SEPSIS

1. SEPSIS Preeta John

2. “SEPSIS AT ITS INCEPTION IS DIFFICULT TO RECOGNIZE BUT EASY TO TREAT; LEFT UNATTENDED IT BECOMES EASY TO RECOGNIZE BUT DIFFICULT TO TREAT” Machiavelli

4. SepsisDefinitions • Based on ACCP/SCCM consensus panel • Infection • Inflammatory response to pathogen • Classically Gram (-) • Bacteremia • Viable bacteria in blood

5. SepsisDefinitions • SIRS • Widespread inflammatory response in absence of documented infection • Need 2 or more: • Temp > 380C (100.40F) or < 360C (96.80F) • Heart rate > 90 bpm • Respiratory rate > 20 /min or PaCO2 < 32 mmHg • WBC > 12,000 cells/mm3, < 4,000 cells/mm3, or > 10% immature (band) form

6. SepsisDefinitions • Sepsis • Systemic response to infection • SIRS + infection • Severe sepsis • Sepsis + hypotension, hypoperfusion or organ dysfunction

7. SepsisDefinitions • Sepsis shock • Sepsis + hypotension, despite fluids + clinical signs of hypoperfusion • ~ 40% of sepsis • Hypotension • SBP < 90 mmHg or reduction of BP >/= 40 mmHg from baseline

8. SepsisDefinitions • MODS • Primary MODS: early organ dysfunction • Secondary MODS: later organ dysfunction • Most common manifestations of severe MODS: • ARDS, acute renal failure, DIC

9. SepsisMortality Rates • Overall = 30% - 50% • By syndrome definition: • SIRS = 7% • Sepsis = 16% • Severe sepsis = 20% • Septic shock = 46%

10. Markers of sepsis • Procalcitonin: *propeptide of calcitonin *c cells of thyroid, extrathyroid in sepsis *normal level <0.05ng/ml *<0.5-rules out infection, *0.5-2- suspected sepsis *>2- 100 sepsis severity *rises after 6hrs, t1/2 24 hrs

11. CRP: acute phase reactant – liver asses severity of sepsis diff b/w bacterial &viral infection poor specificity –MI,RHD, tumors poor predictive value of sepsis normal <6mg/l

12. Surviving Sepsis CampaignGuidelines for Management of Severe Sepsis and Septic Shock Dellinger RP, Carlet JM, Masur H, et al. for the Surviving Sepsis Campaign Management Guidelines Committee.Crit Care Med 2004; 32:858-873.

13. Early goal directed therapy • Goals of therapy within first 6 hours are • C V P 8-12 mm Hg (12-15 on ventilated patients) • Mean arterial pressure > 65 mm Hg • Urine output > 0.5 mL/kg/hr • ScvO2 or SvO2 ≥ 70%; if not achieved, • Transfuse PRBC to hematocrit > 30% • Administer dobutamine (max 20 mcg/kg/min) to goal - Rivers E. N Engl J Med 2001;345:1368-77. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

14. Lung protective ventilation • Low tidal volumes 6 ml/kg, coupled with plateau pressures <30 cm H2O • This decreases mortality from 40 to 31% • Lessens organ dysfunction • A minimum amount of positive end expiratory pressure should be set to prevent lung collapse at end-expiration

15. Antibiotic Therapy • Start antibiotic therapy in the first hour of recognition of severe sepsis after obtaining appropriate cultures • Empirical choice -one or more drugs with activity against likely pathogens, • Penetrate presumed source of infection • Guided by susceptibility patterns in the community and hospital • Continue broad spectrum therapy until the causative organism and its susceptibilities are defined Kreger BE. Am J Med 1980;68:344-355. Ibrahim EH. Chest 2000;118:146-155. Hatala R. Ann Intern Med 1996;124-717-725. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

