Review of SIRS Criteria as a Predictor of Severe Sepsis and Mortality

1. Review of SIRS Criteria as a Predictor of Severe Sepsis and Mortality INTERN 吳 基宏

2. Introduction • Systemic inflammatory response: - triggered by ischemia, inflammation, trauma, infection, etc - to protect the host from the damaging effects of insult - TNF-a, IL-1, IL-6, IL-8  coagulation cascade, complement cascade, etc  microvascular thrombosis, organ dysfunction - IL-4, IL-10  anti-inflammatory effects

3. Introduction

4. Definition • SIRS: 2 or more of - temperature > 38C or < 36C - heart rate > 90 bpm - respiratory rate > 20/min - WBC > 12000 or < 4000 or >10% band form • Sepsis: SIRS + documented infection • Severe sepsis: sepsis + organ dysfunction: hypotension, lactic acidosis, oliguria, altered mental status, etc • Septic shock: sepsis-induced hypotension despite fluid resuscitation

5. Commonly-held assumptions • SIRS, sepsis, severe sepsis, and septic shock represent a continuum of inflammatory response to infection • These stages imply not so much severity of infection as severity of inflammatory response to infection • Mortality correlates with continuum from SIRS to shock • SIRS criteria is too nonspecific • SIRS criteria >3 can predict future sepsis, higher rates of organ dysfunction, and higher mortality

6. Rangel-Frausto’s study, 1995 • Rangel, et al. The Natural History of the Systemic Inflammatory response Syndrome (SIRS).JAMA 1995;273 Aim: To define epidemiology of SIRS, sepsis, severe sepsis and shock Design: Prospective cohort study with follow-up of 28 days Setting:3 ICU and 3 general wards in tertiary health care institution

7. Rangel-Frausto’s study, 1995

8. Rangel’s study: SIRS sepsissever sepsis • The progression of SIRS to sepsis or more severe stages: For those who met 2 criteria 32% developed sepsis by day14 For those who met 3 criteria (1821, 72%) 36% developed sepsis by day 14 For those who met 4 criteria (975, 39%) 45% developed sepsis by day 14 64% septic patient developed severe sepsis by day 14 • SIRS with only 2 criteria is less helpful in defining those with risk for development of sepsis than 3 or 4 criteria

9. Rangel’ study:Mortality with SIRS • Mortality vs. SIRS criteria on day1 Those with 2 criteria (1206): 6% died (69) Those with 3 criteria (924): 9% died (84) Those with 4 criteria (397): 18% (71)

10. Rangel’ study:Mortality with SIRS • Mortality rates correlates with the continuum from SIRS to shock • Mortality rates correlates with SIRS criteria

11. Alberti’s study, 2003 • Alberti et al. Influence of systemic inlammatory response syndrome and sepsis on outcome of critically ill infected patients. Am J Respir Crit care Med 2003;168 Aim: To evaluate value of SIRS criteria on mortality Design: Prospective cohort study over 1-year period Setting:28 ICU from Europe, Canada, Israel

12. Alberti’s study: Mortality with SIRS

13. Alberti’s study: Mortality with SIRS • Mortality ranged from 25% in infection/sepsis to 40% with severe sepsis and 60% for septic shock  Confirm prognostic significance of gradation of severity from sepsis to shock No of SIRScriteria Infectionshock

14. Alberti’s study: Mortality with SIRS • Mild (infection only) to moderate (sepsis) infection had similar outcome  No. of SIRS criteria lose prognostic significance in the least severe stages 0-1 criteria 2-4 criteria 25%

15. Alberti’s study: Mortality with SIRS • The lack of influence of number of SIRS criteria was also true in other stages: Severe sepsis Septic shock

16. Alberti’s study vs. Rangel’s study • SIRS criteria failed to identify those with higher risk of poorer outcome (for infection only and sepsis) • The presence of organ dysfunction, qualifying patients for severe sepsis, is the preferred selection criterion • Possible transition from one stage of sepsis to another was not examined  No. of SIRS criteria may be tool for identifying those at higher risk of subsequent organ dysfunction ??

17. Dremsizov’s study, 2006 • Tony Dremsizov et al. Severe Sepsis in Community-Acquired Pneumonia. Chest 2006;129 Aim: To determine SIRS criteria as a predictor of progression of severe sepsis, septic shock, or death at ER Design: Retrospective analysis: 1339 patients hospitalized for CAP in the PORT study, of which 686 patients were tested for SIRS criteria Setting:4 medical centers in US and Canada

18. Dremsizov’s study: Predictor of severe sepsis • Predictive power of SIRS for severe sepsis, septic shock, and death: Of 686, 562 patients(82%) had 2 SIRS criteria on day 1, 94% met 2 criteria during hospitalization

19. Dremsizov’s study: Predictor of severe sepsis • Of 686 patients, 562 (82%) patients had 2 SIRS criteria on day 1, and 94% met this during the study • Neither 2 nor 3 SIRS criteria at presentation were associated with subsequent severe sepsis or septic shock • Distribution of patients with 0,1,2,3,4 SIRS criteria were no different

20. Dremsizov’s study: Predictor of severe sepsis • Future therapies for severe sepsis may attempt to target patients earlier and outside ICU  early intervention • SIRS criteria poorly predicts subsequent events in the sepsis cascade: severe sepsis, septic shock at the very early stages of hospital care • The study focused on CAP, may not extend to other infection

21. New sepsis definition 2001 SCCM/ESICM/ACCP/ATS/SIS International sepsis definitions conference: • Biomarkers such as IL-6, CRP, procalcitonin may add to SIRS criteria in the future • S/S of sepsis is more varied then the initial criteria in 1991  expanded bed-side list of s/s may better reflect the clinical response to infection • Current definitions do not allow for precise staging of host response to infection  PIRO model 

22. Diagnostic criteria for sepsis • 

23. PIRO model • Staging system for sepsis: Predisposition: premorbid factors, genetic polymorphisms Infection: site, type, and extent of the infection Response: putative biomarkers of response severity, e.g IL-6, procalcitonin Organ dysfunction: SOFA score, etc • May be able to discriminate morbidity from infection or response to infection 

24. Take home message • Comprehensive bed-side s/s examination may better diagnose sepsis than pure SIRS criteria • SIRS criteria on a infected patient serves as a reminder, rather than definite predictor, of subsequent severe sepsis • Organ dysfunction, not number of SIRS criteria, affects outcome and mortality • PIRO model

25. References • Rangel-Frausto, et al. The Natural History of the Systemic Inflammatory Response Syndrome(SIRS). JAMA 1995;273:117-123 • GR Jones, et al. The SIRS as a predictor of bactaeremia and outcome from sepsis. QJ Med 1996; 89:515-522 • 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Critical Care Med 2003;21:1250-1256 • Alberti, et al. Influence of Systemic Inlammatory Response Syndrome and Sepsis on Outcome of Critically Ill... Am J Resp Cri Care Med 2003;168 • Alberti, et al. Systemic Inflammatory Response and Progression to Severe Sepsis in Critically Ill Infected Patients. Am J Resp Cri Care Med 2005;171 • Tony Dremsizov, et al. Severe sepsis in Community-Acquired Pneumonia: When does it happen…Chest 2006;129:968-978 Thank YOU!