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Sepsis

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Sepsis

  1. 1. Journal reading Recent Development in the diagnosis and management of Sepsis ( Chest 2007;132:1968-1976) 2008/1/24 報告: R1 林軒名 醫師 指導: VS 涂智彥 醫師
  2. 2. Outline <ul><li>Definition </li></ul><ul><li>What did we do in the past ? </li></ul><ul><li>Diagnosis and its difficulty </li></ul><ul><li>Prevention and supportive treatment </li></ul><ul><li>The STOP sepsis bundle </li></ul><ul><li>Potentially time-sensitive treatment </li></ul>
  3. 3. Definition of sepsis <ul><li>Systemic  inflammatory  response syndrome ( >2/4) </li></ul><ul><ul><li>Temperature  >38°C  or <36°C </li></ul></ul><ul><ul><li>Pulse 90 beats per minute </li></ul></ul><ul><ul><li>Respiratory rate 20 breaths per minute or PaCO2 <32 mm Hg </li></ul></ul><ul><ul><li>White blood cells > 12,000/mm3 or < 4000/mm3 or > 10% immature (“band”) forms  </li></ul></ul>
  4. 4. Definition of sepsis <ul><li>Sepsis : SIRS due to suspected or confirmed infection </li></ul><ul><li>Severe sepsis: Sepsis associated with organ dysfunction, hypoperfusion or hypotension </li></ul><ul><li>Septic shock: Sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities </li></ul>
  5. 5. What did we do in the past <ul><li>Obtaining culture, empiric antibiotics </li></ul><ul><li>Conventional ventilator setting: </li></ul><ul><ul><li>keep PaO2>60mmhg, SaO2>90%, </li></ul></ul><ul><ul><li>Tidal volume:10-15ml/kg to achieve normal PH and PaCO2 </li></ul></ul><ul><ul><li>Deep sedation </li></ul></ul><ul><li>pulmonary artery catheter (PAC) to confirm a low intravascular pressure and/or low systemic resistance before fluids were given. </li></ul>
  6. 6. What did we do in the past <ul><li>Regularly given dopamine or norepinephrine for hypotensive patient </li></ul><ul><li>Modest anemia was not tolerated,  </li></ul><ul><li>Stress-dose corticosteroids, rarely check adrenocorticotropic hormone (ACTH) </li></ul><ul><li>A blood glucose level of 200 mg/dL was satisfactory. </li></ul>
  7. 7. Diagnostic tool ? <ul><li>History taking, physical examination, routine laboratory studies, radiography </li></ul><ul><li>Procalcitonin </li></ul><ul><li>C-reactive protein </li></ul><ul><li>soluble triggering receptor expressed on myeloid cell-1 </li></ul><ul><li>d-Dimer, IL-6 </li></ul><ul><li>total protein C </li></ul>
  8. 8. Difficult to early diagnosis <ul><li>Difficult to early detect </li></ul><ul><li>Underestimate the severity </li></ul><ul><li>Confusion because of multiple organ failure : </li></ul><ul><ul><li>Failure of respiratory and cardiovascular system are easier to detect </li></ul></ul><ul><ul><li>Otherwise single organ failure is difficult to detect. </li></ul></ul>
  9. 9. Prognosis factor <ul><li>Microorganism characteristics </li></ul><ul><li>Presence of Coagulopathy </li></ul><ul><li>Shock required vasopressor </li></ul><ul><li>Total number and severity of failure organ </li></ul><ul><li>Advanced age </li></ul><ul><li>Presence of cancer </li></ul><ul><li>APACHE II score </li></ul><ul><li>Change in Lactate, IL-6, Protein-C level </li></ul>
  10. 10. Prevention and supportive treatment <ul><li>Infection prevention </li></ul><ul><ul><li>Hand washing </li></ul></ul><ul><ul><li>Skin preparation </li></ul></ul><ul><ul><li>Sterile technique </li></ul></ul><ul><li>Supportive care </li></ul><ul><ul><li>DVT prophylaxis </li></ul></ul><ul><ul><li>GI bleeding prophylaxis </li></ul></ul><ul><ul><li>Nutrition support </li></ul></ul><ul><ul><li>Bed sore or fall prevention </li></ul></ul><ul><ul><li>Acute renal failure prevention </li></ul></ul>
  11. 11. Outline <ul><li>Definition </li></ul><ul><li>What did we do in the past ? </li></ul><ul><li>Diagnosis and its difficulty </li></ul><ul><li>Prevention and supportive treatment </li></ul><ul><li>The STOP sepsis bundle </li></ul><ul><li>Potentially time-sensitive treatment </li></ul>
  12. 12. The STOP sepsis bundle
  13. 13. The STOP sepsis bundle
  14. 14. The STOP sepsis bundle
  15. 15. 24hrs later, STOP sepsis
  16. 16. 24hrs later, STOP sepsis
  17. 17. Potentially time-sensitive treatment <ul><li>Antibiotics therapy </li></ul><ul><li>Hemodynamic management </li></ul><ul><li>Normal tidal volume ventilation </li></ul><ul><li>Glucocoricoid and mineralocorticoid for septic shock </li></ul><ul><li>Glucose control </li></ul><ul><li>Drotrecogin alfa activated </li></ul>
  18. 18. Antibiotics therapy <ul><li>Obtain culture of blood and suspect body fluid . </li></ul><ul><li>Blood and spinal fluid culture are most useful, while sputum and urine cultures are usually contaminated. </li></ul><ul><li>Adequate or appropriate antibiotics . </li></ul><ul><ul><li>Host factor: immune compromise or chronic illness with repeated antibiotics exposure . </li></ul></ul><ul><li>Systemic performance : rapid access and rapid management ; 1 hr delayed increase mortality </li></ul>
  19. 19. Inappropriate antibiotics The influence of inadequate empirical antimicrobial treatment on patients with bloodstream infections in an intensive care unit ( Clin Microbiol Infect 2003; 9: 412–418)
  20. 20. Potentially time-sensitive treatment <ul><li>Antibiotics therapy </li></ul><ul><li>Hemodynamic management </li></ul><ul><li>Normal tidal volume ventilation </li></ul><ul><li>Glucocoricoid and mineralocorticoid for septic shock </li></ul><ul><li>Glucose control </li></ul><ul><li>Drotrecogin alfa activated </li></ul>
  21. 21. Early goal-directed therapy <ul><li>Early goal-directed therapy (6hr goal) </li></ul><ul><ul><li>Keep CVP 8-12cmH2O </li></ul></ul><ul><ul><li>Keep MAP >65mmhg </li></ul></ul><ul><ul><li>Keep ScvO2>70% </li></ul></ul><ul><li>volume replacement ( 6-12L of crystalloid or colloid equivalent) </li></ul><ul><li>blood transfusion </li></ul><ul><li>Vasopressor : Dopamine, Dobutamine, Norepinephrone, Vasopressin, ect.. </li></ul>
  22. 22. Early goal-directed therapy
  23. 23. Comparison of Two Fluid-Management Strategies in Acute Lung Injury <ul><li>A conservative and a liberal strategy of fluid management using explicit protocols applied for seven days in 1000 patients with acute lung injury. </li></ul><ul><li>The primary end point was death at 60 days . </li></ul><ul><li>Secondary end points included the number of ventilator-free days and organ-failure–free days and measures of lung physiology . </li></ul>Comparison of Two Fluid-Management Strategies in Acute Lung ( NEJM 2006;354:2564-75..)
  24. 24. Comparison of Two Fluid-Management Strategies in Acute Lung Injury <ul><li>Although there was no significant difference in the primary outcome of 60-day mortality </li></ul><ul><li>The conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures </li></ul>Comparison of Two Fluid-Management Strategies in Acute Lung ( NEJM 2006;354:2564-75..)
