1. Jay Green, PGY-4 Dr. Jason Lord August 20, 2009

2.  Dr. Jason Lord  Dr. Dan Howes  Dr. Trevor Langhan  Dr. Aric Storck

3.  Case  Definitions  Keys to sepsis management

4.  Why is sepsis important?

5. SIRS (2 of) T 38 HR>90 RR>20, pCO2 < 32 WBC 12 or >10% bands

7.  SIRS  Sepsis  Severe sepsis  Septic shock

8. Sepsis Management SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands

9. Mortality: 46% SEVERE SEPSIS SEPTIC SHOCK SEPSIS SIRS Mortality: 10% Mortality: 16%

10.  You think he’s septic  ?Pulmonary source?

11. Sepsis Management 1. Recognition SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands

12.  #1 priority in sepsis?

13. Kumar et al. Crit Care Med 2006;34(6):1589

14.  Abx keys Get them in fast! Culture first Source control ?MRSA/pseudomonas

15.  Chest  Levo + ceftriaxone  Azithro + ceftriaxone  Tazo/Cipro (nursing home, etc)  Abdo  Pip/tazo or AGF or ceftriaxone/Flagyl  GU  Gent or ceftriaxone  Skin  Ancef +/- vanco  Head  Ceftriazone + vanco + dex

16.  Surviving Sepsis Campaign Crit Care Med 2008;36(1):296  CAEP CJEM 2008 Sept;10(5):443

17. Sepsis Management 1. Recognition 2. ABX! SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands

18.  What does our patient have?

19.  Investigations?  Initial management priorities?

20.  Reassess our patient  Why is lactate important?

21. Mortality: 46% SEVERE SEPSIS SEPTIC SHOCK SEPSIS SIRS Mortality: 10% Mortality: 16% EGDT Mortality: 30% EGDT

23.  In-hospital mortality 46.5% vs 30.5% (NNT = 6!)  60-day mortality 56.9% vs 44.3%  EGDT got more early fluid, pRBC, inotropes

24.  Hinshaw & Cox. The Fundamental Mechanisms in Shock. Plenum Press, New York. 1972.  Hypovolemic  Distributive  Cardiogenic  Obstructive ✓ ✓ ✓ ✗

25. Hypovolemic Distributive Cardiogenic

26.  Why are patients in hypovolemic shock? Venodilation 3 rd spacing Losses (vomiting, diaphoresis) Recent poor PO intake  Crystalloid vs colloid?

27. BMJ 1998;316:961

28. NEJM 2004;350:2247  Cochrane review, 2005  VISEP. NEJM 2008;358:125-39  NS – cheap, available – USE IT

29.  Surviving Sepsis Campaign Colloid or crystalloid  CAEP Colloid or crystalloid Crit Care Med 2008;36(1):296

30.  Voluven Lu et al. 2009 Mar;21(3):143-6  ?lung-protective in rabbits Palumbo et al. 2006;72(7-8):655  Improved hemodynamics and APACHE-II score Franziska et al. 2009;35(9):1539  Similar rates of ARF as albumin in surgical ICU pts

31. Sepsis Management 1. Recognition (lactate, u/o) 2. ABX 3. EGDT (NNT=6) SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands EGDT CVP 8-12 Crystalloid (1L q30min)

32. Distributive

33.  Should we use vasopressin in sepsis?

35. NEJM 2008;358(9)

36. Sepsis Management 1. Recognition (lactate, u/o) 2. ABX 3. EGDT (NNT=6) SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands EGDT CVP 8-12 Crystalloid (1L q30min) MAP > 65 NE 0.1-2ug/kg/min OR dopamine 5-20ug/kg/min

37. Cardiogenic

38.  EGDT If S cv O 2 <70% and hct<0.30  TRICC If Hb > 70g/L  How does this help?  O 2 content = (1.34 x Hb x S a O 2 ) + (0.0031 x PO 2 )

39. NEJM 1999;340:409  Results No difference in 30 or 60 day mortality Restrictive group Lower in-hospital mortality  22.2% vs 28.1% (p=0.005) Less sick pts (APACHE II score <20) did better ARR 7.4% (95%CI 1.0 – 13.6%) No difference in mortality in sepsis sub-group

40.  EGDT Hypovolemic ED patients Actual measurement of suboptimal O2 delivery  TRICC Euvolemic pts enrolled within 72 hours of ICU admit 6% sepsis, 27% had any infection

