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Sepsis

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