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Two Decades of Mortality Trends Among Patients With Severe Sepsis: A Comparative Meta-Analysis*

Stevenson, Elizabeth K. MD, MS1,2; Rubenstein, Amanda R. MD3; Radin, Gregory T. MD3; Wiener, Renda Soylemez MD, MPH1,2,4,5; Walkey, Allan J. MD, MSc1,2

doi: 10.1097/CCM.0000000000000026
Clinical Investigations

Objectives: Trends in severe sepsis mortality derived from administrative data may be biased by changing International Classification of Diseases, 9th Revision, Clinical Modification, coding practices. We sought to determine temporal trends in severe sepsis mortality using clinical trial data that does not rely on International Classification of Diseases, 9th Revision, Clinical Modifications coding and compare mortality trends in trial data with those observed from administrative data.

Design: We searched MEDLINE for multicenter randomized trials that enrolled patients with severe sepsis from 1991 to 2009. We calculated standardized mortality ratios for each trial from observed 28-day mortality of usual care participants and predicted mortality from severity-of-illness scores. To compare mortality trends from clinical trials to administrative data, we identified adult severe sepsis hospitalizations in the Nationwide Inpatient Sample, 1993–2009, using two previously validated algorithms.

Setting: In-patient.

Patients: Patients with severe sepsis or septic shock.

Interventions: None.

Measurements and Main Results: Of 3,244 potentially eligible articles, we included 36 multicenter severe sepsis trials, with a total of 14,418 participants in a usual care arm. Participants with severe sepsis receiving usual care had a 28-day mortality of 33.2%. Observed mortality decreased 3.0% annually (95% CI, 0.8%–5.0%; p = 0.009), decreasing from 46.9% (standardized mortality ratio 0.94; 95% CI, 0.86–1.03) during years 1991–1995 to 29% (standardized mortality ratio 0.53; 95% CI, 0.50–0.57) during years 2006–2009 (3.0% annual change). Trends in hospital mortality among patients with severe sepsis identified from administrative data (Angus definition, 4.7% annual change; 95% CI, 4.1%–5.3%; p = 0.69 and Martin definition, 3.5% annual change; 95% CI, 3.0%–4.1%; p = 0.97) were similar to trends identified from clinical trials.

Conclusion: Since 1991, patients with severe sepsis enrolled in usual care arms of multicenter randomized trials have experienced decreasing mortality. The mortality trends identified in clinical trial participants appear similar to those identified using administrative data and support the use of administrative data to monitor mortality trends in patients with severe sepsis.

Supplemental Digital Content is available in the text.

1The Pulmonary Center, Boston University School of Medicine, Boston, MA.

2Division of Pulmonary, Allergy, and Critical Care Medicine Internal Medicine, Boston Medical Center, Boston, MA.

3Department of Medicine, Boston Medical Center, Boston, MA.

4Center for Healthcare Organization & Implementation Research, Edith Nourse Rogers Memorial VA Hospital, Bedford, MA.

5The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Medical School, Hanover, NH.

* See also p. 747.

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 (

Dr. Wiener received support for article research from National Institutes of Health (NIH). She received grant K07 CA138772 and support from the Department of Veterans Affairs. Her institution received grant support from National Cancer Institute (NCI K07138772). Dr. Walkey received grants K01HL116768 and R21 HL112672 from the National Institutes of Health, National Heart, Lung, and Blood Institute. He received royalties from UpToDate (weaning from mechanical ventilation chapter), support for travel from University of Michigan (visiting Professorship), and support for article research from NIH. His institution received grant support from the NIH (NHLBI R21 and K01 grants). Funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins