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I. ДИАГНОСТИКА И ЛЕЧЕНИЕ
RESULTS OF A COMPARATIVE ANALYSIS OF SEPSIS MARKERS IN NEWBORNS
Nurakhova A.D.1, Batyrbaeva D.Zh.2, Abdilova G.B.3, Maimakova A.M.1, Alibaeva Zh.S.2, Ibraeva N.K.3, Abdraimova A.A.3
1Kazakh Medical University of Continuing Education, Almaty, Kazakhstan
2Kazakh National Medical University under the name of S.D.Asfendiyarov, Almaty, Kazakhstan
3National Scientific Surgery Center under the name of A.N.Syzganov, Almaty, Kazakhstan
Abstract
The paper analyzes the results of a comparative study of sepsis markers: presepsin (PSP), procalcitonin (PCT), C-reactive protein (CRP) in sepsis in newborns. The clinical application of these indicators was assessed, their diagnostic effectiveness and prognostic significance in the perinatal center of Almaty (Republic of Kazakhstan). We have shown that when monitoring the dynamics of the development of sepsis, presepsin, unlike other markers, reliably reflects the real dynamics of its severity, and quickly and adequately changes depending on the effectiveness of therapy.
Жаца туылган нэрестелердеп сепсис маркерлерш салыстырмалы талдау нэтижелерi
Нурахова А.Д.1, Батырбаева Д.Ж.2, Абдилова Г.Б.3,
Маймадова А.М.1, Элiбаева Ж.С.2, Ибраева Н.К.3, Абдраимова А.А.3
1Казактьщ медицалык Yздiксiз бiлiм беру университетi, Алматы каласы, Казахстан
2Атында™ Казак Улттык медициналык университетi Асфендиярова С.Д., Алматы каласы, Казакстан
3Атындаfы Улттык ™лыми хирургия орталыfы Сызfанова А.Н., Алматы каласы, Казакстан
Ацдатпа
Жумыста жаца ту^ан нэрестелердеп сепсис маркерлерш: пресепсин (ПСП), прокальцитонин (ПКТ), С-реактивт1 а%уыз (СРА) салыстырмалы зерттеу нэтижелерше талдаужасалады. Осы индикаторлардыц клиникальщ %олданылуы, диагностикалыщ ти!мд1л1г1 жэне Алматы цаласыныц перинаталды орталыяында (Казахстан Республикасы) болжамды мэн ба€аланды. Б1з сепсистщ даму динамикасын ба^ылау кез1нде пресепсин, баскд маркерлерден айырмашылы€ы, оныц ауырлыщ дэрежес!нщ на%ты динамикасын сен!мд! турде керсетет!н1н жэне терапияныц ти!мд1л1г1не байланысты тез жэне тиЫ турде езгерет!н!н керсетт!.
MPHTM 76.29.50 UDC 616-079.3
ABOUT THE AUTHORS
Nurakhova Alma Dandybaevna - Associate Professor, Department of Clinical Laboratory Diagnostics, Kazakh Medical University of Continuing Education (Ka-zMUNO), candidate of medical sciences nad7788@mail.ru
Batyrbaeva Dinara Zharmukhanovna -
Head of the Scientific Clinical and Diagnostic Laboratory of the Kazakh National Medical University named after S.D. Asfendiyarov. candidate of medical sciences
Abdilova Gulnur Bekmurzaevna - head of the clinical diagnostic laboratory of the National Scientific Center of Surgery named after A.N.Syzganova
Maimakova Akmaral Meirbekovna
- Head of the Department of Clinical Laboratory Diagnostics, Kazakh Medical University of Continuing Education (KazMUNO), candidate of medical sciences
Alibaeva Zhazira Sergazievna - Senior Researcher, Scientific Clinical and Diagnostic Laboratory, Kazakh National Medical University named after S.D. Asfendiyarov
Ibraeva Nazgul Kushikbaevna - specialist in the clinical diagnostic laboratory of the National Scientific Center of Surgery named after A.N.Syzganova
Abdraimova Aliya Asemovna - specialist in the clinical diagnostic laboratory of the National Scientific Center of Surgery named after A.N.Syzganova
Keywords
sepsis, newborns, presepsin, procalcitonin, C-reactive protein.
