However, it is noteworthy that in our study, antibiotic therapy (appropriate or inappropriate) was not shown to be significantly associated sellectchem with time to death, right censored at 28 days, which reflects findings by other authors [50]. It is more probable that the severity, mirrored by the level of organ dysfunction at the time of the shock, and expressed by the SOFA score, is a major determinant of mortality in septic shock patients. Therefore, an organ dysfunction score should be measured at inclusion in sepsis studies, as it can be used for stratification of patients and for adjustment when assessing outcome [38]. In addition to these variables, others factors not measured in our study may also influence outcome in patients with septic shock and thus help refine prognostic prediction.

For example, cytokine levels or other markers of inflammation may have a role to play, as suggested by a recent expert panel [7].This study has several strengths. Diagnosis of septic shock was prospective and used standard criteria similar to those used in most clinical trials in this clinical setting. The sites included both university teaching hospitals and general (non-academic) hospitals of various sizes. Accrual was over a relatively long but contemporary time period, with prospective inclusion of all consecutive patients and practically no loss to follow-up. The population was homogeneous, comprising only patients with septic shock, and not a mix of sepsis, severe sepsis, and septic shock as in many published studies.

The large sample size yields narrow confidence intervals around the estimates of mortality and made it possible to include a considerable number of variables in the regression analysis. Participating sites entered study data directly into a specially designed software programme, and data were of a high standard thanks to extensive data checking at the time of data entry by the clinical research assistants. Similarly, data were monitored, verified, and analyzed by a highly-qualified, central coordinating center (INSERM CIE 1).Conversely, a few limitations of this study deserve to be underlined, and include the lack of detailed pre-ICU-admission data (for example, fluid challenge, exact time of onset of signs of sepsis). The majority of known prognostic factors were included in our analysis, but we cannot exclude that other variables not recorded in our study (for example, biomarkers) may have influenced outcome.

Since selection of the investigating sites was on a voluntary basis, there is a possibility that only the most AV-951 motivated centers participated, and results should not be extrapolated to other contexts. Furthermore, the fact that several participating sites were also participating in the Prowess-Shock study may have influenced prescriptions of drotrecogin alpha in our study.