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New definition of sepsis... sepsis 3
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Sepsis 2016

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this slide highlights current concept of sepsis definition, organ involvement and management.

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Sepsis 2016

  1. 1. Sepsis- overview and management 2016 DR SUBHANKAR CHATTERJEE
  2. 2. Mortality Sepsis: 30% - 50% Septic Shock: 50% - 60% Why we are spending time on sepsis?
  3. 3. Why we are spending time on sepsis? 0 50000 100000 150000 200000 250000 AIDS Breast Cancer AMI SEPSIS Mortality 0 50 100 150 200 250 300 AIDS Breast Cancer 1st MI sepsis Incidence Cases/100,000 Deaths/Year
  4. 4. The third International Consensus 2016 Definition for Sepsis ( Sepsis 3) SEPSIS IS A  LIFE THREATENING  ORGAN DYSFUNCTION  CAUSED BY A DYSREGULATED HOST RESPONSE  TO INFECTION
  5. 5. Epidemiology Martin, G. S., Mannino, D. M., Eaton, S., & Moss, M. (2003). The epidemiology of sepsis in the United States from 1979 through 2000. New England Journal of Medicine, 348(16), 1546–1554. Harrison, D. A., Welch, C. A., & Eddleston, J. M. (2006). The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database. Critical Care, 10(2), R42. Brun-Buisson, C., Meshaka, P., Pinton, P., Vallet, B., EPISEPSIS Study Group. (2004). EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Medicine, 30(4), 580–588. [1993 - 2001]...a 17% reduction in mortality. [1993-2001]...a 75% increase in... severe sepsis... Incidence of Sepsis Mortality of Sepsis
  6. 6. Why the burden of sepsis increasing?  Increased geriatric population  Increasing number of immunocompromised host  Increasing drug resistant organism  Increasing metabolic disorder
  7. 7.  either Bacteraemia (or viraemia/fungaemia/protozoan) is the presence of bacteria within the bloodstream Septic focus (abscess / cavity / tissue mass) Infection
  9. 9. Dysregulated host response leads to..
  10. 10. Immune system Vs. mortality
  11. 11. How to suspect sepsis?
  12. 12. Suspect sepsis…
  13. 13. Altered mental status Edema or increased fluid balance Hyperglycemia (absent diabetes) Hypoglyemia Increased CRP or procalcitonin Hypotension Increased SvO2 CI > 3.5 L/min/m2 Arterial hypoxemia (PaO2/FiO2 < 300) Acute oliguria (> 2 hours) Increased serum Cr (> 0.5 mg/dL) Coagulopathy (INR > 1.5) Ileus (absent bowel sounds) Thrombocytopenia (< 100,000/uL) Hyperbilirubinemia (> 40 mg/dL or 70 mmol/L) Hyperlactatemia (> 1 mmol/L) Decreased capillary refill or mottling Levy MM, et al. Crit Care Med. 2003. How to recognize organ dysfunction?
  14. 14. Change in international guideline Sepsis 2  Sepsis = SIRS + Infection  Infection sepsis severe sepsis septic shock MODS Sepsis 3  Sepsis= infection + >2 SOFA score from baseline  NO Severe sepsis
  15. 15. SIRS to SOFA
  16. 16. Organ failure in sepsis Vincent, J.-L., Sakr, Y., Sprung, C. L., Ranieri, V. M., Reinhart, K., Gerlach, H., Moreno, R., et al. (2006). Sepsis in European intensive care units: results of the SOAP study. Critical Care Medicine, 34(2), 344–353. P/F Platelets Bili BP GCS Cr/UOP
  18. 18. Sequential Organ Failure Assessment (SOFA) ► Previously known as Sepsis-related Organ Failure Assessment because it was initially developed in 1994 to describe the degree of organ dysfunction associated with sepsis in a mixed, medical-surgical ICU patients. ► Nowadays, it has since been validated to describe the degree of organ dysfunction in various ICU patient groups with organ dysfunctions not due to sepsis. ► The SOFA score involves six organ systems (respiratory, cardiovascular, renal, hepatic, central nervous, coagulation), and the function of each is scored from 0 (normal function) to 4 (most abnormal), giving a possible score of 0 to 24.
