Jeremy Cohen on Steroids

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Intensivist Jeremy Cohen drills down on the thinking and value of using steroids in sepsis and the current evidence base. He also discusses a large international trial in progress to find some new answers to all the uncertainty. The Audio can be found on Intensive Care Network and iTunes.

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Jeremy Cohen on Steroids

  1. 1. ‘ROIDS IN SEPSIS Jeremy Cohen, Royal Brisbane Hospital Queensland, Australia Monday, 2 September 13
  2. 2. Monday, 2 September 13
  3. 3. The Steroid Controversy Monday, 2 September 13
  4. 4. Hippocrates Description of Sepsis Girolamo Frascatoro Concept of Contagion SEPSIS TIMELINE 430 BC 1546 Anthony van Leeuwenhoek Description of Bacteria 1683 Monday, 2 September 13
  5. 5. Ignaz Semmelweiss Hand Disinfection Robert Koch & Louis Pasteur Germ Theory 1847 1870 SEPSIS TIMELINE Monday, 2 September 13
  6. 6. Gram negative Sepsis Multiple Organ Failure 1909 Host Response 1912 1975 SEPSIS TIMELINE 1951 32 Studies on Steroids in Infection 1944 Monday, 2 September 13
  7. 7. Bone et al NEJM Annane et al JAMA Sprung et al NEJM 1987 2002 2008 SEPSIS TIMELINE Monday, 2 September 13
  8. 8. 0 15 30 45 60 Poland Germany Belgium Other Europe PercentageuseofLDS 0 15 30 45 60 Brazil Chile Peru ArgentinaMexico Other Latin America PercentageuseofLDS 0 15 30 45 60 India Singapore Phillipines Israel Malaysia Other Asia PercentageuseofLDS 18.0 28.5 39.0 49.5 60.0 N.America Australia Other Rest of World PercentageuseofLDS Low Dose Corticosteroid Use By Region Adapted from Beale at al CC 2010 Monday, 2 September 13
  9. 9. Monday, 2 September 13
  10. 10. Monday, 2 September 13
  11. 11. Patient with Septic Shock Short Synacthen Test Overall Randomised to Steroid or Placebo Non - Responders Responders Monday, 2 September 13
  12. 12. Use of Etomidate Statistical Analysis Outcomes reported as time to death rather than mortality Mortality only significant after using adjusted model Monday, 2 September 13
  13. 13. Overall Non Responders Responders 28 Day Mortality (steroids vs placebo) p value 82 (55%) vs 91(61%) 22 (61%) vs 18(53%) 60 (53%) vs 73 (63%) 0.09 0.96 0.04 0.24 0.63 0.11 Monday, 2 September 13
  14. 14. Patients not as sick Underpowered Did not reach recruitment target Monday, 2 September 13
  15. 15. Severe  Stress Moderate  Stress Mild  Stress Monday, 2 September 13
  16. 16. 0 1000 2000 3000 4000 Rothwell Annane Schein Sibbald Bollaert Sam Bouachour Schroeder Beishuizen Aygen Jarek De Jong Dimopoulou Oppert Cortisolnmol/l Survivors Non Survivors Cortisol values in Sepsis Monday, 2 September 13
  17. 17. “There is no greater tragedy in Science than to witness the slaying of a beautiful hypothesis by an ugly fact” Thomas Huxley Monday, 2 September 13
  18. 18. Annane et al, JAMA 2000 Cortisol < 940, Delta > 250 Cortisol < 940, Delta < 250 Cortisol > 940, Delta > 250 Cortisol > 940, Delta < 250 Monday, 2 September 13
  19. 19. Good Outcome Intermediate Outcome Bad OutcomeCortisol > 940, Delta < 250 Cortisol < 940, Delta > 250 Cortisol < 940, Delta < 250 Cortisol > 940, Delta > 250 Monday, 2 September 13
  20. 20. Monday, 2 September 13
  21. 21. Monday, 2 September 13
  22. 22. 250µg 1-24 ACTH Baseline IncrementPeak 30 min 60 min0 min Monday, 2 September 13
  23. 23. Peak vs. Increment Up to 1/3 healthy controls fail to increase cortisol by 250 n mol/l. Widmer at al JCEM 2005 Increment dependent upon basal concentration May and Carey, Am.J.Med 1985 Increments in repeated tests inversely related to response of the previous challenge Arvat et al, JCEM 2000 Monday, 2 September 13
  24. 24. Correlation vs Causation Monday, 2 September 13
  25. 25. Baseline: Peak Increment 600 900 300 1000 1200 200 Normal Insufficient Monday, 2 September 13
  26. 26. Reproducibility of ACTH tests in Sepsis Loisa et al 2005 Monday, 2 September 13
  27. 27. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 HPLC RAI AAI RAI RAI AAI AAI RAI AAI AAI Centaur RAI RAI RAI RAI RAI RAI RAI AAI NORMAL TDx NORMAL RAI RAI RAI RAI NORMAL RAI AAI NORMAL Immulite NORMAL RAI RAI RAI RAI NORMAL RAI AAI NORMAL Adrenal Status by Assay Monday, 2 September 13
  28. 28. ! Monday, 2 September 13
  29. 29. Monday, 2 September 13
  30. 30. Cohen et al, Shock 2011 Monday, 2 September 13
  31. 31. Cohen et al, Shock 2011 Monday, 2 September 13
  32. 32. Free Cortisol Values in Survivors and Non Survivors 0 50 100 150 Free Cortisol Concentrationnmol/ Baseline + 30 Minutes + 60 Minutes Total Cortisol Values in Survivors and Non Survivors 0 200 400 600 800 1000 Concentrationnmol/ Baseline + 30 Minutes + 60 Minutes Total Cortisol Comparison of Outcomes * * Died Survived Free Cortisol Total Cortisol Cohen et al, Shock 2011 Monday, 2 September 13
  33. 33. ADRENAL Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock 3800 patients 200mg hydrocortisone by infusion for 7 days 90 day mortality Monday, 2 September 13
  34. 34. Queensland   Princess  Alexandra   Royal  Brisbane  &  Womens   Ipswich   Logan   Mater  Health-­‐Public     Mater  Private  Hospital Nambour   Redcliffe Toowoomba Wesley NSW Blacktown Calvary  Mater  –  Newcastle John  Hunter Liverpool Nepean Prince  of  Wales Royal  North  shore Royal  Prince  Alfred St  George St  Vincent’s  Sydney Tamworth Woollongong Northern  Territory Darwin New  Zealand Auckland  DCCM Auckland  CVICU Christchurch Middlemore North  Shore Tauranga Wellington Western  Australia Fremantle Royal    Perth Tasmania Hobart South  Australia Lyell  McEwin Queen  Elizabeth Victoria AusUn Bendigo Dandenong Geelong Monash Northern Royal  Melbourne St  Vincent’s  Melbourne Western ADRENAL Monday, 2 September 13
  35. 35. United  Kingdom St  Georges  NHS  +  7  sites Denmark Righospitalet India Chris8an  Medical  College   Manipal  Hospital Columbia  Asia Saudia  Arabia King  Abdul  Aziz  Medical  City Republic  of  Ireland Cork  University  Hospital Norway ADRENAL Monday, 2 September 13

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