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

doi:10.1016/S0140-6736(19)32989-7

. 2020 Jan 18;395(10219):200-211.

doi: 10.1016/S0140-6736(19)32989-7.

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

Kristina E Rudd¹, Sarah Charlotte Johnson², Kareha M Agesa², Katya Anne Shackelford², Derrick Tsoi², Daniel Rhodes Kievlan¹, Danny V Colombara², Kevin S Ikuta³, Niranjan Kissoon⁴, Simon Finfer⁵, Carolin Fleischmann-Struzek⁶, Flavia R Machado⁷, Konrad K Reinhart⁸, Kathryn Rowan⁹, Christopher W Seymour¹, R Scott Watson¹⁰, T Eoin West¹¹, Fatima Marinho¹², Simon I Hay¹³, Rafael Lozano¹³, Alan D Lopez¹⁴, Derek C Angus¹, Christopher J L Murray¹³, Mohsen Naghavi¹⁵

Affiliations

¹ Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
² Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.
³ Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.
⁴ Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
⁵ The George Institute for Global Health, University of New South Wales, Newtown, NSW, Australia.
⁶ Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
⁷ Anesthesiology, Pain and Intensive Care Department, Federal University of São Paulo, São Paulo, Brazil.
⁸ Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Anästhesiologie mit Sp operative Intensivmeidzin, Charité University Medical Center Berlin, Berlin, Germany.
⁹ Clinical Trials Unit, Intensive Care National Audit & Research Centre (ICNARC), London, UK; Faculty of Public Health & Policy linked to the Department of Health Services Research & Policy, London School of Hygiene & Tropical Medicine, London, UK.
¹⁰ Department of Pediatrics, University of Washington, Seattle, WA, USA; Pediatric Critical Care Medicine, Seattle Children's Hospital, Seattle, WA, USA.
¹¹ Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA.
¹² Institute of Advanced Studies, University of São Paulo, São Paulo, Brazil.
¹³ Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA.
¹⁴ Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; University of Melbourne, Melbourne, QLD, Australia.
¹⁵ Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA. Electronic address: nagham@uw.edu.

PMID: 31954465
PMCID: PMC6970225
DOI: 10.1016/S0140-6736(19)32989-7

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

Kristina E Rudd et al. Lancet. 2020.

. 2020 Jan 18;395(10219):200-211.

doi: 10.1016/S0140-6736(19)32989-7.

Authors

Affiliations

¹ Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
² Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.
³ Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.
⁴ Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
⁵ The George Institute for Global Health, University of New South Wales, Newtown, NSW, Australia.
⁶ Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
⁷ Anesthesiology, Pain and Intensive Care Department, Federal University of São Paulo, São Paulo, Brazil.
⁸ Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Anästhesiologie mit Sp operative Intensivmeidzin, Charité University Medical Center Berlin, Berlin, Germany.
⁹ Clinical Trials Unit, Intensive Care National Audit & Research Centre (ICNARC), London, UK; Faculty of Public Health & Policy linked to the Department of Health Services Research & Policy, London School of Hygiene & Tropical Medicine, London, UK.
¹⁰ Department of Pediatrics, University of Washington, Seattle, WA, USA; Pediatric Critical Care Medicine, Seattle Children's Hospital, Seattle, WA, USA.
¹¹ Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA.
¹² Institute of Advanced Studies, University of São Paulo, São Paulo, Brazil.
¹³ Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA.
¹⁴ Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; University of Melbourne, Melbourne, QLD, Australia.
¹⁵ Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA; Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA. Electronic address: nagham@uw.edu.

PMID: 31954465
PMCID: PMC6970225
DOI: 10.1016/S0140-6736(19)32989-7

Abstract

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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Figures

**Figure 1**
Age-standardised global sepsis incidence per 100 000 population, for both sexes and by underlying cause category, 1990–2017 Shaded areas represent 95% uncertainty intervals.

**Figure 2**
Leading 20 Level 3 causes of global incident sepsis (A) and sepsis-related deaths (B) for both sexes and all ages combined, in 1990, 2007, and 2017 Causes are connected by lines between periods (1990, 2007, and 2017); solid lines are ranked increases (or no change in rank) and dashed lines are ranked decreases. Numbers in bold highlight statistically significant changes between periods. COPD=chronic obstructive pulmonary disease. iNTS=invasive non-typhoidal salmonella.

**Figure 3**
Age-standardised sepsis incidence per 100 000 population for both sexes, in 2017 (A), and percentage of all deaths related to sepsis, age-standardised for both sexes, in 2017 (B) ATG=Antigua and Barbuda. FSM=Federated States of Micronesia. LCA=Saint Lucia. TLS=Timor-Leste. TTO=Trinidad and Tobago. VCT=Saint Vincent and the Grenadines.

**Figure 4**
Age-standardised sepsis incidence (A) and mortality (B) per 100 000 population and SDI, by location and underlying cause category for both sexes, in 2017 Every point represents one country or territory. 195 countries and territories worldwide are categorised according to SDI. SDI=Socio-demographic Index.

**Figure 5**
Percentage of all sepsis-related deaths in each underlying cause category, by age group and for both sexes, in 2017 Bars represent 95% uncertainty intervals.