16. Fluid Therapy: Choice of Fluid Fluid resuscitation - natural or artificial colloids or crystalloid No evidenced-based support for one type of fluid over another Crystalloids have a much larger volume of distribution compared to colloids Crystalloid resuscitation requires more fluid to achieve the same endpoints as colloid Crystalloids results in more edema Choi PTL. Crit Care Med 1999;27:200-210. Cook D. Ann Intern Med 2001;135:205-208. Schierhout G. BMJ 1998;316:961-964. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

17. Steroids • Intravenous corticosteroids are recommended in patients with septic shock who require vasopressor therapy to maintain blood pressure • Administer intravenous hydrocortisone 200-300 mg/day for 7 days in three or four divided doses or by continuous infusion • Shown to reduce mortality rate in patients with relative adrenal insufficiency Annane, D. JAMA, 2002; 288 (7): 868 Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

18. Recombinant human Activated Protein C • Drotrecogin alfa (activated)] is recommended in patients at a high risk of death • APACHE II score  25, or • Sepsis-induced multiple organ failure, or • Septic shock, or • Sepsis induced acute respiratory distress syndrome • Treatment should begin as soon as possible once patient identified as high risk of death • Patients should have no absolute or relative contraindication related to bleeding risk Bernard GR. N Eng J Med 2001;344:699-709. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

19. Contraindications to use of rhAPC • rhAPC (drotrecogin alfa [activated]) increases the risk of bleeding. rhAPC is contraindicated in Active internal bleeding • Recent (within 3 months) hemorrhagic stroke • Recent (within 2 months) intracranial or intraspinal surgery, or severe head trauma • Trauma with increased risk of life-threatening bleeding • Presence of an epidural catheter • Intracranial neoplasm or mass lesion or evidence of cerebral herniation • platelet count be maintained at ≥30,000 during infusion of rhAPC

20. Vasopressors • vasopressor therapy if fluid challenge fails to restore adequate blood pressure and organ perfusion • Either norepinephrine or dopamine are first line agents to correct hypotension in septic shock • Norepinephrine more potent than dopamine • more effective at reversing hypotension in septic shock patients • Dopamine in patients with compromised systolic function but causes tachycardia and is arrhythmogenic • Vasopressin in refractory shock LeDoux D. Crit Care Med 2000;28:2729-2732.Regnier B. Intensive Care Med 1977;3:47-53. Martin C. Chest 1993;103:1826-1831. Martin C. Crit Care Med 2000;28:2758-2765. DeBacker D. Crit Care Med 2003;31:1659-1667.Hollenberg SM. Crit Care Med 1999; 27: 639-660. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

21. Blood Product Administration • Red blood transfusion when hemoglobin < 7 g/dL • in coronary artery disease, acute hemorrhage or lactic acidosis • Target hemoglobin of 7 – 9 g/dL • Routine use of fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures is not recommended Corwin HL. JAMA 2002;288:2827-2835. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

22. Blood Product Administration • Platelet administration • Transfuse for < 5000/mm3 – • Transfuse for 5000/mm3 – 30,000/mm3 with significant bleeding risk • Transfuse < 50,000/mm3 for invasive procedures or bleeding

23. Glucose Control • Best results obtained when blood glucose was maintained between 80 and 110 mg/dL in surgical sicu • Glycemic control strategy should include a nutrition protocol with the preferential use of the enteral route van den Berghe G. N Engl J Med 2001;345:1359-1367. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

24. Bicarbonate Therapy Bicarbonate is not recommended for the purpose of improving hemodynamics or reducing vasopressor requirements for the treatment of hypoperfusion induced lactic acidemia with pH  7.15 Cooper DJ. Ann Intern Med 1990;112:492-498. Mathieu D. Crit Care Med 1991;19:1352-1356. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

25. NEJM OCT 2006

26. Treatment strategies proven to change outcome in severe sepsis • Early goal directed therapy • Lung protective ventilation • Appropriate antibiotic coverage • Activated protein C • Tight control of sugars 80-100mg/dl • Steroids

27. A clinician, armed with the sepsis bundles, attacks the three heads of severe sepsis: hypotension, hypoperfusion and organ dysfunction. Crit Care Med 2004; 320(Suppl):S595-S597