: Results of an International Guideline-based Performance Improvement Program targeting severe sepsis” -Levy, MD 2.“Hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis” -Thiel, MD 3.“Effect of a Rapid Response System for patients in shock on time to treatment and mortality during 5 years” -Sebat,MD 4.“Before–after study of a standardized hospital order set for the management of septic shock” -Micek, PharmD 5.“Early Goal-Directed Therapy: Improving Mortality and Morbidity of Sepsis in the Emergency Department” –Anne Focht, RN 6.“Impact of time to antibiotics on survival in patients with severe sepsis or sepsis shock in whom early goal-directed therapy was initiated in the emergency department” –Gaieski, MD The UGLY: “Factors Associated with Nonadherence to Early Goal-Directed Therapy in the ED” –Mikkelsen, MD “We can’t do this here”, “The patient is not sick enough to have sepsis” Looking at the Literature:

16. $31,011 /admit Decreased Admit Costs: $26,359,350 /yr 136 per year! 3,800 patient days saved per year ! 850 patients/yr Decreased Hospital Costs: Lives Saved: Decreased Hospital Days: Septic Patients: Henry Ford Hospital Data:

17. Admitted From ED to: ICU (n = 266) Hospital (n = 531) Average LOS before EGDT 9.3 days 18.2 days Estimated Cost/Pt/Day $ 4359 $ 2927 Est. Current Cost ( $ 4359)(266pt) (9.3D) $ 10. 8 million $ 28. 3 million Days Reduced with EGDT 3. 5 days 7. 2 days $ Saved $ 4. 0 million $ 11. 2 million Potential Hospital Cost Savings Benefit at University of Virginia:

18. C.E.A.= Cost Effective Analysis: a form of economic analysis that compares the relative costs and outcomes (effects) of two or more courses of action. QALY= Quality Adjusted Life Year: a measure of disease burden, including both the quality and the quantity of life lived. It is used in assessing the value, in money, of a medical intervention. “Exploring the advantages of effectively using EGDT at McLeod; pertaining to quality, cost and lives saved” Dr. David Huang’s Data:

19. 0.51.01.52.0-0.5 -10,000 10,000 20,000 30,000 Difference in costs (US$) Difference in effectiveness (QALY per patient) QALY- Quality Adjusted Life Year 1.0 More costly Less effective More costly More effective Less costly More effective Less costly Less effective 0 0 Less Effective More Effective Less Cost More Cost $20,000/QALY $50,000/QALY Societal perspective Cost-effective analysis:

20. 0.51.01.52.0-0.5 -10,000 10,000 20,000 30,000 Difference in costs (US$) Difference in effectiveness (QALY per patient) 1.0 $20,000/QALY $50,000/QALY 0 0 Cost per QALY = $7,800 More costly Less effective More costly More effective Less costly More effective Less costly Less effective Societal perspective:

21. EGDT Newborn Hep B vaccine Screening mammography 20k $40k $60k $80k $100k $120k $140k $160k $180k 0 $16,000 $105,000 $32,000 $143,000 $5,000 $49,000 $8,000 $69,000 $40,000 $120,000 $24,000 $61,000 Antihypertensive Cholesterol lowering drugs CABG for 2V disease Airbags League Table: modified from Schwartz, Leonard Davis Institute Drotrecogin-alfa E.G.D.T. EGDT in perspective:

22. Difference in survival (number of lives saved) 0 0.250.5-0.25 -30,000 -10,000 -20,000 10,000 Difference in costs (US$) 0 Cost Savings per survivor at 60 Days = $6,500 More costly Less effective More costly More effective Less costly More effective Less costly Less effective Hospital perspective: