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      Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study

      research-article
      , MD a , , MSc c , , BA c , , BA c , , BS c , , MD a , , PhD c , , MD c , d , , Prof, MD g , , Prof, MD h , , MD i , , Prof, PhD j , , Prof, MD i , k , , Prof, PhD l , m , , MD a , , Prof, MD e , n , , MD b , , MD o , , Prof, FMedSci c , f , , Prof, MD c , f , , Prof, PhD c , p , , Prof, MD a , , Prof, DPhil c , f , , Prof, MD c , f , *
      Lancet (London, England)
      Elsevier

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          Summary

          Background

          Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017.

          Methods

          We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates.

          Findings

          In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia.

          Interpretation

          Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa.

          Funding

          The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

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          Most cited references15

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          Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.

          Background In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. Methods We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. Results Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). Conclusions More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).
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            Benchmarking the incidence and mortality of severe sepsis in the United States.

            In 1992, the first consensus definition of severe sepsis was published. Subsequent epidemiologic estimates were collected using administrative data, but ongoing discrepancies in the definition of severe sepsis produced large differences in estimates. We seek to describe the variations in incidence and mortality of severe sepsis in the United States using four methods of database abstraction. We hypothesized that different methodologies of capturing cases of severe sepsis would result in disparate estimates of incidence and mortality. Using a nationally representative sample, four previously published methods (Angus et al, Martin et al, Dombrovskiy et al, and Wang et al) were used to gather cases of severe sepsis over a 6-year period (2004-2009). In addition, the use of new International Statistical Classification of Diseases, 9th Edition (ICD-9), sepsis codes was compared with previous methods. Annual national incidence and in-hospital mortality of severe sepsis. The average annual incidence varied by as much as 3.5-fold depending on method used and ranged from 894,013 (300/100,000 population) to 3,110,630 (1,031/100,000) using the methods of Dombrovskiy et al and Wang et al, respectively. Average annual increase in the incidence of severe sepsis was similar (13.0% to 13.3%) across all methods. In-hospital mortality ranged from 14.7% to 29.9% using abstraction methods of Wang et al and Dombrovskiy et al. Using all methods, there was a decrease in in-hospital mortality across the 6-year period (35.2% to 25.6% [Dombrovskiy et al] and 17.8% to 12.1% [Wang et al]). Use of ICD-9 sepsis codes more than doubled over the 6-year period (158,722 - 489,632 [995.92 severe sepsis], 131,719 - 303,615 [785.52 septic shock]). There is substantial variability in incidence and mortality of severe sepsis depending on the method of database abstraction used. A uniform, consistent method is needed for use in national registries to facilitate accurate assessment of clinical interventions and outcome comparisons between hospitals and regions.
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              Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003.

              To determine recent trends in rates of hospitalization, mortality, and hospital case fatality for severe sepsis in the United States. Trend analysis for the period from 1993 to 2003. U.S. community hospitals from the Nationwide Inpatient Sample that is a 20% stratified sample of all U.S. community hospitals. Subjects of any age with sepsis including severe sepsis who were hospitalized in the United States during the study period. None. Utilizing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for septicemia and major organ dysfunction, we identified 8,403,766 patients with sepsis, including 2,857,476 patients with severe sepsis, who were hospitalized in the United States from 1993 to 2003. The percentage of severe sepsis cases among all sepsis cases increased continuously from 25.6% in 1993 to 43.8% in 2003 (p < .001). Age-adjusted rate of hospitalization for severe sepsis grew from 66.8 +/- 0.16 to 132.0 +/- 0.21 per 100,000 population (p < .001). Age-adjusted, population-based mortality rate within these years increased from 30.3 +/- 0.11 to 49.7 +/- 0.13 per 100,000 population (p < .001), whereas hospital case fatality rate fell from 45.8% +/- 0.17% to 37.8% +/- 0.10% (p < .001). During each study year, the rates of hospitalization, mortality, and case fatality increased with age. Hospitalization and mortality rates in males exceeded those in females, but case fatality rate was greater in females. From 1993 to 2003, age-adjusted rates for severe sepsis hospitalization and mortality increased annually by 8.2% (p < .001) and 5.6% (p < .001), respectively, whereas case fatality rate decreased by 1.4% (p < .001). The rate of severe sepsis hospitalization almost doubled during the 11-yr period studied and is considerably greater than has been previously predicted. Mortality from severe sepsis also increased significantly. However, case fatality rates decreased during the same study period.
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                Author and article information

                Contributors
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier
                0140-6736
                1474-547X
                18 January 2020
                18 January 2020
                : 395
                : 10219
                : 200-211
                Affiliations
                [a ]Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
                [b ]Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA
                [c ]Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
                [d ]Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA
                [e ]Department of Pediatrics, University of Washington, Seattle, WA, USA
                [f ]Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA
                [g ]Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
                [h ]The George Institute for Global Health, University of New South Wales, Newtown, NSW, Australia
                [i ]Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany
                [j ]Anesthesiology, Pain and Intensive Care Department, Federal University of São Paulo, São Paulo, Brazil
                [k ]Anästhesiologie mit Sp operative Intensivmeidzin, Charité University Medical Center Berlin, Berlin, Germany
                [l ]Clinical Trials Unit, Intensive Care National Audit & Research Centre (ICNARC), London, UK
                [m ]Faculty of Public Health & Policy linked to the Department of Health Services Research & Policy, London School of Hygiene & Tropical Medicine, London, UK
                [n ]Pediatric Critical Care Medicine, Seattle Children's Hospital, Seattle, WA, USA
                [o ]Institute of Advanced Studies, University of São Paulo, São Paulo, Brazil
                [p ]University of Melbourne, Melbourne, QLD, Australia
                Author notes
                [* ]Correspondence to: Prof Mohsen Naghavi, Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA 98121, USA nagham@ 123456uw.edu
                Article
                S0140-6736(19)32989-7
                10.1016/S0140-6736(19)32989-7
                6970225
                31954465
                d0545577-02a2-4810-ae19-c644c58b8798
                © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access Article under the CC BY 4.0 licence

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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