1. Early Goal-Directed Therapy in Pediatric Sepsis Derek S. Wheeler, MD, FAAP, FCCP, FCCM Associate Professor of Clinical Pediatrics University of Cincinnati College of Medicine Clinical Director, Division of Critical Care Medicine Cincinnati Children’s Hospital Medical Center The James M. Anderson Center for Health Systems Excellence Co-Director, The Center for Acute Care Nephrology

2. Early Goal-directed Therapy

3. Protocolized Care for Early Septic Shock (ProCESS) NCT00510835 (expected study completion August 2013)

4. Crit Care Med 2010; 38:367 Surviving Sepsis Campaign N=15,022 Sepsis Resuscitation (6 H) Bundle Measure Serum Lactate Administer broad-spectrum antibiotics (<3 h) Early resuscitation to EGDT Targets Sepsis Management Bundle Low-dose corticosteroids Drotrecogin alfa Tight glucose control Plateau Pressure < 30 cm H2O

5. Crit Care Med 2006; 34:1589 N=2,731 adults with septic shock Only 50% of pts received antimicrobial therapy within 6 h of documented hypotension! Early Antibiotics “Door to antibiotics” decreased from 143 to 38 minutes TCH Sepsis Protocol Cruz et al. Pediatrics 2011; 127:e758

6. Crit Care Med 2006; 34:1589 N=2,731 adults with septic shock Only 50% of pts received antimicrobial therapy within 6 h of documented hypotension! Early Antibiotics “Door to Antibiotics” < 3 hours Primary Children’s Sepsis Protocol Larsen et al. Pediatrics 2011; 127:e1585

7. Arch Dis Child 2001; 85:386 Reduction in mortality from 23% to 2.5%! Early Resuscitation

8. Pediatrics 2003; 112:793 Early Resuscitation

9. Intensive Care Med 2008; 34:1065 Minimize variation Early Resuscitation

10. Minimize variation Early Resuscitation Intensive Care Med 2008; 34:1065

11. Minimize variation Early Resuscitation 28-day Mortality 39.2% versus 11.8% Intensive Care Med 2008; 34:1065

12. Minimize variation Early Resuscitation No differences in HR, MAP, CVP, ScvO2, or Lactate at Baseline, 6 H, or 72 H Intensive Care Med 2008; 34:1065

13. Minimize variation Early Resuscitation No differences in TOTAL fluid volume administered at 72 H Significant differences in amount of fluid volume administered at 6 H Early administration of inotropes Intensive Care Med 2008; 34:1065

14. Final Thoughts 1.Protocolized care to minimize practice variations. 2.Early recognition = Early Treatment 3.Better therapeutic endpoints are on the horizon

15. derek.wheeler@cchmc.org R18 HS020455 The James M. Anderson Center for Health Systems Excellence Stephen Muething, MD Patrick Brady, MD Uma Kotagal, MBBS, MSc Janet Jacob, RN, MBA Children’s Hospital of Akron Mary D. Patterson, MD, MEd Cincinnati Children’s Center for Simulation and Research Gary Geis, MD John Whitt, MD Tom LeMaster, RN, MSN, MEd, REMT-P, EMSI University of Cincinnati College of Medicine Amy Bunger, PhD University of Michigan Ross School of Business Kathleen M. Sutcliffe, MSN, PhD Applied Decision Science, LLC Laura Militello, MA MacroCognition, LLC Gary Klein, PhD Division of Critical Care Medicine Hector R. Wong, MD Carley Riley, MD Erika Stalets, MD Thank You!