1. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y j 내과 R2 이지영

2. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y INTRODUCTION  Since 2002, the Surviving Sepsis Campaign (SSC) Singlecenter, proof-of-concept study by Rivers et al. 6 hours of early, goal-directed therapy (EGDT) with early septic shock reduced hospital mortality and hospital stay. Continuous monitoring Intravenous fluids Vasoactive drugs Red-cell transfusions Validity / Complexity / Potential risks

3. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y INTRODUCTION  Multicenter trials of EGDT In the United States (Protocolized Care for Early Septic Shock [ProCESS] trial) Australasia (Australasian Resuscitation in Sepsis Evaluation [ARISE] trial)  No benefit for EGDT as compared with usual care But, both reported lower-than-anticipated mortality Cannot rule out the potential for reduction in 90-day mortality for EGDT, as compared with usual care,  England (Protocolised Management in Sepsis [ProMISe]

4. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y METHODS  Multicenter, parallel-group, randomized, controlled trial  Adults (≥18 years of age) were eligible if within 6 hours after presentation to the emergency department  Two or more criteria of the systemic inflammatory response syndrome(SIRS)  Refractory hypotension or hyperlactatemia sBP<90 mm Hg; or MAP<65 mm Hg, despite 1L of IV fluids in 60 min) Blood lactate level ≥4 mmol per liter) Not meet any exclusion criteria

5. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y METHODS  Randomization within 2 hours after the patient met the inclusion criteria  All patients provided written informed consent  Antimicrobial drugs were initiated before randomization  At least one trained staff member

6. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y METHODS

7. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y METHODS  Primary clinical outcome was all-cause mortality at 90 days  Secondary outcomes Sequential Organ Failure Assessment (SOFA) at 6 hrs & 72 hrs Receipt of advanced cardiovascular, respiratory Length of stay in the emergency department, ICU, and hospital Duration of survival All-cause mortality at 28 days, at hospital discharge, and at 1 year Health-related quality of life (as measured on the European Quality of Life–5 Dimensions [EQ-5D] five-level questionnaire) Costs at 90 days and 1 year.

8. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y RESULTS- Study Patient

9. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y RESULTS- Study Patient

10. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y RESULTS- Intervention period

11. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y RESULTS- Study outcomes

12. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y RESULTS- Study outcomes

13. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y RESULTS- Study outcomes

14. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y Discussions  Two similar studies in the United States & Australasia Shorter time period Reports on quality of life and cost-effectiveness at 90 days  Unlikely Rivers et al. in 2001 Techniques used in usual resuscitation have evolved over 15 yrs Less sick at baseline Much lower volumes of iv fluids & more vasoactive drugs

15. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y Discussions  Limitations As all enroll patients presenting to emergency departments, recruitment was more challenging on weekends and during out-of-office hours 1/3 of eligible patients were recruited, although exclusion from the study by a clinician was rare The intervention could not be blinded

16. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y Conclusions  More patients receiving EGDT were admitted to and spent more days in the ICU.  Significantly higher SOFA scores and more days of receiving advanced cardiovascular support.  Cost-effectivity is low  No significant differences in any other secondary outcomes, including health-related quality of life,

17. Towards Global Eminence K Y U N G H E E U N I V E R S I T Y Conclusions  In septic shock patients, early and received iv antibiotics & adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome.