Abstract

Background: Utility of biomarkers in early prediction of multiple organ dysfunction syndrome (MODS) in suspected cases of sepsis presenting to the Emergency Department (ED).

 Aim and Objectives: To correlate the biomarker values (Pro-calcitonin (PCT), C-reactive protein (CRP), NT-pro BNP and Neutrophil gelatinase associated lipocalin (NGAL) with multiple organ dysfunction (MOD) score and to evaluate their role in early prediction of MODS in suspected sepsis patients presenting to ED.

Methods: This is a prospective observational study conducted on 65 patients with suspected sepsis. Patients of 18-65 years presented in the ED with triage complaints of fever, respiratory, urinary and abdominal infections, who were sepsis screen positive on arrival and admitted, were enrolled in the study. They were categorized into two groups: Group 1 (MODS score Positive at 48 or 72 hours) and Group 2 (MOD score Negative). Biomarker values in both the groups and its correlation with MOD score was analyzed.

Results: At 48 hours, 40 (61.5%) patients were MODS positive with PCT (Sensitivity 100%, OR-12.6, CI-0.6-255.04, p=0.098), CRP (Sensitivity 100%, OR-27.0, CI-1.44-504.0, p=0.027), NTpro BNP (Sensitivity 82.5%, OR-7.07, CI-2.55-22.16, p=0.0008) and NGAL (Sensitivity 77.5%, OR-82.9, CI-9.7-698.16, p=0.0001) with PPV of NGAL (96.88%) and NT-pro BNP (76.74%) and 100% NPV for PCT and CRP.

Conclusion: This study established a good correlation of NT-pro BNP and NGAL with positive MODS score suggestive of and highly predictive of developing MODS in suspected cases of sepsis. The normal value of PCT and CRP on arrival in patients with suspected sepsis rules out MODS even at 72 hours during their hospital stay.
 

• 1.   Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med. 2008 Jan;34(1):17-60.
• 2.   Angus DC, Van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369:840-51.
• 3.   Magrini L, Travaglino F, Marino R, Ferri E, De Berardinis B, Cardelli P, et al. Procalcitonin variations after Emergency Department admission are highly predictive of hospital mortality in patients with acute infectious diseases. Age (yrs). 2013;72(15.1):72-6.
• 4.   Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992 Jun 1;101(6):1644-55.
• 5.   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 Feb 23;315(8):801-10.
• 6.   Raith EP, Udy AA, Bailey M, McGloughlin S, MacIsaac C, Bellomo R, et al. Prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit. JAMA. 2017 Jan 17;317(3):290-300.
• 7.   Baue AE. Multiple, progressive, or sequential systems failure: a syndrome of the 1970s. Arch Surg. 1975 Jul 1;110(7):779-81.
• 8.   Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010 Feb;14(1):1-8.
• 9.   Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995 Oct 1;23(10):1638-52.
• 10.   Assicot M, Bohuon C, Gendrel D, Raymond J, Carsin H, Guilbaud J. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993 Feb 27;341(8844):515-8.
• 11.   Hur M, Kim H, Lee S, Cristofano F, Magrini L, Marino R, et al. Diagnostic and prognostic utilities of multimarkers approach using procalcitonin, B-type natriuretic peptide, and neutrophil gelatinase-associated lipocalin in critically ill patients with suspected sepsis. BMC Infect Dis. 2014 Dec;14(1):1-8.
• 12.   Pandey NB, Shah DJ, Arora P, Mathur AK. Role of N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) for Diagnosing Underlying Cardiac and Extra-cardiac Diseases in Patients presenting with Acute Breathlessness in the Emergency Department. J Adv Res Med. 2021 Dec 30;8(4):1-1.
• 13.   Varpula M, Pulkki K, Karlsson S, Ruokonen E, Pettilä V, FINNSEPSIS Study Group. Predictive value of N-terminal pro–brain natriuretic peptide in severe sepsis and septic shock. Crit Care Med. 2007 May 1;35(5):1277-83.
• 14.   Chiriboga DE, Ma Y, Li W, Stanek III EJ, Hébert JR, Merriam PA, et al. Seasonal and sex variation of high-sensitivity C-reactive protein in healthy adults: a longitudinal study. Clin Chem. 2009 Feb 1;55(2):313-21.
• 15.   Shapiro NI, Trzeciak S, Hollander JE, et al. The Diagnostic Accuracy of Plasma Neutrophil Gelatinase Associated Lipocalin in the Prediction of Acute Kidney Injury in Emergency Department Patients with Suspected Sepsis. Ann Emerg Med. 2010;56:52-9.
• 16.   Pandey NB, Shah DJ, Arora P, Mathur AK. Role Of N-terminal Pro-b-type Natriuretic Peptide (NT-proBNP) as a prognostic marker for the patients of acute breathlessness in the Emergency Department (ED). Int J Sci Res (IJSR). 2021;10(3).
• 17.   Nush MM, Ashok VK, Sarma RI, Pillai SK. Role of C-reactive protein as an indicator for determining the outcome of sepsis. Indian J Crit Care Med. 2019 Jan;23(1):11.
• 18.   Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure.
• 19.   Chan YL, Tseng CP, Tsay PK, Chang SS, Chiu TF, Chen JC. Procalcitonin as a marker of bacterial infection in the emergency department: an observational study. Crit Care. 2003 Feb;8(1):1-9.
• 20.   Bouza C, Lopez-Cuadrado T, Saz-Parkinson Z, Amate-Blanco JM. Epidemiology and recent trends of severe sepsis in Spain: a nationwide population-based analysis (2006-2011). BMC Infect Dis. 2014 Dec;14(1):1-3.
• 21.   Wester AL, Dunlop O, Melby KK, Dahle UR, Wyller TB. Age-related differences in symptoms, diagnosis and prognosis of bacteremia. BMC Infect Dis. 2013 Dec;13(1):1-2.
• 22.   Qu J, Lu X, Liu Y, Wang X. Evaluation of procalcitonin, C-reactive protein, interleukin-6 & serum amyloid A as diagnostic biomarkers of bacterial infection in febrile patients. Indian J Med Res. 2015 Mar;141(3):315.
• 23.   Nanda SK, Dinakaran A, Bhat K, Kanungo R. Diagnostic and prognostic role of Procalcitonin in sepsis in a tertiary care hospital. Biomed Res. 2016 Jan 1;27(1).
• 24.   Pavare J, Grope I, Eihvalde L, Gardovska D. Diagnostic markers for identifying sepsis in patients with systemic inflammatory response syndrome (SIRS): a prospective Study. Open Pediatr Med J. 2009 Jan 6.
• 25.   Castelli GP, Pognani C, Meisner M, Stuani A, Bellomi D, Sgarbi L. Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care. 2004 Aug;8(4):1-9.
• 26.   Li HX, Liu ZM, Zhao SJ, Zhang D, Wang SJ, Wang YS. Measuring both procalcitonin and C-reactive protein for a diagnosis of sepsis in critically ill patients. J Int Med Res. 2014 Aug;42(4):1050-9.
• 27.   Wang F, Wu Y, Tang L, Zhu W, Chen F, Xu T, et al. Brain natriuretic peptide for prediction of mortality in patients with sepsis: a systematic review and meta-analysis. Crit Care. 2012 Jun;16(3):1-2.
• 28.   Mokart D, Sannini A, Brun JP, Faucher M, Blaise D, Blache JL, et al. N-terminal pro-brain natriuretic peptide as an early prognostic factor in cancer patients developing shock. Crit Care. 2007 Apr;11(2):1-0.
• 29.   Angeletti S, Fogolari M, Capone F, Morolla D, Costantino S, Spoto S, et al. Plasma-neutrophil gelatinase-associated lipocalin (NGAL) in combination with procalcitonin (PCT) and MR-proadrenomedullin (MR-proADM) in the diagnosis and prognosis of sepsis and sepsis associated acute kidney injury.

Data Sharing Statement

Funding