1. Sepsis Jayesh Patel UTFP-Resident Jan 21, 2009

8. Relationship of Sepsis, Severe Sepsis, and Septic Shock Sepsis Severe Sepsis Septic shock MODS Death Sepsis and organ dysfunction, hypoperfusion, or hypotension Sepsis-induced hypotension

9. Question?

10. Question? A 70 YO man presents to ER with 2 day history of fever, chills, cough, and right-sided pleuritic chest pain. On the day of admission, the patient’s family noted that he was more lethargic and dizzy. VS: Temp 101.5, HR 120, RR 30, B.P 70/35, O2 sat 80% @RA, CXR shows RLL infiltrate. This patient’s condition can be best defined as 1.Systemic inflammatory response syndrom(SIRS) 2. Multi-organ dysfunction syndrom(MODS) 3.Septic shock 4.Sepsis 5. Sever Sepsis

11. Answer: 5-Severe Sepsis

12. Incidence of Severe Sepsis/Septic Shock Approximate Cases/Year 800,000 600,000 400,000 200,000 0 Severe sepsis 800,000 Septic shock 400,000 Deaths from septic shock 200,000 Sepsis and sequelae are a leading cause of death in ICU Mortality in septic shock remains at 35 - 50%

13. Severe Sepsis: Comparative Incidence and Mortality Angus DC, et al. Crit Care Med. 2001; ACS. Incidence Cases/100,000 Mortality Deaths/Year

15. Projected Incidence of Severe Sepsis in the US: 2001 - 2050 200,000 400,000 600,000 800,000 1,000,000 1,200,000 1,400,000 1,600,000 1,800,000 2001 2025 2050 Year 100,000 200,000 300,000 400,000 500,000 600,000 Severe Sepsis Cases US Population Sepsis Cases Total U.S. Population/1,000 Angus DC, et al. Crit Care Med. 2001.

16. Overall in-hospital mortality rate among patients hospitalized for sepsis, 1979-2000

17. Pathogenesis of Septic Shock

18. Figure B, page 948, reproduced with permission from Dellinger RP. Cardiovascular management of septic shock. Crit Care Med 2003;31:946-955 . Pathogenesis of Septic Shock

25. Early Goal Directed Therapy

26. SEVERE SEPSIS PROTOCOL First 4 hours Primary Objectives Control of Infection ASAP Hemodynamic stabilization History CVP = 8-12 mmHg Physical exam ScvO2 sat ≥ 70% Laboratory and radiologic studies Mean Arterial Pressure (MAP) ≥ 65 mmHg Pan cultures – STAT Gram stain results Urinary Output ≥ 0.5 cc/kg/hr Broad spectrum ATB < 1 hour Arterial O2 saturation ≥ 95%

27. To be started as soon as possible and accomplished in 1 hour 1.Laboratory 2.Antibiotics 3.Monitoring 4.Fluid

35. Hydrocortisone Treatment of Refractory Septic Shock Timing Hydrocortisone Daily dose Loading dose over 30 min 200-mg IV bolus Day 0 until Day 8 IV infusion at 10ml/hr 240 mg Day 8 – Day 10 IV infusion at 5ml/hr 120 mg Day 10 – Day 12 IV infusion at 2.5 ml/hr 60 mg At ICU discharge, the infusion is changed to equivalent daily dosage divided in two IV doses. Day 0 until Day 8 120 mg (2.4 ml) Q 12 h 240 mg Day 8 – Day 10 60 mg (1.2 ml) Q 12 h 120 mg Day 10 – Day 12 30 mg (0.6 ml) Q 12 h 60 mg At hospital discharge or for any condition that might limit IV intake: equivalent oral dose to complete the 11 full days treatment is initiated in two divided doses.

38. Early Goal Directed Therapy

41. APPENDIX I General Rule 1 Avoid re-exposure to B lactam and fluoroquinolones if received within 3 months. Attention: fluoroquinolones also cause resistance to B lactam (AVOID fluroquinolones in first ICU infection if possible) General Rule 2 Do not combine two B lactam antibiotics: Pencillin, Cephalosporin, Monobactam, and Carbapenem. General Rule 3 For Enterobacteriaceae (Klebsiella, E.coli) – use Carbapenem (AVOID Piperacillin/tazobactam) General Rule 4 Antibiotics that prolong QT-Torsade de pointes: Moxifloxacin, Levaquin, TMT-SMT, Erythromycin, Itraconazole, Ketoconazole, Pentamidine General Rule 5 For S. aureus bacteremia: Antibiotic treatment for at least two weeks – stop after 2 weeks if the following are met :1) removal of the intravascular catheter or drainage of the abcess that was presumed to be the source of the bacteremia, 2) the bacteremia is demonstrated to promptly resolve with the removal or drainage 3) there is prompt clinical response, including resolution of fever 4) heart valve are demonstrated to be normal. (Pt. with DM may need 4 weeks treatment) General Rule 6 Fluconazole sensitive Candida: Tropicalis, Albicans, Parapsilosis (TAP), Lusitaniae

42. Drotrecogin alfa activated(Xigris) OR Recombinant Human Activated Protein C (rhAPC)

45. Sepsis and ARF Patients in sepsis and ARF are hypercatabolic states. Patient placed on renal replacement therapy have been shown to have mortality benefit.(2B)

46. Bicarbonate Therapy Bicarbonate therapy not recommended to improve hemodynamics in patients with lactate induced pH > 7.15

48. FAST HUG F eeding(1B) A nalgesia(1B) S edation(1B) T hromboembolic prophylaxis(1A) H ead of bed elevation(1B) U lcer prophylaxis(1A) G lucose control(1B)

50. Questions?

52. Answer:D-Supplimental oxygen and airway management First-Follow ABCD

54. Answer:4-Central venous saturation  70%

56. Answer:D-Norepinephrine or Dopamine simple guide Low cardiac output Normal to high Cardiac output Low SVR Norepinephrine Phenylephrine High SVR Dobutamine Dopamine

58. Answer:C-Dobutamine

59. References Surviving Sepsis Campaign. The New England Journal of Medicine. Uptodate.com. Society of critical care Medicine. European Society of Intensive Care. American College of Chest Physicians. Society of Critical Care Medicine Journal

60. Thank you