  19. 19. Sequential Organ Failure Assessment (SOFA) ► Mortality rate increases as number of organs with dysfunction increases. ► Unlike other scores, the worst value on each day is recorded. ► A key difference is in the cardiovascular component; instead of the composite variable, the SOFA score uses a treatment-related variable (dose of vasopressor agents).
  20. 20. Sequential Organ Failure Assessment (SOFA) ► Maximal (highest total) SOFA score: is the sum of highest scores per individual during the entire ICU stay. A score of >15 predicted mortality of 90%. ► Mean SOFA score (ΔSOFA): is the average of all total SOFA scores in the entire ICU stay. ΔSOFA for 1st 10 days is significantly higher in non-survivors. ► Delta SOFA score: maximum SOFA – admission SOFA Crit Care Med 1998;26:1793-1800
  21. 21. Sequential Organ Failure Assessment
  22. 22. qSOFA for Non ICU patients with Infection – early recognition of severity
  23. 23. SEPTIC SHOCK  Septic shock is a subset of sepsis in which profound circulatory, cellular and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone
  25. 25. Basal lactate production Muscle Brain RBC WBC Platelets Renal medulla Gut mucosa Skin 0.13 mmol/ kg/hr 0.14 mmol/ kg/hr 0.18 mmol/ kg/hr 0.11 mmol/kg/hr 0.11 mmol/ kg/hr Total = 1290 mmol / 24 hours for 70 kg
  26. 26. Hyperlactataemia (> 2mmol/L)
  27. 27. How is lactate produced? If pyruvate production > oxidation in CAC then lactate formation increases PDH
  28. 28.  Hypoxia blocks oxidative phosphorylation  prevents NADH re-oxidation to NAD  increases the NADH/NAD ratio  increases the lactate/pyruvate ratio  Normal ratio around 10:1 Cardiogenic shock L/P ratio 40:1 Consistent with hypoxia Resuscitated septic shock L/P ratio 14:1 Not consistent with hypoxia
  29. 29. When lactate hypoperfusion Cardiogenic shock Hemorrhagic shock Septic shock if Catecholamine resistant + depressed Cardiac Index Unresuscitated (see Rivers)
  30. 30. Prognostic value  Source doesn’t matter  High lactate still a marker of severe physiological stress and risk of death  High lactate often not hypoxia related but represents metabolic changes of severe stress
  32. 32. System-based Approaches to sepsis Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19), 1368–1377.
  33. 33. System-based Approaches to sepsis Early-Goal Directed Therapy INCLUSION = SEPSIS AND [BP < 90 after fluid OR Lactate > 4] CVP 8-12 Fluids CVP 8-12 MAP > 65 Vasopressors MAP > 65 Transfusions Dobutamine ScvO2 > 70% 49% mortality 33% mortality Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19), 1368–1377. Control Intervention EGDT
  34. 34. System-based Approaches to sepsis Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19), 1368–1377. Used to promote: 1. CVP > 8 as an initial target 2. Use of Svo2 monitoring and use of blood/dobutamine
  35. 35. A Multidisciplinary Community Hospital Program for Early and Rapid Resuscitation of Shock in Non-trauma Patients Sebat, F., Johnson, D., Musthafa, A. A., Watnik, M., Moore, S., Henry, K., & Saari, M. (2005). A multidisciplinary community hospital program for early and rapid resuscitation of shock in nontrauma patients. Chest, 127(5), 1729–1743.
  36. 36. A Multidisciplinary Community Hospital Program for Early and Rapid Resuscitation of Shock in Non-trauma Patients Sebat, F., Johnson, D., Musthafa, A. A., Watnik, M., Moore, S., Henry, K., & Saari, M. (2005). A multidisciplinary community hospital program for early and rapid resuscitation of shock in nontrauma patients. Chest, 127(5), 1729–1743.
