Sepsis

1. Sepsis Dr. Ibrahim Hadi Dr. Dalal AL-Matrouk

2. Definitions • Sepsis:proven or suspected infection, with a systemic response (fever, tachycardia, tachypnea, leukocytosis) • Severe Sepsis:sepsis, with organ dysfunction • Septic shock:severe sepsis, with hypotension despite adequate fluid resuscitation

3. 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

4. Sepsis: Defining a Disease Continuum Shock Infection/Trauma Sepsis Severe Sepsis SIRS • Sepsis with 1 sign of organ failure • Cardiovascular (refractory hypotension) • Renal • Respiratory • Hepatic • Hematologic • CNS • Metabolic acidosis

5. SEPSIS PANCREATITIS SEVERE SEPSIS SIRS BURNS INFECTION SEPTICSHOCK TRAUMA OTHER Relationship Of Infection, SIRS, Sepsis Severe Sepsis and Septic Shock

6. 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 Balk, R.A. Crit Care Clin 2000;337:52

7. Clinical Signs of Septic Shock • Hemodynamic Alterations • Hyperdynamic State (“Warm Shock”) • Tachycardia. • Elevated or normal cardiac output. • Decreased systemic vascular resistance. • Hypodynamic State (“Cold Shock”) • Low cardiac output

8. Clinical Signs of Septic Shock • Myocardial Depression. • Altered Vasculature. • Altered Organ Perfusion. • Imbalance of O2 delivery and Consumption. • Metabolic (Lactic) Acidosis.

9. Infection Endothelial Dysfunction Vasodilation Inflammatory Mediators Hypotension Microvascular Plugging Vasoconstriction Edema Maldistribution of Microvascular Blood Flow Ischemia Cell Death Organ Dysfunction

10. Therapy For Sepsis

11. Evidence-Based Sepsis Guidelines • Components: • Early Recognition, early appropriate use of antibiotics • Early Goal-Directed Therapy • Monitoring • Resuscitation • Pressor / Inotropic Support • Steroid Replacement • Source Control • Glycaemic Control • Nutritional Support • Adjuncts: Stress Ulcer Prophylaxis, DVT Prophylaxis, Transfusion, Sedation, Analgesia, Organ Replacement

12. Early Antibiotic Therapy Consensus, CCM’04 • Start abx. therapy as early as possible, after getting cultures • Broad spectrum, including one or two abx. likely effective against the suspected ICU pathogen • Re-assess coverage within 48 – 72 hrs, guided by cultures

13. Strategy For Therapy • Optimize organ perfusion • Control infection source • Support dysfunctional organ system

14. Therapeutic Strategies in Sepsis • Optimize Organ Perfusion • Expand effective blood volume. • Hemodynamic monitoring. • Early goal-directed therapy.

16. Therapeutic Strategies in Sepsis • Optimize Organ Perfusion • Pressors may be necessary. • Norepinephrine • Vasopressin • Epinephrine • Dobutamine + Norepinephrine

17. Therapeutic Strategies in Sepsis • Control Infection Source • Drainage • Surgical • Radiologically-guided • Culture-directed antimicrobial therapy • Support of reticuloendothelial system • Enteral / parenteral nutritional support • Minimize immunosuppressive therapies

18. Therapeutic Strategies in Sepsis • Support Dysfunctional Organ Systems • Renal replacement therapies (CVVHD, HD). • Cardiovascular support (pressors, inotropes). • Mechanical ventilation. • Transfusion for hematologic dysfunction. • Minimize exposure to hepatotoxic and nephrotoxic therapies.

19. Surviving Sepsis Campaign: InternationalGuidelines for Management of Severe Sepsisand Septic Shock: 2012

20. SURVIVING SEPSIS CAMPAIGN BUNDLES TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L

21. SURVIVING SEPSIS CAMPAIGN BUNDLES TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain MAP ≥ 65 mm Hg 6) In the event of persistent arterial hypotension despite volume resuscitation or initial lactate 4 mmol/L: - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of ≥8 mm Hg, ScvO2 of 70%, and normalization of lactate.

