A global accounting of sepsis
Authors: Jordan A Kempker, Greg S Martin
Journal: The Lancet (2020)

For the past two decades, attention to sepsis has intensified because of growing recognition that it is one of the most common and lethal conditions we face, whether as a patient, provider, hospital, or public health agency. Until now, we have had an incomplete accounting of the global epidemiology of sepsis, with several reports from high-income countries and relatively few from countries of low and middle income (LMICs). In The Lancet, Kristina Rudd and colleagues1Rudd KE Johnson SC Agesa KM et al.Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study.Lancet. 2020; (published online Jan 16.)https://doi.org/10.1016/S0140-6736(19)32989-7Summary Full Text Full Text PDF PubMed Scopus (1547) Google Scholar present an analysis of data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, which is the most comprehensive assessment of the worldwide sepsis burden to date. Their results reinforce what many researchers already suspected: sepsis has had an extraordinary impact throughout the world and the toll is greatest in LMICs. GBD is a consortium of more than 3600 researchers studying the world's most important health problems. GBD 2017 contains more than 1 billion datapoints for 282 underlying causes of death in 195 countries.2GBD 2017 Causes of Death CollaboratorsGlobal, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet. 2018; 392: 1736-1788Summary Full Text Full Text PDF PubMed Scopus (3474) Google Scholar However, because sepsis has conventionally been considered an intermediate rather than an underlying cause of death, it has not been properly accounted.3WHOInternational statistical classification of diseases and related health problems (ICD-10): vol 1. World Health Organization, Geneva1992Google Scholar, 4Alexander L Determining causes of death: how we reclassify miscoded deaths.http://www.healthdata.org/acting-data/determining-causes-death-how-we-reclassify-miscoded-deathsDate: July 23, 2018Google Scholar Rudd and colleagues deployed a sequential multistep modelling strategy that leveraged GBD resources to produce the first global estimates of sepsis epidemiology. They used vital records to model (from multiple causes of death) the fraction of deaths for each underlying cause that were sepsis-related, then multiplied these sepsis fractions by countries' death counts for each underlying cause of death to ascertain sepsis deaths in each country. To estimate sepsis incidence, they modelled sepsis case-fatality rates from hospital discharge records for each of the underlying causes and used these case-fatality rates as divisors to calculate sepsis incidence from death counts. For 2017, Rudd and colleagues reported that the global burden of sepsis was twice that of previous estimates, with an estimated 49 million cases and 11 million deaths. Moreover, the annual number of sepsis cases over the past two decades fell worldwide by more than 50%. Yet sepsis still contributed to almost 20% of all deaths every year in the world, more than 20 deaths every minute. As expected from findings of previous studies,5Fleischmann C Scherag A Adhikari NKJ et al.Assessment of global incidence and mortality of hospital-treated sepsis: current estimates and limitations.Am J Respir Crit Care Med. 2016; 193: 259-272Crossref PubMed Scopus (1777) Google Scholar, 6Cribbs SK Martin GS Going global with sepsis: the need for national registries.Crit Care Med. 2009; 37: 338-340Crossref PubMed Scopus (3) Google Scholar the burden of sepsis was associated with income and development in each country, with approximately 85% of all sepsis-related deaths in LMICs. Despite differences in types of patient and health-care resources, the longitudinal changes are remarkably similar across disparate regions and countries, with the exception of southern sub-Saharan Africa. The implications of Rudd and colleagues' findings must be viewed in context with the constraints of the analysis, because modelling assumptions and imputation steps can introduce bias. The model inputs to estimate the burden of sepsis for 195 countries came from the vital records of four countries (Brazil, Mexico, Taiwan, and the USA), and data for hospital case-fatalities were obtained from ten countries (Austria, Brazil, Canada, Chile, Georgia, Italy, Mexico, New Zealand, Philippines, and the USA), resulting in extrapolation from countries of high and middle incomes to low-income countries. Because some continents (notably Africa) are not represented as original sepsis data sources, longitudinal trends might be unreliable. Hypothetically, improvements in Brazil as a primary data source country could create the appearance of benefits for sub-Saharan Africa, irrespective of actual local changes. Moreover, compared with studies not affected by the vagaries of administrative coding,7Rhee C Dantes R Epstein L et al.Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014.JAMA. 2017; 318: 1241-1249Crossref PubMed Scopus (844) Google Scholar Rudd and colleagues' departure from the exemplar implicit and explicit coding strategies could have contributed to the higher rates of sepsis. The effect of including non-infectious conditions (eg, pulmonary embolism) and excluding infectious conditions (eg, non-miliary tuberculosis) in the implicit definition, and broad inclusion of maternal and paediatric infection codes (eg, disorders of amniotic fluid and membranes or neonatal bradycardia) within the explicit sepsis definition might unpredictably affect case-finding in each country.8Martin GS Mannino DM Eaton S Moss M The epidemiology of sepsis in the United States from 1979 through 2000.N Engl J Med. 2003; 348: 1546-1554Crossref PubMed Scopus (4813) Google Scholar, 9Angus DC Linde-Zwirble WT Lidicker J et al.Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.Crit Care Med. 2001; 29: 1303-1310Crossref PubMed Scopus (6628) Google Scholar Furthermore, understanding the total burden of sepsis requires several aspects not yet included, such as health-care use before and after sepsis, particularly to capture post-sepsis complications such as musculoskeletal and neurocognitive deficits, loss of productivity from inability to return to work, and years of life lost. This latest study from GBD 2017 is the first comprehensive global report on the epidemiology of sepsis. It takes the first steps to recording the burden of sepsis throughout the world, including new considerations such as the frequency of sepsis complicating injuries and non-communicable diseases. In view of the complexity in producing global estimates, it is important that countries purported to have a high burden of sepsis undertake studies to confirm their local epidemiology, develop surveillance methodologies using verifiable data sources, and commit resources to sepsis according to their public health priorities.10WHOSepsis: key facts.https://www.who.int/news-room/fact-sheets/detail/sepsisDate: April 19, 2018Google Scholar With additional work, we can remove uncertainties in national incidence and longitudinal changes and leverage the enormous investment by GBD to facilitate national sepsis surveillance in countries with both high and low incomes, to effectuate international sepsis quality improvement. Although the scientific purist might prefer to wait for medical statistics to be nosologically exact,11Greenwood M Medical statistics from Graunt to Farr. Cambridge University Press, Cambridge1948Google Scholar this new benchmark in global sepsis epidemiology is an enormous step and is the foundation for initiatives that can ultimately eliminate sepsis. GSM is supported by grants from the Biomedical Advanced Research and Development Authority, the Marcus Foundation, the National Institutes of Health through the National Center for Advancing Translational Science (UL1 TR-002378), and the National Institute of Biomedical Imaging and Bioengineering (U54 EB-027690). JAK is supported by a grant from the Agency for Healthcare Quality and Research (K08 HS-025240). GSM and JAK have served as consultants to Grifols, outside the area of work commented on here. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease StudyDespite 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. Full-Text PDF Open Access