  37. 37. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock Control EGDT Relative Risk (95% Confidence Interval) P In-Hospital 46.5 30.5 0.58 (0.38-0.87) 0.009 28-day Mortality 49.2 33.3 0.58 (0.39 – 0.87) 0.01 60-day Mortality 56.9 44.3 0.67 (0.46-0.96) 0.03 Rivers E. N Engl J Med. 2001;345: 1368-1377. Slide 39 Copyright 2014 SCCM/ESICM
  38. 38. Surviving Sepsis Campaign Suggests bundled initiative for hospitals to reduce sepsis related mortality. 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Resuscitation Bundle Management Bundle Compliant Non-Compliant
  39. 39. TO BE COMPLETED WITHIN 3 HOURS OF TIME OF PRESENTATION*:1. Measure lactate level 2. Obtain blood cultures prior to administration of antibiotics 3. Administer broad spectrum antibiotics 4. Administer 30ml/kg crystalloid for hypotension or lactate ≥4mmol/L * “Time of presentation” is defined as the time of triage in the emergency department or, if presenting from another care venue, from the earliest chart annotation consistent with all elements of severe sepsis or septic shock ascertained through chart review.
  40. 40. TO BE COMPLETED WITHIN 6 HOURS OF TIME OF PRESENTATION:5. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) ≥65mmHg 6. In the event of persistent hypotension after initial fluid administration (MAP < 65 mm Hg) or if initial lactate was ≥4 mmol/L, re-assess volume status and tissue perfusion and document findings according to Table 1 7. Re-measure lactate if initial lactate elevated
  41. 41. DOCUMENT REASSESSMENT OF VOLUME STATUS AND TISSUE PERFUSION WITH  EITHER • Repeat focused exam (after initial fluid resuscitation) by licensed independent practitioner including vital signs, cardiopulmonary, capillary refill, pulse, and skin findings.  OR TWO OF THE FOLLOWING:  • Measure CVP  • Measure ScvO2  • Bedside cardiovascular ultrasound  • Dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge  Of note, Central Line no harm no gain. Needed for vasoactive drug therapy.  Bedside sonologic assessment of Volume status is prioritized.
  42. 42. fluid in septic shock, How much ?
  43. 43. IVF recommendation  Initial fluid challenge ≥ 1000 mL of crystalloids or minimum of 30 mL/kg of crystalloids in the 1st 4-6 hours  (Strong recommendation; Grade 1C).  Crystalloids is the initial fluid for resuscitation  (Strong recommendation; Grade 1A).  Adding albumin to the initial fluid resuscitation  (Weak recommendation; Grade 2B).  Against hydroxyethyl starches (hetastarches) with MW >200 dalton  (Strong recommendation; Grade 1B).
  44. 44. Timing of Antibiotic Administration
  45. 45. Septic Shock: Timing of Antibiotics Kumar Crit Care Med 2006 0.0 .20 .40 .60 .80 1.00 % Survival % Total receiving antibiotics Percent Time, hrs 14 ICUs; n = 2,731 Only 50% of patients in Septic Shock received antibiotics w/in 6 hrs.
