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SEPSIS ,SEVERE SEPSIS AND SEPTIC SHOCK

SEPSIS ,SEVERE SEPSIS AND SEPTIC SHOCK. 2008 UPDATE J.TAVARES,MD,FCCP,FAASM. Protocol for Early Goal-Directed Therapy. Rivers E et al. N Engl J Med 2001;345:1368-1377. SEPSIS RESUSCITATION BUNDLE: 1-Serum Lactate 2-Blood Cultures 3-Antibiotics within 3 hours/1 hr 4-IVF

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SEPSIS ,SEVERE SEPSIS AND SEPTIC SHOCK

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  1. SEPSIS ,SEVERE SEPSIS AND SEPTIC SHOCK 2008 UPDATE J.TAVARES,MD,FCCP,FAASM

  2. Protocol for Early Goal-Directed Therapy Rivers E et al. N Engl J Med 2001;345:1368-1377

  3. SEPSIS RESUSCITATION BUNDLE: • 1-Serum Lactate • 2-Blood Cultures • 3-Antibiotics within 3 hours/1 hr • 4-IVF • 5-CVP 8-12 or 12-15mmHg • 6-Scv02>70%

  4. LACTIC ACID • High Lactate levels due to liver failure. • Cutoff value still 4mmol/L . • Rapid turnaround time (ABG analyzer).

  5. SEPSIS RESUSCITATION BUNDLE: • 1-Serum Lactate • 2-Blood Cultures • 3-Antibiotics within 3 hours/1 hr • 4-IVF • 5-CVP 8-12 or 12-15mmHg • 6-Scv02>70%

  6. FLUID MANAGEMENT • 1-Crystalloids comparable to Colloids(SAFE Trial:NEJM,2004) • 2-May use Albumin in individuals with Albumin less than 4. • 3- ?Hydroxyethyl starch(HES )

  7. PENTASTARCH • NEJM(358;2; jan 10/08) • Ringer’s Lactate vs Pentastarch • Mortality: no diference at 28 days(24.1% vs 26.7%) ; higher in the Pentastarch group at 90 days(33.9% vs 41.0%; P=0.09)

  8. PENTASTARCH • MORBIDITY: • Higher rate of acute renal failure(22.8% vs 34.9%) • Lower platelets count • More PRBC transfusions

  9. Kaplan-Meier Curves for Overall Survival Brunkhorst F et al. N Engl J Med 2008;358:125-139

  10. SEPSIS RESUSCITATION BUNDLE: • 1-Serum Lactate • 2-Blood Cultures • 3-Antibiotics within 3 hours/1 hr • 4-IVF • 5-CVP 8-12 or 12-15mmHg • 6-Scv02>70%

  11. CVP 8-12:?for how long • Comparison of 2 fluid mngt strategies in ALI(nejm;354,2006 • 1000 Pts(500 conservative fluid mangt;497 liberal) • No difference in 60 day mortality,but less lung injury, faster weaning and fewer days in ICU for conservative.

  12. Protocol for Early Goal-Directed Therapy Rivers E et al. N Engl J Med 2001;345:1368-1377

  13. RBC Transfusion • Controversies in RBC transfusion in the critically ill(chest/131/5/may,2007) • TRICC trial(NEJM 1999;340) • Lack of benefit of RBC transfusions:1-immune suppression(leukocytes);2-prolonged RBC storage

  14. RBC TransfusionClinical Recommendations) • 1-general critically ill:Hb=7g/dl • 2-critically ill with septic shock(<6h):8-10 • 3-critically ill with septic shock(>6h):7g/dl • 4-critically ill with chronic cardiac disease:7g/dl • 5-critically ill with acute cardiac disease:8-10g/dl

  15. Sepsis management bundle • 1-Tightbloodsugarcontrol • 2-Low dose steroids • 3-Drotrecogin alfa • 4-Plateau pressures<30cm H2O • 5-Extubation readiness.

  16. Intensive insulin therapy in the ICU • Leuven study(nejm;nov2001) • 1-BG<110 2-mortality reduced from 8% to 4.6% • 3-Severe hypoglycemia(<40): 0.8% in the conventional group and 5.1% in the intensive treatment group. • 4-Surgical ICU patients.

  17. Kaplan-Meier Curves Showing Cumulative Survival of Patients Who Received Intensive Insulin Treatment or Conventional Treatment in the Intensive Care Unit (ICU) Van den Berghe G et al. N Engl J Med 2001;345:1359-1367

  18. IIT in the ICU • Leuven 2(nejm 2006;354) • 1-Blood glucose 80-110 • 2- patients staying in ICU for 3 or more days: mortality decreased from 52.3% to 43% • 3-Severe hypoglycemia(<40): 3.1% in the conventional group and 18.7% in the treatment group. • 4-medical IICU patients.

  19. IIT in the ICU • VISEP studies and Glucocontrol studies both in Europe(stopped because of increased risk of hypoglycemia). • Both criticized for not having enough number of patients. • Ongoing clinical trial by NIH(NICE-SUGAR) trial may have sufficient statistical power to address the above issues.

