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Septic Shock: The Intensivist Approach

Septic Shock: The Intensivist Approach. Suneel Kumar MD. “Except on few occasions, the patient appears to die from the body's response to infection rather than from it.” Sir William Osler – 1904 The Evolution of Modern Medicine. Sepsis. Major cause of morbidity and mortality worldwide

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Septic Shock: The Intensivist Approach

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  1. Septic Shock:The Intensivist Approach Suneel Kumar MD

  2. “Except on few occasions, the patient appears to die from the body's response to infection rather than from it.” Sir William Osler – 1904 The Evolution of Modern Medicine

  3. Sepsis • Major cause of morbidity and mortality worldwide • Second leading cause of death in noncoronary ICUs† • 10th leading cause of death overall‡ † Parrillo et al. Ann Int Med 1990;113:227-42 ‡ National Center for Health Statistics 2001;49(8)

  4. Future 1,800,000 600,000 Severe Sepsis Cases 1,600,000 US Population 500,000 >750,000 cases of severe sepsis/year in the US* 1,400,000 1,200,000 400,000 Total US Population/1,000 1,000,000 Sepsis Cases 300,000 800,000 200,000 600,000 400,000 100,000 200,000 2001 2025 2050 Year Severe Sepsis:A Growing Healthcare Challenge Today *Angus DC. Crit Care Med 2001;29:1303-10

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

  6. Martin et al. NEJM 2003;348:1546-54

  7. Martin et al. NEJM 2003;348:1546-54

  8. Martin et al. NEJM 2003;348:1546-54

  9. Martin et al. NEJM 2003;348:1546-54

  10. Sepsis: A Complex Disease • This Venn diagram provides a conceptual framework to view the relationships between various components of sepsis • The inflammatory changes of sepsis are tightly linked to disturbed hemostasis Adapted from: Bone RC et al. Chest 1992;101:1644-55 Opal SM et al. Crit Care Med 2000;28:S81-2

  11. 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 • Recent evidence indicates that hemostatic changes are also involved Adapted from: Bone RC et al. Chest 1992;101:1644-55 Opal SM et al. Crit Care Med 2000;28:S81-2

  12. Sepsis • Sepsis: • Known or suspected infection • Two or more SIRS criteria • A significant link to disordered hemostasis Adapted from: Bone RC et al. Chest 1992;101:1644-55

  13. Severe Sepsis • Severe Sepsis: Sepsis with signs of organ dysfunction in 1 of the following systems: • Cardiovascular • Renal • Respiratory • Hepatic • Hemostasis • CNS • Unexplained metabolic acidosis Adapted from: Bone RC et al. Chest 1992;101:1644-55

  14. Acute Organ Dysfunction Altered Consciousness Confusion Psychosis Tachycardia Hypotension  CVP  PAOP Tachypnea PaO2 <70 mm Hg SaO2 <90% PaO2/FiO2300 Oliguria Anuria  Creatinine  Platelets  PT/APTT  Protein C  D-dimer Jaundice  Enzymes  Albumin  PT Balk. Crit Care Clin 2000;16:337-52

  15. Crit Care Med 2004;32:858-73 www.NISE.cc

  16. Initial Resuscitation • Fluid resuscitation as soon as sepsis suspected • Should not wait until ICU admission • Elevated lactate identifies tissue hypoperfusion in at-risk patients who are not hypotensive Rivers et al. NEJM 2001;345:1368-77

  17. Fluid Resuscitation Goals • CVP 8 to 12 mmHg • MAP  65 mmHg • Urine output  0.5 cc/kg/hr • Central venous or mixed venous oxygen saturation  70%

  18. Initial Resuscitation • During the first 6 hours, if the SvO2 < 70% despite CVP 8-12 mmHg, then consider transfusion of PRBC and/or dobutamine (to max 20 mcg/kg/min) to achieve goal

  19. Rivers et al. NEJM 2001;345:1368-77

  20. Rivers et al. NEJM 2001;345:1368-77

  21. Sublingual Microcirculation • Healthy volunteer • BP 120/80 • SaO2 98%

  22. www.opsimaging.net

  23. Sublingual Microcirculation • Patient with septic shock • Resuscitated with: • Colloids and crystalloids • Lowest dose of dopamine needed • To following goals: • MAP > 60 mmHg • CVP > 12 mmHg

  24. Sublingual Microcirculation • At time of video capture: • HR 82 • BP 90/35 • SaO2 98% • CVP 25 mmHg

  25. www.opsimaging.net

  26. Diagnosis • Obtain blood cultures, then antibiotics according to immune status and most likely source of infection • Diagnostic tests if warranted

  27. Source Control • Drainage • Debridement • Device removal • Definitive control

  28. Fluids • Natural or artificial crystalloids or colloids • No evidence to use one over the other • Fluid challenge with 500-1000 cc crystalloids or 300-500 cc colloids over 30 minutes • Repeat as needed

  29. p = 0.96 SAFE Study Investigators. NEJM 2004;350:2247-56

  30. SAFE Study Investigators. NEJM 2004;350:2247-56

  31. Vasopressors • When fluid resuscitation is inadequate, vasopressors may be needed • Initial pressors used are dopamine and norepinephrine

  32. Vasopressors • Dopamine causes an increase in MAP and CO (by increasing HR and SV) • Norepinephrine increases MAP via vasoconstriction, and has little change in HR and milder increase in SV • Norepinephrine is more potent than dopamine

  33. Vasopressors • “Renal dose” dopamine not recommended • Not been proven to change peak serum creatinine, need for dialysis, urine output, time to recovery of renal function, or survival Bellomo et al. Lancet 2000;356:2139-43 Kellem et al. Crit Care Med 2001;29:1526-31

  34. Vasopressors • Vasopressin can be considered for refractory shock despite adequate fluid resuscitation and high-dose conventional pressors • Given in range of 0.01-0.04 U/min • Works by direct vasoconstriction

  35. Vasopressors • Vasopressin may diminish SV; no inotropic or chronotropic effects • Use vasopressin in caution with those with low CO (CI < 2-2.5 L/min/m2) • Higher doses have been associated with myocardial ischemia

  36. Vasopressors • Vasopressin levels initially high early in septic shock, but then fall to normal levels in 24-48 hrs • Possible “relative vasopressin deficiency” Sharshar et al. Crit Care Med 2003;31:1752-58

  37. Vasopressors • Epinephrine may cause tachycardia and possibly reduce splanchnic blood flow • Phenylephrine may cause a reduction in stroke volume

  38. Inotropes • In those with low CO despite fluid resuscitation, dobutamine may be needed • May cause a fall in BP, so often add vasopressor • Goal is to achieve adequate levels of O2 delivery and avoid flow-dependent tissue hypoxia

  39. Oxygen Delivery • Oxygen Content (CaO2): • CaO2 = (amount carried by Hb) + (amount dissolved in plasma) • CaO2 = (1.3 x Hb x SaO2) + (0.003 x PaO2) • Oxygen Delivery (DO2): • DO2 = CI x CaO2

  40. Inotropes • Strategy to increase CI to achieve an arbitrarily preferred elevated level not recommended • Not shown benefit in two large prospective studies* Gattinoni et al. NEJM 1995;333:1025-32 Hayes et al. NEJM 1994;330:1717-22

  41. Corticosteroids • IV corticosteroids (hydrocortisone 200-300 mg/d) for 7 days recommended in patients with septic shock who, despite adequate fluid replacement, require pressors to maintain adequate BP • Decreased mortality in patients with relative adrenal insufficiency* Annane et al. JAMA 2002;288:862-71 Briegel et al. Crit Care Med 1999;27:723-32 Bollaert et al. Crit Care Med 1998;26:645-50

  42. Corticosteroids • ACTH 250 mcg given, and cortisol levels checked at baseline, 30 and 60 minutes • < 9 mcg/dl rise is considered a nonresponder • Start empiric stress-dose steroids until results received • Dexamethasone does not affect cortisol assay

  43. Corticosteroids • Responders to ACTH shown to predict survival in septic shock* • Stress dose steroids in nonresponders improved survival • Steroids ineffective in responders† *Annane et al. JAMA 2000;283:1038-45 †Annane et al. JAMA 2002;288:862-71

  44. Responders Responders with low baseline cortisol Annane et al. JAMA 2000;283:1038-45

  45. Steroids Annane et al. JAMA 2002;288:862-71

  46. Corticosteroids • Doses of hydrocortisone > 300 mg/d is not more effective, and may be harmful in septic shock* • In absence of septic shock, steroids should not be used for treatment of sepsis Bone et al. NEJM 1987;317:653-58 Cronin et al. Crit Care Med 1995;23:1430-39 VA Systemic Sepsis Cooperative Study Group. NEJM 1987;317:659-65

  47. Corticosteroids • No contraindications for stress dose steroids for those on chronic steroid use

  48. Activated Protein C • Recombinant human activated protein C (drotrecogin alpha, Xigris) recommended in patients with high risk of death • These include APACHE  25, sepsis-induced multiorgan failure, septic shock, or sepsis-induced ARDS Bernard et al. NEJM 2001;344:699-709

  49. National Initiative in Sepsis Education (NISE)

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