Implications of Study Findings
Our study provides evidence that sepsis-related mortality has steadily decreased over time even after adjustments for illness severity, center effect, regional effects, hospital size, risk of being septic, and other key variables. It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy according to severity of the disease32,39 contributed to this change. The observation that an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings. These changes in outcome remained after multiple adjustments for confounders, including illness severity, and even after taking into account changes in discharge destinations. This makes it unlikely that the decrease in mortality is dependent only on less sick patients being admitted to ICU or on patients being discharged to other hospitals or to rehabilitation.
Comorbidities were present in 35% of patients. This implies that, if such a significant proportion of sepsis patients were excluded from RCTs, there would be a risk of selection bias and recruitment failure. If such patients are excluded, the mortality figures used for power calculations should be based on the lower mortality rate seen in comorbidity-free patients (14.0% in 2012). Young septic patients without comorbidities represent a group of patients where the mortality attributable to sepsis can be assessed with fewer confounders.40 The mortality of severe sepsis in these patients was 4.6% in 2012. Given such low mortality rates, long-term morbidity and quality of life will likely become the focus of future trials
Implications of Study FindingsOur study provides evidence that sepsis-related mortality has steadily decreased over time even after adjustments for illness severity, center effect, regional effects, hospital size, risk of being septic, and other key variables. It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy according to severity of the disease32,39 contributed to this change. The observation that an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings. These changes in outcome remained after multiple adjustments for confounders, including illness severity, and even after taking into account changes in discharge destinations. This makes it unlikely that the decrease in mortality is dependent only on less sick patients being admitted to ICU or on patients being discharged to other hospitals or to rehabilitation. Comorbidities were present in 35% of patients. This implies that, if such a significant proportion of sepsis patients were excluded from RCTs, there would be a risk of selection bias and recruitment failure. If such patients are excluded, the mortality figures used for power calculations should be based on the lower mortality rate seen in comorbidity-free patients (14.0% in 2012). Young septic patients without comorbidities represent a group of patients where the mortality attributable to sepsis can be assessed with fewer confounders.40 The mortality of severe sepsis in these patients was 4.6% in 2012. Given such low mortality rates, long-term morbidity and quality of life will likely become the focus of future trials
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