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Meral SÖNMEZOĞLU, Assoc Prof Yeditepe University Hospital Infectious Diseases Department

Sepsis, Severe Sepsis & Septic Shock. Meral SÖNMEZOĞLU, Assoc Prof Yeditepe University Hospital Infectious Diseases Department. Overview. Differentiation between Septic Shock in relation to other conditions in current code, Sepsis, and Severe Sepsis

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Meral SÖNMEZOĞLU, Assoc Prof Yeditepe University Hospital Infectious Diseases Department

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  1. Sepsis, Severe Sepsis & Septic Shock Meral SÖNMEZOĞLU, Assoc Prof Yeditepe University Hospital Infectious Diseases Department 1

  2. Overview • Differentiation between Septic Shock in relation to other conditions in current code, Sepsis, and Severe Sepsis • Disease Epidemiology, Incidence and Mortality • Inadequacy of Current Diagnostic Codes • Proposed Modifications and Clarification • Discussion 2

  3. Systemic Inflammatory Response • At least 2 of 4 ( abnormal temp or leukocytes count is amust) • Coretemp>38.5 or <36 • Tachycardia: HR >2 sd above Normal for age orbradycardia <10% forage • Tachypnea: RR >2 sd for age or mechanical ventilationforacuteprocess • Leukocyte elevated or depressed for age or >10%immatureneutrophils 3

  4. Definitions • Infection: Suspected or proven caused byany pathogen Or clinical syndromeassociated with high probability of infection • Sepsis: SIRS in the presence of or as a resultof suspected of proven infection 4

  5. Definitions • Severe Sepsis: sepsis + one • Cardiovasculardysfunction • ARDS • OR 2 or more other organ dysfunctions • Septicshock • Sepsis and cardiovascular organ dysfunction 5

  6. Sepsis: Defining a Disease Continuum Infection/Trauma Sepsis Severe Sepsis SIRS SIRS with a presumed or confirmed infectious process A clinical response arising from 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 SIRS = Systemic Inflammatory Response Syndrome Adapted from: Bone RC, et al. Chest 1992;101:1644 Opal SM, et al. Crit Care Med 2000;28:S81 6

  7. 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 • Metabolic acidosis 7 Bone et al. Chest 1992;101:1644; Wheeler and Bernard. N Engl J Med 1999;340:207

  8. SEPSIS PANCREATITIS SEVERE SEPSIS SIRS BURNS INFECTION SEPTICSHOCK TRAUMA OTHER Relationship Of Infection, SIRS, Sepsis Severe Sepsis and Septic Shock 8 Bone et al. Chest 1992;101:1644

  9. Monocytic Cells Inflamatory Cascade Chemotaxis Superoxide Radicals Lysosomal Enzymes Complement Gram-negative Bacteria/Endotoxin System Neutrophil Accumulation Capillary Leak Neutrophils Adhesion Molecules Hypotension, ARDS, DIC, Multiple Organ Failure, Death Fever Metabolic Changes Cytokines Hormonal Changes* TNF-a, IL-1, IL-6, IL-8, etc. Vasodilation Lipid Mediators Nitric Oxide Clotting Abnormalities Endothelial Cells Bradykinin Tissue Factor = inhibited by rBPI in vivo or in vitro = not investigated Coagulation System * 9

  10. SEPSIS MEDIATORS 10 Russell J. N Engl J Med 2006;355:1699-1713

  11. Sepsis 400,000 7-17% Severe Sepsis 300,000 20-53% Septic Shock 53-63% Mortality Increases in Septic Shock Patients Incidence Mortality Approximately 200,000 patients including 70,000 Medicare patients have septic shock annually 11 Balk, R.A. Crit Care Clin 2000;337:52

  12. Septic Shock is Unique within 785.59 785.5 Unspecified Shock 7% 785.59 Other Shock 62% 785.59 Details 10,100 45,200 88,600 785.51 Cardiogenic Shock 31% * Represents Septic Shock Patients ICD-9-CM code 785.5X Population Septic Shock patients have a longer length of stay and a higher cost than other patients within 785.59 12

  13. Severe Sepsis: A Significant Healthcare Challenge • Major cause of morbidity and mortality worldwide • Leading cause of death in noncoronary ICU (US)* • 11th leading cause of death overall (US) †§ 1 About 1,000,000 cases of severe sepsis in US annually‡ 2 In the US, about 600-1000 patients die of severe sepsis daily 3 *Sands KE et al. JAMA. 1997;278:234-40; †Based on data for septicemia. §Murphy SL. National Vital Statistics Reports. ‡Angus DC et al. Crit Care Med. 2001 (In Press); reflects hospital-wide cases of severe sepsis as defined by infection in the presence of organ failure. www.themegallery.com

  14. Sepsis Epidemiology: Effect of the Aging Population www.themegallery.com

  15. Severe Sepsis: Comparison With Other Major Diseases Incidence of Severe Sepsis Mortality of Severe Sepsis Cases/100,000 Deaths/Year AIDS* Breast CHF† Severe Sepsis‡ Colon Severe Sepsis‡ AIDS* Breast Cancer§ AMI† Cancer§ †National Center for Health Statistics, 2001.§American Cancer Society, 2001. *American Heart Association. 2000. ‡Angus DC et al. Crit Care Med. 2001 www.themegallery.com

  16. Mortality of Sepsis over Time Proportion of Patients with Sepsis Who Died 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 www.themegallery.com

  17. Economics of Sepsis • Severe Sepsis • $22,000 per case • US annual cost $16.7Billion • Nosocomial Sepsis • increased LOS - ICU 8 days, Hosp 24 days • $40,890 per case Angus CCM, 2001 Pittet JAMA, 1994 www.themegallery.com

  18. Time Sensitive Interventions “Door to PCI”Focus on the timely return of blood flow to the affected areas of the heart.(percutanous coronary intervention) AMI “Time is Brain” The sooner that treatment begins, the better are one’s chances of survival without disability. Stroke “The Golden Hour” Requires immediate response and medical care “on the scene.” Patients typically transferred to a qualified trauma center for care. Trauma www.themegallery.com

  19. Trauma vs. Sepsis Patient CareWhere we spend our efforts www.themegallery.com

  20. Severe Sepsis vs. Current Care Priorities Source: (1) Ryan TJ, et al. ACC/AHA Guidelines for management of patients with AMI. JACC. 1996; 28: 1328-1428. (2) American Heart Association. Heart Disease and Stroke Statistics – 2005 Update. Available at: www.americanheart.org. (3) National Highway Traffic Safety Administration. Traffic Safety Facts 2003: A Compilation of Motor Vehicle Crash Data from the Fatality Analysis Reporting System and the General Estimates System. Available at http://www.nhtsa.dot.gov/. (4) Angus DC et al. Crit Care Med 2001;29(7): 1303-1310. www.themegallery.com

  21. The Surviving Sepsis Campaign 25% Reduction In Sepsis Mortality within next 5 yrs • = ~ 50,000 people in the United States each year. • = ~ 1,100,000 individuals worldwide each year. Angus DC, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Critical Care Medicine. Jul 2001;29(7):1303-1310. www.themegallery.com

  22. Cardiovascular Dysfunction • Despite administration of isotonic intravenous fluid • bolus ≥40 mL/kg in 1 hr • Hypotension: BP <5th % or <2 sd OR • Need for vasoactive drug to maintain BP (dopamine >5mcg/kg/min or dob, epi, or norepi at any dose) OR • Two of the following • Unexplained metabolic acidosis: Base deficit >5.0 mEq/L • Arterial lactate: >2 times upper limit of normal • Oliguria: Urine output <0.5 mL/kg/hr • Capillary refill: >5 secs • Core to peripheral temperature gap >3°C 22

  23. Respiratory Dysfunction • PaO2 /Fio2 <300 in absence of cyanotic heart • disease or preexisting lung disease OR • PaCo2 >65 or 20 mm Hg over baseline Paco2 OR • Need or >50% Fio2 to maintain saturation ≥92% OR • Need for non-elective invasive or non-invasive • mechanical ventilation 23

  24. Neurologic Dysfunction • Glasgow Coma Score ≤11 OR • Acute change in mental status with adecrease in Glasgow Coma Score ≥3 points from abnormal baseline 24

  25. Hematologic Dysfunction • Platelet count <80,000/mm or a decline of50% in platelet count from highest valuerecorded over the past 3 days • INR >2 25

  26. Renal Dysfunction • Serum creatinine ≥2 times upper limit of • normal for age or • 2-fold increase in baseline creatinine 26

  27. Hepatic Dysfunction • Total bilirubin ≥4 mg/dL (not applicable for • newborn) OR • ALT 2 times upper limit of normal for age 27

  28. Mortality and SIRS 28

  29. Mortality

  30. Mortality

  31. Conclusion • Septic shock has distinct characteristics that support the creation of a unique code (785.52) • Septic shock should be linked to severe sepsis • Modification of current SIRS coding will better represent the clinical presentation of the sepsis syndrome • 995.51, sepsis • Modification to “code also” list in 995.92 31

  32. Deficiencies of 1991 Consensus Conference • Limitations inherent in these definitions: • Incomplete agreement as to what defines “Systemic Response" • Inflammation only? • Organ/System failures not defined • Except hypotension (SBP <90 mmHg or >40 mmHg decline from baseline; need for vasopressor support) "Dear SIRS, I do not like you" Jean Louis Vincent

  33. 2001 Sepsis Definitions Conference • Current definitions will remain unchanged • However, will accept the uncertainty of definitions • SIRS expanded to signs and symptoms • Chills • Alteration in temperature • Tachypnea • Change in mental status • Tachycardia • Altered WBC, Bandemia • Thrombocytopenia • Decreased perfusion: mottling, poor capillary refill • Increased blood sugar • Petichiae/Purpura 33

  34. 2001 Sepsis Definitions Conference • PIRO staging system proposed • Predisposition: Genetics, Chronic illness • Insult: Infection, Injury, Ischemia • Response: Physiologic, Mediators, Markers • Organ Dysfunction: Outcome, Organ dysfunction 34 To be published 2002 (Verbal communication Mitchell Levy, SCCM 2002)

  35. Inflammatory Responses to Sepsis Russell J. N Engl J Med 2006;355:1699-1713 35

  36. Procoagulant Response in Sepsis Russell J. N Engl J Med 2006;355:1699-1713 36

  37. 37

  38. 38

  39. 39

  40. Treatment

  41. Severe Sepsis/Septic Shock Goals CVP 8 – 12 mmHg MAP 65 mmHg SBP > 90 mmHg SaO2  93% ScVO2 > 70%

  42. Sepsis Resuscitation Emergency Department and Intensive Care Unit

  43. Sepsis Resuscitation Bundle • Serum lactate measured • Blood cultures obtained prior to antibiotic administration • From the time of presentation, broad-spectrum antibiotics administered: • within 3 hours for ED admissions • within 1 hourfor non-ED ICU admissions • In the event of hypotension and/or lactate > 4 mmol/L (36 mg/dl): • Deliver an initial minimum of 20-30 ml/kg of crystalloid(or colloid equivalent) • Apply vasopressorsfor hypotension not responding to initial fluid resuscitation to maintain MAP > 65 mmHg • In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L (36 mg/dl): • Achieve central venous pressure (CVP) of > 8 mmHg • Achieve central venous oxygen saturation (ScvO2) of > 70% Information taken from Institute for Healthcare Improvement, Sepsis Module: http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/

  44. SOP

  45. Bundle Completion and OutcomeA 2-year Implementation Experience Total Patients = 330 patients from Oct 2003 – Sept 2005 Bundle Not Completed = 253; Bundle Completed = 77 Mortality (p=0.003) Hospital LOS (p=0.22) Nguyen, Ann Emerg Med, 2005 - ACEP Annual Meeting; and Crit Care Med, 2005 - Critical Care Congress www.themegallery.com

  46. Serum Lactate • Hyperlactatemia is typically present in patients with severe sepsis or septic shock and may be secondary to anaerobic metabolism due to hypoperfusion.  • The prognostic value of raised blood lactate levels has been well established in septic shock patients, particularly if the high levels persist (that’s why we trend them). • Obtaining serum lactate is essential to identifying tissue hypoperfusion in patients who are not yet hypotensive but who are at risk for septic shock. Information taken from Institute for Healthcare Improvement, Sepsis Module: http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/

  47. Blood cultures • The incidence of sepsis and bacteremia in critically ill patients has been increasing in the past two decades.   • 30 - 50% of patients presenting with a clinical syndrome of severe sepsis or shock have positive blood cultures. • Therefore, blood should be obtained for culture in any critically ill septic patient.  • Collecting blood cultures prior to antibiotic administration offers the best hope of identifying the organism that caused severe sepsis in an individual patient.  • Failure to check blood cultures prior to antibiotic infusion will perhaps affect the growth of any blood borne bacteria and prevent a culture from becoming positive later.  Information taken from Institute for Healthcare Improvement, Sepsis Module: http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/

  48. Broad Spectrum Antibiotics • The balance of evidence unwaveringly suggests that early administration of appropriate antibiotics reduces mortality in patients with Gram-positive and Gram-negative bacteremias. • Some of the evidence supporting early administration is based upon the assumption that patients who fail to receive appropriate antibiotics essentially represent a set of patients for whom delay has occurred in antibiotic delivery.  • Several studies have confirmed the mortality benefit associated with appropriate antimicrobials in patients with severe infections due to Gram-negative and Gram-positive bacteria. • All patients should receive a full loading doseof each antimicrobial. • However, patients with sepsis or septic shock often have abnormal renal or hepatic function and may have abnormal volumes of distribution due to aggressive fluid resuscitation. The ICU pharmacist should be consulted to ensure that serum concentrations are attained that maximize efficacy and minimize toxicity Information taken from Institute for Healthcare Improvement, Sepsis Module: http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/

  49. p = 0.006 p = 0.01 Antibiotics and Mortality • In addition, the major sources of infection in severe sepsis or shock are pneumonia and intra-abdominal infections and other sources generally account for < 5 percent of cases.  • The prevalence of pneumonia as a cause of sepsis lends support to the case for treating severe sepsis with early antibiotic administration.  • In a recent study of ventilator acquired pneumonia, patients with significant organ dysfunction who received antibiotics later had far greater ICU mortality: 37 percent vs. 7 percent, P=0.006; hospital mortality: 44 percent vs. 15 percent, P=0.01. Information taken from Institute for Healthcare Improvement, Sepsis Module: http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/

  50. Fluid Resuscitation • The Severe Sepsis Resuscitation Bundle calls for an initial administration of 20 – 30 ml/kg of crystalloid as a fluid challenge in cases of suspected hypovolemia or actual cases of serum lactate greater than 4 mmol/L (36 g/dl).    • A colloid equivalent is an acceptable alternative to crystalloid, and an equivalent dose generally ranges from 0.2 g/kg to 0.3 g/kg depending upon the colloid.  • Fluid resuscitation should be commenced as early as possible in the course of septic shock (even before intensive care unit admission). Requirements for fluid infusion are not easily determined so that repeated fluid challenges should be performed. • The bundle does not restrict the amount and extent of an initial fluid challenge, but rather defines a minimum challenge.  Subsequent actions in the bundle are undertaken only for hypotension not responding to fluid challenge or for an elevated lactate level as above. Information taken from Institute for Healthcare Improvement, Sepsis Module: http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/

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