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Sex- and Diagnosis-Dependent Differences in Mortality and Admission Cytokine Levels Among Patients Admitted for Intensive Care*

Guidry, Christopher A. MD, MS1; Swenson, Brian R. MD, MS1,2; Davies, Stephen W. MD, MPH1; Dossett, Lesly A. MD, MS3; Popovsky, Kimberley A. BSN1; Bonatti, Hugo MD1; Evans, Heather L. MD, MS4; Metzger, Rosemarie MD, MPH1; Hedrick, Traci L. MD1; Tache-Léon, Carlos A. MD1; Hranjec, Tjasa MD, MS1; Chaudry, Irshad H. PhD5; Pruett, Timothy L. MD2; May, Addison K. MD3; Sawyer, Robert G. MD1,6

Critical Care Medicine:
doi: 10.1097/CCM.0000000000000139
Clinical Investigations
Abstract

Objectives: To investigate the role of sex on cytokine expression and mortality in critically ill patients.

Design: A cohort of patients admitted to were enrolled and followed over a 5-year period.

Setting: Two university-affiliated hospital surgical and trauma ICUs.

Patients: Patients 18 years old and older admitted for at least 48 hours to the surgical or trauma ICU.

Interventions: Observation only.

Measurements and Main Results: Major outcomes included admission cytokine levels, prevalence of ICU-acquired infection, and mortality during hospitalization conditioned on trauma status and sex. The final cohort included 2,291 patients (1,407 trauma and 884 nontrauma). The prevalence of ICU-acquired infection was similar for men (46.5%) and women (44.5%). All-cause in-hospital mortality was 12.7% for trauma male patient and 9.1% for trauma female patient (p = 0.065) and 22.9% for nontrauma male patients and 20.6% for nontrauma female patients (p = 0.40). Among trauma patients, logistic regression analysis identified female sex as protective for all-cause mortality (odds ratio, 0.57). Among trauma patients, men had significantly higher admission serum levels of interleukin-2, interleukin-12, interferon-γ, and tumor necrosis factor-α, and among nontrauma patients, men had higher admission levels of interleukin-8 and tumor necrosis factor-α.

Conclusions: The relationship between sex and outcomes in critically ill patients is complex and depends on underlying illness. Women appear to be better adapted to survive traumatic events, while sex may be less important in other forms of critical illness. The mechanisms accounting for this gender dimorphism may, in part, involve differential cytokine responses to injury, with men expressing a more robust proinflammatory profile.

Author Information

1Department of Surgery, University of Virginia Health System, Charlottesville, VA.

2Department of Surgery, University of Minnesota, Minneapolis, MN.

3Department of Surgery, Vanderbilt University Medical Center, Nashville, TN.

4Department of Surgery, University of Washington, Seattle, WA.

5Department of Surgery, University of Alabama-Birmingham, Birmingham, AL.

6Department of Public Health Sciences, University of Virginia Health System, Charlottesville, VA.

* See also p. 1294.

This study is registered with ClinicalTrials.gov under identifier NCT00170560.

Drs. Swenson, Evans, Chaudry, Pruett, May, and Sawyer conceived and designed the study. Drs. Swenson, Tache-Léon, Hranjec, and Sawyer analyzed and interpreted the data. All authors drafted the manuscript for important intellectual content.

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).

Supported, in part, by National Institutes of Health (grants R01 AI49989 and F32 AI051882) and the University of Virginia General Clinical Research Center.

Dr. Guidry received grant support for article research from NIH. His institution received grant support from NIH. Dr. Swenson consulted and lectured for 3M Medical and received support for article research from NIH. His institution received grant support from NIH and 3M Medical. Dr. Davies, Dr. Dossett, and Ms. Popovsky received grant support for article research from NIH. Their institutions received grant support from NIH. Dr. Bonatti received support for article research from NIH. Dr. Evans received grant support from Agency for Healthcare Research & Quality/American Recovery and Reinvestment Act (UW K12 Comparative effectiveness research Scholar) and support for article research from NIH. Her institution received grant support from NIH and AHRQ/ARA. Drs. Metzger, Hedrick, Tache-Léon, and Hranjec received grant support for article research from NIH. Their institutions received grant support from NIH. Dr. Chaudry has a patent filed with the U.S. Patent office for the use of estrogen following trauma and received support for article research from NIH. His institution received grant support from NIH. Dr. Pruett received grant support for article research from NIH. His institution received grant support from NIH. Dr. May consulted for Atox Bio and Dr. Reddy’s Laboratories, received support for travel from BHR Pharma, and received support for article research from NIH. Dr. Sawyer received grant support for article research from NIH. His institution received grant support from NIH.

For information regarding this article, E-mail: rws2k@hscmail.mcc.virginia.edu

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins