innovation in pediatric sepsis: is there anything new on the horizon? derek s. wheeler, md, faap,...
TRANSCRIPT
Innovation in Pediatric Sepsis:Is there anything new on the horizon?
Derek S. Wheeler, MD, FAAP, FCCP, FCCMAssociate Professor of Clinical Pediatrics
University of Cincinnati College of Medicine
Clinical Director, Division of Critical Care MedicineCincinnati Children’s Hospital Medical Center
The James M. Anderson Center for Health Systems Excellence
Co-Director, The Center for Acute Care Nephrology
Top Ten Causes of Death in the U.S.
1. Heart Disease2. Cancer3. Stroke (Cerebrovascular Disease)4. Chronic lower respiratory disease5. Accidents6. Alzheimer’s Disease7. Diabetes8. Influenza and Pneumonia9. Nephritis, Nephrotic Syndrome, and Nephrosis10. Septicemia
Source National Center for Health Statistics, 2007
#6 and #8 in neonatal and pediatric age group, respectively
Sepsis is a Common Cause of Death
Sepsis is a Common Cause of Death
Many of these patients will die from sepsis!
Sepsis is #1 killer Sepsis is #1 killer worldwideworldwide
Lancet 2010; 375:1969
2008 worldwide data from WHO, UNICEF, and Bill and Melinda Gates Foundation
8.8 million deaths in children <5 years of age68% (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!
Sepsis is a Common Cause of Death
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Heart Disease
Cancer
Stroke
COPD
Accidents
Alzheimer's Disease
Diabetes
Influenza and Pneumonia
Kidney Disease
Septicemia
Source NIH Funding Levels for Categories Research, Condition, and Disease Categorization (RCDC)
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Septicemia
HIV/AIDS
Small Pox
…Yet Sepsis Receives Comparably Little Funding
Nature Rev Drug Discovery 2003, 2:391
1. Complexity (nonlinear)
2. Redundancy
3. Obligatory
“No More Talk of Magic Bullets Please!”
Sepsis recognition is inconsistent at best
Early Recognition = Early Treatment = Better OutcomesEarly Recognition = Early Treatment = Better Outcomes
Sepsis is a syndrome, not a disease
Minimize heterogeneity via better definition Minimize heterogeneity via better definition of target populations and severityof target populations and severity
Sepsis management is highly variable
Minimize variation via explicit control of co-interventionsMinimize 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 diseaseSepsis is a syndrome, not a disease
Minimize heterogeneity via better definition Minimize heterogeneity via better definition of target populations and severityof target populations and severity
Sepsis management is highly variableSepsis management is highly variable
Minimize variation via explicit control of co-interventionsMinimize variation via explicit control of co-interventions
Key Innovations in Sepsis
Innovations in Recognition
Fever + Tachycardia + Risk Factor => Activation of EGDT Protocol
“Door to antibiotics” decreased from 143 to 38 minutes
TCH Sepsis ProtocolCruz et al. Pediatrics 2011; 127:e758
Computerized Best Practice Alerts(4,552 triggers/39,697 visits)
81% Sensitivity89% Specificity
PPV 4%NPV 99.9%
Cruz et al. Pediatr Emerg Care 2012;28:889
Sepsis recognition is inconsistent at bestSepsis recognition is inconsistent at best
Early Recognition = Early Treatment = Better OutcomesEarly 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 variableSepsis management is highly variable
Minimize variation via explicit control of co-interventionsMinimize variation via explicit control of co-interventions
Key Innovations in Sepsis
Innovations in Definition
LPS changed gene expression of 3,714 unique genes!
Calvano et al. Nature 2005; 437:1032
Sepsis recognition is inconsistent at bestSepsis recognition is inconsistent at best
Early Recognition = Early Treatment = Better OutcomesEarly Recognition = Early Treatment = Better Outcomes
Sepsis is a syndrome, not a diseaseSepsis is a syndrome, not a disease
Minimize heterogeneity via better definition Minimize heterogeneity via better definition of target populations and severityof target populations and severity
Sepsis management is highly variable
Minimize variation via explicit control of co-interventions
Key Innovations in Sepsis
Infection 2009; 37:222
Prospective registry276 ICU’s in 37 countries
N=12,881 pts
Minimize variationToo Much Variation in Treatment!
Open Crit Care Med 2010; 3:51
Retrospective analysisN=51 critically ill children with septic shockSignificant variation in duration of treatment, use of weaning taper, duration of taper
Practice variation at CCHMC (informal chart audit):
1. Choice, timing, and duration of antibiotic therapy2. Choice and indication for vasoactive infusions3. Choice and indication of mechanical ventilatory support4. Route and threshold for nutritional support5. Choice of sedative and level of sedation required6. Threshold for Renal Replacement Therapy (RRT)
Minimize variationToo Much Variation in Treatment!
Innovations in Study Design
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
R18 HS020455
The James M. Anderson Center for Health Systems ExcellenceStephen Muething, MDPatrick Brady, MDUma Kotagal, MBBS, MScJanet Jacob, RN, MBA
Children’s Hospital of AkronMary D. Patterson, MD, MEd
Cincinnati Children’s Center for Simulation and ResearchGary Geis, MDJohn Whitt, MDTom LeMaster, RN, MSN, MEd, REMT-P, EMSI
University of Cincinnati College of MedicineAmy Bunger, PhD
University of Michigan Ross School of BusinessKathleen M. Sutcliffe, MSN, PhD
Applied Decision Science, LLCLaura Militello, MA
MacroCognition, LLCGary Klein, PhD
Division of Critical Care MedicineHector R. Wong, MDCarley Riley, MDErika Stalets, MD
Thank You!