See this image and copyright information in PMC

Comment in

A global accounting of sepsis.
Kempker JA, Martin GS. Kempker JA, et al. Lancet. 2020 Jan 18;395(10219):168-170. doi: 10.1016/S0140-6736(19)33065-X. Lancet. 2020. PMID: 31954445 No abstract available.
Highlighting the huge global burden of sepsis.
Vincent JL. Vincent JL. Anaesth Crit Care Pain Med. 2020 Apr;39(2):171-172. doi: 10.1016/j.accpm.2020.03.004. Epub 2020 Mar 4. Anaesth Crit Care Pain Med. 2020. PMID: 32145433 No abstract available.
Sepsis.
Minderhoud TC, Azijli K, Nanayakkara PWB. Minderhoud TC, et al. Lancet. 2020 Dec 5;396(10265):1804. doi: 10.1016/S0140-6736(20)32401-6. Lancet. 2020. PMID: 33278929 No abstract available.
Sepsis.
von Cube M, Schumacher M, Timsit JF. von Cube M, et al. Lancet. 2020 Dec 5;396(10265):1804. doi: 10.1016/S0140-6736(20)31609-3. Lancet. 2020. PMID: 33278930 No abstract available.
Sepsis - Authors' reply.
Rudd KE, Ikuta KS, Naghavi M. Rudd KE, et al. Lancet. 2020 Dec 5;396(10265):1805-1806. doi: 10.1016/S0140-6736(20)32535-6. Lancet. 2020. PMID: 33278931 No abstract available.
Sepsis.
Duke GJ, Moran JL, Santamaria JD, Pilcher DV. Duke GJ, et al. Lancet. 2020 Dec 5;396(10265):1805. doi: 10.1016/S0140-6736(20)31606-8. Lancet. 2020. PMID: 33278932 No abstract available.
Sepsis.
Joshi M, Ashrafian H, Khan S, Darzi A. Joshi M, et al. Lancet. 2020 Dec 5;396(10265):1805. doi: 10.1016/S0140-6736(20)31608-1. Lancet. 2020. PMID: 33278933 No abstract available.
Severe community-acquired pneumonia: in search of the guiding star.
Póvoa P, Nseir S, Salluh J. Póvoa P, et al. Intensive Care Med. 2023 Jun;49(6):656-658. doi: 10.1007/s00134-023-07063-2. Epub 2023 Apr 27. Intensive Care Med. 2023. PMID: 37100928 Free PMC article. No abstract available.
Challenges in combating sepsis in Germany-Learning from others and the COVID-19 pandemic.
Reinhart K, Kluge S, Welte T. Reinhart K, et al. Med Klin Intensivmed Notfmed. 2023 Dec;118(Suppl 2):65-67. doi: 10.1007/s00063-023-01100-0. Epub 2023 Dec 20. Med Klin Intensivmed Notfmed. 2023. PMID: 38117340 English. No abstract available.

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References

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[1] Singer M, Deutschman CS, Seymour CW. The third international consensus definitions for sepsis and septic shock (Sepsis-3) JAMA. 2016;315:801–810. - PMC - PubMed

[2] Singer M, Deutschman CS, Seymour CW. The third international consensus definitions for sepsis and septic shock (Sepsis-3) JAMA. 2016;315:801–810. - PMC - PubMed

[3] Liu V, Escobar GJ, Greene JD. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312:90–92. - PubMed

[4] Liu V, Escobar GJ, Greene JD. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312:90–92. - PubMed

[5] Torio CM, Moore BJ. National inpatient hospital costs: the most expensive conditions by payer, 2013. May, 2016. https://www.hcup-us.ahrq.gov/reports/statbriefs/sb204-Most-Expensive-Hos... (accessed Nov 6, 2019). - PubMed

[6] Torio CM, Moore BJ. National inpatient hospital costs: the most expensive conditions by payer, 2013. May, 2016. https://www.hcup-us.ahrq.gov/reports/statbriefs/sb204-Most-Expensive-Hos... (accessed Nov 6, 2019). - PubMed

[7] Thorrington D, Andrews N, Stowe J, Miller E, van Hoek AJ. Elucidating the impact of the pneumococcal conjugate vaccine programme on pneumonia, sepsis and otitis media hospital admissions in England using a composite control. BMC Med. 2018;16:1–14. - PMC - PubMed

[8] Thorrington D, Andrews N, Stowe J, Miller E, van Hoek AJ. Elucidating the impact of the pneumococcal conjugate vaccine programme on pneumonia, sepsis and otitis media hospital admissions in England using a composite control. BMC Med. 2018;16:1–14. - PMC - PubMed

[9] Martischang R, Pires D, Masson-Roy S, Saito H, Pittet D. Promoting and sustaining a historical and global effort to prevent sepsis: the 2018 World Health Organization SAVE LIVES, Clean Your Hands campaign. Crit Care. 2018;22:7–9. - PMC - PubMed

[10] Martischang R, Pires D, Masson-Roy S, Saito H, Pittet D. Promoting and sustaining a historical and global effort to prevent sepsis: the 2018 World Health Organization SAVE LIVES, Clean Your Hands campaign. Crit Care. 2018;22:7–9. - PMC - PubMed

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

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

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