1. SEPSIS & SEPTIC SHOCK 10.15. 2009 Jaime Palomino, MD Pulmonary & Critical Care Medicine Tulane University Health Sciences Center New Orleans, Louisiana

2. Epidemiology  Sepsis yearly incidence  50 – 95 cases / 100,000  Increasing by 9% each year  2% hospital admissions  9% sepsis  severe sepsis  3% severe sepsis  septic shock 10% of ICU admissions 10% of ICU admissions

3. Annane D et al. Lancet 2005;365:63-78

4. Russell J. NEJM 2006;355:1699-713

7. Septic Shock – Treatment  Initial Resuscitation

8. Rivers E et al. NEJM 2001;345:1368-1377

10. Septic Shock – Treatment  What are the recommended vasopressors in septic shock patients? MAP ≥ 65 mmHg MAP ≥ 65 mmHg Norepinephrine and Dopamine  initial vasopressors of choice Norepinephrine and Dopamine  initial vasopressors of choice Epinephrine  first alternative when BP is poorly responsive to Norepinephrine or Dopamine Epinephrine  first alternative when BP is poorly responsive to Norepinephrine or Dopamine

11. Annane D et al. Lancet 2007;370:676-84

12. Septic Shock – Treatment  Vasopressors Vasopressin Vasopressin May be subsequently added to Norepinephrine (Dose: 0.03units/min) with anticipation of an effect equivalent to Norepinephrine alone.May be subsequently added to Norepinephrine (Dose: 0.03units/min) with anticipation of an effect equivalent to Norepinephrine alone.

13. Russell J et al. NEJM 2008;358:877-887

16. Povoa P et al. CCM 2009;37:410-416

17. Septic Shock – Treatment  Vasopressors Comparison of Dopamine and Norepinephrine as the First Vasopressor Agent in the Management of Shock Comparison of Dopamine and Norepinephrine as the First Vasopressor Agent in the Management of Shock De Backer D. NCT00314704 De Backer D. NCT00314704 Primary Outcome Measures: 28 day survival Primary Outcome Measures: 28 day survival Estimated Enrollment: 1600 Estimated Enrollment: 1600 Study Start Date: December 2003 Study Start Date: December 2003 Estimated Study Completion Date: December 2010 Estimated Study Completion Date: December 2010

18. Septic Shock – Treatment  Steroids

21. Sprung et al. NEJM 2008;358:111-24

26. Relative Adrenal Insufficiency Diagnosis Thomas Z et al. Ann Pharmacother 2007;41:1456-65

28. Dellinger R et al. Crit Care Med 2008; 36:296-327

29. Annane et al. JAMA 2009;301:2362-2375

33. Septic Shock – Treatment  Glucose Control

34. Van Den Berghe G et al. NEJM 2001;345:1359-1367

36. Van Den Berghe G et al. NEJM 2006;354:449-461

38. Brunkhorst FM et al. NEJM 2008;358:125-139

41. NEJM 2009;360:1283-97

47. Septic Shock– Treatment  Activated Protein C

48. Bernard GR et al. NEJM 2001;344:699-709

50. Abraham E et al. NEJM 2005;353:1332-1341

53. Dellinger R et al. Crit Care Med 2008; 36:296-327

56. Early Versus Delayed Enteral Feeding and Omega-3 Fatty Acid/Antioxidant Supplementation for Treating People With Acute Lung Injury or Acute Respiratory Distress Syndrome (The EDEN-Omega Study)  This study has been terminated.  ( The Omega arm of this study was stopped for futility. The EDEN arm continues to recruit patients as a separate independent study. )  http://clinicaltrials.gov/ct2/show/study/NCT00609180 http://clinicaltrials.gov/ct2/show/study/NCT00609180

57. Early Versus Delayed Enteral Feeding and Omega-3 Fatty Acid/Antioxidant Supplementation for Treating People With Acute Lung Injury or Acute Respiratory Distress Syndrome (The EDEN-Omega Study)  Interim analysis: Mortality @ day 60: Mortality @ day 60: 26.6% Omega-3 Vs 16.3% Control26.6% Omega-3 Vs 16.3% Control Ventilator-Free days (within 28 days): Ventilator-Free days (within 28 days): 14.6 days Omega-3 Vs 17.4 days Control14.6 days Omega-3 Vs 17.4 days Control ICU-Free days (within 28 days): ICU-Free days (within 28 days): 13.9 days Omega-3 Vs 16.8 days Control13.9 days Omega-3 Vs 16.8 days Control Chest Physician. August 2009. Elsevier.

58. Septic Shock – Diagnosis  Serum Markers

59. Annane D et al. Lancet 2005;365:63-78

60. Nobre V et al. AJRCCM 2008;177:498-505

61. Tang B et al. AJRCCM 2007;176:676-684

62. Wurfel M et al. AJRCCM 2008;178:710-720

63. Cinel I et al. CCM 2009;37:291-304

64. Russell J. NEJM 2006;355:1699-713

65. Septic Shock – Treatment  Last but not less important… Sedation protocol Sedation protocol Sedation GoalSedation Goal Daily awakening trialsDaily awakening trials Avoid NMBAs as much as possibleAvoid NMBAs as much as possible DVT prophylaxis DVT prophylaxis Stress Ulcer (GI) prophylaxis Stress Ulcer (GI) prophylaxis Consideration for Limitation of Support Consideration for Limitation of Support