Management of Severe Sepsis Update
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An Updated presentation of the management of severe sepsis including best evidence for fluid resuscitation, vasopressors, blood pressure target, steroid replacement, blood transfusion and other moralities.
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Management of Severe Sepsis Update
- 1. Update in the Management of Severe Sepsis
- 2. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 3. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 4. EGDT vs UC ProCESS ARISE ProMISe EGDT PB-ST UC EGDT UC EGDT UC 20.8 20.6 20.7 15.4 15.8 18.7 18 21% 18% 18.9% 18.6% 18.8% 29.5% 29.2% APACHE II Mortality APCHE II 20 vs 21 46% vs 30%
- 5. In Conclusions These studies confirm the most important elements in management of sepsis: If these essential aspects of care are in place, NO ADDED VALUE of protocolized measurements of central hemodynamics and oxygen saturation Early Recognition Early Administration of Antibiotics Early adequate Volume Resuscitation using Clinical Parameters Adequate Source Control
- 6. Fluids in Severe Sepsis Why Fluids What Type How Much How Fast End Points
- 8. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 9. Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis Perner et al ,NEJM, N Engl J Med 2012; 367:124-134 798 ICU patients, 26 centers December 23, 2009, and November 15, 2011 HES 130/0.42 Ringer Acetate # of Patients 398 400 90 Day Mortality 51% 43% Renal Replacement Therapy 22% 16% √ 0.04 √ 0.03
- 10. Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis Perner et al ,NEJM, N Engl J Med 2012; 367:124-134
- 11. Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis Perner et al ,NEJM, N Engl J Med 2012; 367:124-134
- 12. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 13. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care John A. Myburgh, et al. N Engl J Med 2012;367:1901-11 6651 ICU patients, 32 centers December 2009 through January 2012 Hydroxyethyl Starch Saline # of Patients 3315 3336 90 Day Mortality 18% 17% Acute Kidney Injury 7% 5.8% X 0.26 √ 0.04
- 14. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care John A. Myburgh, et al. N Engl J Med 2012;367:1901-11 90-day mortality: 18.0% vs 17.0% (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P = 0.26).
- 15. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care John A. Myburgh, et al. N Engl J Med 2012;367:1901-11
- 16. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care John A. Myburgh, et al. N Engl J Med 2012;367:1901-11
- 20. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 21. Safe Study: Albumin vs Saline in ICU The SAFE Study Investigator, Simon Finfers, N Engl J Med 2004;350:2247 SAFE Study 6997 ICU patients, 16 centers November 2001 and June 2003 Albumin Saline # of Patients 3497 3500 28 Day Mortality 20.9% 21.1% X
- 22. Safe Study: Probability of Survival The SAFE Study Investigator, Simon Finfers, N Engl J Med 2004;350:2247
- 23. Safe Study: Albumin vs Saline The SAFE Study Investigators, Simon Finfer, N Engl J Med 2004;350:2247
- 24. Colloids versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) Study
- 25. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 26. Albumin Replacement for Patients with Severe Sepsis or Septic Shock ALBIOS Trial 1818 patients with severe sepsis, in 100 ICUs Aug 2008 to Feb 2012 20% Albumin Crystalloids # of Patients 895 900 28 Day Mortality 31.8% 32% 90 Day Mortality 41.1% 43.6% X X Gattinoni Et Al. March 18, 2014, At NEJM.Org.
- 27. Gattinoni Et Al. March 18, 2014, At NEJM.Org. Serum Albumin Levels through Day 28
- 28. Gattinoni Et Al. March 18, 2014, At NEJM.Org. 90-day mortality: 41.1% vs 43.6% (P=0.29) Albumin Replacement for Patients with Severe Sepsis or Septic Shock
- 29. Gattinoni Et Al. March 18, 2014, At NEJM.Org. Albumin Replacement for Patients with Severe Sepsis or Septic Shock
- 30. Gattinoni Et Al. March 18, 2014, At NEJM.Org. Albumin Replacement for Patients with Septic Shock
- 31. Gattinoni Et Al. March 18, 2014, At NEJM.Org. Albumin Replacement for Patients with Septic Shock
- 32. Albumin Replacement for Patients with Septic Shock ALBIOS Trial 1135 patients with septic shock, in 100 ICUs Aug 2008 to Feb 2012 20% Albumin Crystalloids # of Patients 565 570 28 Day Mortality 35% 37% 90 Day Mortality 43.6% 49.9% X √ Gattinoni Et Al. March 18, 2014, At NEJM.Org.
