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  • Hypovolemic, cardiogenic, distributive
  • RiskFactors:bacteremiaage >=65immunosuppressionDM and cancerCAPgenetic factors
  • N Engl J Med. 2003 Apr 17;348(16):1546-54.The epidemiology of sepsis in the United States from 1979 through 2000.Martin GS, Mannino DM, Eaton S, Moss M.We analyzed the occurrence of sepsis from 1979 through 2000 using a nationally representative sample of all nonfederal acute care hospitals in the United States. Data on new cases were obtained from hospital discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification.
  • Long-term survival after intensive care unit admission with sepsis.Sasse KC, Nauenberg E, Long A, Anton B, Tucker HJ, Hu TWCrit Care Med. 1995;23(6):1040.All patients admitted to the ICU from January 1, 1987 to March 31, 1991 who both demonstrated clinical evidence of the systemic inflammatory response syndrome and yielded blood cultures positive for a bacterium or fungus (n = 153). Follow-up evaluation utilizing the National Death Index provided survival outcome for all patients 1 yr after hospital discharge. The mortality rate at hospital discharge was 51.0%, and mortality rates at 1 month, 6 months, and 1 yr after admission date were 40.5%, 64.7%, and 71.9%, 
  • Long-term survival after intensive care unit admission with sepsis.Sasse KC, Nauenberg E, Long A, Anton B, Tucker HJ, Hu TWCrit Care Med. 1995;23(6):1040.All patients admitted to the ICU from January 1, 1987 to March 31, 1991 who both demonstrated clinical evidence of the systemic inflammatory response syndrome and yielded blood cultures positive for a bacterium or fungus (n = 153). Follow-up evaluation utilizing the National Death Index provided survival outcome for all patients 1 yr after hospital discharge. The mortality rate at hospital discharge was 51.0%, and mortality rates at 1 month, 6 months, and 1 yr after admission date were 40.5%, 64.7%, and 71.9%, 
  • PRO: stimulate PMNs, macrophages and endothelial cells to release a number of downstream inflammatory mediators, including platelet activating factor and nitric oxide (NO), further amplifying the inflammatory responseANTI:
  • Hypotension due to diffuse vasodilation unintended consequence of the release of vasoactive mediators, whose purpose is to improve metabolic autoregulation (the process that matches oxygen availability to changing tissue oxygen needs) by inducing appropriate vasodilation. Mediators include the vasodilators prostacyclin and nitric oxide (NO), which are produced by endothelial cells.
  • Blood samples were taken from 11 healthy volunteers, nine ventilated intensive care unit (ICU) control patients without sepsis, eight patients with sepsis but without shock, and 15 patients with septic shock. Circulating endothelial cells were identified by indirect immunofluorescence, using antibodies to von Willebrand factor (vWf). Distributive shock, capillary leak
  • NOT myocardial hypoperfusion/hypoxia
  • Also feedsback to microcirculatory hypoperfusion
  • n=263 with severe sepsis or septic shockurban ED randomized to early goal-directed therapy v. standard therapy x 6 hrs --> then to ICUICU team blinded in-hospital morality 30.5% v. 46.5% (p=0.009)central venous sat 70.4% v. 65.3% (p<0.001)
  • Usual care group = target CVP 8-12, MAP>65, UOP>0.5mL/kg/hr  ICU ASAPEarly goal-directed = protocol x 6 hoursAll rec’d: a-line, central lineEarly goal-directed group: constant central venous sat monitoring CVP 500cc PRN until 8-12 arterial sBP if95 start vasodilators central venous sat  if 30% if still <70% start dobutamine @ 2.5ug/kg/min and uptitrate until 20 if HD optimization could not achieved, mechanical ventilation + sedatives to decr O2 demand
  • During initial 6 hours: no difference in HR, CVPMAP lower in standard therapy group, although everyone MAP>65Central venous sat met by 60% in standard therapy v. 95% in early-goal directed group & lower avg valuesimilar lactate and pH valuesHours 7-72:HR higher and MAP lower in standard therapy group similar CVPsLower central venous sat, higher lactate, greater base deficit, lower pH in standard group

Transcript

  • 1. SEPSIS Stephanie Tang
  • 2. Page #1:  10:40pm: “Patient Chen spiked fever to 38.7oC. Other vitals are BP 100/60, HR 110, RR 20, SaO2 95% on RA”
  • 3. Fever  work up should include (at least) the following:  blood cultures  at least two with one being peripheral  if pt has central access, must culture each port  UA and urine culture  CXR  a careful exam
  • 4. Page #2  12:15am: “Patient Peterson spiked fever to 38.7oC. Other vitals are BP 92/55, HR 120, RR 24, SaO2 95% on RA”
  • 5. SIRS sepsis severe sepsis septic shock multiple organ dysfunction syndrome (MODS)
  • 6. Systemic Inflammatory Response Syndrome (SIRS)  T >38.3oC OR T <36oC  HR >90/min  RR >20/min OR PaCO2 <32mmHg  WBC >12,000 OR <4,000 OR >10% immature forms American College of Chest Physicians & Society of Critical Care Medicine 1991
  • 7. Systemic Inflammatory Response Syndrome (SIRS)  dysregulated inflammatory response to an insult  autoimmune disorder  pancreatitis  vasculitis  thromboembolism  burns  surgery
  • 8. Sepsis  SIRS + source of infection (probable or documented source)
  • 9. Severe Sepsis  sepsis + evidence of hypoperfusion  oliguria or acute renal failure  encephalopathy  coagulopathy  acute respiratory failure  ischemic hepatopathy  skin mottling  elevated lactate  low central venous saturation
  • 10. Septic Shock  severe sepsis refractory to fluid resuscitation of 30mL/kg - ex. 70 kg  2.1 L of IVF  distributive shock
  • 11. Why Do We Care about Sepsis?  1,665,000 cases in the United States each year Chest. 2011;140(5):1223-1231
  • 12. In-hospital mortality N Engl J Med. 2003;348(16):1546
  • 13. Long term Mortality Crit Care Med. 1995 Jun;23(6):1040-7.
  • 14. Long term Mortality Crit Care Med. 1995 Jun;23(6):1040-7.
  • 15. WHAT HAPPENS?
  • 16. Normally… proinflammatory mediators TNFα, IL-1 anti-inflammatory mediators IL-10, transforming growth factor β, IL-1 receptor antagonist
  • 17. Sepsis  occurs these responses to an infection exceeds the boundaries of the local environment, leading to a more generalized response
  • 18. Mitochondrial Dysfunction  Peripheral blood monocytes in sepsis  Assay membrane potential at admission, 3 days and at hospital discharge Christophe et al. Am. J. Respir. Crit. Care Med 2001 164: 389-395
  • 19. Circulatory Failure ↑ nitric oxide ↑ prostacyclin (improve metabolic autoregulation) hypotension (high CO, low SVR state)
  • 20. Endothelial Damage Mutunga et al. Am. J. Respir. Crit. Care Med., Volume 163, 2001, 195-200
  • 21. Myocardial Dysfunction  circulating depressant factors Parrillo. J Clin Invest. 1985;76:1539–1553
  • 22. Myocardial Dysfunction  reduced ventricular function  even in setting of elevated CO  reversible (usually 7-10 days) Kumar et al J Exp Med 1996;183:949-953 TNF IL-1
  • 23. Coagulopathy  Endothelial expression of Tissue Factor  Decreased endothelial expression of thrombomodulin Marshall Nature Rev Drug Disc 2003;2-391-405.
  • 24. Coagulopathy of Sepsis  In-situ thrombosis  Skin biopsy in meningococcal sepsis Faust et al.N Engl J Med 345 (6): 408, August 9, 2001
  • 25. In Summary… Riedemann et al, Novel strategies for the treatment of sepsis, Nat Med, 9(5):517-524
  • 26. TREATMENT OF SEVERE SEPSIS
  • 27. Monitoring  close monitoring of heart rate and blood pressure  foley (to monitor urine output)  frequent clinical reassessments
  • 28. Goals fluid resuscitation stabilize breathing source control SEPSIS
  • 29. Resuscitation  Fluids should be bolused  Large bore IVs are best  22g IV = max 35 ml/minute  20g IV = max 60 ml/min  18g IV = max 105 ml/min  16g IV = max 205 ml/min  14g IV = max 333 ml/min rate ∞ length radius4
  • 30. Resuscitation  crystalloid  lactated ringers  normal saline  nongap (hyperchloremic) acidosis  hypokalemia  colloid  blood  albumin 130 109 154 154 4 + lactate 28 HCO3 (by liver)
  • 31. Respiratory Status oxygenation ventilation airway
  • 32. Respiratory Status oxygenation pulmonary edema ARDS ventilation airway
  • 33. Respiratory Status oxygenation ventilation primary respiratory alkalosis ↑ work of breathing ↔ ↑ O2 consumption airway
  • 34. Respiratory Status oxygenation ventilation airway altered mental status
  • 35. Source Control  appropriate antibiotic coverage  abscesses or closed space infections  ascending cholangitis  obstructive pyelonephropathy
  • 36. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson, Ph.D., Michael Tomlanovich, M.D., for the Early Goal-Directed Therapy Collaborative Group N Engl J Med 2001;345: 1368-1377
  • 37. Early Goal-Directed Therapy  Rationale: early hemodynamic assessment (physical findings, vital signs, CVP, UOP) fail to detect persistent global tissue hypoxia  Goal: resuscitation strategy targeted to optimize cardiac preload, afterload, and contractility to achieve balance between systemic oxygen delivery and oxygen demand  Endpoints: mixed venous O2 sat, arterial lactate, base deficit, pH
  • 38. Early Goal-Directed Therapy  n = 263  In ED: SIRS + sBP< 90 or lactate >4  after 30cc/kg fluid bolus  Randomized to: usual care vs. early goal-directed therapy protocol
  • 39. In-hospital mortality  Mortality: 30.5% vs. 46.5% (p=0.009)  ARR 16%, NNT 6.3  Larger initial fluid resuscitation in EGDT arm  4.9L vs. 3.5L (p<0.001)
  • 40. Lessons from EGDT  up front aggressive monitoring for hypoperfusion is critical  early aggressive IVF is beneficial  clinical markers are important but we need to also track markers for occult hypoperfusion (mixed venous sat, lactate)