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Traitements non Antibiotiques du Choc Septique

Traitements non Antibiotiques du Choc Septique. Djillali ANNANE, Hôpital Raymond Poincaré 92380 Garches, Djillali.annane@rpc.ap-hop-paris.fr. TIME IS IMPORTANT. GOLDEN HOUR. Patients with global tissue hypoxia and early stage of disease. Fluid Therapy - Liters. *. *. * = P<0.01.

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Traitements non Antibiotiques du Choc Septique

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  1. Traitements non Antibiotiques du Choc Septique Djillali ANNANE, Hôpital Raymond Poincaré 92380 Garches, Djillali.annane@rpc.ap-hop-paris.fr

  2. TIME IS IMPORTANT GOLDEN HOUR

  3. Patients with global tissue hypoxia and early stage of disease

  4. Fluid Therapy - Liters * * * = P<0.01

  5. TYPE OF FLUID DOES NOT REALLY MATTER

  6. SAFE Flow Chart Finfer et al, NEJM 2004

  7. SAFE - Outcome Data Finfer et al, NEJM 2004

  8. CRISTAL OBJECTIVE MULTI-NATIONAL RCT publicly funded (French Ministry for Health) TO COMPARE THE EFFICACY AND SAFETY OF CRYSTALLOIDS AND SYNTHETIC COLLOIDS WHEN GIVEN FOR FLUID RESUSCITATION IN CRITICALLY ILL PATIENTS

  9. TYPE OF CATECHOLAMINES DOES NOT REALLY MATTER

  10. Vasopressors for shock. Müllner M et al, Cochrane Database Syst Rev. 2004;(3):CD003709.

  11. Vasopressors for shock. Müllner M et al, Cochrane Database Syst Rev. 2004;(3):CD003709.

  12. ADJUVANT THERAPIES

  13. Insulin Signaling Pathways That Regulate Glucose Metabolism in Muscle Cells and Adipocytes

  14. Role of Muscles Expression of Cytokines in Insulin Resistance Syndrome Saghizadeh, JCI 1996 (triangles) Insulin sensitive (circles) Insulin resistant (squares) Diabetic

  15. Tumor Necrosis Factor-–Induced Insulin Resistance in Adipocytes Qi, Exp Biol Med 2000

  16. Marked Reduction of GLUT4 in Muscle or Adipose Tissue Causes Insulin Resistance Minokoshi, JBC, 2003

  17. Hyperglycemia and Outcome in the Acutely IllUmpierrez, JCEM 2002

  18. Effects of Intensive Insulin Therapy on Survival in Surgical ICU patients. Van den Berghe, NEJM 2002

  19. Intensive insulin therapy in the medical ICU

  20. Intensive insulin therapy in the medical ICU

  21. Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP Trial) This study has been suspended.Verified by German Competence Network Sepsis August 2005

  22. GLUCOCORTICOIDS

  23. Keh et al, AJRCCM 2003

  24. COCHRANE INFECTIOUS GROUP SYSTEMATIC REVIEW

  25. CORTISOL RESPONSE TO ACTH 250 Rothwell, Lancet 1991

  26. Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock NON RESPONDERS Annane et al, JAMA. 2002 RR=1.889 P=0.002

  27. Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock RESPONDERS Annane et al, JAMA. 2002 RR=0.853 P=0.637

  28. AI AND SYSTEMIC INFLAMMATION * * *

  29. 1.00 D max > 9 µg/dl 0.75 Probabilityof survival 0.50 0.25 D max  9 µg/dl 0.00 0 7 14 21 28 Time (days) AI AND SURVIVAL Annane, JAMA 2000

  30. 28-DAY SURVIVAL IN NON RESPONDERS HR = 0.670 p=0.023 Annane, JAMA 2002

  31. 28-DAY SURVIVAL IN RESPONDERS Annane, JAMA 2002

  32. Coagulation Is Activated in Sepsis 16 6.0 * 5.0 12 * * 4.0 * TATcomplex(ng/L) D-dimer(mg/L) 8 3.0 2.0 *P <.05 vs controls 4 1.0 Controls 0.0 0 60 120 180 240 300 1 4 7 Time After Administration (min) Time After Hosp. Admission (day) Healthy volunteers + TNF (n=6) Healthy volunteers + LPS (n=6) Survivors (n=23) Nonsurvivors (n=25) Levi et al. JAMA. 1993;270:975. Lorente et al. Chest. 1993;103:1536.

  33. Fibrinolysis Is Suppressed in Sepsis 500 50 400 40 300 30 PAI-1 (ng/mL) tPA Activity (%) 200 20 100 10 0 0 60 120 180 240 300 60 120 180 240 300 Time after Administration (min) Time after Administration (min) Healthy volunteers + TNF (n=6) Healthy volunteers + LPS (n=6) Levi et al. JAMA. 1993;270:975.

  34. AT in Severe Sepsis : Kybersept • Primary end-point : 28-day all cause mortality • N = 2314 total • AT levels achieved : 180% nl (120-230) • Concomitant heparin : 1616 pts. 38.9 38.7 Warren et al. JAMA 2001;286:1869-78

  35. TFP007 Primary Cohort - 28-Day Mortality P value from logistic regression adjusted for baseline APACHE II score and baseline log10 IL-6, per protocol.

  36. Summary of 28-Day All Cause Mortality Primary Analysis Results2-sided p-value 0.005Relative Risk Reduction 19.4%Increase in Odds of Survival 38.1% 30.8% 24.7% Drotrecogin Alfa (activated) (N=850) Placebo (N=840) G. Bernard, et al. N Engl J Med 2001;344:699-709

  37. N Trt Plc 1690 24.7 30.8 Primary APACHE II 433 15.1 12.1 1st Quartile 440 22.5 25.7 2nd Quartile 366 23.5 35.8 3rd Quartile 451 38.1 49.0 4th Quartile Cardiovascular Organ Failure 1214 25.1 32.0 Yes 476 23.8 27.6 No Cardiovascular SOFA 494 19.1 26.6 0 or 1 1196 27.3 32.4 2 to 4 Shock Within 6 Hours 1200 26.3 34.2 Yes 490 21.0 22.3 No Any Shock 1362 26.0 32.5 Yes 328 19.7 23.3 No Respiratory Organ Failure 1272 25.6 31.6 Yes 418 22.0 28.5 No Respiratory SOFA 184 12.9 26.4 0 or 1 1479 26.4 31.7 2 to 4 Mechanical Ventilation 1275 27.3 33.1 Yes 415 17.6 22.9 No 0.5 0.7 1.25 0.8 0.9 1.67 0.6 1 2 Relative Risk of Death (Point Estimate and 95% CI) Subgroups – Disease Severity Measures

  38. BLEEDING RISKS

  39. Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death Edward Abraham, NEJM 2005

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