Procalcitonin and Interleukin-6 in pediatric patients admitted with suspected sepsis at Tertiary Care Hospital
Keywords:
Procalcitonin, Interleukin-6, systemic inflammatory response syndrome, bacterial sepsis, final bacterial sepsis scoreAbstract
Background : Bacterial sepsis remains one of the leading causes of mortality and morbidity among children. Early identification of individuals at risk of developing life-threatening sepsis could enable early treatment and improve outcomes. Procalcitonin (PCT), the peptide hormone precursor of calcitonin, and Interleukin-6 (IL-6), the pro-inflammatory cytokine, are both substances that present in higher concentrations after inflammation. The potential value of measuring PCT and IL-6 levels are recognized as biological markers in pediatric patients with systemic inflammatory response syndrome (SIRS) in both early diagnosis of sepsis and to differentiate sepsis from the other SIRS non-septic conditions, has higher accuracy than the routine laboratory tests pragmatically such as total leukocytes count and C-reactive protein (CRP).
Objectives : To define the clinical and laboratory predictive factors for early diagnosis in pediatric bacterial sepsis and distinguishing from the other SIRS non-septic conditions, including the development of the risk scoring system for pediatric bacterial sepsis prediction.
Methods : The diagnostic prediction research was designed from the prospective data from September 2015 to June 2016 at the Department of Pediatrics, Bhumibol Adulyadej Hospital, Bangkok, Thailand. Forty-nine patients from the age of 1 month to 15 years old who met the criteria of SIRS definition were recruited into the study. Multivariable logistic regression was performed to select the strongest predictors then transformed to develop the final bacterial sepsis score (FBAC score).
Results : The best clinical and laboratory predictors included female gender, PCT, IL-6, CRP levels prior to treatment on admission date and CRP level at 24 hours after starting of the treatment. The developed FBAC score predicted bacterial sepsis correctly with an AuROC of 86.5%. The patients who have FBAC scores below 10 (low risk category) will have the chance to be bacterial sepsis 10 times less (likelihood ratio of positive; LHR + 0.1, P - value 0.01) and the potential bacterial septic patients will have more than 6 times increasingly (LHR+ 6.13, P - value 0.02) if their total FBAC scores are higher than 30 (high risk category).
Conclusions : The developed FBAC scores will help pediatricians to predict bacterial sepsis for early treatment intervention and can distinguish bacterial sepsis from the other SIRS non-septic conditions.
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Nanda SK, Dinakaran A, Bhat S, Ravichandran K, Kanungo R. Diagnostic and prognostic role of Procalcitonin in sepsis in a tertiary care hospital. Biomed Res 2016;27:79-83.
Mat-Nor MB, Md RA, Abdulah NZ, Pickering JW. The diagnostic ability of procalcitonin and interleukin-6 to differentiate infectious from noninfectious systemic inflammatory response syndrome and to predict mortality. J Crit Care 2016;33:245-51. https://doi.org/10.1016/j.jcrc.2016.01.002
Fioretto JR, Borin FC, Bonatto RC, Ricchetti SM, Kurokawa CS, de Moraes M, et al. Procalcitonin in children with sepsis and septic shock. J Pediatr (Rio J ) 2007;83:323-8.
https://doi.org/10.1590/S0021-75572007000500007
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89-95.https://doi.org/10.1067/mcp.2001.113989
Schelonka RL, Infante AJ. Neonatal immunology. Semin Perinatol 1998;22:2-14.
https://doi.org/10.1016/S0146-0005(98)80003-7
Carrol ED, Thomson AP, Hart CA. Procalcitonin as a marker of sepsis. Int J Antimicrob Agents 2002;20:1-9. https://doi.org/10.1016/S0924-8579(02)00047-X
Casado-Flores J, Blanco-Quiros A, Asensio J, Arranz E, Garrote JA, Nieto M. Serum procalcitonin in children with suspected sepsis: a comparison with C-reactive protein and neutrophil count. Pediatr Crit Care Med 2003;4:190-5. https://doi.org/10.1097/01.PCC.0000059420.15811.2D
Sherwin C, Broadbent R, Young S, Worth J, McCaffrey F, Medlicott NJ, et al. Utility of interleukin-12 and interleukin-10 in comparison with other cytokines and acute-phase reactants in the diagnosis of neonatal sepsis. Am J Perinatol 2008;25:629-36. https://doi.org/10.1055/s-0028-1090585
Simon L, Saint-Louis P, Amre DK, Lacroix J, Gauvin F. Procalcitonin and C-reactive protein as markers of bacterial infection in critically ill children at onset of systemic inflammatory response syndrome. Pediatr Crit Care Med 2008;9:407-13. https://doi.org/10.1097/PCC.0b013e31817285a6
Sakha K, Husseini MB, Seyyedsadri N. The role of the procalcitonin in diagnosis of neonatal sepsis and correlation between procalcitonin and C-reactive protein in these patients. Pak J Biol Sci 2008;11:1785-90. https://doi.org/10.3923/pjbs.2008.1785.1790
Meisner M, Adina H, Schmidt J. Correlation of procalcitonin and C-reactive protein to inflammation, complications, and outcome during the intensive care unit course of multiple-trauma patients. Crit Care 2006;10: R1. https://doi.org/10.1186/cc3910
Andreola B, Bressan S, Callegaro S, Liverani A, Plebani M, Da Dalt L. Procalcitonin and Creactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department. Pediatr Infect Dis J 2007;26:672-7.