  46. 46. G. Fluid Therapy of Severe Sepsis H. Vasopressors I. Inotropic Therapy J. Corticosteroids 2. Hemodynamic Support and Adjunctive Therapy
  47. 47. Adrenergic Agents Isoproterenol Dobutamine Dopamine Epinephrine Norepinephrine Phenylephrine Beta Alpha
  48. 48. Which Inotropes to use?  Norepinephrine as the first choice  ( Grade 1B)  Adding or substituting epinephrine when an additional drug is needed  (Strong recommendation; Grade 1B).  Vasopressin 0.03 units/min may be added  (Weak recommendation; Grade 2A)  Dopamine only in highly selected patients at very low risk of arrhythmias or low heart rate  (Weak recommendation; Grade 2C).  Dobutamine infusion be started or added with low cardiac output) or ongoing signs of hypoperfusion, even after adequate intravascular volume  (Strong recommendation; Grade 1C)
  49. 49. Inotropic Therapy • We recommend that a trial of dobutamine infusion up to 20 μg/kg/min be administered or added to vasopressor (if in use) in the presence of: • myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or • ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate mean arterial pressure. (Grade 1C) • We recommend against the use of a strategy to increase cardiac index to predetermined supranormal levels. (Grade 1B) Slide 53 Copyright 2014 SCCM/ESICM
  50. 50. Diagnosis of Infection  Appropriate cultures before antimicrobial therapy as soon as possible (<45 minutes) (Grade 1C).  At least two sets of blood cultures (both aerobic and anaerobic bottles) before antimicrobial therapy, with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was recently (<48 hours) inserted. Blood cultures can be drawn at the same time if from a different anatomic site (Grade 1C). Slide 54 Copyright 2014 SCCM/ESICM
  51. 51. Diagnosis  Cultures of other sites (preferably quantitative where appropriate), such as urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids that may be the source of infection, should also be obtained before antimicrobial therapy if doing so does not cause significant delay in antibiotic administration (Grade 1C).  We suggest the use of the 1,3 β-D-glucan assay (Grade 2B), mannan and anti-mannan antibody assays (Grade 2C) when invasive candidiasis is in the differential diagnosis of infection. Slide 55 Copyright 2014 SCCM/ESICM
  52. 52. Diagnosis  Imaging studies be performed promptly in attempts to confirm a potential source of obscure infection. and aggressive monitoring if the decision is made to transport for a CT-guided needle aspiration) .  Bedside studies, such as ultrasound, may avoid patient transport (Ungraded). Slide 56 Copyright 2014 SCCM/ESICM
  53. 53. Antimicrobial Therapy  The administration of effective intravenous antimicrobials as soon as possible , but never beyond the first hour of recognition of SEPSIS  Initial empiric anti-infective therapy include one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into the tissues presumed to be the source of sepsis (Grade 1B).  The antimicrobial regimen should be reassessed daily for potential de-escalation to prevent the development of resistance, to reduce toxicity, and to reduce costs (Grade 1B). Slide 57 Copyright 2014 SCCM/ESICM
  54. 54. Antibiotics • Abx within 1 hr hypotension: 79.9% survival • Survival decreased 7.6% with each hour of delay • Mortality increased by 2nd hour post hypotension • Time to initiation of Antibiotics was the single strongest predictor of outcome
  55. 55. Antimicrobial Therapy …  use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who appeared septic, but have no subsequent evidence of infection  Empiric therapy should attempt to provide antimicrobial activity against the most likely pathogens based upon each patient’s presenting illness and local patterns of infection.  We suggest combination empiric therapy for neutropenic patients with severe sepsis (Grade 2B) and for patients with difficult-to-treat, multidrug-resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp.
  56. 56. Antimicrobial Therapy …  Duration of therapy typically be 7 to 10 days if clinically indicated;  longer courses may be appropriate in patients  who have a slow clinical response,  Undrainable foci of infection,  Bacteremia with Staphylococcus aureus,  some fungal and viral Infections, or  Immunologic deficiencies, including neutropenia
  57. 57. Source Control  When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess) (Ungraded).  If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established (Ungraded).
