The Combined Use of Interleukin-6 with Serum Albumin for Mortality Prediction in Critically Ill Elderly Patients: The Interleukin-6-to-albumin Ratio
Kai Yang Lim, Wan Fadzlina Wan Muhd Shukeri, Wan Mohd Nazaruddin Wan Hassan, Mohd Basri Mat-Nor, Muhammad Hafiz Hanafi
Keywords :
Albumin, Elderly, Intensive care unit, Intensive care unit mortality, Interleukin-6
Citation Information :
Lim KY, Shukeri WF, Hassan WM, Mat-Nor MB, Hanafi MH. The Combined Use of Interleukin-6 with Serum Albumin for Mortality Prediction in Critically Ill Elderly Patients: The Interleukin-6-to-albumin Ratio. Indian J Crit Care Med 2022; 26 (10):1126-1130.
Background: The association between interleukin-6 (IL-6) and serum albumin (ALB) with mortality in critically ill elderly patients, either as stand-alone biomarkers or in combination, has been scarcely reported. We, therefore, aimed to investigate the prognostic value of the IL-6-to-albumin ratio in this special population.
Patients and methods: This was a cross-sectional study conducted in the mixed intensive care unit (ICU) of two university-affiliated hospitals in Malaysia. Consecutive elderly patients (aged above or equal to 60 years) admitted to the ICU, who underwent simultaneous measurement of plasma IL-6 and serum ALB, were recruited. The prognostic value of the IL-6-to-albumin ratio was assessed by analysis of the receiver-operating characteristic (ROC) curve.
Results: A total of 112 critically ill elderly patients were recruited. The outcome of all-cause ICU mortality was 22.3%. The calculated IL-6-to-albumin ratio was significantly higher in the non-survivors compared to the survivors {14.1 [interquartile range (IQR), 6.5–26.7] vs 2.5 [(IQR, 0.6–9.2) pg/mL, p <0.001]}. The area under the curve (AUC) of IL-6-to-albumin ratio for discrimination of ICU mortality was 0.766 [95% confidence interval (CI), 0.667–0.865, p <0.001] which was slightly higher than that of IL-6 and albumin alone. The ideal cut-off value of the IL-6-to-albumin ratio was above 5.7 with a sensitivity of 80.0% and specificity of 64.4%. After adjusting for severity of illness, the IL-6-to-albumin ratio remained as an independent predictor of ICU mortality with an adjusted odd ratio of 0.975 (95% CI, 0.952–0.999, p = 0.039).
Conclusion: The IL-6-to-albumin ratio offers a slight improvement in mortality prediction than either of its constituent individual biomarkers and as such, it may be a potential tool to aid in the prognostication of critically ill elderly patients although this requires further validation in a larger prospective study.
Mitchell E, Walker R. Global ageing: Successes, challenges and opportunities. Br J Hosp Med 2020;81(2):1–9. DOI: 10.12968/hmed.2019.0377.
Oud L. Evolving Demand for critical care services for elderly adults with dementia in Texas: A population-based study. J Am Geriatr Soc 2016;64:432–434. DOI: 10.1111/jgs.13971.
Andersen FH, Kvåle R. Do elderly intensive care unit patients receive less intensive care treatment and have higher mortality? Acta Anaesthesiol Scand 2012;56(10):1298–1305. DOI: 10.1111/j.1399-6576.2012.02782.x.
Tripathy S. Geriatric critical care in India. Indian J Crit Care Med 2015;19(3):191–192. DOI: 10.4103/0972-5229.152788.
Haas LEM, van Beusekom I, van Dijk D, Hamaker ME, Bakhshi–Raiez F, de Lange DW, et al. Healthcare-related costs in very elderly intensive care patients. Intensive Care Med 2018;44(11):1896–1903. DOI: 10.1007/s00134-018-5381-8.
Gupta V, Karnik ND, Agrawal D. SOFA score and critically ill elderly patients. J Assoc Physicians India 2017;65(7):47–50. PMID: 28792169.
