Citation Information :
Paul A, Newbigging NS, Gowri M, Varghese JS, Nell AJ, Binu AJ, Varghese GM. Role of Neutrophil Gelatinase-associated Lipocalin (NGAL) and Other Clinical Parameters as Predictors of Bacterial Sepsis in Patients Presenting to the Emergency Department with Fever. Indian J Crit Care Med 2023; 27 (3):176-182.
Background: Bacterial sepsis is associated with significant morbidity and mortality. However, to date, there is no single test that predicts sepsis with reproducible results. We proposed that using a combination of clinical and laboratory parameters and a novel biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL) may aid in early diagnosis.
Method: A prospective cohort study was conducted at a tertiary care center in South India (June 2017 to April 2018) on patients with acute febrile episodes fulfilling the Systemic Inflammatory Response Syndrome (SIRS) criteria. Plasma NGAL and standard clinical and laboratory parameters were collected at the admission. Bacterial sepsis was diagnosed based on blood culture positivity or clinical diagnosis. Clinically relevant plasma NGAL cut-off values were identified using the receive operating characteristic (ROC) curve. Clinically relevant clinical parameters along with plasma NGAL's risk ratios estimated from the multivariable Poisson regression model were rounded and used as weights to create a new scoring tool.
Results: Of 100 patients enrolled, 37 had bacterial sepsis. The optimal plasma NGAL cut-off value to predict sepsis was 570 ng/mL [area under the curve (AUC): 0.69]. The NGAL sepsis screening tool consists of the following clinical parameter: diabetes mellitus, the presence of rigors, quick sequential organ failure assessment (qSOFA) >2, a clear focus of infection, and the plasma NGAL >570 ng/mL. A score of <3 ruled out bacterial sepsis and a score >7 were highly suggestive of bacterial sepsis with an interval likelihood ratio (LR) of 7.77.
Conclusion: The NGAL sepsis screening tool with a score >7 can be used in the emergency department (ED) to identify bacterial sepsis.
Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study. Available from: http://minerva-access.unimelb.edu.au/handle/11343/273829 (last accessed Jan 18, 2020 [cited Jan 20, 2022]).
Cohen J, Vincent JL, Adhikari NKJ, Machado FR, Angus DC, Calandra T, et al. Sepsis: A roadmap for future research. Lancet Infect Dis 2015;15(5):581–614. DOI: 10.1016/S1473-3099(15)70112-X.
Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing Sepsis as a Global Health Priority—A WHO Resolution [Internet]. Massachusetts Medical Society; 2017 Available from: https://www.nejm.org/doi/10.1056/NEJMp1707170 (Nov 26, 2021). DOI: http://dx.doi.org/10.1056/NEJMp1707170.
Chatterjee S, Bhattacharya M. Epidemiology of adult-population sepsis in India: A single center 5 year experience. Indian J Crit Care Med 2017;21(9):573–577. DOI: 10.4103/ijccm.IJCCM_240_17.
Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: Results from a guideline-based performance improvement program. Crit Care Med 2014;42(8):1749–1755. DOI: 10.1097/CCM.0000000000000330.
Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017;376(23):2235–2244. DOI: 10.1056/NEJMoa1703058.
Palatty B, Kassyap CK, Abraham SV, Krishnan S, Rajeev PC. Factors affecting early treatment goals of sepsis patients presenting to the emergency department. Indian J Crit Care Med 2018;22(11):797–800. DOI: 10.4103/ijccm.IJCCM_27_18.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315(8):801. DOI: 10.1001/jama.2016.0287.
Adegbite BR, Edoa JR, Ndzebe Ndoumba WF, Dimessa Mbadinga LB, Mombo-Ngoma G, Jacob ST, et al. A comparison of different scores for diagnosis and mortality prediction of adults with sepsis in Low-and-Middle-Income Countries: a systematic review and meta-analysis. EClinicalMedicine 2021;42:101184. DOI:10.1016/j.eclinm.2021.101184.
Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369(9):840–851. DOI: 10.1056/NEJMra1208623.
Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Aguilar GR, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 2022;399(10325):629–655. DOI: 10.1016/S0140-6736(21)02724-0.
Teggert A, Datta H, Ali Z. Biomarkers for point-of-care diagnosis of sepsis. Micromachines 2020;11(3):E286. DOI: 10.3390/mi11030286.
Vincent JL. The clinical challenge of sepsis identification and monitoring. PLoS Med 2016;13(5):e1002022. DOI: 10.1371/journal.pmed.1002022.
Bao G, Clifton M, Hoette TM, Mori K, Deng SX, Qiu A, et al. Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nat Chem Biol 2010;6(8):602–609. DOI: 10.1038/nchembio.402.
Zhang A, Cai Y, Wang PF, Qu JN, Luo ZC, Chen XD, et al. Diagnosis and prognosis of neutrophil gelatinase-associated lipocalin for acute kidney injury with sepsis: A systematic review and meta-analysis. Crit Care 2016;20:41. DOI: 10.1186/s13054-016-1212-x.
Mårtensson J, Bell M, Oldner A, Xu S, Venge P, Martling CR. Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med 2010;36(8):1333–1340. DOI: 10.1007/s00134-010-1887-4.
Mårtensson J, Bell M, Xu S, Bottai M, Ravn B, Venge P, et al. Association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with sepsis and acute kidney dysfunction. Biomarkers 2013;18(4):349–356. DOI: 10.3109/1354750X.2013.787460.
Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): The TRIPOD statement | EQUATOR Network [Internet]. Available from: https://www.equator-network.org/reporting-guidelines/tripod-statement/ (cited Dec 6, 2022).
Chase M, Klasco RS, Joyce NR, Donnino MW, Wolfe RE, Shapiro NI. Predictors of bacteremia in emergency department patients with suspected infection. Am J Emerg Med 2012;30(9):1691–1697. DOI: 10.1016/j.ajem.2012.01.018.
Phungoen P, Lerdprawat N, Sawanyawisuth K, Chotmongkol V, Ienghong K, Sumritrin S, et al. Clinical factors associated with bloodstream infection at the emergency department. BMC Emerg Med 2021;21:30. DOI: 10.1186/s12873-021-00426-2.
Fabre V, Sharara SL, Salinas AB, Carroll KC, Desai S, Cosgrove SE. Does this patient need blood cultures? A scoping review of indications for blood cultures in adult nonneutropenic inpatients. Clin Infect Dis 2020;71(5):1339–1347. DOI: 10.1093/cid/ciaa039.
Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021;47(11):1181–1247. DOI: 10.1097/CCM.0000000000005337.
Sparks R, Harada A, Chavada R, Trethewy C. Comparison of different sepsis scoring systems and pathways: qSOFA, SIRS, Shapiro criteria and CEC SEPSIS KILLS pathway in bacteraemic and non-bacteraemic patients presenting to the emergency department. BMC Infect Dis 2022;22:76. DOI: 10.1186/s12879-022-07070-6.
Baduashvili A, Guyatt G, Evans AT. ROC anatomy—getting the most out of your diagnostic test. J Gen Intern Med 2019;34(9):1892–1898. DOI: 10.1007/s11606-019-05125-0.
Hong DY, Kim JW, Paik JH, Jung HM, Baek KJ, Park SO, et al. Value of plasma neutrophil gelatinase-associated lipocalin in predicting the mortality of patients with sepsis at the emergency department. Clin Chim Acta Int J Clin Chem 2016;452:177–181. DOI: 10.1016/j.cca.2015.11.026.
Tokuda Y, Miyasato H, Stein GH. A simple prediction algorithm for bacteraemia in patients with acute febrile illness. QJM Int J Med 2005;98(11):813–820. DOI: 10.1093/qjmed/hci120.