Sex-related mortality differences in young adult septic shock patients
1School of Medicine, Vita-Salute San Raffaele University, 87046 Milan, Italy
2Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, 20151 Milan, Italy
3Department of Anesthesia and Intensive Care, University Hospital of Modena, 87106 Modena, Italy
4Università degli Studi dell’Insubria, Azienda Ospedaliera Ospedale di Circolo e Fondazione, 16021 Macchi- Varese, Italy
5Division of Experimental Oncology/Unit of Urology, IRCCS Ospedale San Raffaele, 87046 Milan, Italy
6Department of Gynecology and Obstetrics, IRCCS San Raffaele Scientific Institute, 20151 Milan, Italy
7Department of Anesthesia and Intensive Care Medicine, Cernusco sul Naviglio Hospital, ASST Melegnano e Martesana, 20063 Milan, Italy
8Department of Medicine, Anesthesia and Intensive Care Clinic, University of Udine, 33100 Udine, Italy
9Department of Anesthesia and Intensive Care, “Cardinal Massaia” Hospital, 14100 Asti, Italy
10Department of Anesthesia and Intensive Care, 35139 Padua, Italy
DOI: 10.22514/sv.2022.017 Vol.19,Issue 1,January 2023 pp.50-56
Submitted: 18 October 2021 Accepted: 28 December 2021
Published: 08 January 2023
† These authors contributed equally.
Septic shock survival rate and host immune response are intimately interlaced. In the last years, biological and pre-clinical studies demonstrated sex-specific differences in the immune response to infection. In the hypothesis that survival rate is related to the hormonal framework, the aim of the present study was to observe sex-specific differences in 28-day mortality rate between women of childbearing potential and same-age men. This multicenter study was conducted in six Italian intensive care units (ICUs). We enrolled consecutive patients ≤ 55 years old admitted to the Intensive Care Unit from January 2011 to January 2020, who were diagnosed with septic shock at the time of ICU admission or during the ICU stay. We gathered baseline characteristics and outcomes. The primary outcome was 28-day mortality; secondary outcomes included ICU mortality, in-hospital mortality and length of stay in the ICU and in the hospital. Moreover, data from >55 years old patients were collected and analyzed. We enrolled 361 young patients with septic shock: 215 were males (60%) and 146 females (40%). While baseline and ICU characteristics were similar between the two groups, males had a higher 28-day mortality rate (39.5% vs. 29%, p = 0.035), ICU mortality rate (49%vs. 38%, p = 0.040) and hospital mortality rate (61% vs. 50%, p = 0.040) as compared to females. Findings were confirmed in patients with septic shock at ICU admission. Young adult females developed septic shock less frequently than young males, displaying a reduced mortality rate as compared to that of their same-age male counterpart. These findings may stimulate future research and therapies.
Sex; Gender; Septic shock; Intensive Care Unit; Mortality
Alberto Zangrillo,Federica Morselli,Emanuela Biagioni,Roberta Di Stella,Irene Coloretti,Elena Moizo,Valentina Paola Plumari,Giacomo Monti,Giovanni Borghi,Andrea Salonia,Giada Almirante,Davide Maraggia,Massimo Zambon,Nicola Langiano,Agostino Roasio,Laura Pasin,Milena Mucci,Paolo Federico Beccaria,Nicola Pasculli,Martina Baiardo Redaelli,Ottavia Pallanch,Giulia Gallo,Giovanni Real,Marta Nava,Sophie Venturelli,Martina Tosi,Elena Munari,Maria Grazia Visconti,Silvia Perno,Massimo Girardis,Giovanni Landoni. Sex-related mortality differences in young adult septic shock patients. Signa Vitae. 2023. 19(1);50-56.
 Vincent JL, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Critical Care. 2019; 23: 196.
 Campanelli F, Landoni G, Cabrini L, Zangrillo A. Gender differences in septic intensive care unit patients. Minerva Anestesiologica. 2018; 84: 504–508.