АВТОРЛАР ТУРАЛЫ
Нурахова Алма Дандыбайцызы -
%аза% медициналык уздксЬ б/л/м беру университетнщ клиникалык зертханалык диагностика кафедрасыныц доцентi (КазМУБУ) M.F.K. nad7788@mail.ru,
Батырбаева Динара Жармуцанцызы
- С.Д. Асфендияров атында¥ы Казак Улттык медициналык университетщ FbrnbiMtt клиникалык-диагностикалык зертханасыныц мецпзруша, m.f.k.
Абдилова Гулнур Бекмырзацызы -
А.Н.Сыз¥анов атында¥ы Улттык FbrnbiMtt хирургия орталь^ыньщ клиникалык-диагностикалык зертханасыныц Metírepytyici
Маймацова Ацмарал Мешрбекцызы
- Казак медициналык уздксЬ б/л/м беру университетнщ клиникалык зертханалык диагностика кафедрасыньщ мецгеруш^ (КазМУБУ), м.р.к.
Ибраева Назгул Куш'кбайцызы -
А.Н.Сыз¥анов атында¥ы Улттык Fылыми хирургия орталь^ыньщ клиникалык-диагностикалык зертханасыныц маманы
Абдраимова Элия Эсемцызы -
А.Н.Сыз¥анов атында¥ы Улттык Fылыми хирургия орталь^ыньщ клиникалык-диагностикалык зертханасыныц маманы
Туйш сездер
сепсис, жаца туылган нэрестелер, препепсин, про-калцитонин, С-реактивт акуыз.
Результаты сравнительного анализа маркеров сепсиса у новорожденных
ОБ АВТОРАХ
Нурахова Алма Дандыбаевна - доцент кафедры клинической лабораторной диагностики Казахского медицинского университета непрерывного образования (КазМУНО), к.м.н.. nad7788@mail.ru,
Батырбаева Динара Жармухановна
- заведующая научной клинико-диагностической лабораторией Казахского Национального медицинского университета им. С.Д.Асфендиярова, к.м.н.
Абдилова Гулнур Бекмурзаевна -
заведующая клинико-диагностической лабораторией Национального научного центра хирургии им. А.Н.Сызганова,
Маймакова Акмарал Мейрбековна
- заведующая кафедрой клинической лабораторной диагностики Казахского медицинского университета непрерывного образования (КазМУНО), к.м.н.
Ибраева Назгуль Кушикбаевна -
специалист клинико-диагностической лабораторией Национального научного центра хирургии им. А.Н.Сызганова
Абдраимова АлияАсемовна - специалист клинико-диагностической лабораторией Национального научного центра хирургии им. А.Н.Сызганова
Ключевые слова
сепсис, новорожденные, пресепсин, прокальцитонин, С-реактивный белок.
Нурахова А.Д.1, Батырбаева Д.Ж.2, Абдилова Г.Б.3,
Маймакова А.М.1, Алибаева Ж.С.2, Ибраева Н.К.3, Абдраимова А.А.3
1Казахский медицинский университет непрерывного образования, г. Алматы, Казахстан 2Казахский Национальный медицинский университет им. С.Д.Асфендиярова, г. Алматы, Казахстан Национальный научный центр хирургии им. А.Н.Сызганова, г. Алматы, Казахстан
Аннотация
В работе выполнен анализ результатов сравнительного изучения маркеров сепсиса: пресепсина (ПСП), прокальцитонина (ПКТ), С-реактивного белка (СРБ) при сепсисе у новорожденных детей. Проведена оценка клинического применения указанных показателей, их диагностическая эффективность и прогностическая значимость в перинатальном центре г. Алматы (Республика Казахстан). Нами показано, что при наблюдении за динамикой развития сепсиса пресепсин, в отличие от других маркеров, надежно отражает реальную динамику его тяжести, быстро и адекватно изменяется в зависимости от эффективности терапии.
Introduction
Sepsis is a severe inflammatory condition of the whole organism in response to infection by bacteria, fungi or other microorganisms. Severe sepsis is accompanied by dysfunction of one or more organs, which often leads to death.
Mortality among patients with sepsis is high, most patients die in the first month after the onset of the disease. In patients with severe sepsis, mortality reaches 50% and higher.
World statistics annually record more than 18 million cases of severe sepsis, while the incidence is growing by 1.5% per year [1, 2].
