Subjects (%) N = 15,022 Sites (%) N = 165 19.3 39.8 40.9 69.3 30.7 17.0 78.4 4.6 41.0 47.0 12.0 227 and maintaining blood glucose control (OR 0.67, 95% CI 0.62–0.71, P \ 0.0001) were all associated with lower hospital mortality. Measuring lactate was not associated with improved outcome (OR 0.97, 95% CI 0.90–1.05, P = 0.48) (Table 5). The administration of drotrecogin alfa in the ﬁrst 24 h was associated with improved sur- vival in those with shock (OR 0.81, 95% CI 0.68–0.96, P = 0.02). For those who required mechanical ventila- tion, achieving plateau pressure control was associated with improved outcome (OR 0.70, 95% CI 0.62–0.78, P \ 0.0001). In those with septic shock, there was no association between mortality and the use of low-dose steroids, the ability to achieve a CVP C8 mmHg, or demonstration of ScvO2 C70%. Table 2 Cohort characteristics Site characteristics Hospital size \250 beds 250–500 beds [500 beds Teaching status Teaching Non-teaching ICU Type Medical Medical/surgical Other Region Europe North America South America Patient characteristics 9.9 42.3 47.8 69.2 30.8 23.3 71.3 5.4 31.1 58.9 10.0 Subjects (%) Hospital mortality (%) Discussion All 100 34.8 The Surviving Sepsis Campaign—a performance Source 52.4 27.6 improvement effort by hospitals across Europe, South ED 12.8 41.3 America, and the US—recruited the largest prospective ICU Ward 34.8 46.8 series of severe sepsis patients yet studied. The effort took Site of infection place in 30 countries, was voluntary (no sites or clinicians Pneumonia 2404..84 2358..12 were paid for data collection or for becoming part of the UTI 21.1 40.8 Campaign), and was multidisciplinary, reﬂecting the Abdominal 1.6 23.0 ethos of the founding professional societies. By instituting Meningitis Skin 5.9 28.6 a practice improvement program grounded in evidence- Bone 13..28 3312..92 based guidelines, SSC increased compliance with the Wound 4.1 33.9 change bundles that was associated with better patient Catheter 1.1 41.0 outcomes. These results are consistent with other pub- Endocarditis Device 1.1 42.5 lished studies that established the impact of performance Other infection 12.7 33.1 ‘‘bundles’’ on outcomes [32–35]. Baseline acute organ dysfunctions 85.6 35.4 SSC was a performance improvement process, and not Cardiovasculara 30.8 41.5 a dedicated scientiﬁc evaluation of the impact of the Pulmonaryb Renab 39.5 40.5 guidelines on clinical outcome. Efﬁcacy was inferred by Hepaticb 10.2 45.1 observation of change over time, rather than through the Hematologicb 25.7 45.0 more rigorous approach of a randomized controlled trial. Number of acute organ Thus, conclusions regarding the clinical impact of bundle dysfunctions 1 41.8 27.4 elements, or even of the process itself, must be interpreted 2 32.2 34.4 with caution. The observation that early detection of 43 61.74.8 4532..75 infection and institution of antibiotic therapy led to 5 1.8 63.6 improved survival is consistent with both empirical data Cardiovascular [36] and generally held professional opinion. On the other No cardiovascular dysfunction 13.5 31.0 hand, the observation that achievement of glucose control Cardiovascular dysfunction no 15.0 21.2 is associated with better outcome is not necessarily sup- Shhoycpkotension ported by recent RCT data [37]. Lactate [4 only 5.4 29.9 Certain limitations must be considered in interpreting Vasopressors only 49.5 36.7 these ﬁndings. Participation in the process was entirely Lactate [4 and vasopressors 16.6 46.1 voluntary. The hospitals themselves are not necessarily Total shock 71.5 38.4 representative of hospitals that did not participate, and the a Includes hypotension regardless of response to ﬂuids and elevated generalizability of our ﬁndings is, therefore, speculative. lactate Further, we do not know whether the patients were a b Per severe sepsis screening tool, supplemental Fig. 1 online comprehensive or representative sample of all potentially