1. < 회기-강동 합동 컨퍼런스>
Systemic Inflammatory Response Syndrome criteria in Defining Severe sepsis Kirsi-Maija Kaukonen, M.D., Ph.D., Michael Bailey, Ph.D., David Pilcher N Engl J Med 2015;372:
호흡기내과 황인경

2. INTRODUCTION Definition of Sepsis SIRS Infection
Systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock were defined in 1992 and 2001 by a international consensus panel
Definition of Sepsis
Infection
documented or suspected
SIRS
Two or more of the followings:
BT >38°C or <36°C
HR >90 bpm
RR >20/min
(or PaCO2 < 32mmHg)
WBC >12000/mm³
(or <4000/mm³)
SEPSIS

3. INTRODUCTION
2012 SSC updated

4. INTRODUCTION
Harrison’s principles of internal medicine, 18e

5. INTRODUCTION Severe sepsis
Major cause of admission to the ICU and death
The need to meet two or more SIRS criteria has been criticized because of a low specificity for infection within 24 hours after admission and some patients (e.g. elderly) may not have symptoms, despite having infection and organ failure
the face validity and sensitivity of two or more SIRS criteria in the diagnosis of severe sepsis remain unclear
Validity: sensitivity, specificity, predictive value, liklihood ratio, ROC curve(AUC, discrimination 측정)

6. INTRODUCTION
We hypothesized that the presence of symptoms meeting two or more SIRS criteria would have low face validity and sensitivity and that the fulfillment of two criteria would not identify a transitional increase in an otherwise linear increased risk of death that would be logically expected with each additional criterion

7. METHODS
STUDY DESIGN
Retrospective study, ~ (14yr), using data from the Australia and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD), a high-quality database for Outcome and Resource Evaluation

8. Two or more of the followings:
APACHE Diagnostic groups used to define infection:
Non operative group: endocarditis, pneumonia, parasitic pneumonia, bacterial pneumonia, viral pneumonia, gastrointestinal tract perforation, cholangitis, gastrointestinal abscess/cyst, peritonitis, neurologic infection, renal infection/abscess, myositis(viral), arthritis (septic), cellulitis and localized soft tissue infections; or the following
Post-­operative group: respiratory infection, gastrointestinal tract perforation or rupture, cholecystitis or cholangitis, appendicitis, fistula or abscess surgery, peritonitis, cranial infection/abscess, cellulitis and localized soft tissue infections
SIRS
Two or more of the followings:
BT >38°C or <36°C
HR >90 bpm
RR >20/min
(or PaCO2 < 32mmHg)
WBC >12000/mm³
(or <4000/mm³)
METHODS
DEFINITIONS
Sepsis, Severe sepsis, and Septic shock: according to the ACCP/SCCM consensus definition
Infection: according to APACHE III at admission to infer the suspected or proven infection
Organ failure: first 24hr after ICU admission as a SOFA score of 3 or high
Consensus SIRS criteria (within the first 24hr after ICU adm)
follow-up: the duration of hospital stay
primary outcome: in-hospital mortality
American College of Chest Physicians–Society of Critical Care Medicine consensus definition
Acute Physiology and Chronic Health Evaluation (APACHE) III at admission to infer the presence of suspected or proven infection
Sequential Organ Failure Assessment (SOFA) score of 3 or higher (on a scale from 0 to 4, with higher scores indicating more severe organ failure

9. METHODS STUDY POPULATIONS
Patients with SIRS-positive severe sepsis: Symptoms meeting two or more SIRS criteria + APACHE III diagnosis of severe sepsis or septic shock
Patients with SIRS-negative severe sepsis: Symptoms meeting fewer than two SIRS criteria + APACHE III diagnosis of severe sepsis or septic shock

10. METHODS STATISTICAL ANALYSIS
To identify independent differences at baseline between patients with SIRS-positive and SIRS-negative severe sepsis  ‘multivariable logistic regression model’
To investigate the similarities of differences in hospital outcomes over time  ‘logistic-regression models with the Australian and New Zealand calibrated Risk of Death (ANZROD) model’
To determine whether predictors of death differed between SIRS-positive and SIRS-negative sepsis  ‘multivariable logistic-regression model’