Qiao Q, Lu G, Li M, Shen Y, Xu D. Prediction of outcome in critically ill elderly patients using APACHE II and SOFA scores. J Int Med Res 2012;40(3):1114–1121. DOI: 10.1177/147323001204000331.
Sánchez–Hurtado LA, Ángeles–Veléz A, Tejeda–Huezo BC, García–Cruz JC, Juárez–Cedillo T. Validation of a prognostic score for mortality in elderly patients admitted to intensive care unit. Indian J Crit Care Med 2016;20(12):695–700. DOI: 10.4103/0972-5229.195702.
Yamamoto R, Sasaki J, Shibusawa T, Nakada TA, Mayumi T, Takasu O, et al. Accuracy for mortality prediction with additive biomarkers including interleukin-6 in critically ill patients: A multicenter prospective observational study. Crit Care Explor 2021;3(4):e0387. DOI: 10.1097/CCE.0000000000000387.
Franco DM, Arevalo–Rodriguez I, Roqué I Figuls M, Oleas NGM, Nuvials X, Zamora J. Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults. Cochrane Database Syst Rev 2019;4. DOI: 10.1002/14651858.CD011811.pub2.
Lindmark E, Diderholm E, Wallentin L, Siegbahn A. Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: Effects of an early invasive or noninvasive strategy. JAMA 2001;286(17):2107–2113. DOI: 10.1001/jama.286.17.2107.
Atrash AK, de Vasconcellos K. Low albumin levels are associated with mortality in the critically ill: A retrospective observational study in a multidisciplinary intensive care unit. South Afr J Crit Care 2020;36(2):10.7196/SAJCC.2020.v36i2.422. DOI: 10.7196/SAJCC.2020.v36i2.422.
Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and age-related diseases: Role of inflammation riggers and cytokines. Front Immunol 2018;9:586. DOI: 10.3389/fimmu.2018.00586.
Cabrerizo S, Cuadras D, Gomez–Busto F, Artaza–Artabe I, Marín–Ciancas F, Malafarina V. Serum albumin and health in older people: Review and meta-analysis. Maturitas 2015;81(1):17–27. DOI: 10.1016/j.maturitas.2015.02.009.
Rizo–Tellez SA, Mendez–Garcia LA, Rivera–Rugeles AC, Miranda–García M, Manjarrez–Reyna AN, Viurcos–Sanabria R, et al. The combined use of cytokine serum values with laboratory parameters improves mortality prediction of COVID-19 patients: The interleukin-15-to-albumin ratio. Microorganisms 2021;9:2159. DOI: 10.3390/microorganisms9102159.
United Nations Department of Economic and Social Affairs, Population Division (2020). World Population Ageing 2020 Highlights: Living arrangements of older persons (ST/ESA/SER.A/451). Available at: https://www.un.org/development/desa/pd/news/world-population-ageing-2020-highlights. Accessed date: 13 August 2022.
Nielsson MS, Christiansen CF, Johansen MB, Rasmussen BS, Tønnesen E, Nørgaard M. Mortality in elderly ICU patients: A cohort study. Acta Anaesthesiol Scand 2014;58(1):19–26. DOI: 10.1111/aas.12211.
Gom I, Fukushima H, Shiraki M, Miwa Y, Ando T, Takai K, et al. Relationship between serum albumin level and aging in community-dwelling self-supported elderly population. J Nutr Sci Vitaminol 2007;53:37–42. DOI: 10.3177/jnsv.53.37.
Maggio M, Guralnik JM, Longo DL, Ferrucci L. Interleukin-6 in aging and chronic disease: A magnificent pathway. J Gerontol A Biol Sci Med Sci 2006;61:575–584. DOI: 10.1093/gerona/61.6.575.
Todi S, Choudhuri R. Critical care research in elderly population: an uncharted territory. Indian J Crit Care Med 2020;24(7):500–501. DOI: 10.5005/jp-journals-10071-23492.