Since the manuscript was primarily rejected by CCM, we did not send a revised version to CCM.
However, we extensively reacted to the points made by the veviewers as explained in detail.
Von: journals@sccm.org
Datum: 31. Mai 2008 22:25:11 MESZ
An: manfred.weiss.ulm@online.de
Betreff: Critical Care Medicine-Manuscript CCM-00603-2008 Decision
31-May-2008
Reviewers' Critiques:
Reviewer: 1
Nothing to change.
Reviewer: 2
It is no longer hypothesised that the sepsis definitions criteria (original 1992 versus the revision) are used to predict outcome.
Reviewer: 3
It is now stated througout the manuscript that the patient population was entirely comprised of postoperative and posttraumatic patients. Considerable clarification for language have been performed. Finally, the conclusion has been clarified.
General comments:
Abstract: The conclusions now refer to the specific population studied. The proportion of trauma patients in the study is mentioned now. The very specific population has been made clear now throughout the manuscript, particularly in the conclusions of both the abstract and the main manuscript.
Introduction:
Pg 2: The reason for the expanded list in the 2003 paper to better reflect the clinical reality of how physicians diagnose sepsis in practice, rather than to facilitate earlier diagnosis is given now.
Results:
We apply the term SIRS to the 2003 definitions for our patient population using the expanded list of signs and symptoms to describe the inflammatory response in the subgroup of patients without infection.
Para 2, last sentence: The “SIRS subgroup” has been separated from the „sepsis subgroup“ in the results section.
Discussion:
Pg 5, para 3: It is written now that if the mortality rate in the septic shock group with the new definitions is low, then a properly powered study would have to be larger, in order to demonstrate an equivalent mortality reduction compared with a population with the old definitions in which the mortality rate is higher.
Pg 5, para 4: The paragraph with biomarkers and clinical scores to improve diagnosis and valid classification of patients with sepsis has been put in the right context.
Pg 5, para 5: This paragraph has been clarified.

Conclusions:
This paragraph has been rewritten for clarity.
Reviewer: 4
WEAKNESSES. o The primary hypothesis of this study is to find out the case mix within the same collective of postoperative/posttraumatic patients applying either the original 1992 ACCP/SCCM or the
2003 SCCM/ESICM/ACCP/ATS/SIS sepsis definitions. o From 01/2007 to 12/2007, 827 postoperative/posttraumatic patients were admitted to the ICU, 765 were surveyed daily using computer-assistance with respect to SIRS and sepsis.
Scores with the 1992 and the 2003 definitions were available in 742 patients. o Patients admitted and discharged from the ICU within less than 24 hours without beeing scored were excluded. o
It is now described in the “Materials and methods, Patients and data collection section“ how patients were screened. o It is now described in the “Materials and methods, Patients and data collection section“ how the diagnoses were ascertained, was checked and how physicians were adjudicated. Score relevant data were entered on a daily base in standardized electronic case report forms leading through the different organ systems and relevant infection parameters.
After completion of data input, scores were automatically calulated. o states?
The patients were screened daily for the presence or absence of the SIRS and/or sepsis o The most severe state was counted, i. e., if a patient with SIRS at entry in the ICU contracted a severe sepsis while he was in the ICU, he counted as severe sepsis patient. o o
The most severe state of every patient was counted only once.
The patients included in this study are described in detail now. Their SAPSII score describing their severity of illness, their age and gender, the number of cases of trauma, type of surgery, infections detected in patients with sepsis, and SOFA scores reflecting organ dysfunctions are given now. o It was mortality in the ICU. o o
The statistical tests used are described in detail now.
The prevalence of severe SIRS and SIRS shock as well as severe sepsis and septic shock according to the 1992 and the 2003 definitions are now compared by McNemar’s test.
Logistic regression for the outcome death among patients with documented infections was applied to simultaneously assess the impact of the 1992 and the 2003 sepsis definitions. Odds ratios (ORs), with corresponding 95% confidence interval (CI) and p-values are presented.
Sensitivity and specificity of the 1992 and 2003 definitions to predict deaths among patients with documented infections were calculated with 95% CI. o It is now stated that the most important message of this paper is that we cannot compare the results of clinical trials where SIRS and sepsis states are diagnosed with the 1992 versus the 2003 sets of definitions, because the case mix will be different. This is now clearly written in the discussion. o Sensitivity and secificity are given now. Potential consequences of the higher detection of patients with severe sepsis and septic shock by the 2003 definitions are discussed now.

o Sensitivity and specificity of the 1992 and 2003 definitions to predict deaths among patients with documented infections were calculated with 95% CI, and are carefully interpreted.
o The limitations of this study are better highlighted. It is underlined that this study involved only cases of surgery and of trauma and have to be investigated in medical cases. o Statements have been clarified. It is cleary stated that the diagnostic criteria of SIRS and septic states advocated in year 2003 were not developed to predict death.
CONCLUSION OF THE GENERAL COMMENTS. The the science has been improved, and significant information is provided now in the manuscript, such as a description of the case mix.
SPECIFIC COMMENTS
Abbreviations and acronyms are defined in the body text and repeated.
INTRODUCTION, 2nd paragraph. Cut-off vlaues of variables changed.
DISCUSSION. A new paragraph on what can be done in the future to improve the validity of the criteria advocated to diagnose SIRS and septic states has been included.
REFERENCES The references have been formatted according to the editorial standards of the journal Critical Care.
TABLES
Table 2 focuses now on patients with documented infections.
Reviewer: 5
General Comments:
1) The 2003 criteria have not essentially replaced the 1992 criteria.
2) The findings reported would be expected but up to now, the case mixes resulting within the same patient collective using the 1992 or the 2003 criteria have not been compared.
3) The use to either a clinician or researcher may be to get aware that definition of sepsis criteria strongly influences prevalence and mortality rates of sepsis, that we cannot compare the results of clinical trials where SIRS and sepsis states are diagnosed with the 1992 versus the 2003 sets of definitions, because the case mix will be different, and that uniformity of sepsis/SIRS definition is essential in the evaluation of new therapies in the ICU. The present study underlines the need for a widespread use of common sepsis definitions to optimize comparability, diagnosis, treatment recommendations, and enrollment strategies for clinical trials of surgical patients with sepsis.
4) It is clearly stated that he results and conclusions are limited primarily to post-operative and trauma associated SIRS and sepsis.