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Methods: We evaluated patients in annual intervals before and after bundle implementation in March 2013. We evaluated bundle compliance and compared outcome measures across groups with multivariable logistic regression. Because of their perceived risk for iatrogenic fluid overload, we also evaluated patients with a history of heart failure and/or chronic kidney disease.Measurements and Main Results: We identified 18,122 patients with sepsis and intermediate lactate values, including 36.1% treated after implementation. Full bundle compliance increased from 32.2% in 2011 to 44.9% after bundle implementation (P , 0.01). Hospital mortality was 8.8% in 2011, 9.3% in 2012, and 7.9% in 2013 (P = 0.02). Treatment after bundle implementation was associated with an adjusted hospital mortality odds ratio of 0.81 (95% confidence interval, 0.66-0.99; P = 0.04). Decreased hospital mortality was observed primarily in patients with a heart failure and/or kidney disease history (P , 0.01) compared with patients without this history (P . 0.40). This corresponded to notable changes in the volume of fluid resuscitation in patients with heart failure and/or kidney disease after implementation.Conclusions: Multicenter implementation of a treatment bundle for patients with sepsis and intermediate lactate values improved bundle compliance and was associated with decreased hospital mortality. These decreases were mediated by improved mortality and increased fluid administration among patients with a history of heart failure and/or chronic kidney disease.

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