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Sepsis Sepsis Presentation Transcript

  • 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
  • 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
  • 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 
  • 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
  • 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.
  • 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.
  • 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
  • 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.
  • 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
  • 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
  • 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
  • The STOP sepsis bundle
  • The STOP sepsis bundle
  • The STOP sepsis bundle
  • 24hrs later, STOP sepsis
  • 24hrs later, STOP sepsis
  • Potentially time-sensitive treatment
    • Antibiotics therapy
    • Hemodynamic management
    • Normal tidal volume ventilation
    • Glucocoricoid and mineralocorticoid for septic shock
    • Glucose control
    • Drotrecogin alfa activated
  • 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
  • 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)
  • Potentially time-sensitive treatment
    • Antibiotics therapy
    • Hemodynamic management
    • Normal tidal volume ventilation
    • Glucocoricoid and mineralocorticoid for septic shock
    • Glucose control
    • Drotrecogin alfa activated
  • 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..
  • Early goal-directed therapy
  • 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..)
  • 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..)
  • Comparison of two fluid strategy
    • Early goal-directed therapy :
      • First 6 hrs of shock
    • Conservative strategy of fluid replacement:
      • Apply after shock recovery
  • 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.
  • Potentially time-sensitive treatment
    • Antibiotics therapy
    • Hemodynamic management
    • Normal tidal volume ventilation
    • Glucocoricoid and mineralocorticoid for septic shock
    • Glucose control
    • Drotrecogin alfa activated
  • 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.
  • 24hrs later, STOP sepsis
  • 24hrs later, STOP sepsis
  • Potentially time-sensitive treatment
    • Antibiotics therapy
    • Hemodynamic management
    • Normal tidal volume ventilation
    • Glucocoricoid and mineralocorticoid for septic shock
    • Glucose control
    • Drotrecogin alfa activated
  • 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)
  • 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)
  • 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)
  • 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
  • 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.)
  • Kaplan–Meier Curves for Survival at 28 Days Hydrocortisone Therapy for Patients with Septic Shock ( NEJM 2008;358:111-24.)
  • 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.)
  • Potentially time-sensitive treatment
    • Antibiotics therapy
    • Hemodynamic management
    • Normal tidal volume ventilation
    • Glucocoricoid and mineralocorticoid for septic shock
    • Glucose control
    • Drotrecogin alfa activated
  • 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.
  • 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
  • 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.)
  • Results Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis ( N Engl J Med 2008;358:125-39.)
  • Results Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis ( N Engl J Med 2008;358:125-39.)
  • Potentially time-sensitive treatment
    • Antibiotics therapy
    • Hemodynamic management
    • Normal tidal volume ventilation
    • Glucocoricoid and mineralocorticoid for septic shock
    • Glucose control
    • Drotrecogin alfa activated
  • Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis ( NEJM 2001;344:699-709)
  • 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%
  • 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.
  • The STOP sepsis bundle
  • The STOP sepsis bundle
  • The STOP sepsis bundle
  • 24hrs later, STOP sepsis
  • 24hrs later, STOP sepsis
  • My Opinion
    • Early-goal = early-go
      • Early diagnosis and early treatment
    • Adequate Antibiotics
    • Perfusion = Life
    • Personalize therapy
  • Thanks for your attention
  • Inflammatory Responses to Sepsis Management of Sepsis ( NEJM 2006;355:1699-713.)
  • Procoagulant Response in Sepsis Management of Sepsis ( NEJM 2006;355:1699-713.)
  • Pathways and Mediators of Sepsis Management of Sepsis ( NEJM 2006;355:1699-713.)
  • Pathways and Mediators of Sepsis Management of Sepsis ( NEJM 2006;355:1699-713.)
  • Results of Positive Randomized, Controlled Trials Management of Sepsis ( NEJM 2006;355:1699-713.)
  • Risk factor of sepsis Sepsis (AJM (2007) 120, 1012-1022)
  • 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)
    • 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)
  • Low-Tidal-Volume Ventilation in the ARDS Low-Tidal-Volume Ventilation in the ARDS ( NEJM 2007;357:1113-20.)
  • Risk factor of sepsis Sepsis (AJM (2007) 120, 1012-1022)
  • SOAP study Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*(Crit Care Med 2006; 34:589–597)
  • SOAP study Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*(Crit Care Med 2006; 34:589–597)
  • Shock in any course Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*(Crit Care Med 2006; 34:589–597)
  • Septic shock Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study*(Crit Care Med 2006; 34:589–597)
  • Comparison of Two Fluid-Management Strategies in Acute Lung Injury
  • Comparison of Two Fluid-Management Strategies in Acute Lung Injury