42. Sepsis Management 1. Recognition (lactate, u/o) 2. ABX 3. EGDT (NNT=6) SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands EGDT CVP 8-12 Crystalloid (1L q30min) MAP > 65 NE 0.1-2ug/kg/min OR dopamine 5-20ug/kg/min S cv O 2 > 70% pRBC (hct>0.30) dob 2-20ug/kg/min

44.  Absalom 1999, Malerba 2005, Vinclair 2007 Single dose inhibits cortisol synthesis for 24-48h  Mohammed 2006, Ray 2007, Riche 2007 Studies designed for etomidate vs no etomidate No increase in mortality  CORTICUS (2008) >28d mort with one dose (OR 1.53 (1.06-2.26)) Etomidate non-randomized, post-hoc analysis  Bottom line Avoid in sepsis

47. NEJM 2000;342(18)

48. Sepsis Management 1. Recognition (lactate, u/o) 2. ABX 3. EGDT (NNT=6) 4. ARDS vent settings (NNT=11) SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands EGDT CVP 8-12 Crystalloid (1L q30min) MAP > 65 NE 0.1-2ug/kg/min OR dopamine 5-20ug/kg/min S cv O 2 > 70% pRBC (hct>0.30) dob 2-20ug/kg/min ARDSNet TV 6cc/kg PEEP P plateau <30

49.  Early studies - no benefit  NEJM 1987; 317: 659-65, NEJM 1987; 317: 653-58  Increased mortality at higher doses  Crit Care Med. 1995; 23: 1430-39  Annane – benefit in non-responders  JAMA 2002;288(7)  CORTICUS – no benefit  NEJM 2008;358(2)  Annane - benefit in subgroup  JAMA 2009 June;301(22)

51. Sepsis Management 1. Recognition (lactate, u/o) 2. ABX 3. EGDT (NNT=6) 4. ARDS vent settings (NNT=11) 5. ?Hydrocortisone 50mg q6h -vasopressor-unresponsive pts SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands EGDT CVP 8-12 Crystalloid (1L q30min) MAP > 65 NE 0.1-2ug/kg/min OR dopamine 5-20ug/kg/min S cv O 2 > 70% pRBC (hct>0.30) dob 2-20ug/kg/min ARDSNet TV 6cc/kg PEEP P plateau <30

52.  Van den Berghe et al. NEJM 2001;345(19) Overall mortality benefit  Glucontrol. Presented Oct 2007 Stopped early, hypoglycemia, protocol violations  VISEP. NEJM 2008;358:125-39 Stopped early, hypoglycemia concerns  Guidelines SSC – Glucose management in ICU CAEP – Reasonable to target glu 4-8mmol/L

53. Sepsis Management 1. Recognition (lactate, u/o) 2. ABX 3. EGDT (NNT=6) 4. ARDS vent settings (NNT=11) 5. Hydrocortisone 50mg q6h -vasopressor-unresponsive pts 6. ?Insulin (ICU unless v. high) SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands EGDT CVP 8-12 Crystalloid (1L q30min) MAP > 65 NE 0.1-2ug/kg/min OR dopamine 5-20ug/kg/min S cv O 2 > 70% pRBC (hct>0.30) dob 2-20ug/kg/min ARDSNet TV 6cc/kg PEEP P plateau <30

55.  PROWESS. NEJM 2001;344(10) Improved survival, NNT = 6  Post-hoc PROWESS. Int Care Med 2003;29 PROWESS benefit only in very sick  ADDRESS. NEJM 2005; 353:13 Stopped early, no effect, increased bleeding  RESOLVE. Lancet 2007;369:836 Peds, no difference in any outcome  Cochrane review 2008  BOTTOM LINE: Not for ED use

56. Sepsis Management 1. Recognition (lactate, u/o) 2. ABX 3. EGDT (NNT=6) 4. ARDS vent settings (NNT=11) 5. ?Hydrocortisone 50mg q6h -vasopressor-unresponsive pts 6. ?Insulin (BG~10) 7. ?APC (maybe in ICU) SIRS T 38 HR>90 RR>20, pCO2<32 WBC 12 or >10% bands EGDT CVP 8-12 Crystalloid (1L q30min) MAP > 65 NE 0.1-2ug/kg/min OR dopamine 5-20ug/kg/min S cv O 2 > 70% pRBC (hct>0.30) dob 2-20ug/kg/min ARDSNet TV 6cc/kg PEEP P plateau <30