  25. 25. Comparison of two fluid strategy <ul><li>Early goal-directed therapy : </li></ul><ul><ul><li>First 6 hrs of shock </li></ul></ul><ul><li>Conservative strategy of fluid replacement: </li></ul><ul><ul><li>Apply after shock recovery </li></ul></ul>
  26. 26. Vasopressor <ul><li>Low dose Dopamine : no evidence to protect kidney in sepsis or septic shock . </li></ul><ul><li>NO difference between vasopressor </li></ul><ul><li>SOAP study: dopamine administration may be associated with increased mortality rates in shock . </li></ul><ul><li>Vasopressin : reduce dose of other vasopressor, but do not suggest significant benefit in mortality. </li></ul>
  27. 27. Potentially time-sensitive treatment <ul><li>Antibiotics therapy </li></ul><ul><li>Hemodynamic management </li></ul><ul><li>Normal tidal volume ventilation </li></ul><ul><li>Glucocoricoid and mineralocorticoid for septic shock </li></ul><ul><li>Glucose control </li></ul><ul><li>Drotrecogin alfa activated </li></ul>
  28. 28. Normal tidal volume ventilation <ul><li>“ NORMAL” tidal volume ventilation is better. ( 6-12ml/kg ); May reduced to 4ml/kg to maintain plateau pressure <30 cm H2O. </li></ul><ul><li>Keep PEEP >5cm H2O , to achieve SaO2 88-95%, to lower tidal volume and FiO2 </li></ul><ul><li>Recruitment strategy: improve CXR findings and index of oxygenation, but didn’t change outcome. </li></ul>
  29. 29. 24hrs later, STOP sepsis
  30. 30. 24hrs later, STOP sepsis
  31. 31. Potentially time-sensitive treatment <ul><li>Antibiotics therapy </li></ul><ul><li>Hemodynamic management </li></ul><ul><li>Normal tidal volume ventilation </li></ul><ul><li>Glucocoricoid and mineralocorticoid for septic shock </li></ul><ul><li>Glucose control </li></ul><ul><li>Drotrecogin alfa activated </li></ul>
  32. 32. Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock <ul><li>300 adults, randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50-µg tablet once daily) (n=151) or matching placebos (n=149) for 7 days. </li></ul><ul><li>Outcome: 28 days survival distribution in patients with relative adrenal insufficiency ( nonresponders to the corticotropin test). </li></ul>Effect of Treatment With Low Doses of hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock( JAMA. 2002;288:862-871)
  33. 33. Survival of Patients With Septic Shock of non-responders Effect of Treatment With Low Doses of hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock( JAMA. 2002;288:862-871)
  34. 34. Survival of Patients With Septic Shock of all patient Effect of Treatment With Low Doses of hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock( JAMA. 2002;288:862-871)
  35. 35. Controversy and discussion <ul><li>If ATCH stimulation test is needed? </li></ul><ul><li>Cortisol level tests are not available for days </li></ul><ul><li>Free or total Cortisol level </li></ul><ul><li>Dose of steroid </li></ul>
  36. 36. Hydrocortisone Therapy for Patients with Septic Shock <ul><li>251 patients to receive 50 mg of IV hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days ; the dose was then tapered during a 6-day period. </li></ul><ul><li>At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test . </li></ul>Hydrocortisone Therapy for Patients with Septic Shock ( NEJM 2008;358:111-24.)
  37. 37. Kaplan–Meier Curves for Survival at 28 Days Hydrocortisone Therapy for Patients with Septic Shock ( NEJM 2008;358:111-24.)
  38. 38. Kaplan–Meier Curves for the Time to Reversal of Shock P = 0.06 Hydrocortisone Therapy for Patients with Septic Shock ( NEJM 2008;358:111-24.)
  39. 39. Potentially time-sensitive treatment <ul><li>Antibiotics therapy </li></ul><ul><li>Hemodynamic management </li></ul><ul><li>Normal tidal volume ventilation </li></ul><ul><li>Glucocoricoid and mineralocorticoid for septic shock </li></ul><ul><li>Glucose control </li></ul><ul><li>Drotrecogin alfa activated </li></ul>
  40. 40. Intensive insulin therapy <ul><li>Intensive insulin therapy for critical illness patients (NEJM 2001;345:1359-67) </li></ul><ul><ul><li>Intensisve insulin therapy to control blood sugar between 80-120mg/dl , reduce mortalitiy in postoperative patient. </li></ul></ul><ul><li>Intensive Insulin Therapy in the Medical ICU (NEJM 2006;354:449-61) </li></ul><ul><ul><li>Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU. </li></ul></ul><ul><ul><li>Among those who stayed in the ICU for three or more days , intensive insulin therapy reduced morbidity and mortality. </li></ul></ul>
  41. 41. Questions need discussion <ul><li>Does glycemia control improved the outcomes of septic patient? </li></ul><ul><li>What is the optimal glucose level? </li></ul><ul><li>What is the protocol to achieve maximized benefit while minimal hypoglycemia </li></ul>
  42. 42. Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis <ul><li>two-by-two factorial, open-label design </li></ul><ul><li>compared intensive insulin therapy with conventional insulin therapy and HES with Ringer’s lactate </li></ul><ul><li>Conventional-insulin-therapy: control blood glucose between 180-200 mg/dl. </li></ul><ul><li>intensive-insulin-therapy group : control blood glucose between 80-110 mg/dl. </li></ul><ul><li>Conclusion: </li></ul><ul><li>Intensive insulin therapy didn’t improved mortality but increased risk of hypoglycemia. </li></ul>Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis ( N Engl J Med 2008;358:125-39.)
