Table 5 Risk-adjusted impact of bundle targets on hospital mortality Bundle target Measure lactate Obtain blood cultures before antibiotics Commence broad-spectrum antibiotics Achieve tight glucose control Administer drotrecogin alfa Administer drotrecogin alfa Administer low-dose steroids Demonstrate CVP C8 mmHg Demonstrate ScvO2 C70% Achieve low plateau pressure control Population Alla Alla Alla Alla Multi-organ failureb Shock despite ﬂuidsc Shock despite ﬂuidsc Shock despite ﬂuidsc Shock despite ﬂuidsc Mechanical ventilationd N 15,022 15,022 15,022 15,022 8,733 7,854 7,854 7,854 7,854 7,860 Unadjusted Risk-adjusted OR 0.86 0.70 0.78 0.65 0.90 0.91 1.06 1.08 0.94 0.67 P value \0.0001 \0.0001 \0.0001 \0.0001 0.26 0.30 0.18 0.10 0.24 \0.0001 OR 0.97 0.76 0.86 0.67 0.84 0.81 1.06 1.00 0.98 0.70 95% CI [0.90, 1.05] [0.70, 0.83] [0.79, 0.93] [0.62, 0.71] [0.69, 1.02] [0.68, 0.96] [0.96, 1.17] [0.89, 1.12] [0.86, 1.10] [0.62, 0.78] a Model ﬁt statistics: C = 22.2 with 18 df, P = 0.22, log-likelihood R2 28.1%, a v2 dispersion of 1.05 b Model ﬁt statistics: C = 28.7 with 18 df, P = 0.053, log-likelihood R2 20.5%, a v2 dispersion of 1.08 c Model ﬁt statistics: C = 24.3 with 18 df, P = 0.15, log-likelihood R2 11.4%, a v2 dispersion of 1.00 d Model ﬁt statistics: C = 6.61 with 18 df, P = 0.99, log-likelihood R2 27.0%, a v2 dispersion of 1.06 229 P value 0.48 \0.0001 \0.0001 \0.0001 0.07 0.02 0.24 0.98 0.69 \0.0001 mortality. Therefore, attention to adjustment for severity In conclusion, the results of this study demonstrate of patient illness at time of enrollment should be that the use of a multifaceted performance improvement attempted. initiative was successful in changing sepsis treatment Similarly, failure to achieve blood glucose control behavior as evidenced by a signiﬁcant increase in com- despite attempting to do so is not the same as failure to pliance with sepsis performance measures. This make the attempt. Attempting to discriminate failure to compliance was associated with a signiﬁcant reduction in achieve a target versus patient responsiveness adds a layer hospital mortality in patients with severe sepsis and septic of complexity and subjectivity to the scoring process that shock over the duration of the 2-year study, but the study would be difﬁcult to validate. Nevertheless, because design does not allow us to say, with certainty, whether patient responsiveness is unlikely to change over time, the this was due to some or all bundle elements, increased scoring should reﬂect each hospital’s improvement awareness of severe sepsis, or other unrelated factors. attempts. By combining a number of elements in the care Many unanswered questions remain that could provide bundles, the Campaign sought to maximize outcome direction for future research, including the mortality trend improvement. At the same time, such an approach com- in hospitals that have not implemented the bundles, and promises measuring the effect of individual elements. conﬁrmation of which components of the bundles reduce The fact that performance improvement studies are mortality. These results are consistent with an earlier susceptible to general trends in the change in mortality report from Spain [38], and extend the ﬁndings of that and clinical practice patterns over time is another poten- study by suggesting that the improvement in achievement tial limitation of the study, but the variable start times for of bundle targets and association with improved outcome each site established that such effects were unlikely to is sustained over time and is demonstrated across a wide explain the improvement in mortality. The baseline number of countries and settings. Professional societies mortality rate for sites entering at variable times frequently generate evidence-based clinical practice throughout the 2-year study period did not change. For- guidelines, but efforts to disseminate such guidelines have mal severity scores were not obtained for patients entered rarely been of a scale comparable to this Campaign. The into the database due to limited personnel resources in the results of this study should encourage similar efforts to absence of external site funding and conﬁdentiality con- implement guidelines as a means to improve outcomes. cerns. Therefore, decreasing mortality seen over the 2- year initiative might be explained by the enrollment of Acknowledgments The authors gratefully acknowledge the dedi- less severely ill patients over time, in spite of the static cation and efforts of Deb McBride during the Campaign and in the baseline center mortality. To control for entry of less vdiedvuealolsplmeaednitngofththeiesffmoratnautscprairptti.ciWpaetinaglssoiteasckwnhoowmleaddgee atlhleofinthdiis- severely ill patients in the database over time as the rea- happen as volunteers who believed in the Campaign and what we son for decreasing mortality, severity was assessed based were trying to accomplish as their sole motivation. The work was on variables linked to patient mortality that were available supported by Eli Lilly and Co., Edwards Lifesciences, Philips in the database (Table 4). When mortality was adjusted EMuerdoipceaalnSSyoscteiemtys,ofthIenteSnosciiveetyCaorfe MCreitdiiccailneC.are Medicine, and accordingly, although the magnitude of the effect was Dr. Levy has received grants from Eli Lilly & Co and Philips slightly reduced, it remained statistically signiﬁcant. Medical Systems. Dr. Marshall has consultancies with Eisai, Eli