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SIRS, Sepsis, and MODS

SIRS, Sepsis, and MODS. Claudio Martin, MSc, MD. Objectives. To know definitions of SIRS, sepsis, septic shock, MODS To become familiar with the epidemiology of sepsis To learn basic pathophysiology (inflammation, cardiovascular physiology) of SIRS and sepsis But first , a real case:.

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SIRS, Sepsis, and MODS

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  1. SIRS, Sepsis, and MODS Claudio Martin, MSc, MD

  2. Objectives • To know definitions of SIRS, sepsis, septic shock, MODS • To become familiar with the epidemiology of sepsis • To learn basic pathophysiology (inflammation, cardiovascular physiology) of SIRS and sepsis But first, a real case:

  3. Case presentation • 43-year-old male • Flu-like symptoms for 1 day • In ER • Temp 39.5 • Pulse 130 • Blood pressure 70/30 • Respirations 32 • Petechial rash • Chest, CV, Abdominal exam normal

  4. Case presentation - 2 • Laboratory • pH 7.29, PaO2 82, PaCO2 29 • Investigations pending • Blood, urine cultures • Orally intubated and placed on mechanical ventilation • Central venous catheter inserted • Cefotaxime 2 g iv • Normal saline 2 litres initially, repeated • Admitted to ICU

  5. Case presentation - 3 • In ICU: • Noradrenaline started to support blood pressure • Additional fluid (saline and pentastarch) given based on low CVP • Pulmonary artery catheter inserted to aid further hemodynamic management • Despite therapy patient remained anuric • Continuous venovenous hemofiltration initiated

  6. Case presentation - 4 • Early gram stain on blood revealed gram negative rods • Patient started on: • Hydrocortisone 100 mg iv q8h • Recombinant activated protein C 24g/kg/hour for 96 hours • Enrolled in RCT (double-blind) of vasopressin vs norepinephrine for BP support • Enteral nutrition via nasojejunal feeding tube • Prophylaxis for stress ulcers, deep venous thromboses

  7. Case Presentation - Resolution • Patient gradually stabilized and improved with complete resolution of organ dysfunction over 5 days • Final cultures confirmed diagnosis as meningococcemia

  8. Infection: Part of a bigger picture • Infection: • Presence of organisms in a closed space or location where not normally found Infection Adapted from: Bone RC et al. Chest. 1992;101:1644-55. Opal SM et al. Crit Care Med. 2000;28:S81-2.

  9. SIRS: Systemic Inflammatory Response Syndrome • SIRS: A clinical response arising from a nonspecific insult manifested by 2 of the following: • Temperature 38°C or 36°C • HR 90 beats/min • Respirations 20/min • WBC count 12,000/mL or 4,000/mL or >10% immature neutrophils Adapted from: Bone RC et al. Chest. 1992;101:1644-55. Opal SM et al. Crit Care Med. 2000;28:S81-2.

  10. Sepsis: More Than Just Inflammation • Sepsis: • Known or suspected infection • SIRS criteria Adapted from: Bone RC et al. Chest. 1992;101:1644-55.

  11. Severe Sepsis: Acute Organ Dysfunction • Severe Sepsis = Sepsis with signs of acute organ dysfunction in any of the following systems: • Cardiovascular (septic shock) • Renal • Respiratory • Hepatic • Hemostasis • CNS • Unexplained metabolic acidosis Adapted from: Bone RC et al. Chest. 1992;101:1644-55.

  12. Sepsis: A Complex Disease Adapted from: Bone RC et al. Chest. 1992;101:1644-55. Opal SM et al. Crit Care Med. 2000;28:S81-2.

  13. Jargon 2002: PIRO Predisposition Insult Response Infection Physiologic Inflammation Biochemical Severe Sepsis Specific Organ Severity Organ Dysfunction

  14. Predisposition • Pre-existing disease • Cardiac, Pulmonary, Renal • HIV • Age (extremes of age) • Gender (males) • Genetics • TNF polymorphisms (TNF promoter high secretor genotype)

  15. Physiology Heart rate Respiration Fever Blood pressure Cardiac output WBC Hyperglycemia Markers of Inflammation TNF IL-1 IL-6 Procalcitonin PAF Response

  16. Lungs Kidneys CVS CNS PNS Coagulation GI Liver Endocrine Skeletal Muscle Adult Respiratory Distress Syndrome Acute Tubular Necrosis Shock Metabolic encephalopathy Critical Illness Polyneuropathy Disseminated Intravascular Coagulopathy Gastroparesis and ileus Cholestasis Adrenal insufficiency Rhabdomyolysis Organ Dysfunction • Specific therapy exists

  17. Magnitude of the Problem • Estimated 215,000 deaths from US 1995 data • High cost for management (ICU care, diagnostic testing, drugs) • Estimated 20 day LOS; $22,000 cost • Represents 9.3% of all deaths • Equals deaths after acute myocardial infarction

  18. A clinical response arisingfrom a nonspecific insult, including 2 of the following: Temperature ≥38oC or ≤36oC HR ≥90 beats/min Respirations ≥20/min WBC count ≥12,000/mm3or≤4,000/mm3 or >10% immature neutrophils Sepsis: Defining a Disease Continuum Infection/Trauma Sepsis Severe Sepsis SIRS SIRS with a presumed or confirmed infectious process SIRS = systemic inflammatory response syndrome. Bone et al. Chest. 1992;101:1644.

  19. Shock Sepsis: Defining a Disease Continuum Infection/Trauma Sepsis Severe Sepsis SIRS • Sepsis with ≥1 sign of organ failure • Cardiovascular (refractory hypotension) • Renal • Respiratory • Hepatic • Hematologic • CNS • Unexplained metabolic acidosis Bone et al. Chest. 1992;101:1644; Wheeler and Bernard. N Engl J Med. 1999;340:207.

  20. Epidemiology of SepsisThe International Cohort Study Septic Shock Severe Sepsis Sepsis Infection Percent of cases within each category 8353 patients with LOS > 24h 4277 infections (2696 on admission) Alberti, Int Care Med 2002

  21. Sources of SepsisThe International Cohort Study Severe Sepsis Septic Shock

  22. Microbiology of SepsisThe International Cohort Study Severe Sepsis Septic Shock

  23. Preoperative Illness Trauma or Operation Tissue Injury optimal oxygen delivery and support Excessive Inflammatory Response Inadequate Resuscitation Recovery SIRS/MODS Pathogenesis of SIRS/MODS

  24. Initiation of Inflammatory Response From Wheeler & Bernard, NEJM 1999

  25. Homeostasis Is Unbalanced in Severe Sepsis Carvalho AC, Freeman NJ. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock. 1996;5:223-8; Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44.

  26. Coagulation and Fibrinolysis Bernard, GR. NEJM 2001;344;10:699-709

  27. Preoperative Illness Trauma or Operation Tissue Injury optimal oxygen delivery and support Excessive Inflammatory Response Inadequate Resuscitation Recovery SIRS/MODS Pathogenesis of SIRS/MODS

  28. Cardiac Output regional distribution regional distribution Intra Organ Distribution Intra Organ Distribution Microcirculation Microcirculation Regulation of oxygen delivery Normal Abnormal Cardiac output BP=CO * SVR QO2 = Flow * O2 content

  29. Oxygen Delivery • Delivery:Demand mismatch • Diffusion limitation (edema)

  30. Cytc H+ H+ H+ H+ III I Q IV NADH+H+ H2O 1/2 O2+H+ H+ NAD+ ADP + Pi ATP Oxygen Consumption • Pyruvate Dehydrogenase (PDH) activity decreased • Decreased delivery of Acetyl CoA to TCA cycle • Mitochondrial dysfunction

  31. Severe Sepsis: The Final Common Pathway Endothelial Dysfunction and Microvascular Thrombosis Hypoperfusion/Ischemia Acute Organ Dysfunction (Severe Sepsis) Death

  32. Severe Sepsis: Management of Our Case rhAPC Corticosteroids Endothelial Dysfunction and Microvascular Thrombosis Fluids Vasopressors Hypoperfusion/Ischemia CVVHF Enteral nutrition Acute Organ Dysfunction (Severe Sepsis) Survival Death

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