Importance Severe sepsis and septic shock are major causes of mortality in intensive care unit (ICU) patients. It is unknown whether progress has been made in decreasing their mortality rate.Objective To describe changes in mortality for severe sepsis with and without shock in ICU patients.Design, Setting, and Participants Retrospective, observational study from 2000 to 2012 including 101 064 patients with severe sepsis from 171 ICUs with various patient case mix in Australia and New Zealand.Main Outcomes and Measures Hospital outcome (mortality and discharge to home, to other hospital, or to rehabilitation).Results Absolute mortality in severe sepsis decreased from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12 512; P < .001), representing an overall decrease of 16.7% (95% CI, 14.8%-18.6%), an annual rate of absolute decrease of 1.3%, and a relative risk reduction of 47.5% (95% CI, 44.1%-50.8%). After adjusted analysis, mortality decreased throughout the study period with an odds ratio (OR) of 0.49 (95% CI, 0.46-0.52) in 2012, using the year 2000 as the reference (P < .001). The annual decline in mortality did not differ significantly between patients with severe sepsis and those with all other diagnoses (OR, 0.94 [95% CI, 0.94-0.95] vs 0.94 [95% CI, 0.94-0.94]; P = .37). The annual increase in rates of discharge to home was significantly greater in patients with severe sepsis compared with all other diagnoses (OR, 1.03 [95% CI, 1.02-1.03] vs 1.01 [95% CI, 1.01-1.01]; P < .001). Conversely, the annual increase in the rate of patients discharged to rehabilitation facilities was significantly less in severe sepsis compared with all other diagnoses (OR, 1.08 [95% CI, 1.07-1.09] vs 1.09 [95% CI, 1.09-1.10]; P < .001). In the absence of comorbidities and older age, mortality was less than 5%.Conclusions and Relevance In critically ill patients in Australia and New Zealand with severe sepsis with and without shock, there was a decrease in mortality from 2000 to 2012. These findings were accompanied by changes in the patterns of discharge to home, rehabilitation, and other hospitals. joi140034f1.pngjoi140034f2.pngSevere sepsis and septic shock are the biggest cause of mortality in critically ill patients.1,2 Over the last 20 years, multiple randomized controlled trials (RCTs) have attempted to identify new treatments to improve the survival of these patients. Earlier RCTs of activated protein C,3 early goal-directed therapy,4 and low-dose hydrocortisone5 showed promise. However, later pivotal RCTs6- 15 and observational studies failed to confirm improvements in mortality or challenged their external validity.16,17 Randomized controlled trials of antithrombin III,6 tifacogin,7 activated protein C,8,9 vasoactive drugs,10,12 hydrocortisone,13 fludrocortisone,14 intensive insulin therapy,11,14 large-molecular-size hydroxyethyl starch,11 and eritoran15 all failed to improve mortality despite positive phase 2 studies and highly supportive animal studies. These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis18,19 and a view that improvements are unlikely. However, the accuracy of these negative views has not been tested in a large population of intensive care unit (ICU) patients with severe sepsis. Accordingly, we sought to estimate trends in mortality in a large cohort of patients with severe sepsis from 2000 to 2012. We hypothesized that mortality rates have decreased significantly over the last decade.
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