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Age-Related Differences in Biomarkers of Acute Inflammation During Hospitalization for Sepsis

Ginde, Adit A.*; Blatchford, Patrick J.; Trzeciak, Stephen; Hollander, Judd E.§; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M.**; Moretti, Eugene††; Nguyen, H. Bryant‡‡; Gunnerson, Kyle J.¶§§; Milzman, David∥∥; Gaieski, David F.§; Goyal, Munish∥∥¶¶; Cairns, Charles B.***; Rivers, Emanuel P.†††; Shapiro, Nathan I.‡‡‡

doi: 10.1097/SHK.0000000000000182
Clinical Aspects

ABSTRACT The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed—chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase–associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)—measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 – 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.

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*Department of Emergency Medicine, University of Colorado School of Medicine; and Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado; Department of Emergency Medicine, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, New Jersey; §Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; New York Methodist Hospital, Brooklyn; and Weill Cornell Medical Center, New York, New York; Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan; **Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; ††Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; ‡‡Departments of Emergency Medicine and Medicine, Loma Linda University Medical Center, Loma Linda, California; §§Departments of Anesthesiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan; ∥∥Departments of Emergency Medicine, and ¶¶Internal Medicine, MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, District of Columbia; ***Department of Emergency Medicine, University of North Carolina, Chapel Hill, North Carolina; †††Department of Emergency Medicine, Wayne State University, Detroit, Michigan; and ‡‡‡Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Received 7 Feb 2014; first review completed 25 Feb 2014; accepted in final form 24 Mar 2014

Address reprint requests to Adit A. Ginde, MD, MPH, Department of Emergency Medicine, University of Colorado School of Medicine, 12401 E. 17th Ave, B-215; Aurora, CO 80045. E-mail:

This study was supported by Alere, Inc (formerly Biosite), and by the National Institutes of Health (grant no. K23AG040708 to A.A.G. and grant no. R01HL091757 to N.I.S.).

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© 2014 by the Shock Society