Although no single explanation can be offered for our findings, they challenge the view that little progress has been made in the management of severe sepsis. They also suggest that outcomes for severe sepsis should be interpreted according to the year of data collection and that, on average, a yearly 1% improvement in crude mortality can be expected. Accordingly, RCTs in this field that last several years should consider this effect when estimating statistical power. Mortality in severe sepsis or septic shock appears lower than in published figures used for calculations of trial sample size.6,9- 15 This overestimation of mortality may lead to underpowered studies and to potentially useful therapies being abandoned because of lack of evidence.18 Finally, our findings provide a point of reference for current and evolving hospital mortality rates in septic patients overall and in specific subgroups of septic patients.
Strengths and Weaknesses
To our knowledge, our study is the only investigation of changes in mortality in septic ICU patients over an entire decade with adjustment for APACHE III risk of death and for multiple other relevant covariates and with identification and consistent use of the same full criteria for severe sepsis and septic shock on the day of admission. Second, we retrieved the data from a database that, by 2012, included more than 90% of all ICU admission in the binational area of Australia and New Zealand. The data were collected prospectively for routine quality surveillance purposes. Such data, therefore, are unlikely to be biased or affected by changing diagnostic criteria. Third, the size of the study cohort enabled robust annual analysis of mortality rates. Fourth, the findings were consistent in subgroups and consistent with existing literature. Finally, the incidence of severe sepsis in ICU patients was identical to that reported in the previous prospective study of the same ICUs.
Our findings are limited by the fact that the diagnosis of severe sepsis only applied to patient characteristic during the first 24 hours in ICU. Thus, patients who developed severe sepsis later while in the ICU were not analyzed. The accuracy of severe sepsis diagnosis was not monitored, but the data were collected by trained collectors and we used physiological coding for systemic inflammatory response syndrome and organ failure, which are less subject to coding artifact. We also accounted for the APACHE admission diagnoses of sepsis as well as APACHE admission diagnoses for infection to ensure that diagnostic coding changes would not affect the capture of all severe sepsis.42 In addition, the diagnostic criteria for severe sepsis were kept constant throughout the study, enabling us to detect changes in mortality over time in an unbiased way. Finally, we can only report hospital mortality, which may be higher than 28-day mortality8,27,43 but is likely lower than 90-day mortality10,14 and can be used as a surrogate for 30-day mortality