Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*

Abstract

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.

Figure 1

Flow diagram for selection of severe sepsis trials.

Figure 2

Severe sepsis mortality trends comparing multicenter trials by date of patient enrollment, Martin administrative definition and Angus administrative definition. ICD-9-CM codes for severe sepsis and septic shock were introduced in 2002 and 2003 respectively.