NEUTROPHIL CD64 INDEX IN SEPSIS DIAGNOSIS AFTER CARDIAC SURGERY IN INFANTS

Early diagnosis of sepsis in neonates is especially relevant due to the persistently high rate neonatal mortality caused by this pathology. Active search for new laboratory markers, which would help to predict onset of a generalized infectious process with high probability, has been going on in recent years. The study was aimed at determining sensitivity and specificity of the CD64 index, evaluating the possibility of using it as an early marker of sepsis in infants after cardiac surgery during artificial circulation and comparing prognostic value of the CD64 index and the routinely used parameters. Patients and methods: the study involved 36 postoperative ICU. Retrospective analysis of bacterial inflammation markers has been conducted in groups of children at the postoperative stage: with (n = 16) and without (n = 20) sepsis. Results: the CD64 index in patients with sepsis was significantly higher than in the children without sepsis – 2.29 (p = 0.01). At the same time, blood serum C-reactive protein concentration and the absolute peripheral blood leukocyte count were similar in patients from both groups. Procalcitonin (PCT) test sensitivity for sepsis diagnosis was 65%, specificity – 67%. At the same time, the negative prognostic value of PCT reached 76%, the positive one – 63%. The performed analysis demonstrated that the CD64 index is a reliable early marker of sepsis with high sensitivity (80%) and specificity (90%); AUC – 0.895 (0.753-1.000) at cut-off point 2.00. Conclusions: C-reactive protein may not be seen as a reliable early marker of sepsis due to, it appears, peculiarities of its dynamics in the postoperative period. Specificity of this parameter is low and amounts to 50%. The study also demonstrated lower information value of the procalcitonin test compared to the CD64 index. The CD64 index over 2.00 indicates high risk of sepsis development in neonates in the postoperative period.

1. Bizzarro M. J., Raskind C., Baltimore R. S., Gallagher P. G. Seventyfive years of neonatal sepsis at Yale: 1928–2003. Pediatrics. 2005 Sep; 116 (3): 595–602.

2. The UN Inter-agency Group for Child Mortality Estimation (IGME), Levels and trends in Child Mortality: Report, UNICEF. New York. 2013. Available at: http://www.childinfo.org/files/Child_Mortality_Report_2013.pdf

3. Strunin O. V., Gorbatyh Ju. N., Shun'kin A. V., Novikova M. A. Features an answer for the correction of congenital heart defects in infants under extracorporeal circulation. Patologiya krovoobrashcheniya i kardiokhirurgiya = Pathology of vascular system and cardiosurgery. 2009; 1: 55–58.

4. Wheeler D. S., Jeffries H. E., Zimmerman J. J., Wong H. R., Carcillo J. A. Sepsis in the pediatric cardiac intensive care unit. World J. Pediatr. Congenit Heart Surg. 2011 Jul 1; 2 (3): 393–9.

5. Goldstein B., Giroir B., Randolph A. International consensus conference on pediatric sepsis: international pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr. Crit Care Med. 2005; 6: 2–8.

6. Davis B. H. Improved diagnostic approaches to infection/sepsis detection. Expert Rev. Mol Diagn. 2005; 5: 193–207.

7. Ng P. C., Lam H. S. Diagnostical markers for neonatal sepsis. Curr. Opin. Pediatr. 2006; 18: 125–131.

8. Casado-Flores J., Blanco-Quiros A., Asensio J., Arranz E., Garrote J. A., Nieto M. Serum procalcitonin in children with suspected sesis: a comparison with C-reactive protein and neutrophil count. Pediatric Critical Care Med. 2003; 4: 190–195.

9. Goia C. Procalcitonin in preterm infants during the first few days of life: introducing an age related monogram. Arch. Dis. Child Fetal. Neonatal Ed. 2006; 91: 283–286.

10. Livaditi O., Kotanidou A., Psarra A., Dimopoulou I., Sotiropoulou C., Augustatou K. et al. Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis. Cytokine. 2006; 36: 283–290.

11. Davis B. H., Olsen S. H., Ahmad E., Bigelow N. C. Neutrophil CD64 is an improved indicator of infection or sepsis in emergency department patients. Arch. Pathol. Lab. Med. 2006; 130: 654–661.

12. Davis B. H., Bigelow N. C. Comparison of neutrophil CD64 expression, manual myeloid immaturity counts, and automated hematology analyzer flags as indicators of infection or sepsis. Lab. Hematol. 2005; 11: 137–147.

13. Nuutila J., Hohenthal U., Laitinen I., Kotilainen P., Rajamaki A., Nikoskelainen J. et al. Simultaneous quantitative analysis of Fc-gamma-RI (CD64) expression on neutrophils and monocytes: a new, improved way to detect infections. J. Immunol. Methods. 2007; 328: 189–200.

14. Ng P. C., Li G., Chui K. M., Chu W. C., Li K., Wong R. P. et al. Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection. Pediatr. Res. 2004; 56: 796–803.

15. Layseca-Espinosa E., Perez-Gonzalez L. F., Torres-Montes A., Baranda L., de la Fuente H., Rosenstein Y. et al. Expression of CD64 as a potential marker of neonatal sepsis. Pediatr. Allergy Immunol. 2002; 13: 319–327.

16. Bhandari V., Wang C., Rinder C., Rinder H. Hematologic profile of sepsis in neonates: neutrophil CD64 as a diagnostic marker. Pediatrics. 2008; 121: 129–134.

17. Mojca Groselj-Grenc, Alojz Ihan, Maja Pavcnik-Arnol, Andreja Natasa Kopitar, Tanja Gmeiner-Stopar et al. Neutrophil and monocyte CD64 indexes, lipopolysaccharide-binding protein, procalcitonin and C-reactive protein in sepsis of critically ill neonates and children. Intensive Care Med. 2009; 35: 1950–1958.

18. Bhandari V. Cytokines in neonatal sepsis: diagnostic and therapeutic considerations. In: Singhi S. ed. Current Concepts in Pediatric Intensive Care. Chandigarh, India: Relume Printec. 2000. Р. 92–107.

19. Davidson J., Tong S., Hauck A., Lawson D. S., da Cruz E., Kaufman J. Kinetics of procalcitonin and C-reactive protein and the relationship to postoperative infection in young infants undergoing cardiovascular surgery. Pediatric Research. 2013; 74 (4): 413–419.

20. Gonzalez B. E., Mercado C. K., Johnson L., Brodsky N. L., Bhandari V. Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile. J. Perinat Med. 2003; 31: 60–68.

21. Romagnoli C., Frezza S., Cingolani A. et al. Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis. Eur. J. Pediatr. 2001; 160: 345–350.

22. Tepaev R.F. Use of polyclonal immunoglobulins in the treatment of sepsis. Pediatricheskaya farmakologiya = Pediatric pharmacology. 2011; 8 (3): 19–23.

23. Luyt C. E. Viral disease in ICU patients: a long time underestimated; but aware of overestimation. Intensive Care Med. 2006; 32: 968–970.