Authors
Alekseeva E. V.
candidate of medical sciences, anesthesiologist-reanimatologist, Federal State Budgetary Institution “Central Clinical Hospital and Outpatient Department” Department for President Affairs of the Russian Federation, Moscow
Abstract
Abstract. First metabolomic studies were conducted in patients being in critical condition on admission in the resuscitation department (during the initial 24-72 hours), to determine prognostic significance of the levels of a wide variety of low molecular weight substances in relation to 28-day survival. In this study, we determined levels of 32 amino acids in the blood plasma of 62 patients being in a critical condition (CC) in the first 6 hours on admission to the intensive care unit (ICU) by the method of high performance liquid chromatography - mass spectrometry. In retrospect, we allocated two groups of ICU patients in accordance with 28-day survival rate: Group 1 (n = 25) - survivors, Group 2 (n = 37) - deceased. Aminograms were compared in groups of patients, and analyzed by using classical methods of statistical analysis (software package Statistica 12) and meta-data mining (Data Mining Statistica 12 applications). Results: 1) Initial aminograms of the blood plasma are different in groups of patients who subsequently died and survived within 28-day period. 2) Accounting of aminogram parameters in predicting probable outcomes increase the accuracy of its determination. 3) The most significant predictors of adverse course of the pathological process in patients being in critical condition in amino acid composition of the blood plasma are the following: changes, compared to the reference values of citrulline level/odds ratio (OR) = 15.3; predictive test - 0.89; specificity - 0.88), and decreased levels of glutamic acid (OR = 5.0; predictability - 0.82; specificity - 0.84). Conclusions. More rapid inclusion of patients in the study revealed earlier pathogenetic mechanisms leading to the adverse outcome of the pathological process in patients being in critical condition.
Key words
patients in critical condition, metabolites, amino acids, prediction
References
1. Aleksandrova E. V. Dysfunction Syndromes of neurotransmitter systems in the process of recovery of consciousness after severe traumatic brain injury. PhD Thesis, Moscow, 2013.
2. Aleksandrova E.V., Zajcev O.S., Potapov A.A, "Clinical syndromes of neurotransmitter systems dysfunction in severe brain injury." Êëèíè÷åñêèå ñèíäðîìû äèñôóíêöèè íåéðîìåäèàòîðíûõ ñèñòåì ïðè òÿæåëîé òðàâìå ìîçãà. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2015; 7: 40-6.
3. Kochetov A.G., Lyang O.V., Ogurcov P.P, Preparation of the patient, rules for taking, biomaterial storage and transportation of laboratory analysis: Guidelines for medical students, doctors, employees of treatment rooms and clinical diagnostic laboratories. General rules. Moscow: RUDN, 2012. Print.
4. Lang T.A., Sesik M, How to describe the statistics in medicine. Annotated Guide for authors, editors and reviewers. Moscow: Prakticheskaya medicina. 2011. Print.
5. Marmanis H. Babenko D, Mining Algorithms in Internet. Best practices in data collection, analysis and data processing. St. Petersburg: Simvol-Plyus, 2011. Print.
6. Antcliffe D., Gordon A.C. Metabonomics and intensive care Crit Care. 2016; 20(1): 68.
7. Bao L., Zhang M., Yan P., Wu X., Shao J., Zheng R. Retrospective analysis of the value of arterial blood lactate level and its clearance rate on the prognosis of septic shock patients. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015; 27(1): 38-42.
8. Brosnan J.T., Brosnan M. E. Glutamate: a truly functional amino acid. Amino Acids. 2013; 45(3): 413-8
9. Chan D.L., Rozanski E.A., Freeman L.M. Relationship among plasma amino acids, C-reactive protein, illness severity, and outcome in critically ill dogs. J.Vet Intern Med. 2009; 23 (3):559-63.