  20. Kaplan-Meier Curves for Overall Survival Brunkhorst F et al. N Engl J Med 2008;358:125-139

  21. ITT in the ICU • Glycemic control needs to be done safely. • Use of computerized systems: • Glucommander(can be loaded in a bedside computer,hanheld computer or nursing station computer

  22. Glucommander • 5 parameters: • 1-low end of target range for blood glucose • 2-high end of target range for glucose • 3-the initial multiplier(adjusted for insulin sensitivity) • 4-the maximum time interval between measurements • 5-the insulin concentration

  23. Sepsis management bundle • 1-Tight blood sugar control • 2-Low dose steroids • 3-Drotrecogin alfa • 4-Plateau pressures<30cm H2O • 5-Extubation readiness.

  24. Adrenal Insufficiency • 2002:Annane et al(JAMA;288):299 patients-76% of nonresponders to cosyntropin stimulation test,on ventilator were randomized to hydrocortisone plus fludrocortisone for 7 days:13% reduction in mortality for those treated

  25. Adrenal Insufficiency • The CORTICUS trial(double-blinded,randomized,placebo-controlled multicenter European trial)( Goal:800 patients): • Comparing hydrocortisone(50mg IV q6h for 5 days,taper to 50mg IV q12h for 3 days,then 50mg daily for 3 days)with placebo in septic shock.

  26. Adrenal Insufficiency • The retrospective Corticus cohort study(Critical Care Medicine:Volume 35(4) April 2007pp 1012-1018) • Total of 562 patients(after exclusion:477pts were left)

  27. Enrollment and Outcomes Sprung C et al. N Engl J Med 2008;358:111-124

  28. CORTICUS • 1-Hydrocortisone did not improve survival or reversal of shock even in patients who did not respond to Cosyntropin test • 2- Hydrocortisone hastened reversal of shock.

  29. Sepsis management bundle • 1-Tight blood sugar control • 2-Low dose steroids • 3-Drotrecogin alpha • 4-Plateau pressures<30cm H2O • 5-Extubation readiness.

  30. Proposed Actions of Activated Protein C in Modulating the Systemic Inflammatory, Procoagulant, and Fibrinolytic Host Responses to Infection Bernard G et al. N Engl J Med 2001;344:699-709

  31. Drotrecogin Alfa • 1-PROWESS trial:NEJM 2001;344:699-709. • 2-ADDRESS trial:(APACHE<25 or only one organ dysfunction at baseline)-NEJM 2005;353:1332-1341.:no significant reduction in 28-day mortality. • 3-ADDRESS one year follow-up(critical care medicine 2007;35:1457-1463):no increased risk of death or evidence of harm at 1 year.

  32. 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

  33. Incidence of Serious Adverse Events Bernard G et al. N Engl J Med 2001;344:699-709

  34. How do I do it(Resuscitation Phase) • Septic shock: • 1-IVF (up to 20cc/kg bolus to keep MAP>=65 • 2-if unable to achieve above,place central line for CVP monitoring:keep CVP 8-12mmHg(12-15 if PPV). • 3-If CVP goal achieved but MAP<65,start vasopressors

  35. How do I do it(Resuscitation Phase) • 4-NE,DA,PE,Vasopressin • 5-follow serial lactate levels 6-If MAP>65,check ScVo2(goal is ScVo2>70%). 7-If ScVo2<70% and Ht<30%,transfuse PRBC

  36. How do I do it(Resuscitation Phase) • 9-If Ht>30% and ScVo2 still <70%,start Dobutamine. If ScVo2>70%,goal achieved

  37. FLUIDS • Normal Saline:500 cc boluses • Albumin:25g iv x 3 doses • Avoid Hespan

  38. Vasopressin • 0.01-0.04 units/mn IV • Do not titrate.

  39. How do I do it(Management Phase) • STEROIDS • 1-No need for baseline cortisol level or Cosyntropin test: If BP is not responding to IVF and Vasopressors after 1 to 2 hours,start HYDROCORTISONE at 50mg IV every 6 hours for 5 days(do not taper)

  40. How do I do it(Management) • ACTIVATED PROTEIN C • 2-APACHE>25 or at least two organs failure,start drotrecogin alpha. • 3-If APACHE<25 or only one organ failure,may consider drotrecogin.

  41. How do I do it(management) • BLOOD GLUCOSE • 4-Tight Blood Sugar control: use hospital protocol). Acceptable to keep blood sugar less than 150.

  42. How do I do it(Management) • Mechanical ventilation • 5-keep plateau pressure below 30 cmH20 • 6-Spontaneous Awakening Trials • 7-Spontaneous Breathing Trials

  43. Antibiotics • USE HOSPITAL PROTOCOL

  44. Goal for 2009 • DECREASE SEPSIS MORTALITY BY 25%

  45. Material for Research • 1-Procalcitonin • 2-C Reactive Protein • 3-Statins

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