Article Text

Original research
Sex as a prognostic factor for mortality in critically ill adults with sepsis: a systematic review and meta-analysis
  1. Alba Antequera1,
  2. Jesus Lopez-Alcalde2,3,4,5,
  3. Elena Stallings3,5,
  4. Alfonso Muriel3,5,6,
  5. Borja Fernández Félix3,5,
  6. Rosa del Campo7,
  7. Manuel Ponce-Alonso7,
  8. Pilar Fidalgo2,8,
  9. Ana Veronica Halperin7,
  10. Olaya Madrid-Pascual9,
  11. Noelia Álvarez-Díaz10,
  12. Ivan Solà11,12,
  13. Federico Gordo2,13,
  14. Gerard Urrutia11,12,
  15. Javier Zamora3,5,14
  1. 1Institut d’Investigació Biomèdica Sant Pau IIB Sant Pau, Barcelona, Spain
  2. 2Faculty of Health Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Spain
  3. 3Clinical Biostatistics Unit, Instituto Ramon y Cajal de Investigacion Sanitaria, Madrid, Spain
  4. 4Institute for Complementary and Integrative Medicine, University Hospital Zurich and University Zurich, Zurich, Switzerland
  5. 5CIBERESP, Madrid, Spain
  6. 6Department of Nursing and Physiotherapy, Universidad de Alcala de Henares, Alcala de Henares, Spain
  7. 7Department of Microbiology, Hospital Universitario Ramon y Cajal, Madrid, Spain
  8. 8Department of Internal Medicine, Hospital Universitario del Henares, Coslada, Spain
  9. 9Arztpraxis Kalkbreite, Zurich, Switzerland
  10. 10Medical Library, Hospital Universitario Ramon y Cajal, Madrid, Spain
  11. 11Iberoamerican Cochrane Centre, Institut d’Investigació Biomèdica Sant Pau IIB Sant Pau, Barcelona, Spain
  12. 12CIBERESP, Barcelona, Spain
  13. 13Department of Intensive Care, Hospital Universitario del Henares, Coslada, Spain
  14. 14Institute of metabolism and systems research, University of Birmingham, Birmingham, UK
  1. Correspondence to Dr Alba Antequera; alba.antequera.martin{at}


Objective To assess the role of sex as an independent prognostic factor for mortality in patients with sepsis admitted to intensive care units (ICUs).

Design Systematic review and meta-analysis.

Data sources MEDLINE, Embase, Web of Science, and the WHO Clinical Trials Registry from inception to 17 July 2020.

Study selection Studies evaluating independent associations between sex and mortality in critically ill adults with sepsis controlling for at least one of five core covariate domains prespecified following a literature search and consensus among experts.

Data extraction and synthesis Two authors independently extracted and assessed the risk of bias using Quality In Prognosis Studies tool. Meta-analysis was performed by pooling adjusted estimates. The Grades of Recommendations, Assessment, Development and Evaluation approach was used to rate the certainty of evidence.

Results From 14 304 records, 13 studies (80 520 participants) were included. Meta-analysis did not find sex-based differences in all-cause hospital mortality (OR 1.02, 95% CI 0.79 to 1.32; very low-certainty evidence) and all-cause ICU mortality (OR 1.19, 95% CI 0.79 to 1.78; very low-certainty evidence). However, females presented higher 28-day all-cause mortality (OR 1.18, 95% CI 1.05 to 1.32; very low-certainty evidence) and lower 1-year all-cause mortality (OR 0.83, 95% CI 0.68 to 0.98; low-certainty evidence). There was a moderate risk of bias in the domain adjustment for other prognostic factors in six studies, and the certainty of evidence was further affected by inconsistency and imprecision.

Conclusion The prognostic independent effect of sex on all-cause hospital mortality, 28-day all-cause mortality and all-cause ICU mortality for critically ill adults with sepsis was uncertain. Female sex may be associated with decreased 1-year all-cause mortality.

PROSPERO registration number CRD42019145054.

  • epidemiology
  • adult intensive & critical care

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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  • Contributors JL-A, JZ and AA conceived the systematic review. AA coordinated the systematic review. AA, JL-A, ES, JZ, and IS designed the systematic review. JL-A, NÁ-D, AA, and IS designed the search strategy. AA, ES, BFF, AVH, MP-A, PF, RdC, OM-P, AM, JZ and JL-A screened abstracts and full texts. AA, ES and OM-P extracted data and assessed. AA, JL-A, ES, AM and BFF elaborated the analysis plan. AA performed the statistical analyses. JL-A and AA conducted the GRADE assessment. AA, AVH, FG, PF, MP-A, RdC and OM-P provided clinical perspective. JL-A, AA, AM, IS, JZ, ES and GU provided methodological perspective. AA drafted the first version of the manuscript. All authors had the opportunity to read approved the final manuscript. JZ, JL-A and GU secured funding for the systematic review. AA is the guarantor. AA is a doctoral candidate in Methodology of Biomedical Research and Public Health, at the Department of Pediatrics, Obstetrics, Gynaecology and Preventive Medicine at Universitat Autònoma de Barcelona (Spain) and this work is part of her PhD.

  • Funding The SEXCOMPLEX project was supported by Instituto de Salud Carlos III (Plan Estatal de I+D + i 2013–2016) and cofinanced by the European Development Regional Fund 'A way to achieve Europe' (ERDF) grant number PIE16/00050. AA was funded by the Instituto de Salud Carlos III through the 'Acción Estratégica en Salud 2013–2016/Contratos Río Hortega call 2018/ CM18/00141' (Co-funded by European Social Fund 2014–2020, 'Investing in your future'). MP-A is also the recipient of a Río Hortega Contract (CM19/00069). CIBERESP funded BF-F.

  • Disclaimer These funding sources had no role in the design of this review, its execution, analyses, interpretation of the data, or decision to submit results.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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