Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2018 Aug;85(2):247-255.
doi: 10.1097/TA.0000000000001921.

The impact of age on the innate immune response and outcomes after severe sepsis/septic shock in trauma and surgical intensive care unit patients

Scott C Brakenridge  1 , Philip A Efron, Julie A Stortz, Teczan Ozrazgat-Baslanti, Gabriela Ghita, Zhongkai Wang, Azra Bihorac, Alicia M Mohr, Babette A Brumback, Lyle L Moldawer, Frederick A Moore
Affiliations
Observational Study

The impact of age on the innate immune response and outcomes after severe sepsis/septic shock in trauma and surgical intensive care unit patients

Scott C Brakenridge et al. J Trauma Acute Care Surg. 2018 Aug.

Abstract

Background: Advancing age is a strong risk factor for adverse outcomes across multiple disease processes. However, septic surgical and trauma patients are unique in that they incur two or more inflammatory insults. The effects of advanced age on sepsis pathophysiology and outcomes remain unclear.

Methods: We performed a single-center, prospective observational cohort study of surgical intensive care unit patients with severe sepsis/septic shock. Peripheral blood was collected for genomic, cytokine, and biomarker analysis at 0.5 day, 1 day, 4 days, 7 days, 14 days, 21 days, and 28 days after sepsis onset. Based on sensitivity analysis, cohorts were defined as "young" (<55 years) and "aged" (≥55 years). We compared age-defined cohorts to determine differences in patient characteristics, biomarker profiles, and clinical outcomes.

Results: The cohort included 173 patients with severe sepsis (n = 93; 53.8%) or septic shock (n = 80; 46.2%), with a mean age of 60.9 (±14.5) years. Intra-abdominal sepsis was the leading source (n = 81; 46.8%), followed by necrotizing soft tissue infection (n = 33, 19.1%) and pneumonia (n = 30; 17.3%). Aged patients had a higher comorbidity burden, but were otherwise similar to the young cohort. The aged cohort had a higher severity of early physiologic derangement (median APACHE II, 23 vs. 18; p = 0.002), greater incidence of multiple organ failure (64.3% vs. 40.4%, p = 0.006), and hospital mortality (15.9% vs. 2.1%; p = 0.016). Six-month mortality was significantly higher in the aged cohort as compared with young cohort (31% vs. 9%; p = 0.003). Aged septic patients biomarker trajectories suggestive of persistent immunosuppression (absolute lymphocyte count, soluble programed death ligand-1) and catabolism (Urine 3MH-Cr ratio, insulin growth factor, IGF1BP3, albumin) out to 28 days after sepsis.

Conclusion: Aged, critically ill surgical patients have greater organ dysfunction and incidence of adverse clinical outcomes after sepsis. Biomarker profiles suggest an immunophenotype of persistent immunosuppression and catabolism. Advanced age may necessitate novel therapeutic strategies to promote multisystem organ recovery and improve survival after sepsis.

Level of evidence: Prognostic, level II.

PubMed Disclaimer

Figures

Figure 1
Figure 1
6-month survival of aged compared to young sepsis patients.
Figure 2
Figure 2
Circulating inflammatory biomarker analysis of aged compared to young sepsis patients.
Figure 3
Figure 3
Circulating immunosuppression and catabolism biomarker analysis of aged compared to young sepsis patients.
See this image and copyright information in PMC

References

    1. Vanzant EL, Hilton RE, Lopez CM, Zhang J, Ungaro RF, Gentile LF, Szpila BE, Maier RV, Cuschieri J, Bihorac A, et al. Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock. Crit Care. 2015;19:77. - PMC - PubMed
    1. Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, Hayden DL, Hennessy L, Moore EE, Minei JP, et al. A genomic storm in critically injured humans. J Exp Med. 2011;208(13):2581–90. - PMC - PubMed
    1. Mira JC, Cuschieri J, Ozrazgat-Baslanti T, Wang Z, Ghita GL, Loftus TJ, Stortz JA, Raymond SL, Lanz JD, Hennessy LV, et al. The Epidemiology of Chronic Critical Illness After Severe Traumatic Injury at Two Level-One Trauma Centers. Crit Care Med. 2017;45(12):1989–96. - PMC - PubMed
    1. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl 1):S4–9. - PubMed
    1. Melton DW, Roberts AC, Wang H, Sarwar Z, Wetzel MD, Wells JT, Porter L, Berton MT, McManus LM, Shireman PK. Absence of CCR2 results in an inflammaging environment in young mice with age-independent impairments in muscle regeneration. J Leukoc Biol. 2016;100(5):1011–25. - PMC - PubMed

Publication types