Assessing Treatment of Severe Sepsis and Septic Shock: How Are We Performing?

1. Assessing Treatment of Severe Sepsis and Septic Shock: How Are We Performing? A Case-Comparison Study to Evaluate the Treatment of Severe Sepsis and Septic Shock in Critical Care Patients at Sisters of Charity Hospital in Buffalo, NY Erik Diringer, DO Mentor: Thomas Brewer, DO

2. Background • Severe sepsis and septic shock are complex disease states that carry high rates of mortality. • 28.6% overall and 38.4% in those >85 yrs. old1 • International efforts, such as the Surviving Sepsis Campaign, have been made to define, diagnose and treat sepsis in attempts to improve morbidity and mortality2.

3. Background • Evidence suggests that early goal-directed therapy (EGDT) contributes to a significant improvement in morality in severe sepsis and septic shock3. • On December 1, 2008, the Catholic Health System released a new clinical standards order set for the septic patient. This order set is designed to utilize recommendations from the Surviving Sepsis Campaign.

4. Introduction • Definitions4: • Systemic inflammatory response syndrome (SIRS) • Sepsis is comprised of SIRS with a known source of infection. • Severe sepsis involves dysfunction in one or more vital organs with hypotension that is responsive to adequate fluid resuscitation. • Septic shock is comprised of the same criteria, however, it is not responsive to fluid resuscitation.

5. Introduction • As a result of global tissue hypoxia, these conditions can quickly progress to multiorgan dysfunction syndrome (MODS), multiorgan failure (MOF) and death5. • Global tissue hypoxia is difficult to evaluate using traditional hemodynamic measurements, such as physical findings,vital signs, central venous pressure (CVP), and urinary output.

6. Introduction • The Cost of Sepsis • Despite major advances in medicine and technology, mortality rates remain high. • In the United States, treatment of sepsis costs $16.7 billion annually and is projected to increase by 1.5% per year1.

7. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson, Ph.D., Michael Tomlanovich, M.D., for the Early Goal-Directed Therapy Collaborative Group November 8, 2001

9. SCVO2 Monitoring6 • Surrogate of global tissue hypoxia • Sepsis results in increased metabolic stress at the tissue level • Response is to increase cardiac output and/or O2 utilization • When O2 supply is overwhelmed by the disease, SCVO2 continues to decrease (O2 demand > supply) • Thus, SCVO2 is proposed to be a marker of adequate O2 utilization at the tissue level as a response to metabolic stress

10. EGDT Treatment

11. EGDT Results • Significant (P=0.009) decrease in in-hospital mortality from 46.5 to 30.5% when EGDT was used over of standard therapy • significant decrease in 28-day mortality • Rapid identification and treatment • These results were seen when therapy was initiated immediately and continued for at least six hours.

12. 12/01/08 – CHS Sepsis Order Set • 3 page admission order set  •  Provides option to initiate EGDT • Access: CVC, arterial line • Monitoring: CVP/MAP monitoring, I/O • Treatment: fluids, transfusions, vasopressors, inotropic therapy

16. Study Objective • The goal of this study is compare set outcomes in patients at Sisters of Charity Hospital (SOCH) in Buffalo, NY diagnosed with severe sepsis and/or septic shock prior to and following the release of the new sepsis order set.

17. Study Design • A case-comparison study of 100 ICU patients with the diagnosis of severe sepsis and/or septic shock prior to and following the release of the sepsis standardized order set.

18. Methods • Approved by SOCH Institutional Review Board • Using December 1, 2008 as a reference, a chart review of SOCH ICU patients with the diagnosis of severe sepsis and/or septic shock was performed until 100 charts that met inclusion criteria were reviewed prior to and following the release of the CHS sepsis order set

19. Methods • Inclusion criteria: similar to EGDT • fulfillment of two of four criteria for SIRS • systolic bloodpressure no higher than 90 mm Hg (after a crystalloid-fluidchallenge) or a blood lactate concentration 36 mg/dL

20. Methods • Exclusion criteria: • age <18 years • pregnancy • CVA • ACS • Acute pulm. edema • Cardiac dysrhythmias(as a primary diagnosis) • active gastrointestinal hemorrhage • seizure/drug overdose • contraindication to CVC • burn injury/trauma • requirement for immediatesurgery • uncured cancer (during chemotherapy) • immunosuppression • do-not-resuscitatestatus