In 20-40% of septic patients, sepsis develops even before hospitalization. By the time of diagnosis, the time to start therapy with a wide range of antimicrobials, fluids, medications to stabilize blood circulation, and other steps may already be missed, so the main task is to quickly diagnose and early targeted treatment of sepsis [3, 4, 5].
In the arsenal of modern medicine there are more than 100 biological markers. Currently, the most valuable and frequently used in clinical practice are procalcitonin (PCT), lipopolysaccha-
ride-binding protein, interleukin-6 and C-reactive protein (CRP). For an objective assessment of the severity of septic patients, the well-known SOFA, SAPS-II scales are used, as well as indicators of general clinical routine analyzes, in particular, the qualitative and quantitative composition of leukocytes, the level of proteins of the acute phase of inflammation (fibrinogen). The disadvantages of the above parameters and methods include low specificity (leukocytes, CRP) and the likelihood of receiving a false negative result in patients with severe sepsis (PCT). Bacteriological confirmation of infection is not sensitive and requires a long time. With antibiotic therapy, the result of blood culture is often false negative. In addition, this method is not suitable for recognizing the reaction of the host to systemic inflammation and the onset of organ failure.
The speed and timeliness of diagnosis, as well as the ability to predict favorable and unfavorable outcomes, are a powerful barrier to the development of septic reactions. The first use of a specific and highly sensitive marker of sepsis - presepsin (PSP) for diagnosing diseases, evaluating its prog-
nostic significance, as well as studying changes in prespepsin levels depending on the effectiveness of the chosen treatment tactics, is an urgent area of the modern laboratory [6, 7].
Purpose of the study
Assessment of the clinical use of sepsis markers - presepsin, procalcitonin, CRP: diagnostic efficiency and prognostic significance in the perinatal center of Almaty (Republic of Kazakhstan).
Materials and methods
On the basis of the scientific clinical diagnostic laboratory of KazNMU under the name of S.D.Asfendiyarov conducted laboratory tests for markers of sepsis. The study involved 76 newborns. The experimental group included 51 newborns, the control group - 25 newborns, in this group the level of presepsin was less than 200 pg/ml. Laboratory studies to determine sepsis were performed in ne-onates with suspected sepsis. During the first 72 hours, biomarker levels were measured - presepsin, procalcitonin and CRP.
Prespepsin concentration in newborns was measured using a PATHFAST analyzer manufactured by LCI Medience Corporation, Japan, which is a fully automated system for immunochemilumines-cent analysis. Normal prespepsin levels should not exceed 200 pg/ml.
Ready-to-use reagents in special cartridges, automatic reading from the bar code of the reagent name, expiration date, prevent the error associated with the human factor. The only consumables are tips, the surface of which is pollinated with special magnetic particles. The whole reaction takes place in these tips, after analysis, the tips are disposed of. This feature of the analyzer eliminates the contamination of samples and allows the use of the PATHFAST analyzer in clinical diagnostic laboratories or express laboratories for resuscitation that does not require strict special requirements and conditions for microbiological laboratories.
High productivity of results, minimum sample volume (100 ^l), compact design and low weight, obtaining accurate results in 15 minutes facilitates
the adoption of quick clinical decisions and the timely provision of adequate emergency care.
Determination of procalcitonin in blood serum was performed using the "Procalcitonin" test of the "Vector-Best" company by enzyme-linked immuno-sorbent assay on a semi-automatic analyzer of the company Tecan, Austria. Normal values of procalcitonin are 0.02-1.00 ng/ml.
CRP was determined on a Cobas Integra 400 plus automatic biochemical analyzer, which is a closed system, since reagents of only a certain type and a specific manufacturer (Roche company) are used in the work. Normal values of this indicator are 0-5.0 mg/L.
