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A Comparison of Mortality From Sepsis in Brazil and England: The Impact of Heterogeneity in General and Sepsis-Specific Patient Characteristics*

Ranzani, Otavio T. MD1,2; Shankar-Hari, Manu MSc, MD, PhD1,3,4; Harrison, David A. PhD1; Rabello, Lígia S. MD, MSc, PhD†,5; Salluh, Jorge I. F. MD, PhD5; Rowan, Kathryn M. PhD1; Soares, Marcio MD, PhD5

doi: 10.1097/CCM.0000000000003438
Clinical Investigations
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Objectives: To test whether differences in both general and sepsis-specific patient characteristics explain the observed differences in sepsis mortality between countries, using two national critical care (ICU) databases.

Design: Cohort study.

Setting: We analyzed 62 and 164 ICUs in Brazil and England, respectively.

Patients: Twenty-two–thousand four-hundred twenty-six adult ICU admissions from January 2013 to December 2013.

Interventions: None.

Measurements and Main Results: After harmonizing relevant variables, we merged the first ICU episode of adult medical admissions from Brazil (ORganizational CHaractEeriSTics in cRitical cAre study) and England (Intensive Care National Audit & Research Centre Case Mix Programme). Sepsis-3 definition was used, and the primary outcome was hospital mortality. We used multilevel logistic regression models to evaluate the impact of country (Brazil vs England) on mortality, after adjustment for general (age, sex, comorbidities, functional status, admission source, time to admission) and sepsis-specific (site of infection, organ dysfunction type and number) patient characteristics. Of medical ICU admissions, 13.2% (4,505/34,150) in Brazil and 30.7% (17,921/58,316) in England met the sepsis definition. The Brazil cohort was older, had greater prevalence of severe comorbidities and dependency compared with England. Respiratory was the most common infection site in both countries. The most common organ dysfunction was cardiovascular in Brazil (41.2%) and respiratory in England (85.8%). Crude hospital mortality was similar (Brazil 41.4% vs England 39.3%; odds ratio, 1.12 [0.98–1.30]). After adjusting for general patient characteristics, there was an important change in the point-estimate of the odds ratio (0.88 [0.75–1.02]). However, after adjusting for sepsis-specific patient characteristics, the direction of effect reversed again with Brazil having higher risk-adjusted mortality (odds ratio, 1.22 [1.05–1.43]).

Conclusions: Patients with sepsis admitted to ICUs in Brazil and England have important differences in general and sepsis-specific characteristics, from source of admission to organ dysfunctions. We show that comparing crude mortality from sepsis patients admitted to the ICU between countries, as currently performed, is not reliable and that the adjustment for both general and sepsis-specific patient characteristics is essential for valid international comparisons of mortality amongst sepsis patients admitted to critical care units.

1Intensive Care National Audit & Research Centre (ICNARC), London, United Kingdom.

2Pulmonary Division, Heart Institute (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.

3Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, United Kingdom.

4School of Immunology & Microbial Sciences, Kings College London, London, United Kingdom.

5Department of Critical Care and Graduate Program in Translational Medicine, D’Or Institute for Research and Education - IDOR, Rio De Janeiro, Brazil.

*See also p. 135.

Drs. Rowan and Soares are senior authors.

In memoriam.

The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health.

Drs. Ranzani and Shankar-Hari are equal contributors.

Dr. Ranzani did data analyses. Drs. Ranzani and Shankar-Hari wrote the first draft of the article. Drs. Harrison, Rabello, Salluh, Rowan, and Soares led data collection. Dr. Rabello died during the peer-review process of this article. All authors unanimously agreed on her fundamental contribution for this study. All authors conceptualized and designed the study, interpreted data, and critically revised the article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

The original ORganizational CHaractEeriSTics in cRitical cAre study was supported by the National Council for Scientific and Technological Development (Grant number 304240/2014-1), Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro and by departmental funds from the D’Or Institute for Research and Education. The Case Mix Programme is a subscription-based, national quality assessment program. The current study was funded internally by Intensive Care National Audit & Research Centre. The funding sources had no role in the design, conduct or analyses of the study.

Dr. Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (NIHR-CS-2016-16-011). Dr. Soares disclosed that he is founder and equity shareholder at Epimed Solutions. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: otavioranzani@usp.br

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