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Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.
The report was simultaneously published online March 18 in JAMA.
In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.
At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.
The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).
A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But 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," they wrote.
During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.
Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.
This "compelling" study "overcomes many of the limitations of prior studies" concerning sepsis-related mortality by virtue of its careful design, according to Dr. Theodore J. Iwashyna and Dr. Derek C. Angus.
The study investigators first amassed a huge amount of data to examine from an ICU registry of more than 1 million patients seen during an extended (12-year) period. Then they diligently identified all hospitalizations for infection, even those that weren’t labeled as "severe sepsis," then applied "objective definitions of acute organ dysfunction carefully abstracted at the bedside by nurse abstractors."
Dr. Kaukonen and her colleagues used a variety of analytical strategies to verify that what they found were not misleading artifacts but "true changes in the epidemiology of severe sepsis." And they performed several sensitivity analyses of the data, all of which confirmed the results of the main analysis.
These observations were taken from an editorial by Dr. Iwashyna and Dr. Angus accompanying Dr. Kaukonen’s report (JAMA 2014 March 18 [doi:10.1001/jama.2014.2639]). Dr. Iwashyna is with the division of pulmonary and critical care in the department of internal medicine at the University of Michigan, Ann Arbor, and is with the Veterans Affairs Ann Arbor Health System. Dr. Angus, a contributing editor at JAMA, in the department of critical care medicine at the University of Pittsburgh. Dr. Iwashyna reported no potential financial conflicts of interest; Dr. Angus reported ties to several pharmaceutical firms.
This "compelling" study "overcomes many of the limitations of prior studies" concerning sepsis-related mortality by virtue of its careful design, according to Dr. Theodore J. Iwashyna and Dr. Derek C. Angus.
The study investigators first amassed a huge amount of data to examine from an ICU registry of more than 1 million patients seen during an extended (12-year) period. Then they diligently identified all hospitalizations for infection, even those that weren’t labeled as "severe sepsis," then applied "objective definitions of acute organ dysfunction carefully abstracted at the bedside by nurse abstractors."
Dr. Kaukonen and her colleagues used a variety of analytical strategies to verify that what they found were not misleading artifacts but "true changes in the epidemiology of severe sepsis." And they performed several sensitivity analyses of the data, all of which confirmed the results of the main analysis.
These observations were taken from an editorial by Dr. Iwashyna and Dr. Angus accompanying Dr. Kaukonen’s report (JAMA 2014 March 18 [doi:10.1001/jama.2014.2639]). Dr. Iwashyna is with the division of pulmonary and critical care in the department of internal medicine at the University of Michigan, Ann Arbor, and is with the Veterans Affairs Ann Arbor Health System. Dr. Angus, a contributing editor at JAMA, in the department of critical care medicine at the University of Pittsburgh. Dr. Iwashyna reported no potential financial conflicts of interest; Dr. Angus reported ties to several pharmaceutical firms.
This "compelling" study "overcomes many of the limitations of prior studies" concerning sepsis-related mortality by virtue of its careful design, according to Dr. Theodore J. Iwashyna and Dr. Derek C. Angus.
The study investigators first amassed a huge amount of data to examine from an ICU registry of more than 1 million patients seen during an extended (12-year) period. Then they diligently identified all hospitalizations for infection, even those that weren’t labeled as "severe sepsis," then applied "objective definitions of acute organ dysfunction carefully abstracted at the bedside by nurse abstractors."
Dr. Kaukonen and her colleagues used a variety of analytical strategies to verify that what they found were not misleading artifacts but "true changes in the epidemiology of severe sepsis." And they performed several sensitivity analyses of the data, all of which confirmed the results of the main analysis.
These observations were taken from an editorial by Dr. Iwashyna and Dr. Angus accompanying Dr. Kaukonen’s report (JAMA 2014 March 18 [doi:10.1001/jama.2014.2639]). Dr. Iwashyna is with the division of pulmonary and critical care in the department of internal medicine at the University of Michigan, Ann Arbor, and is with the Veterans Affairs Ann Arbor Health System. Dr. Angus, a contributing editor at JAMA, in the department of critical care medicine at the University of Pittsburgh. Dr. Iwashyna reported no potential financial conflicts of interest; Dr. Angus reported ties to several pharmaceutical firms.
Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.
The report was simultaneously published online March 18 in JAMA.
In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.
At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.
The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).
A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But 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," they wrote.
During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.
Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.
Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.
The report was simultaneously published online March 18 in JAMA.
In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.
At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.
The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).
A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But 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," they wrote.
During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.
Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.
FROM JAMA
Major Finding: Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012.
Data Source: A retrospective epidemiologic analysis of time trends in 101,064 hospitalizations for severe sepsis that occurred across Australia and New Zealand from 2000 through 2012.
Disclosures: Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.