22. Initial Resuscitation and Infection Issues Goals during the first 6 hrs of resuscitation: a) Central venous pressure 8–12 mm Hg b) Mean arterial pressure (MAP) ≥ 65 mm Hg c) Urine output ≥ 0.5 mL/kg/hr d) Central venous or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C). In patients with elevated lactate levels targeting resuscitation to normalize lactate

23. Initial Resuscitation and Infection Issues Antimicrobial Therapy • 1. Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis (grade 1C) as the goal of therapy. 2. Reasses AB therapy daily for deescalation 3. PCT level or other biomarkers for discontinuation for pts who have no subsequent evidence of infection Source control Infection prevention

24. Hemodynamic Support and Adjunctive Therapy A. Fluid Therapy of Severe Sepsis : Crystalloids as the initial fluid of choice in the resuscitation (grade 1B). Against the use of hydroxyethyl starches for fluid resuscitation (grade 1B). Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C). Initial fluid challenge in patients with tissue hypoperfusion &suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids .

25. Hemodynamic Support and Adjunctive Therapy B. Vasopressors: Norepinephrine as the first choice vasopressor (grade 1B). Epinephrine (added to and substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B). Vasopressin 0.03 units/minute can be added to norepinephrine with intent of either raising MAP or decreasing NE dosage Low dose vasopressin is not recommended as the single initial vasopressor

26. B. Vasopressors Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia) (grade 2C). Low-dose dopamine should not be used for renal protection

27. B. Vasopressors Phenylephrine is not recommended in the treatment of septic shock except in circumstances where (a) norepinephrine is associated with serious arrhythmias (b) cardiac output is known to be high and blood pressure persistently low (c) as salvage therapy when combined inotrope/vasopressors have failed to achieve MAP target (grade 1C).

28. Hemodynamic Support and Adjunctive Therapy C. Inotropic Therapy: A trial of dobutamine infusion up to 20 mcg/kg/min be administered or added to vasopressor in the presence of • myocardial dysfunction • ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP (grade 1C)

29. Hemodynamic Support and Adjunctive Therapy D. Corticosteroids: Not using hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. In case this is not achievable, we suggest intravenous hydrocortisone at a dose of 200 mg per day (grade 2C). 2. Not using the ACTH stimulation test to identify adults with septic shock who should receive hydrocortisone (grade 2B). 3. hydrocortisone tapered when vasopressors are no longer required (grade 2D). 4. Corticosteroids not be administered for the treatment of sepsis in the absence of shock (grade 1D). 5. When hydrocortisone is given, use continuous flow (grade 2D).

30. Other Supportive Therapy of Severe Sepsis Blood Product Administration Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease, we recommend that red blood cell transfusion occur only when hemoglobin concentration decreases to <7.0 g/dL to target a hemoglobin concentration of 7.0 –9.0 g/dL in adults (grade 1B). Not using erythropoietin as a specific treatment of anemia associated with severe sepsis (grade 1B).

31. Blood products administrationcont’d Fresh frozen plasmanot be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (grade 2D). Administer platelets prophylactically when counts are <10,000/mm3 in the absence of apparent bleeding. We suggest prophylactic platelet transfusion when counts are < 20,000/mm3 if the patient has a significant risk of bleeding. Higher platelet counts (≥50,000/mm3 are advised for active bleeding, surgery, or invasive procedures (grade 2D).

32. Other Supportive Therapy of Severe Sepsis Immunoglobulins Not using intravenous immunoglobulins in adult patients with severe sepsis or septic shock (grade 2B). Selenium Not using intravenous selenium for the treatment of severe sepsis (grade 2C).

33. Other Supportive Therapy of Severe Sepsis Glucose Control • target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL (grade 1A). Renal Replacement Therapy 1. Continuous renal replacement therapies and intermittent hemodialysis are equivalent in patients with severe sepsis and acute renal failure (grade 2B).

34. Other Supportive Therapy of Severe Sepsis Bicarbonate Therapy Not using sodium bicarbonate for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15 (grade 2B).

35. Other Supportive Therapy of Severe Sepsis DVT Prophylaxis: LMWH (grade 1B versus twice daily UFH, grade 2C). If creatinine clearance is <30 mL/min, use dalteparin (grade 1A) or another form of LMWH that has a low degree of renal metabolism (grade 2C) or UFH (grade 1A). Combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible (grade 2C). Septic patients who have a contraindication for heparin  mechanical prophylactic treatment unless contraindicated.

36. Other Supportive Therapy of Severe Sepsis • Sedation, analgesia, MR • Mechanichal ventilator setting in ARDS • Nutrition • Stress ulcer prophylaxis

37. Thank you