  43. 43. Results Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis ( N Engl J Med 2008;358:125-39.)
  44. 44. Results Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis ( N Engl J Med 2008;358:125-39.)
  45. 45. Potentially time-sensitive treatment <ul><li>Antibiotics therapy </li></ul><ul><li>Hemodynamic management </li></ul><ul><li>Normal tidal volume ventilation </li></ul><ul><li>Glucocoricoid and mineralocorticoid for septic shock </li></ul><ul><li>Glucose control </li></ul><ul><li>Drotrecogin alfa activated </li></ul>
  46. 46. Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis ( NEJM 2001;344:699-709)
  47. 47. Drotrecogin alfa activated <ul><li>Reduced absolute mortality of patients with severe sepsis by approximately 6%. Long term (2-3 years) survival benefit is persistent. </li></ul><ul><li>Shorter time of using vasopressor and ventilator . </li></ul><ul><li>“ High-risk-of-death” group (APACHE II score >25), reduce mortality 13%. </li></ul><ul><li>“ Low-risk-of-death” group (APACHE II score <25), reduce mortality 1-2% </li></ul>
  48. 48. Drotrecogin alfa activated <ul><li>Increased the risk of ICH of 0.1-0.3% in APACHE II <25 patient) </li></ul><ul><li>Early treatment </li></ul><ul><ul><li>to receive rhAPC in 1st day and in 2nd day </li></ul></ul><ul><ul><li>Survival is better. </li></ul></ul><ul><ul><li>Time receiving ventilator in ICU is less. </li></ul></ul>
  49. 49. The STOP sepsis bundle
  50. 50. The STOP sepsis bundle
  51. 51. The STOP sepsis bundle
  52. 52. 24hrs later, STOP sepsis
  53. 53. 24hrs later, STOP sepsis
  54. 54. My Opinion <ul><li>Early-goal = early-go </li></ul><ul><ul><li>Early diagnosis and early treatment </li></ul></ul><ul><li>Adequate Antibiotics </li></ul><ul><li>Perfusion = Life </li></ul><ul><li>Personalize therapy </li></ul>
  55. 55. Thanks for your attention
  56. 56. Inflammatory Responses to Sepsis Management of Sepsis ( NEJM 2006;355:1699-713.)
  57. 57. Procoagulant Response in Sepsis Management of Sepsis ( NEJM 2006;355:1699-713.)
  58. 58. Pathways and Mediators of Sepsis Management of Sepsis ( NEJM 2006;355:1699-713.)
  59. 59. Pathways and Mediators of Sepsis Management of Sepsis ( NEJM 2006;355:1699-713.)
  60. 60. Results of Positive Randomized, Controlled Trials Management of Sepsis ( NEJM 2006;355:1699-713.)
  61. 61. Risk factor of sepsis Sepsis (AJM (2007) 120, 1012-1022)
  62. 62. Reference <ul><li>Recent Developments in the Diagnosis and Management of Severe Sepsis*(CHEST 2007; 132:1967–1976) </li></ul><ul><li>Sepsis ( The American Journal of Medicine (2007) 120, 1012-1022) </li></ul><ul><li>The STOP sepsis bundle toolkit </li></ul><ul><li>Sepsis in the 21st century: recent definitions and therapeutic advances (American Journal of Emergency Medicine (2007) 25, 564–571) </li></ul><ul><li>Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 (Crit Care Med 2008 Vol. 36, No. 1) </li></ul>
  63. 63. <ul><li>EFFICACY AND SAFETY OF RECOMBINANT HUMAN ACTIVATED PROTEIN C FOR SEVERE SEPSIS(N Engl J Med 2001;344:699-709) </li></ul><ul><li>Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death (N Engl J Med 2005;353:1332-41) </li></ul>
  64. 64. Low-Tidal-Volume Ventilation in the ARDS Low-Tidal-Volume Ventilation in the ARDS ( NEJM 2007;357:1113-20.)
  65. 65. Risk factor of sepsis Sepsis (AJM (2007) 120, 1012-1022)
  66. 66. SOAP study Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*(Crit Care Med 2006; 34:589–597)
  67. 67. SOAP study Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*(Crit Care Med 2006; 34:589–597)
  68. 68. Shock in any course Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*(Crit Care Med 2006; 34:589–597)
  69. 69. Septic shock Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*(Crit Care Med 2006; 34:589–597)
  70. 70. Comparison of Two Fluid-Management Strategies in Acute Lung Injury
  71. 71. Comparison of Two Fluid-Management Strategies in Acute Lung Injury

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