  58. 58. Corticosteroids  Only when Blood Pessure is not maintained with adquate flid resuscitation and vasoacive  Intravenous hydrocortisone alone at a dose of 200 mg per day. Continuous Infusion preferred over bolus doses.  Taper steroid when vasopressors are no longer required Slide 62 Copyright 2014 SCCM/ESICM
  59. 59. Blood product Administration  Transfuse PRBC only when Hb%v<7.0 g/dL to target a hemoglobin concentration of 7.0 to 9.0 g/dL in adults (Grade 1B).  Exceptions are myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic coronary artery disease.  NO Erythropoetin in sepsis  No FFP to correct lab abnormality in absence of Bleeding or planned invasive procedure.  Platelet transfusion –  <10,000 in absence of bleeding  <20000 if bleeding risk high  <50,000 if planned procedure, active bleeding or surgery
  60. 60. Glucose Control • We recommend protocolized approach to blood glucose management, commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL. • This protocolized approach should target upper blood glucose <180 mg/dL rather than <110 mg/dL (Grade 1A). • Treatment should avoid hyperglycemia (>180 mg/dL), hypoglycemia, and wide swings in glucose levels Slide 64 Copyright 2014 SCCM/ESICM
  61. 61. Glucose control…  Glucometer measured capillary blood be interpreted with caution, as such measurements may not accurately estimate arterial blood or plasma glucose values  Capillary point-of-care testing found to be inaccurate with frequent false glucose elevations over range of glucose levels, but especially in hypoglycemic and hyperglycemic glucose ranges and in hypotensive patients or patients receiving catecholamines..
  62. 62. Bicarbonate Therapy • No to sodium bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15 (Grade 2B), in absence of Renal acidosis. Slide 66 Copyright 2014 SCCM/ESICM
  63. 63. Nutrition • We suggest administering oral or enteral feedings, as tolerated, rather than complete fasting or provision of only intravenous glucose within the first 48 hours after a diagnosis of severe sepsis/septic shock (Grade 2C). • We suggest avoiding mandatory full caloric feeding in the first week, but rather suggest low-dose feeding (e.g., up to 500 kcal per day), advancing only as tolerated Slide 67 Copyright 2014 SCCM/ESICM Marik and Zaloga. Crit Care Med. 2001;29:2264–2270 Heyland et al. JPEN J Parenter Enteral Nutr. 2003;27:355-373 Doig et al. Intensive Care Med. 2009;35:2018–2027
  64. 64. • Enteral nurtrition combined with IV Glucose supplementation is preferred than Total parenteral Nutrition • No evidence for the use of Arginine, Glutamine and Omega 3 fatty acid therapy during acute illness with sepsis Nutrition…
  65. 65. Renal Replacement Therapy • Continuous renal replacement therapies and intermittent hemodialysis are equivalent in patients with sepsis and acute renal failure because they achieve similar short-term survival rates (Grade 2B). • We suggest the use of continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients (Grade 2D). Slide 69 Copyright 2014 SCCM/ESICM
  66. 66. Prophylaxis for VTE  We recommend that patients with severe sepsis receive daily pharmacoprophylaxis against VTE (Grade 1B).  We recommend that septic patients who have a contraindication to heparin not receive pharmacoprophylaxis (Grade 1B).  Rather, we suggest they receive mechanical prophylactic treatment, such as graduated compression stockings or intermittent compression devices, unless contraindicated (Grade 2C).  When the risk decreases, we suggest starting pharmacoprophylaxis (Grade 2C). Slide 70 Copyright 2014 SCCM/ESICM
  67. 67. Stress Ulcer Prophylaxis • We recommend that stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to patients with sepsis/septic shock who have bleeding risk factors (Grade 1B). • We suggest that patients without risk factors should not receive prophylaxis (Grade 2B). Slide 71 Copyright 2014 SCCM/ESICM
  68. 68. Setting Goals of Care  We recommend that goals of care and prognosis be discussed with patients and families (Grade 1B).  Goals of care be incorporated into treatment and end-of-life care planning, utilizing palliative care principles where appropriate  Goals of care be addressed as early as feasible, but no later than within 72 hours of ICU admission Slide 72 Copyright 2014 SCCM/ESICM
  69. 69. Take Home message
  70. 70. Take home message…  Identify sepsis early  More and faster fluid  Send cultures early  Antibiotic Fast <1 hr, consider early antifungals, use biomarkers to deescalate or stop  Earlier Inotropes, Use norepineprine  Chase Lactic acid clearance  Sonologic volume assessment is better than CVP  Wet first, dry later  Higher PEEP
  71. 71. THE END
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