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The Impact of Acute Organ Dysfunction on Long-Term Survival in Sepsis*

Schuler, Alejandro, MS1; Wulf, David, A., BS2; Lu, Yun, MD, MPH2; Iwashyna, Theodore, J., MD, PhD3; Escobar, Gabriel, J., MD2; Shah, Nigam, H., MBBS, PhD1; Liu, Vincent, X., MD, MS2

doi: 10.1097/CCM.0000000000003023
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Objectives: To estimate the impact of each of six types of acute organ dysfunction (hepatic, renal, coagulation, neurologic, cardiac, and respiratory) on long-term mortality after surviving sepsis hospitalization.

Design: Multicenter, retrospective study.

Settings: Twenty-one hospitals within an integrated healthcare delivery system in Northern California.

Patients: Thirty thousand one hundred sixty-three sepsis patients admitted through the emergency department between 2010 and 2013, with mortality follow-up through April 2015.

Interventions: None.

Measurements and Main Results: Acute organ dysfunction was quantified using modified Sequential Organ Failure Assessment scores. The main outcome was long-term mortality among sepsis patients who survived hospitalization. The estimates of the impact of each type of acute organ dysfunction on long-term mortality were based on adjusted Cox proportional hazards models. Sensitivity analyses were conducted based on propensity score–matching and adjusted logistic regression. Hospital mortality was 9.4% and mortality was 31.7% at 1 year. Median follow-up time among sepsis survivors was 797 days (interquartile range: 384–1,219 d). Acute neurologic (odds ratio, 1.86; p < 0.001), respiratory (odds ratio, 1.43; p < 0.001), and cardiac (odds ratio, 1.31; p < 0.001) dysfunction were most strongly associated with short-term hospital mortality, compared with sepsis patients without these organ dysfunctions. Evaluating only patients surviving their sepsis hospitalization, acute neurologic dysfunction was also most strongly associated with long-term mortality (odds ratio, 1.52; p < 0.001) corresponding to a marginal increase in predicted 1-year mortality of 6.0% for the presence of any neurologic dysfunction (p < 0.001). Liver dysfunction was also associated with long-term mortality in all models, whereas the association for other organ dysfunction subtypes was inconsistent between models.

Conclusions: Acute sepsis-related neurologic dysfunction was the organ dysfunction most strongly associated with short- and long-term mortality and represents a key mediator of long-term adverse outcomes following sepsis.

1Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA.

2Division of Research, Kaiser Permanente Northern California, Oakland, CA.

3Department of Medicine and Institute for Social Research, University of Michigan and VA Center for Clinical Management Research, VA Ann Arbor Health Healthcare System, Ann Arbor, MI.

*See also p. 1001.

This work does not necessarily represent the views of the U.S. Government or Department of Veterans Affairs.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Supported, in part, by The Permanente Medical Group. Dr. Liu was supported by the National Institutes of Health K23GM112018; Dr. Iwashyna was supported by VA HSR&D IIR 13–079.

Dr. Schuler disclosed work for hire. Dr. Iwashyna disclosed government work. Dr. Escobar’s institution received funding from National Institute of General Medical Sciences. Drs. Escobar, Shah, and Liu received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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