 Sakr Y, Jaschinski U, Wittebole X, Szakmany T, Lipman J, Ñamendys-Silva SA, et al. Sepsis in intensive care unit patients: worldwide data from the intensive care over nations audit. Open Forum Infectious Diseases. 2018; 5: ofy313.
 Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Critical Care Medicine. 2006; 34: 344–353.
 Rhodes A., Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Medicine. 2017; 43: 304–377.
 Angele MK, Pratschke S, Hubbard WJ, Chaudry IH. Gender differences in sepsis: cardiovascular and immunological aspect. Virulence. 2014; 5: 12–19.
 López-Alcalde J, Stallings E, Cabir Nunes S, Fernández Chávez A, Daheron M, Bonfill Cosp X, et al. Consideration of sex and gender in cochrane reviews of interventions for preventing healthcare-associated infections: a methodology study. BMC Health Services Research. 2019; 19: 169.
 Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the united states from 1979 through 2000. New England Journal of Medicine. 2003; 348: 1546–1554.
 Bion J, Jaeschke R, Thompson BT, Levy M, Dellinger RP. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Medicine. 2008; 34: 1163–1164.
 Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Critical Care Medicine. 2013; 41: 580–637.
 Brinton LA, Brogan DR, Coates RJ, Swanson CA, Potischman N, Stanford JL. Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy. Menopause. 2018; 25: 1195–1200.
 Palacios S, Henderson VW, Siseles N, Tan D, Villaseca P. Age of menopause and impact of climacteric symptoms by geographical region. Climacteric. 2010; 13: 419–428.
 Luís Â, Domingues F, Pereira L. Effects of red clover on perimenopausal and postmenopausal women’s blood lipid profile: a meta-analysis. Climacteric. 2018; 21: 446–453.
 Baiardo Redaelli M, Landoni G, Di Napoli D, Morselli F, Sartorelli M, Sartini C, et al. Novel coronavirus disease (COVID–19) in Italian patients: gender differences in presentation and severity. Saudi Journal of Medicine and Medical Sciences. 2021; 9: 59–62.
 Bindl L, Buderus S, Dahlem P, Demirakca S, Goldner M, Huth R, et al. Gender-based differences in children with sepsis and ARDS: the ESPNIC ARDS database group. Intensive Care Medicine. 2003; 29: 1770–1773.
 Maat M, Buysse CM, Emonts M, Spanjaard L, Joosten KF, de Groot R, et al. Improved survival of children with sepsis and purpura: effects of age, gender, and era. Critical Care. 2007; 11: R112.
 Niu B, Kim B, Limketkai BN, Sun J, Li Z, Woreta T, et al. Mortality from spontaneous bacterial peritonitis among hospitalized patients in the USA. Digestive Diseases and Sciences. 2018; 63: 1327–1333.
 Xu J, Tong L, Yao J, Guo Z, Lui KY, Hu X, et al. Association of sex with clinical outcome in critically Ill sepsis patients: a retrospective analysis of the large clinical database MIMIC-III. Shock. 2019; 52: 146–151.
 Otterbein LE, Foresti R, Motterlini R. Heme oxygenase-1 and carbon monoxide in the heart: the balancing act between danger signaling and pro-survival. Circulation Research. 2016; 118: 1940–1959.
 Caruso JM, Xu DZ, Lu Q, Dayal SD, Deitch EA. The female gender protects against pulmonary injury after trauma hemorrhagic shock. Surgical Infections. 2001; 2: 231–240.
 Bösch F, Angele MK, Chaudry IH. Gender differences in trauma, shock and sepsis. Military Medical Research. 2018; 5: 35.
 Hubbard WJ, Chaudry IH. The use of estrogen for the treatment of traumatic brain injury. New Therapeutics for Traumatic Brain Injury. 2017; 6: 161–177.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.
Index Copernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.
Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.
Scopus: CiteScore 0.5(2021) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.