- 33. Michael Lafan. BMJ 2014 22;349:g4561. Epub 2014 Jul 22
- 34. Michael Lafan. BMJ 2014 22;349:g4561. Epub 2014 Jul 22
- 35. Hopefully the final word on Albumin in Sepsis
- 36. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 37. Comparison of Dopamine and Norepinephrine in the Treatment of Shock SOAP II Trial 1679 patients with septic shock, 8 centers Dec 2003 to Oct 2007 Dopamine Norepinephrine # of Patients 858 821 28 Day Mortality 52.5% 48.5% X Vincent, J. L. et al. N Engl J Med 2010;362:779-89
- 38. Comparison of Dopamine and Norepinephrine in the Treatment of Shock Vincent, J. L. et al. N Engl J Med 2010;362:779-89 28-day mortality: 52.5% vs 48.5% (odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P = 0.10)
- 39. Comparison of Dopamine and Norepinephrine in the Treatment of Shock SOAP II Trial 1679 patients with septic shock, 8 centers Dec 2003 to Oct 2007 Dopamine Norepinephrine # of Patients 858 821 Arrythmias 24.1% 12.4% Vincent, J. L. et al. N Engl J Med 2010;362:779-89 √ <0.001
- 40. Comparison of Dopamine and Norepinephrine in the Treatment of Shock Vincent, J. L. et al. N Engl J Med 2010;362:779-89
- 41. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 42. Holst, L. N Engl J Med 2014; 371:1381-1391 TRISS Trial 998 patients in 32 general ICUs in Denmark, Sweden, Norway, and Finland Dec 2011 to Dec 2013 7 g/dL 9 g/dL # of Patients 502 496 90 Day Mortality 43% 45% X Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock
- 43. Blood Hemoglobin Levels in Patients in the ICU at Baseline and after Randomization Holst, L. N Engl J Med 2014; 371:1381-1391
- 44. Time to Death and Relative Risk of Death at 90 Days Holst, L. N Engl J Med 2014; 371:1381-1391 90-day mortality: 43% vs 45% (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P = 0.44).
- 45. Primary and Secondary Outcome Measures Holst, L. N Engl J Med 2014; 371:1381-1391
- 46. Primary and Secondary Outcome Measures Holst, L. N Engl J Med 2014; 371:1381-1391
- 47. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 48. Adequate Resusciattion Do not uses HES Do not uses HES Albumin same as Saline No need for albumin except septic shock Norepinephrine is the preferred vasopressor Maintain Hg >7 Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 49. 63% vs 53% Mortality
- 50. Hydrocortisone Therapy for Patients with Septic Shock Charles L. Sprung, et al. N Engl J Med 2008;358:111-24 CORTICUS Study 499 patients with septic shock, 52 ICUs Mar 2002 to Nov. 2005 Hydrocortisone Placebo # of Patients 251 248 28 Day Mortality 34.3% 31.5% X
- 51. Hydrocortisone Therapy for Patients with Septic Shock Charles L. Sprung, et al. N Engl J Med 2008;358:111-24 28-day mortality: 34.3% vs 31.5%
- 52. Hydrocortisone Therapy for Patients with Septic Shock Charles L. Sprung, et al. N Engl J Med 2008;358:111-24 28-day mortality: 39.2% vs 36.1% , P = 0.69 28-day mortality: 28.8% vs 28.7% , P = 1.00
- 53. Kaplan–Meier Curves for the Time to Reversal of Shock Charles L. Sprung, et al. N Engl J Med 2008;358:111-24 P<0.001
- 54. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 55. High versus Low Blood-Pressure Target in Patients with Septic Shock SEPSISPAM Trial 776 patients with septic shock, 29 centers Mar 2010 to Dec 2011 Low MAP 65 to 70 mm Hg High MAP 80 to 85 mm Hg # of Patients 388 388 28 Day Mortality 34% 36.6% 90 Day Mortality 42.3% 43.8% X X Pierre Asfar , Peter Radermacher, Et al. N Engl J Med 2014; 370:1583-159
- 56. High versus Low Blood-Pressure Target in Patients with Septic Shock MAP 65-70 MAP 80-85 Pierre Asfar , Peter Radermacher, Et al. N Engl J Med 2014; 370:1583-159
- 57. High versus Low Blood-Pressure Target in Patients with Septic Shock 90-day mortality: 43.8% vs 42.3% (hazard ratio, 1.04; 95% CI, 0.83 to 1.30; P = 0.74) Pierre Asfar , Peter Radermacher, Et al. N Engl J Med 2014; 370:1583-159
- 58. High versus Low Blood-Pressure Target in Patients with Septic Shock SEPSISPAM Trial 776 patients with septic shock, 29 centers Mar 2010 to Dec 2011 Low MAP 65 to 70 mm Hg High MAP 80 to 85 mm Hg Doubling of S-Cr (ALL) 41.6% 38.6% No Chronic HTN 33% 38.5% Chronic HTN 52.3% 38.6% Renal Replacement Therapy (ALL) 35.8% 33.5% No Chronic HTN 30.7% 34.8% Chronic HTN 42.2% 31.7% X 0.42 Pierre Asfar , Peter Radermacher, Et al. N Engl J Med 2014; 370:1583-159 X 0.32 √ 0.02 X 0.05 X 0.36 √ 0.046
- 59. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 60. Mortality 8.0% with conventional treatment to 4.6% with Intensive Insulin Therapy
