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Innovation in Pediatric Sepsis:
Is there anything new on the horizon?
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
Sepsis is a Common Cause of Death
Top Ten Causes of Death in the U.S.
1. Heart Disease
2. Cancer
3. Stroke (Cerebrovascular Disease)
4. Chronic lower respiratory disease
5. Accidents
6. Alzheimer’s Disease
7. Diabetes
8. Influenza and Pneumonia
9. Nephritis, Nephrotic Syndrome, and Nephrosis
10. Septicemia
#6 and #8 in neonatal and pediatric age group, respectively
Source National Center for Health Statistics, 2007
Sepsis is a Common Cause of Death
Many of these patients will die
from sepsis!
Sepsis is a Common Cause of Death
Sepsis is #1 killer
worldwide
2008 worldwide data from WHO, UNICEF, and Bill
and Melinda Gates Foundation
8.8 million deaths in children <5 years of age
68% (5.97 million) due to infectious diseases
Sepsis is the final common pathway in deaths from
malaria, dengue fever, pneumonia, HIV/AIDS, and
diarrheal illness!
Lancet 2010; 375:1969
…Yet Sepsis Receives Comparably Little Funding
4000
NIH RCDC Funding
3500
8000
7000
2500
2000
1500
6000
Dollars (in millions)
Dollars (in millions)
3000
Heart Disease
5000
Cancer
Septicemia
Stroke
HIV/AIDS
COPD
Small Pox
Accidents
4000
Alzheimer's Disease
Diabetes
Influenza and Pneumonia
3000
1000
Kidney Disease
Septicemia
2000
500
1000
0
0
2006
2007
2006
2007
2008
2008
2009
2009
Source NIH Funding Levels for Categories
Research, Condition, and Disease Categorization (RCDC)
“No More Talk of Magic Bullets Please!”
1. Complexity (nonlinear)
2. Redundancy
3. Obligatory
Nature Rev Drug Discovery 2003, 2:391
Key Innovations in Sepsis
Sepsis recognition is inconsistent at best
Early Recognition = Early Treatment = Better Outcomes
Sepsis is a syndrome, not a disease
Minimize heterogeneity via better definition
of target populations and severity
Sepsis management is highly variable
Minimize variation via explicit control of co-interventions
Key Innovations in Sepsis
Sepsis recognition is inconsistent at best
Early Recognition = Early Treatment = Better Outcomes
Sepsis is a syndrome, not a disease
Minimize heterogeneity via better definition
of target populations and severity
Sepsis management is highly variable
Minimize variation via explicit control of co-interventions
Innovations in Recognition
Fever + Tachycardia + Risk Factor => Activation of EGDT Protocol
Computerized Best Practice Alerts
(4,552 triggers/39,697 visits)
81% Sensitivity
89% Specificity
PPV 4%
NPV 99.9%
“Door to antibiotics” decreased
from 143 to 38 minutes
TCH Sepsis Protocol
Cruz et al. Pediatrics 2011; 127:e758
Cruz et al. Pediatr Emerg Care 2012;28:889
Key Innovations in Sepsis
Sepsis recognition is inconsistent at best
Early Recognition = Early Treatment = Better Outcomes
Sepsis is a syndrome, not a disease
Minimize heterogeneity via better definition
of target populations and severity
Sepsis management is highly variable
Minimize variation via explicit control of co-interventions
Innovations in Definition
LPS changed gene expression of 3,714
unique genes!
Calvano et al. Nature 2005; 437:1032
Key Innovations in Sepsis
Sepsis recognition is inconsistent at best
Early Recognition = Early Treatment = Better Outcomes
Sepsis is a syndrome, not a disease
Minimize heterogeneity via better definition
of target populations and severity
Sepsis management is highly variable
Minimize variation via explicit control of co-interventions
Too Much Variation in Treatment!
Minimize variation
Prospective registry
276 ICU’s in 37 countries
N=12,881 pts
Infection 2009; 37:222
Too Much Variation in Treatment!
Minimize variation
Retrospective analysis
N=51 critically ill children with septic shock
Significant variation in duration of treatment, use of weaning taper, duration of
taper
Open Crit Care Med 2010; 3:51
Practice variation at CCHMC (informal chart audit):
1.
2.
3.
4.
5.
6.
Choice, timing, and duration of antibiotic therapy
Choice and indication for vasoactive infusions
Choice and indication of mechanical ventilatory support
Route and threshold for nutritional support
Choice of sedative and level of sedation required
Threshold for Renal Replacement Therapy (RRT)
Innovations in Study Design
Key Innovations in Sepsis
Sepsis recognition is inconsistent at best
Early Recognition = Early Treatment = Better Outcomes
Sepsis is a syndrome, not a disease
Minimize heterogeneity via better definition
of target populations and severity
Sepsis management is highly variable
Minimize variation via explicit control of co-interventions
Thank You!
Division of Critical Care Medicine
Hector R. Wong, MD
Carley Riley, MD
Erika Stalets, MD
The James M. Anderson Center for Health Systems Excellence
Stephen Muething, MD
Patrick Brady, MD
Uma Kotagal, MBBS, MSc
Janet Jacob, RN, MBA
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
Children’s Hospital of Akron
Mary D. Patterson, MD, MEd
University of Michigan Ross School of Business
Kathleen M. Sutcliffe, MSN, PhD
R18 HS020455
Applied Decision Science, LLC
Laura Militello, MA
MacroCognition, LLC
Gary Klein, PhD
[email protected]