11. RESULT

12. STUDY PATIENTS
Severe sepsis 109,663 patients in 172 ICUs = SIRS-positive 96,385(87.9%) + SIRS-negative 13,278(12.1%)
SIRS+ -보다 나이가 젊고 더 병의 severelity가 높고 mortality가 높았다.
Septic shock, AKI 가 동반된 퍼센트가 높고 surgical admission이나 집으로 퇴원하는 환자의 비율은 적었다.
** APACHE III score 0-299까지이고 점수가 높을수록 병의 severity가 중하다는 것을 의미한다.
** APACHE III model로 사망의 위험성을 assess 하는 것은 미국의 40개의 병원을 대상으로 하였고 ANZROD라고 New Zealand calibrated Risk of Death model로 사망 위험성을 assess 하는 것이 뉴질랜드와 오스트리아에서는 APACHE III 보다 더 잘 assessment 되었다.

13. Annual proportion of SIRS-positive & negative sepsis

14. SIRS IN SEVERE SEPSIS

15. OUTCOMES
Mortality
36.1%
18.3%
27.7%
8.5%

16. Discharge to rehabilitation
OUTCOMES
Discharge to rehabilitation
Discharge home
Adjusted Mortality & Discharge

17. PREDICTION OF MORTALITY (risk of death)
13% linear increase in mortality was associated with each additional SIRS criterion (odds ratio=1.13) without any transitional increase in risk

18. PREDICTION OF MORTALITY (risk of death)
Multivariable analysis for mortality in severe sepsis
Model 1: SIRS criteria as a binomial variable (≥2 vs. <2 criteria)
Model 2: SIRS criteria as a continuous variable (0 to 4)
SIRS criteria를 이항변수와 연속변수
Auc= area under the curve

19. PREDICTION OF MORTALITY ACCORDING TO SIRS-POSITIVE OR SIRS-NEGATIVE STATUS
Of 16 identified predictors of mortality, the only variable that differed significantly between the two groups was illness severity

20. DISCUSSION
We studied the sensitivity, face validity, and construct validity of the rule of 2 or more SIRS criteria for the diagnosis of severe sepsis in the first 24 hours after ICU admission
We found that the SIRS-criteria rule missed one patient in eight with severe sepsis (SIRS negative severe sepsis)
lower but still substantial mortality and the incidence, proportion, and mortality decreased over time almost identically to the rates among patients with SIRS positive sepsis
their discharge rates to a rehabilitation or longterm care facility were also similar
mortality increased linearly with each additional SIRS criterion from 0 to 4 without any transitional increase in risk at a threshold of two criteria
the cutoff point of two SIRS criteria does not define any specific transition point for risk

21. DISCUSSION Several strengths
Investigates the effect of SIRS criteria within 24 hrs after ICU adm on the diagnosis of severe sepsis over 14 years
Large-scale study
the SIRS data that were prospectively collected for routine quality-surveillance purposes and are therefore unlikely to be biased
our findings are broadly consistent with the limited existing literature and include data from 172 ICUs, which increases external validity, and data obtained in 2013, which increases contemporary relevance

22. DISCUSSION Limitations
The data were collected primarily for quality-control purposes and not for study purposes
Symptoms meeting SIRS criteria only during the first 24 hours as recorded either every 30 minutes or every 60 minutes on the charts
The accuracy of specific diagnostic coding of infections was not independently monitored
Our definition of organ failure related only to the first 24 hours  organ failure on the second day were missed

23. CONCLUSION
In this epidemiologic study, the requirement of two or more SIRS criteria for the diagnosis of severe sepsis excluded a sizable group of patients in the ICU with infection and organ failure  “SIRS-negative severe sepsis”
These patients had substantial mortality and, had epidemiologic characteristics and changes that were essentially identical to those of patients with SIRS-positive severe sepsis  indirect empirical evidence that these two groups of patients represent separate phenotypes of the same condition

24. CONCLUSION
The risk of death in the two groups increased linearly with each additional SIRS criteria from 0 to 4, without a transitional increase in risk at two criteria
Our findings challenge the sensitivity, face validity, and construct validity of the rule regarding two or more SIRS criteria in defining severe sepsis in patients in the ICU