https://doi.org/10.1097/INF.0b013e31806215e3
Enguix A, Rey C, Concha A, Medina A, Coto D, Dieguez MA. Comparison of procalcitonin with C-reactive protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children. Intensive Care Med 2001;27:211-5.
https://doi.org/10.1007/s001340000709
Magudumana MO, Ballot DE, Cooper PA, Trusler J, Cory BJ, Viljoen E, et al. Serial interleukin 6 measurements in the early diagnosis of neonatal sepsis. J Trop Pediatr 2000;46:267-71.
https://doi.org/10.1093/tropej/46.5.267
Reinhart K, Meisner M, Brunkhorst FM. Markers for sepsis diagnosis: what is useful? Crit Care Clin 2006;22:503-x. https://doi.org/10.1016/j.ccc.2006.03.003
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6: 2-8.
https://doi.org/10.1097/01.PCC.0000149131.72248.E6
Yulianto S, Runtunuwu AL, Pateda V, Mandei JM, Lolombulan JH. Correlation between interleukin-6 and septic shock in children. Paediatr Indones 2012;52:352.
https://doi.org/10.14238/pi52.6.2012.352-5
Pavare J, Grope I, Kalnins I, Gardovska D. High-mobility group box-1 protein, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in children with community acquired infections and bacteraemia: a prospective study. BMC Infect Dis 2010;10:28.
https://doi.org/10.1186/1471-2334-10-28
Fioretto JR, Martin JG, Kurokawa CS, Carpi MF, Bonatto RC, Ricchetti SM, et al. Interleukin-6 and procalcitonin in children with sepsis and septic shock. Cytokine 2008;43:160-4.
https://doi.org/10.1016/j.cyto.2008.05.005
Briassoulis G, Venkataraman S, Thompson A. Cytokines and metabolic patterns in pediatric patients with critical illness. Clin Dev Immunol 2010;2010:354047.
https://doi.org/10.1155/2010/354047
Luzzani A, Polati E, Dorizzi R, Rungatscher A, Pavan R, Merlini A. Comparison of procalcitonin and C-reactive protein as markers of sepsis. Crit Care Med 2003;31: 1737-41.
https://doi.org/10.1097/01.CCM.0000063440.19188.ED
Urbonas V, Eidukaite A, Tamuliene I. The diagnostic value of interleukin-6 and interleukin-8 for early prediction of bacteremia and sepsis in children with febrile neutropenia and cancer. J Pediatr Hematol Oncol 2012; 34:122-7. https://doi.org/10.1097/MPH.0b013e3182446a60
Wynn JL, Wong HR. Pathophysiology and treatment of septic shock in neonates. Clin Perinatol 2010;37:439-79. https://doi.org/10.1016/j.clp.2010.04.002
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39: 165-228. https://doi.org/10.1007/s00134-012-2769-8
Mathias B, Mira JC, Larson SD. Pediatric sepsis. Curr Opin Pediatr 2016;28:380-7.
https://doi.org/10.1097/MOP.0000000000000337
Standage SW, Wong HR. Biomarkers for pediatric sepsis and septic shock. Expert Rev Anti Infect Ther 2011;9:71-9. https://doi.org/10.1586/eri.10.154
Meisner M. Procalcitonin-Biochemistry and Clinical Diagnosis. Bremen: Uni-Med Verlag Ag; 2010.
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864-74. https://doi.org/10.1097/00003246-199206000-00025
Povoa P, Almeida E, Moreira P, Fernandes A, Mealha R, Aragao A, et al. C-reactive protein as an indicator of sepsis. Intensive Care Med 1998;24:1052-6.
https://doi.org/10.1007/s001340050715
Balci C, Sivaci R, Akbulut G, Karabekir HS. Procalcitonin levels as an early marker in patients with multiple trauma under intensive care. J Int Med Res 2009;37:1709-17.
https://doi.org/10.1177/147323000903700606
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;3:1-7.
https://doi.org/10.2174/1874309900903010001
Angele MK, Pratschke S, Hubbard WJ, Chaudry IH. Gender differences in sepsis: cardiovascular and immunological aspects. Virulence 2014;5:12-9. https://doi.org/10.4161/viru.26982
Seigel TA, Cocchi MN, Salciccioli J, Shapiro NI, Howell M, Tang A, et al. Inadequacy of temperature and white blood cell count in predicting bacteremia in patients with suspected infection. J Emerg Med 2012;42: 254-9. https://doi.org/10.1016/j.jemermed.2010.05.038
Samraj RS, Zingarelli B, Wong HR. Role of biomarkers in sepsis care. Shock 2013;40: 358-65.
https://doi.org/10.1097/SHK.0b013e3182a66bd6
Yang Y, Xie J, Guo F, Longhini F, Gao Z, Huang Y, et al. Combination of C-reactive protein, procalcitonin and sepsis-related organ failure score for the diagnosis of sepsis in critical patients. Ann Intensive Care 2016;6:51. https://doi.org/10.1186/s13613-016-0153-5
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