- 61. Intensive versus Conventional Glucose Control in Critically Ill Patients NICE-SUGAR Study 6022 ICU patients, 42 hospitals Dec 2004 to Nov 2008 Intensive 81 to 108 mg/dL Conventional <180 mg/dL # of Patients 3010 3012 28 Day Mortality 22.3% 20.8% 90 Day Mortality 27.5% 24.9% √ P = 0.02 Simon Finfer,, et al. N Engl J Med 2009;360:1283-97 X p= 0.17
- 62. Intensive versus Conventional Glucose Control in Critically Ill Patients Simon Finfer,, et al. N Engl J Med 2009;360:1283-97
- 63. Intensive versus Conventional Glucose Control in Critically Ill Patients Simon Finfer,, et al. N Engl J Med 2009;360:1283-97
- 64. Hypoglycemia NICE-SUGAR Study 6104 ICU patients, 42 hospitals Dec 2004 to Nov 2008 Intensive 81 to 108 mg/dL Conventional <180 mg/dL # of Patients 3016 3014 Severe Hypoglycemia 6.8% 0.5% √ P <0.001 Simon Finfer,, et al. N Engl J Med 2009;360:1283-97
- 65. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 66. Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death ADDRESS Study 2613 patients with severe sepsis, 52 ICUs Sept 2002 to Feb. 2004 Drotrecogin Alfa Placebo # of Patients 1316 1297 28 Day Mortality 18.5% 17% X Edward Abraham, et al. N Engl J Med 2005;353:1332-41
- 67. Adverse Events Edward Abraham, et al. N Engl J Med 2005;353:1332-41
- 68. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 69. Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial Robert L. Lins, et al. Nephrol Dial Transplant (2009) 24: 512–518 X p= 0.42 SHARF 4 Study 316 patients with ARF in ICU, 42 hospitals April 2001 to March 2004 CRRT IRRT # of Patients 172 144 Hospital Mortality 58.1% 62.5%
- 70. Outcome in patients randomized to intermittent or continuous renal replacement therapy Robert L. Lins, et al. Nephrol Dial Transplant (2009) 24: 512–518
- 71. Outcome in patients randomized to intermittent or continuous renal replacement therapy Robert L. Lins, et al. Nephrol Dial Transplant (2009) 24: 512–518
- 72. Outcome in patients randomized to intermittent or continuous renal replacement therapy Robert L. Lins, et al. Nephrol Dial Transplant (2009) 24: 512–518
- 73. Intermittent versus continuous renal replacement therapy for acute renal failure in adults Robert Rabindranath et al. Cochrane Database Syst Rev2007;3:CD003773-CD003773
- 74. Comparison CRRT versus IRRT, Outcome: Mean arterial pressure at end of study period Robert Rabindranath et al. Cochrane Database Syst Rev2007;3:CD003773-CD003773
- 75. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 76. Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients RENAL Study 1464 patients with ARF, in 35 ICUs Dec 2005 to Nov 2008 Low Intensity 25 ml/kg/hr High Intensity 40 ml/kg/hr # of Patients 743 721 90 Day Mortality 44.7% 44.7% X Rinaldo Bellomo et al. N Engl J Med 2009;361:1627-38
- 77. Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients Rinaldo Bellomo et al. N Engl J Med 2009;361:1627-38
- 78. EGDT vs UC HES vs LR HES vs Saline Albumin vs Saline Albumin Replacement vs Crystalloids Dopamine vs Norepinephrine Low vs High Hg Steroids High vs Low BP Intensive vs Conventional BS Control Drotrecogin Alfa CRRT vs Intermittent RRT Intensity of CRRT Fresh vs Old Blood
- 79. Age of Transfused Blood in Critically Ill Adults RENAL Study 2430 ICU patients with need for blood, in 64 Centers March 2009 and May 2014 Fresh Blood <8 days Old Blood Oldest Units # of Patients 1211 1219 90 Day Mortality 37% 35% Lacroix J et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1500704 X
- 80. Forest Plot of Absolute Risk Differences in Primary and Secondary Outcomes Lacroix J et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1500704
- 81. Forest Plot of Absolute Risk Differences in Primary and Secondary Outcomes. Lacroix J et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1500704
- 82. Kaplan–Meier Survival Analysis of Time to Death in the Intention-to-Treat Population Lacroix J et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1500704 Hazard ratio for death was 1.1 (95% CI, 0.9 to 1.2; P = 0.38).
- 83. Adequate Resusciattion Do not uses HES Do not uses HES Albumin same as Saline No need for albumin except septic shock Norepinephrine is the preferred vasopressor Maintain Hg >7 Steroids in refractory shock No need for higher MAP except HTN Maintain BS <180 Do not use Drotrecogin Alfa CRRT for shock, otherwise CRRT or IRRT No need for high Intensity CRRT Fresh or Old Blood is the same