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SEPSIS ,SEVERE SEPSIS AND SEPTIC SHOCK 2008 UPDATE J.TAVARES,MD,FCCP,FAASM
Rivers E et al. N Engl J Med 2001;345:1368-1377 Protocol for Early Goal-Directed Therapy
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LACTIC ACID ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
FLUID MANAGEMENT ,[object Object],[object Object],[object Object]
PENTASTARCH ,[object Object],[object Object],[object Object]
PENTASTARCH ,[object Object],[object Object],[object Object],[object Object]
Brunkhorst F et al. N Engl J Med 2008;358:125-139 Kaplan-Meier Curves for Overall Survival
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
CVP 8-12:?for how long ,[object Object],[object Object],[object Object]
 
 
 
 
 
Rivers E et al. N Engl J Med 2001;345:1368-1377 Protocol for Early Goal-Directed Therapy
RBC Transfusion ,[object Object],[object Object],[object Object]
RBC TransfusionClinical Recommendations) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Sepsis management bundle ,[object Object],[object Object],[object Object],[object Object],[object Object]
Intensive insulin therapy in the ICU ,[object Object],[object Object],[object Object],[object Object],[object Object]
Van den Berghe G et al. N Engl J Med 2001;345:1359-1367 Kaplan-Meier Curves Showing Cumulative Survival of Patients Who Received Intensive Insulin Treatment or Conventional Treatment in the Intensive Care Unit (ICU)
IIT in the ICU ,[object Object],[object Object],[object Object],[object Object],[object Object]
IIT in the ICU ,[object Object],[object Object],[object Object]
Brunkhorst F et al. N Engl J Med 2008;358:125-139 Kaplan-Meier Curves for Overall Survival
ITT in the ICU ,[object Object],[object Object],[object Object]
Glucommander ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Sepsis management bundle ,[object Object],[object Object],[object Object],[object Object],[object Object]
Adrenal  Insufficiency ,[object Object]
Adrenal Insufficiency ,[object Object],[object Object]
Adrenal Insufficiency ,[object Object],[object Object]
Sprung C et al. N Engl J Med 2008;358:111-124 Enrollment and Outcomes
CORTICUS ,[object Object],[object Object]
Sepsis management bundle ,[object Object],[object Object],[object Object],[object Object],[object Object]
Bernard G et al. N Engl J Med 2001;344:699-709 Proposed Actions of Activated Protein C in Modulating the Systemic Inflammatory, Procoagulant, and Fibrinolytic Host Responses to Infection
Drotrecogin Alfa ,[object Object],[object Object],[object Object]
Bernard G et al. N Engl J Med 2001;344:699-709 Kaplan-Meier Estimates of Survival among 850 Patients with Severe Sepsis in the Drotrecogin Alfa Activated Group and 840 Patients with Severe Sepsis in the Placebo Group
Bernard G et al. N Engl J Med 2001;344:699-709 Incidence of Serious Adverse Events
How do I do it(Resuscitation Phase) ,[object Object],[object Object],[object Object],[object Object]
How do I do it(Resuscitation Phase) ,[object Object],[object Object],[object Object],[object Object]
How do I do it(Resuscitation Phase) ,[object Object],[object Object]
FLUIDS ,[object Object],[object Object],[object Object]
Vasopressin ,[object Object],[object Object]
How do I do it(Management Phase) ,[object Object],[object Object]
How do I do it(Management) ,[object Object],[object Object],[object Object]
How do I do it(management) ,[object Object],[object Object]
How do I do it(Management) ,[object Object],[object Object],[object Object],[object Object]
Antibiotics ,[object Object]
Goal for 2009 ,[object Object]
Material for Research ,[object Object],[object Object],[object Object]

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Sepsisandseveresepsis

  • 1. SEPSIS ,SEVERE SEPSIS AND SEPTIC SHOCK 2008 UPDATE J.TAVARES,MD,FCCP,FAASM
  • 2. Rivers E et al. N Engl J Med 2001;345:1368-1377 Protocol for Early Goal-Directed Therapy
  • 3.
  • 4.
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  • 9. Brunkhorst F et al. N Engl J Med 2008;358:125-139 Kaplan-Meier Curves for Overall Survival
  • 10.
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  • 17. Rivers E et al. N Engl J Med 2001;345:1368-1377 Protocol for Early Goal-Directed Therapy
  • 18.
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  • 21.
  • 22. Van den Berghe G et al. N Engl J Med 2001;345:1359-1367 Kaplan-Meier Curves Showing Cumulative Survival of Patients Who Received Intensive Insulin Treatment or Conventional Treatment in the Intensive Care Unit (ICU)
  • 23.
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  • 25. Brunkhorst F et al. N Engl J Med 2008;358:125-139 Kaplan-Meier Curves for Overall Survival
  • 26.
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  • 32. Sprung C et al. N Engl J Med 2008;358:111-124 Enrollment and Outcomes
  • 33.
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  • 35. Bernard G et al. N Engl J Med 2001;344:699-709 Proposed Actions of Activated Protein C in Modulating the Systemic Inflammatory, Procoagulant, and Fibrinolytic Host Responses to Infection
  • 36.
  • 37. Bernard G et al. N Engl J Med 2001;344:699-709 Kaplan-Meier Estimates of Survival among 850 Patients with Severe Sepsis in the Drotrecogin Alfa Activated Group and 840 Patients with Severe Sepsis in the Placebo Group
  • 38. Bernard G et al. N Engl J Med 2001;344:699-709 Incidence of Serious Adverse Events
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Editor's Notes

