1. SIRS Dr. Jonathan R. Goodall M62 Coloproctology Course 31 st March 2006

5. SIRS

7.  Definitions  Recognising the patient with SIRS  Management of the patient with SIRS Activated Protein C Use of Steroids Glucose Control

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13. SIRSSIRS omething nfrequently ecognised by HOs

14. Definitions  Systemic Inflammatory Response Syndrome (SIRS)  Severe Sepsis  Septic Shock  Refractory Shock

15. Definitions  SIRS: 2 or more of: Temperature > 38°C or < 36°C Heart rate > 90 bpm Resp rate > 20 breaths.min -1 or PaCO2 < 4.3kPa (32mmg) WBCs > 12 or 10% immature forms)

16. Definitions  Sepsis = SIRS with documented infection site  Severe Sepsis Sepsis + organ dysfunction, hypoperfusion or hypotension  Septic Shock Severe sepsis (SBP < 90mmHg) despite adequate fluid resuscitation

20. Crit Care Med 2004 Vol. 32 No 3

21.  Experts from 11 international organisations (2003)  Management guidelines that would be of practical use for the bedside clinician  International effort to increase awareness & improve outcome… Dellinger et al, Crit Care Med 2004 Vol 32, No 3

22. Key Recommendations  Recommendations on groups of treatments  Total consensus reached on all but two of recommendations  Most of recommendations are not supported by ‘high-level’ evidence Dellinger et al, Crit Care Med 2004 Vol 32, No 3

24. A. Initial Resuscitation  Resuscitation should begin as soon as condition is recognised  In first 6 hours should include all of the following: CVP 8-12mmHg MAP > 65mmHg UO > 0.5ml.kg -1.hr -1 CvO 2 > 70% Grade B: Early Goal Directed Therapy in the Treatment of Severe Sepsis. Rivers et al NEJM 2001; 345:1368-77 Dellinger et al, Crit Care Med 2004 Vol 32, No 3

25. B. Diagnosis  Appropriate cultures should always be obtained before antimicrobial therapy At least 2 blood cultures One from each IV device >48 hours old Other cultures as appropriate Grade D/E Dellinger et al, Crit Care Med 2004 Vol 32, No 3

26. C. Antibiotic Therapy  Appropriate antimicrobial therapy should be started within 1 hour of onset Grade E  Initial empirical therapy Grade D  Focussed after 48-72 hours ? Monotherapy 7-10 day course Grade E  Stop if non-infective cause found Grade E Dellinger et al, Crit Care Med 2004 Vol 32, No 3

28. D. Source control  Evaluate all patients for the presence of a focus of infection amenable to ‘source control measures’ (SCM) (Grade E)  Method of SCM must weigh benefits & risks (Grade E)  Once a source of infection identified, SCM should be instituted as soon as possible (Grade E)  IV access devices should be removed promptly (Grade E) Dellinger et al, Crit Care Med 2004 Vol 32, No 3

29. E. Fluid Therapy  Fluid resuscitation may consist of natural or artificial colloids or crystalloids. There is no evidence- based support for one type of fluid over another.  Rates: 500-1000ml crystalloids over 30 mins 300-500ml colloids over 30 mins Grade C Dellinger et al, Crit Care Med 2004 Vol 32, No 3

30. F & G Vasopressors & Inotropes  Use when appropriate fluid resuscitation fails to restore adequate MAP  Noradrenaline or dopamine ± dobutamine (Grade D)  Low-dose (renal) dopamine should not be used. (Grade B) Bellomo et al Lancet 2000: 356:2139-2143 Dellinger et al, Crit Care Med 2004 Vol 32, No 3

32. H. Steroids  IV hydrocortisone (200-300mg/day) should be used for 7 days in patients requiring vasopressor therapy (Grade C)  > 300mg/day should not be used  Steroids should not be for the treatment of sepsis in the absence of shock (Grade E) Dellinger et al, Crit Care Med 2004 Vol 32, No 3

33. I. Activated Protein C  Recommended in patients at high risk of death without contraindications (Grade B) Bernard GR et al, N Engl J Med 2001;344:699- 709 Dellinger et al, Crit Care Med 2004 Vol 32, No 3

35. Activated Protein C - properties  Anticoagulant Degrades factor Va & VIIIa thereby inhibiting generation of thrombin  Pro-fibrinolytic Promoted fibrinolysis by inhibiting plasminogen activator inhibitor  Anti-inflammatory Direct effects on endothelium and neutrophils

36. PROWESS Study Group  1690 patients with sepsis enrolled  Mortality rate 30.8% in placebo group vs 24.7% in APC group  Relative risk of death reduction 19%; absolute risk reduction 6% (P=0.005)  Increased incidence serious bleeding (3.5 vs 2 %) Bernard GR et al, N Engl J Med 2001;344:699-709

37. M. Glucose Control  Following initial stablisation maintain blood glucose < 8.3 mmol/l (Grade B) Intensive Insulin Therapy in Critically Ill Patients. van den Berghe et al N Engl J Med 2001;345:1359 Dellinger et al, Crit Care Med 2004 Vol 32, No 3

38. Intensive Insulin Therapy  1548 patients admitted to ICU  Intensive Treatment Group Insulin started if glucose > 6.1 mmol.l -1 Glucose controlled 4.4 - 6.1 mmol.l -1  Conventional Treatment Group Insulin started if glucose > 12 mmol.l -1 Glucose controlled 10.0 – 11.1mmol.l -1 van den Berghe NEJM 2001;345:1359

39. Intensive Insulin Therapy  Mortality Rates Treatment Group4.6% Conventional Group8.0%  Unbiased risk reduction 32%  Also reduced incidence of complications (eg septicaemia, acute renal failure) van den Berghe NEJM 2001;345:1359

40. M. Glucose Control  …There is no reason to think these data are not generalisable to all severely septic patients…  Intensive Insulin Therapy in the Medical ICU. van den Berghe et al N Eng J Med 2006; 354: 449-461 Dellinger et al, Crit Care Med 2004 Vol 32, No 3

42. P. DVT Prophylaxis  Use unfractionated or LMW heparin  For patients with contraindication to heparin, use of a mechanical prophylactic device is recommended  In very high risk patients, use both pharmacological and mechanical prophylaxis Grade A Dellinger et al, Crit Care Med 2004 Vol 32, No 3

43. Q. Stress Ulcer Prophylaxis  H 2 receptor antagonsists are more efficacious than sucralfate and are the preferred agents  Proton pump inhibitors have not been assessed in a direct comparison to H 2 receptor antagonsists, and their relative efficacy is not known. Grade A Dellinger et al, Crit Care Med 2004 Vol 32, No 3

45. Summary  SIRS is very common  SIRS is a difficult problem It is a complex disease It is not easy to recognise  Steroids probably useful  APC is useful  Tight glucose control is useful (in surgical patients)

46. www.survivingsepsis.org