Table of Contents
- ABOUT DATAMONITOR HEALTHCARE
- About the Infectious & Respiratory Disease pharmaceutical analysis
team
- CHAPTER 1 EXECUTIVE SUMMARY
- Objective of the analysis
- Datamonitor insight into sepsis
- A highly motivated Critical Care Community is gaining a singular
momentum
- Old dogs, new tricks? Current interventions meet new thinking
- The new era: personalized medicine in infectious disease
- Related reports
- Upcoming related reports
- CHAPTER 2 BACKGROUND
- Catalyst
- Scope
- Acknowledgements
- CHAPTER 3 DEFINITIONS
- Sepsis defined - the lynchpin of progress
- Matching definitions to working criteria for clinical inclusion
- Taking an oncologist' s view of sepsis: the PIRO model
- CHAPTER 4 ORDER FROM CHAOS - THE IMPACT OF SEPSIS STAGING
- P is for Predisposition and Prophylaxis targets
- Age
- Co-morbidities
- Genetic predisposition
- I is for Infection - a plethora of pathogens
- The diagnostic shortfall
- Anti-infectives: trialed for infection, not sepsis indications
- Supply and demand: how do available anti-infectives stack up?
- Too much of a gram-positive focus
- Indication semantics - site of infection in sepsis
- Matching infection indications to sepsis sites of infection
- R is for Response to infection: when is too much and what to treat?
- Multiple pathways
- Beyond early goal directed therapy - current targets for new and novel
therapeutics
- Upstream versus downstream
- Early versus late onset
- Neither upstream, nor downstream
- Sepsis, severe sepsis and clinical trials
- Continuity of outcomes across progressive trials
- Recruitment
- Endpoints
- O is for Organ dysfunction
- Discrete organ dysfunction versus multiple organ dysfunction
- Modeling sepsis-related organ failure
- Measuring an outcome versus a target for intervention
- Binary versus linear scales
- With or without interventions
- CHAPTER 5 CASE STUDY: THE SURVIVING SEPSIS CAMPAIGN
- Mandate, leadership and direction
- Singular view
- Achievable principles versus specifics
- Ethical responsibility
- Legal liability
- Coherence and continuous improvement - the evolution of SSC Guidelines
- Backing
- Creating a balance through non-industry grants
- Diluting the "Lilly-effect" with more corporate sponsorship
- Private foundations and government funding
- New versus old guidelines
- Balancing consistency with improvement
- The big question: so what happened to Xigris recommendations?
- Corticosteroids - CORTICUS prompts subtle changes
- Glycemic controls and vasopressors
- Vasopressin - more subtle changes, but why?
- APPENDIX A - EPIDEMIOLOGY DATA
- Sepsis by pathogen
- Sepsis by deaths pathogen
- Sepsis sites of infection
- APPENDIX B - SSC GUIDELINE OUTLINES
- Initial Resuscitation
- Initial resuscitation (first 6 hours)
- Diagnosis
- Antibiotic Therapy
- Source identification and control
- Hemodynamic Support and Adjunctive Therapy
- Fluid Therapy
- Vasopressors
- Inotropic therapy
- Steroids
- Recombinant human activated protein C (rhAPC)
- Blood product administration
- Mechanical ventilation of sepsis-induced acute lung injury (ALI)/Adult
Respiratory Distress Syndrome (ARDS)
- Sedation, analgesia, and neuromuscular blockade in sepsis
- Glucose control
- Renal replacement
- Bicarbonate therapy
- Deep vein thrombosis (DVT) prophylaxis
- Stress ulcer prophylaxis
- Consideration for limitation of support
- APPENDIX C - PIPELINE DATA
- Cell Signalling Targets
- Coagulation Cascade Targets
- Endotoxin Targets
- Immodulation Targets
- APPENDIX D
- Bibliography
- Definitions
- Epidemiology
- Websites
- Clinical trial data
- Contributing experts
- Report methodology
- About Datamonitor
- About Datamonitor Healthcare
- About the Infectious & Respiratory Disease analysis team
- About the Infectious Disease analysis team
- Key therapy team members
- Holger Rovini, Head of Respiratory and Infectious Diseases
- Disclaimer
- List of Tables
- Table 1: Evidence based preventative strategies for Septic Shock
- Table 2: Candidate genes and severe sepsis
- Table 3: Examples of microbial diagnostic tests
- Table 4: Signs and symptoms of organ dysfunction
- Table 5: Sponsors of the SSC Guidelines
- Table 6: Relative frequency of sepsis by pathogen
- Table 7: SOAP trial - mortality by pathogen type, and ICU/hospital
attribution
- Table 8: Site of infection in Sepsis Patients - SOAP study outcomes
- Table 9: The Sepsis Pipeline: Cell-signaling targets by development
stage
- Table 10: The Sepsis Pipeline: Coagulation cascade targets by
development stage
- Table 11: The Sepsis Pipeline: Endotoxin targets by development stage
- Table 12: The Sepsis Pipeline: Immunomodulation targets by development
stage
- Table 13: The Sepsis Pipeline: Specific Mediator targets by
development stage
- Table 14: The Sepsis Pipeline: Unknown targets by development stage
- List of Figures
- Figure 1: Defining Sepsis - the ACCP, SCCM, ATS, ESICM and SIS
consensus conference 2001
- Figure 2: The PIRO model
- Figure 3: Increasing importance of the over 65s as a high risk group
for sepsis, 1979-2001
- Figure 4: Over 65s and sepsis - higher incidence, higher mortality
rates
- Figure 5: Co-morbidities in sepsis patients stratified by age
- Figure 6: Pathogen, site, origin - the complexities of infection
- Figure 7: Impact of timing of antimicrobial initiation on survival in
sepsis
- Figure 8: Diagnostic capabilities - different roles in assisting
treatment strategy decisions
- Figure 9: Stratifying diagnostic tools for sepsis
- Figure 10: Top five marketed brand and pipeline coverage of
antibiotics by indication, 2007
- Figure 11: Site of infection in sepsis patients according to the onset
from routine postoperative monitoring of sepsis
- Figure 12: Stylized and simplified - sepsis progression
- Figure 13: Main effector pathways for sepsis
- Figure 14: The sepsis pipeline by target and stage of development, 2008
- Figure 15: Theories of pathogenesis
- Figure 16: Organ failure by type, 2000
- Figure 17: SOFA, MODS and LODS - Parameters and scores used in
assessing organ dysfunction
- Figure 18: Key elements of the Barcelona Declaration
- Figure 19: Can' t comply, won' t comply - barriers to uptake and
facilitators of change
- Figure 20: Early Goal Directed Therapy in Sepsis
- Figure 21: Relative frequency of sepsis by pathogen
- Figure 22: SOAP trial - mortality by pathogen type, and ICU/hospital
attribution
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