  1. Figure 2. Protocol for Early Goal-Directed Therapy. CVP denotes central venous pressure, MAP mean arterial pressure, and ScvO2 central venous oxygen saturation.
  2. Figure 2. Kaplan-Meier Curves for Overall Survival. Panel A shows the comparison of overall survival between patients receiving intensive insulin therapy and those receiving conventional insulin therapy (P=0.36 by the log-rank test). Panel B shows the comparison between patients receiving pentastarch (HES) for volume resuscitation and those receiving Ringer's lactate (P=0.14 by the log-rank test). Panel C shows the comparison between patients in the low-dose HES subgroup (<=22 ml per kilogram of body weight per day), who received a median cumulative dose of 48.3 ml per kilogram (interquartile range, 21.9 to 96.2), and those in the high-dose subgroup (>22 ml per kilogram for at least 1 day during the study period), who received a median cumulative dose of 136.0 ml per kilogram (interquartile range, 79.0 to 180.0) (P<0.001 by the log-rank test).
  3. Figure 2. Protocol for Early Goal-Directed Therapy. CVP denotes central venous pressure, MAP mean arterial pressure, and ScvO2 central venous oxygen saturation.
  4. Figure 1. Kaplan-Meier Curves Showing Cumulative Survival of Patients Who Received Intensive Insulin Treatment or Conventional Treatment in the Intensive Care Unit (ICU). Patients discharged alive from the ICU (Panel A) and from the hospital (Panel B) were considered to have survived. In both cases, the differences between the treatment groups were significant (survival in ICU, nominal P=0.005 and adjusted P<0.04; in-hospital survival, nominal P=0.01). P values were determined with the use of the Mantel-Cox log-rank test.
  5. Figure 2. Kaplan-Meier Curves for Overall Survival. Panel A shows the comparison of overall survival between patients receiving intensive insulin therapy and those receiving conventional insulin therapy (P=0.36 by the log-rank test). Panel B shows the comparison between patients receiving pentastarch (HES) for volume resuscitation and those receiving Ringer's lactate (P=0.14 by the log-rank test). Panel C shows the comparison between patients in the low-dose HES subgroup (<=22 ml per kilogram of body weight per day), who received a median cumulative dose of 48.3 ml per kilogram (interquartile range, 21.9 to 96.2), and those in the high-dose subgroup (>22 ml per kilogram for at least 1 day during the study period), who received a median cumulative dose of 136.0 ml per kilogram (interquartile range, 79.0 to 180.0) (P<0.001 by the log-rank test).
  6. Figure 1. Enrollment and Outcomes.
  7. Figure 1. Proposed Actions of Activated Protein C in Modulating the Systemic Inflammatory, Procoagulant, and Fibrinolytic Host Responses to Infection. The inflammatory and procoagulant host responses to infection are intricately linked. Infectious agents and inflammatory cytokines such as tumor necrosis factor {alpha} (TNF-{alpha}) and interleukin-1 activate coagulation by stimulating the release of tissue factor from monocytes and the endothelium. The presentation of tissue factor leads to the formation of thrombin and a fibrin clot. Inflammatory cytokines and thrombin can both impair the endogenous fibrinolytic potential by stimulating the release of plasminogen-activator inhibitor 1 (PAI-1) from platelets and the endothelium. PAI-1 is a potent inhibitor of tissue plasminogen activator, the endogenous pathway for lysing a fibrin clot. In addition, the procoagulant thrombin is capable of stimulating multiple inflammatory pathways and further suppressing the endogenous fibrinolytic system by activating thrombin-activatable fibrinolysis inhibitor (TAFI). The conversion of protein C, by thrombin bound to thrombomodulin, to the serine protease activated protein C is impaired by the inflammatory response. Endothelial injury results in decreased thrombomodulin levels. The end result of the host response to infection may be the development of diffuse endovascular injury, microvascular thrombosis, organ ischemia, multiorgan dysfunction, and death. Activated protein C can intervene at multiple points during the systemic response to infection. It exerts an antithrombotic effect by inactivating factors Va and VIIIa, limiting the generation of thrombin. As a result of decreased thrombin levels, the inflammatory, procoagulant, and antifibrinolytic response induced by thrombin is reduced. In vitro data indicate that activated protein C exerts an antiinflammatory effect by inhibiting the production of inflammatory cytokines (TNF-{alpha}, interleukin-1, and interleukin-6) by monocytes and limiting the rolling of monocytes and neutrophils on injured endothelium by binding selectins. Activated protein C indirectly increases the fibrinolytic response by inhibiting PAI-1.12,13,14,15,16,17
  8. Figure 2. Kaplan-Meier Estimates of Survival among 850 Patients with Severe Sepsis in the Drotrecogin Alfa Activated Group and 840 Patients with Severe Sepsis in the Placebo Group. Treatment with drotrecogin alfa activated was associated with a significantly higher rate of survival (P=0.006 by the stratified log-rank test).
  9. Table 5. Incidence of Serious Adverse Events.