Stakeholder Opinions: Sepsis - The Critical Care Community Gains Critical Mass

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?
      • Xigris, the data
    • 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
      • Clinical
      • Industry
  • 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