10. Du J., Li X.H, Li Y.J. Glutamate in peripheral organs: biology and pharmacology. Eur J. Pharmacol. 2016 May 6.
11. Ferrario M., Cambiaghi A., Brunelli L., Giordano S., Caironi P., Guatteri L. et al. Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach. Sci Rep. 2016; 6:20391.
12. Gielen M., Vanhorebeek I., Wouters P.J., Mesotten D., Wernerman J., Van den Berghe G., rooyackers O. Amino acid concentrations in critically ill children following cardiac surgery. Pediatr Crit Care Med. 2014;15 (4):314-28.
13. Kulu R., Akyildiz H., Akcan A., Oztürk A., Sozuer E. Plasma citrulline measurement in the diagnosis of acute mesenteric ischaemia. ANZ J Surg. 2016; Apr 8.
14. Liu J., Cheng Q., Yang Q., Li X., Shen X., Zhang L. et al. Prognosis-related factors in intensive care unit (ICU) patients with hematological malignancies: A retrospective cohort analysis in a Chinese population. Hematology. 2015; Jan 13.
15. Martínez MJ, Giráldez J. Plasma aminogram in critical patients. Nutr Hosp. 1993; 8(2):79-93.
16. Mickiewicz B., Vogel H.J., Wong H.R., Winston B.W. Metabolomics as a novel approach for early diagnosis of pediatric septic shock and its mortality. Am J Respir Crit Care Med 2013; 187(9): 967-76.
17. Newsholme P., Lima M.M., Procopio J., Pithon-Curi T.C, Doi S.Q., Bazotte R.B. et al. Glutamine and glutamate as vital metabolites. Braz J Med Biol Res. 2003; 36 (2):153-63.
18. Oudemans-van Straaten H.M., Bosman R.J., Treskes M., van der Spoel, H.J., Zandstra D.F. Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med. 2001; 27: 84–90
19. Piton G., Belon F., Cypriani B., Regnard J., Puyraveau M., Manzon C. et al. Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality. Crit Care Med. 2013; 41(9): 2169-76.
20. Piton G., Capellier G. Plasma citrulline in the critically ill: intriguing biomarker, cautious interpretation. Crit Care. 2015; 19:204.
21. Piton G., Manzon C., Monnet E., Cypriani B., Barbot O., Navellou J.C et al. Plasma citrulline kinetics and prognostic value in critically ill patients // Intensive Care Med. 2010; 36(4):702-6
22. Poole A., Deane A., Summers M., Fletcher J., Chapman M. The relationship between fasting plasma citrulline concentration and small intestinal function in the critically ill. Crit Care. 2015; 19:16.
23. Rodas, P.C., Rooyackers, O., Hebert C., Norberg, A., Wernerman J. Glutamine and glutathione at ICU admission in relation to outcome. Clin Sci (Lond). 2012; 122: 591–7
24. Rogers A.J, McGeachie M., Baron rM., Gazourian L., Haspel J.A., Nakahira K. et al. Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS One. 2014; 9(1):e87538.
25. Seymour C.W., Yende S., Scott M.J., Pribis J., Mohney R.P., Bell L.N. et al. Metabolomics in pneumonia and sepsis: an analysis of the GenIMS cohort study. Intensive Care Med. 2013; 39(8):1423-34.
26. van Waardenburg D.A., de Betue C.T., Luiking Y.C., Engel M., Deutz N.E. Plasma arginine and citrulline concentrations in critically ill children: strong relation withinflammation. Am J. Clin Nutr. 2007; 86 (5):1438-44.
27. Wang H., McNeil Y.R., Yeo T.W., Anstey N.M. Simultaneous determination of multiple amino acids in plasma in critical illness by high performance liquid chromatography with ultraviolet and fluorescence detection. J. Chromatogr B Analyt Technol Biomed Life Sci. 2013; 940:53-8.
28. Wang S., Chen D. The correlation between procalcitonin, C-reactive protein and severity scores in patients with sepsis and their value in assessment of prognosis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015; 27(2):97-101.