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. 2022 Jan 7;77(1):188-196.
doi: 10.1093/gerona/glab080.

Older Adults Demonstrate Biomarker Evidence of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) After Sepsis

Robert T Mankowski  1 , Stephen D Anton  2 , Gabriela L Ghita  3 , Babette Brumback  3   4 , Dijoia B Darden  4 , Azra Bihorac  2 , Christiaan Leeuwenburgh  1 , Lyle L Moldawer  4 , Philip A Efron  4 , Scott C Brakenridge  4 , Frederick A Moore  4
Affiliations

Older Adults Demonstrate Biomarker Evidence of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) After Sepsis

Robert T Mankowski et al. J Gerontol A Biol Sci Med Sci. .

Abstract

Background: Hospital deaths after sepsis have decreased substantially and most young adult survivors rapidly recover (RAP). However, many older survivors develop chronic critical illness (CCI) with poor long-term outcomes. The etiology of CCI is multifactorial and the relative importance remains unclear. Sepsis is caused by a dysregulated immune response and biomarkers reflecting a persistent inflammation, immunosuppression, and catabolism syndrome (PICS) have been observed in CCI after sepsis. Therefore, the purpose of this study was to compare serial PICS biomarkers in (i) older (vs young) adults and (ii) older CCI (vs older RAP) patients to gain insight into underlying pathobiology of CCI in older adults.

Method: Prospective longitudinal study with young (≤45 years) and older (≥65 years) septic adults, who were characterized by (i) baseline predisposition, (ii) hospital outcomes, (iii) serial Sequential Organ Failure Assessment (SOFA) organ dysfunction scores over 14 days, (iv) Zubrod Performance status at 3-, 6-, and 12-month follow-up, and (v) mortality over 12 months, was conducted. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS.

Results: Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status, and mortality over 12 months. Additionally, older (vs young) and older CCI (vs older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism, and antiangiogenesis over 14 days after sepsis.

Conclusion: Older (vs young) and older CCI (vs older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS.

Keywords: Aging; Chronic critical illness; Critical illness; Infection.

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Figures

Figure 1.
Figure 1.
Clinical outcomes over 12 mo after sepsis onset between the older and young sepsis survivors. (A) A 14-d serial Sequential Organ Failure Assessment (SOFA), (B) 12-mo Zubrod score, and (C) 1-y survival estimates. Data presented as mean ± SE with statistical significance set at p <.05 and asterisk represents statistical significance.
Figure 2.
Figure 2.
Comparison of biomarkers of proinflammation and immunosuppression between older and young sepsis patients. Proinflammation: (A) interleukin-6 (IL-6), (B) IL-8, (C) monocyte chemoattractant protein 1 (MCP-1), and (D) C-reactive protein (CRP) and (E) absolute neutrophil count (ANC). Immunosuppression: (F) soluble programmed death ligand 1 (sPDL-1), (G) IL-10, and (H) absolute lymphocyte count (ALC) biomarkers. Perforated line represents biomarker levels in matched control subjects. Shaded area represents published normal reference ranges. Data presented as median (25% and 75%) with statistical significance set at p <.05 and asterisk represents statistical significance of the older (vs young) and older chronic critical illness (CCI) (vs older rapidly recover [RAP]) cohorts.
Figure 3.
Figure 3.
Comparison of stress and catabolism biomarkers between older and young sepsis patients. Stress metabolism: (A) glucagon-like peptide 1 (GLP-1) and (B) serum albumin level. Anabolism: (C) insulin-like growth factor (IGF-1) and (D) insulin-like growth factor-binding protein 3 (IGFBP-3) biomarkers. Perforated line represents biomarker levels in matched control subjects. Shaded area represents published normal reference ranges. Data presented as median (25% and 75%) with statistical significance set at p <.05 and asterisk represents statistical significance of the older (vs young) and older chronic critical illness (CCI) (vs older rapidly recover [RAP]) cohorts.
Figure 4.
Figure 4.
Comparison of biomarkers of angiogenesis between older and young sepsis patients. Angiogenesis biomarkers: (A) soluble vascular endothelial growth factor receptor 1 (sFlt-1), (B) interferon gamma-induced protein 10 (IP-10), (C) vascular endothelial growth factor (VEGF), and (D) angiopoietin 2 (Ang2). Perforated line represents biomarker levels in matched control subjects. Data presented as median (25% and 75%) with statistical significance set at p <.05 and asterisk represents statistical significance of the older (vs young) and older chronic critical illness (CCI) (vs older rapidly recover [RAP]) cohorts.
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