21. Methods • Data collection • Hemodynamic parameters at 0, 4, 8, 12, 16, 20, 24h • Temp, HR, input, output (when available), systolic pressure, diastolic pressure, MAP (calculated) • Age, sex, weight, APACHE II score • Sepsis order set used? • LOS in ED, ICU • Mortality (all-cause, in-hospital)

22. Methods • Statistical analysis • Unpaired, two-tailed t-test • Chi-square test

23. Results

24. Baseline Characteristics SOS = sepsis order set APACHE II = Acute Physiologic and Chronic Health Evaluation II, scale range from 0 to 71, with higher values indicating more severe disease. CVP = central venous pressure *Average time to CVP placement 10.17h

25. Results SOS = sepsis order set

26. Results SOS = sepsis order set *Urine output available 0-4h in 24% of patients

27. Results SOS = sepsis order set MAP = mean arterial pressure

28. Results SOS = Sepsis order set LOS = Length of stay *Lactate available within 24h in 50% of patients pre-SOS and 68% post-SOS

29. Discussion • No significant difference in hemodynamic parameters • SOCH mortality rate similar to those reported nationally1 • CVP lines placed in 21% of pts • Average time to line was 10.17h • Average IVF in 1324ml in first 4h; 2467ml in first 8h • EGDT averaged 4981ml in first 6h3 • Urine output only available in 24% of pts in first 4h • Sepsis order set only used in 14% of pts

30. Can EGDT be done in real-world clinical practice?

31. Discussion • A 1-Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department7 • Academic center in Camden, NJ • 22 pts treated with EGDT protocol in ED • Executed by ED/ICU physicians and nurses as part of regular duties • ED physicians identify and initiate • ICU physicians ensure outcomes are achieved • Required no extra staffing or modification to physical plant

32. Discussion • Future consideration • Early identification of severe sepsis and septic shock • Hemodynamic parameters, lab values • “Door-to-EGDT” <60min in original trial3 • In-hospital mortality in STEMI 3% with door-to-balloon time <90min8 • Collaboration between ED and ICU teams • Modification of sepsis order set • “Sepsis bundles”9 • Modification of EGDT?

33. Discussion • Role of the resident • Diagnosis of severe sepsis and septic shock • EGDT • Procedural competency

34. References • Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. CritCare Med. 2001; 29: 1303-1310. • Surviving Sepsis Campaign®. http://www.survivingsepsis.org. 2009. • Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368–1377. • Marino P. The ICU Book, Third Edition. Philadelphia: Lippincott Williams & Wilkins, 2007. • Beal AL, Cerra FB. Multiple organ failure syndrome in the 1990s: systemic inflammatory response and organ dysfunction. JAMA 1994; 271: 226-233. • Pinsky R, Brochard L, Mancebo J. Applied Physiology in Intensive Care Medicine. Springer-Verlag Berlin Heidelberg 2006 • Trzeciak JES, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, Zanotti S. A 1-Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department. Chest. 2006; 129: 225-232. • McNamara RL, Wang Y, Herrin J, Curtis JP, Bradley EH, Magid DJ, Peterson ED, Blaney M, Frederick PD, Krumholz HM. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J Am CollCardiol. 2006. Jun 6;47 (11): 2180-6. • Institute for Health Care Improvement. http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis. Accessed May 2010.

35. ProCESS Study • Protocolized Care for Early Septic Shock • Funded by NIH, coordinated by UPMC • 24 US sites • 3-pronged • Clinical efficacy • Do we need SCVO2, blood transfusions? • Mechanism of action • Trend markers of cellular hypoxia, oxidative stress, inflammation, and coagulation/thrombosis • Costs and cost-effectiveness

36. Baseline Characteristics SOS = sepsis order set APACHE II = Acute Physiologic and Chronic Health Evaluation II, scale range from 0 to 71, with higher values indicating more severe disease. CVP = central venous pressure *Average time to CVP placement 10.17h

37. Results SOS = sepsis order set

38. Results SOS = sepsis order set

39. Results SOS = sepsis order set MAP = mean arterial pressure

40. Results SOS = Sepsis order set LOS = Length of stay *Lactate available within 24h in 50% of patients pre-SOS and 68% post-SOS