Research results
The research results are shown in table 1. According to table 1, in the control group (25 newborns), the prespepsin content was less than 200 pg/ml, while in two newborns the level of proca-cytonin was higher than 1.00 ng/ml, and CRP exceeded 5.0 mg/l in three examined. In the experimental group (51 people) in 41 (80%) newborns, the concentration of the presepsin sepsis marker is from 200 to 499 pg/ml, which indicates the likelihood or moderate risk of developing systemic infection (severe sepsis). In 7 (13%) newborns, the concentration of prespepsin in the blood was more than 500 pg/ml, that is, in this group of newborns there was an increased risk of an adverse outcome. Moreover, in 3 (7%) newborns, the concentration of prespepsin is more than 1000 pg/ml, which indicates a high risk of developing a systemic infection (severe sepsis / septic shock), as well as a high risk of 30-day mortality, comparable to risk on the APACNE>25 scale. Laboratory studies on procalcitonin in 8 (15%) newborns showed that in the experimental group procalcitonin was within normal limits, in 43 (85%) newborns the concentration procalcitonin was more than 1.00 ng/ml. Also, the results of laboratory studies on CRP in newborns suspected of sepsis revealed that in 39 (76%) - within the standard values, and in 12 (24%) newborns - above physiological limits, i.e. more than 5.0 mg/l.
Sepsis markers
No. Group Presepsin C-reactive protein
<1,00 ng/ml >1,00 ng/ml <5,0 mg/l >5,0 mg/l
1 Control group less than 200 pg/ml 25 (100%) 23(92%) 2 (8%) 23 (88%) 3 (12%)
200-499 pg/ml
41 (80%)
2 Experienced group 500-999 pg/ml 7 (13%) 8 (15%) 43 (85%) 39 (76%) 12(24%)
more than 1000 pg/ml 3 (7%)
Table 1
Markers of sepsis in newborns
Fig. 1
Concentrations of pres-pepsin in the dynamics of patient F.
pg/rnl
Presepsin
■Presepsin
Days
Fig. 2
Concentrations of procal-citonin in the dynamics of patient F.
Primary blood sampling Blood sampling the next day Procalcitonin
ig/ml
■Procalciton
Days
Fig. 3
Concentrations of C-reac-tive protein in dynamics in patient F.
mg/l 2
1
8
6
4
2
0
Primary blood sampling Blood sampling the next day C-reactive protein
0,1
0,1
■CRP
Primary blood sampling
Blood sampling the next day
Days
Also, in the experimental group, studies were conducted in dynamics for sepsis markers up to and after antibiotic therapy to assess the effectiveness of the treatment. A decrease in the concentration of the marker of sepsis - presepsin was observed on the next day on average 1.5 times. To study the state of newborns in the dynamics, laboratory studies were performed in 15 newborns who had high prespepsin values during the first analysis. Repeated studies on markers of sepsis were conducted within 1-2 days. The results are shown in the figures.
In Figure 1 clearly shows a decrease in the level of presepsin after the start of antibiotic therapy: at
the first blood sampling, the indicator was 735 pg/ ml, the next day it was 154 pg/ml. In fig. Figure 2 shows the dynamics of changes in procalcitonin before and after antimicrobial treatment: at the first blood sampling, procalcitonin was 12.4 ng/ml, on the next day the indicated parameter corresponded to 1.4 ng/ml. While the level of CRP did not change: at the first blood sampling - 0.1 mg/l, on the second day - also 0.1 mg/l (Fig. 3).
As follows from these figures, in the case of determination of presepsin and procalcitonin, there is a tendency to a decrease in the concentration of sepsis markers, which indicates the effectiveness
of antibiotic therapy. However, the level of CRP does not show such dynamics.
Discussion
Performed study emphasizes existing need for presence complementary and interchangeable methods. Moreover, if we take into account that the processes in the septic state in newborns are much faster and harder. None of the widely used indicators of sepsis today does not combine the possibility of early diagnosis of sepsis, stratification of risks, with it related, predicting and monitoring the course of sepsis. While presepsin is a new, promising marker, which after a short period of time (15 minutes) allows for early and accurate diagnosis of sepsis.
As follows from the literature, presepsin (PSP) is a protein (molecular weight 13 KDa), which is the N-terminal fragment of the macrophage receptor CD14. In turn, CD14 is also a protein that has two forms: 1) associated with the membrane (mCD14) and present on the surface of macrophages, monocytes and granulocytes, and 2) soluble (sCD14, s - soluble), circulating in the bloodstream. mCD14 is a receptor that is responsible for transduction of the endotoxin signal into cells. The release of mCD14 into the bloodstream and the formation of sCD14 are associated with infection and some other pathological conditions. When bacterial phagocytosis is activated, sCD14 and mCD14 are cleaved by ly-
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1. Presepsin can be used for the early diagnosis of sepsis and the timely initiation of treatment.
2. Presepsin allows predicting possible outcomes of sepsis.
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