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DYNAMICS OF INTRA-ABDOMINAL PRESSURE AND PROCALCITONIN LEVEL IN THE BLOOD IN INTESTINAL OBSTRUCTION: EXPERIMENT
ZH.M. KOISHIBAYEV1, L.M. KOISHIBAYEVA2, M.KH. KUZBAKOV2, B. SERIK3, M.T. KULTENOVA3
'Aktobe Medical Center, Aktobe, Kazakhstan 2Aktobe Medical College named after the Hero of the Soviet Union Manshuk Mametova, Aktobe, Kazakhstan
Koishibayev Zh.M. Koishibayeva L.M. Kuzbakov M.KH. Serik B. Kultenova M.T.
3West Kazakhstan Medical University, Aktobe, Kazakhstan
http://orcid.org/0000-0002-1426-4379; SPIN 6602-1308 http://orcid.org/0000-0002-3651-0147; SPIN 96441874 http://orcid.org/0000-0002-2762-2518 http://orcid.org/0000-0003-4141-2565 http://orcid.org/0000-0002-1301-0318
For citing/
библиографияльщ сттеме/ библиографическая ссылка:
Koishibayev ZhM, Koishibayeva LM, Kuzbakov MKh, Serik B, Kultenova MT. Dynamics of intra-abdominal pressure and procalcitonin level in the blood in intestinal obstruction: experiment. West Kazakhstan Medical Journal 2019;61(4):237-242.
Койшибаев ЖМ, Койшибаева ЛМ, Кузбаков МХ, Серик Б, Культенова МТ. Тэжiрибе кезшдеп ^урса^шЫк ^ысым мен шек в^маздт кезiндегi ^андаFы прокальцитонин децгешшн, динамикасы. West Kazakhstan Medical Journal 2019;61(4):237—242.
Койшибаев ЖМ, Койшибаева ЛМ, Кузбаков МХ, Серик Б, Культенова МТ. Динамика внутрибрюшного давления и уровня прокальцитонина в крови при кишечной непроходимости в эксперименте. West Kazakhstan Medical Journal 2019;61(4):237—242.
Dynamics of intra-abdominal pressure and procalcitonin level in the blood in intestinal obstruction: experiment
Zh.M. Koishibayev1, L.M. Koishibayeva2, M.Kh. Kuzbakov2, B. Serik3, M.T. Kultenova3
'Aktobe Medical Center, Aktobe, Kazakhstan
2Aktobe Medical College named after the Hero of the Soviet Union Manshuk Mametova, Aktobe, Kazakhstan
3West Kazakhstan Medical University, Aktobe, Kazakhstan
This article presents the results of an experimental study of the dynamics of intraabdominal pressure and Procalcitonin with intestinal obstruction. Purpose of the research: to study the dynamics of Procalcitonin and intra-abdominal pressure during intestinal obstruction in the experiment.
Methods. The study was conducted on 131 white mongrel rats. They were divided into two groups: 1st group - 91 rats with acute small intestinal obstruction, 2nd -comparison group (Sham-surgery) - 40 rats. In both groups of animals are equally divided into 4 groups depending on the time of observation (1, 3, 5 and 7 days). Results: The study indicated a statistically significant increase of Procalcitonin by more than 5 times (p < 0.05) since the 1st day with the reaching of the maximum values to 5th day. As well as a significant increase in intra-abdominal pressure on 3, 7 experiment day (p <0,007) and compared with the comparison group. Conclusion: The obtained experimental data indicate the need to monitor indicators of intra-abdominal pressure in acute intestinal obstruction as an early diagnosis and prompt treatment.
A study of the dynamics of Procalcitonin in acute intestinal obstruction showed that this marker can effectively record the initial stages of translocation of microorganisms. It also can serve as a reliable early marker of bacterial migration and translocation in the initial period of acute small intestinal obstruction early septic complications of this pathology.
Keywords: abdominal pressure, Procalcitonin, experiment, bacterial translocation, small bowel obstruction.
Тэжiрибе кезшдеп кдасавдшшж цысым мен шек еттаздич кезшдеп к;андаFы прокальцитонин децгешнщ динамикасы
Ж.М. Койшибаев1, Л.М. Койшибаева2, М.Х. Кузбаков2, Б. Серик3, М.Т. Культеноваз
1Ак;тебе медицинальщ орталыгы, А;тебе, ^аза;стан
2Кецес Одагыньщ батыры МэншYK Мэметова атындагы А;тебе жогары
медицинальщ колледш, А;тебе, ^аза;стан
зМарат Оспанов атындагы Батыс ^аза;стан медицина университета, А;тебе, ^аза;стан
Ма;алада im шек eтiмсiздiгi кезшдеп im куысы цысымы мен прокальцитониннщ динамикасын эксперимент™ зерттеудщ нэтижелерi ^сынылды.
á^^k 8. Serik j e-mail: bakhtiyarserik@gmail. com ReceivedT ^лт tyctíT Пocтyпилa■ 02.12.2019 AcceptedT БacылымFa к1aбылдaндыT Пpинятa к публи^ции 24.12.2019 ISSN 1814-5620 (Print) © 2019 The Authors Published by West Kazakhstan Marat Ospanov Medical University
Мак;саты. Жт аш шек етгмиздтнщ даму динамикасында ш ;уысы к;ысымыньщ динамикасын жэне ;ан сарысуы прокальцитоныньщ децгежн тэжiрибеде зерттеу.
Эдктерь 1-шiсi жт обтурацияльщ аш шек eтiмсiздiгiмен жэне 2-ш1и салыстыру тобы ^ат-операция) болып екi тоща белшген 131 текиз а; егеук^рьщтарга экспериментгiк зерттеу жасалды. ^ан сарысуында бактериалды транслокация бимаркерлершщ динамикасы жэне жiтi шек еттмаздт дамуыньщ 1,3,5,7 тэулiктерiнде ш ;уысы к;ысымыньщ кeрсеткiштерi зерттелдi. Е^орытынды. Зерттеу нэтижелерi бойынша 5-тэулiкте максимальды мэндi жетiстiкпен 1-тэул1кте-а; 5 есе кеп (р<0,05) прокальцитониннщ статистикальщ едэуiр есу1 бащалады. Сонымен ;атар салыстыру тобына Караганда тэжiрибенiн 3,7-ш1 тэулiктерiнде кщ>сак;штк к;ысымньщ есу1 де орын алды. Тушн. Алынган зерттеу мэл1меттер1 ш куысыньщ жогары к;ысымыньщ паталогияльщ эсер1 оынн эсер1 мен кeрiнiсiнiн ^зактыгына байланысты болгандьщтан жт iшек етгмиздтнщ ас;ынуларын диагностикалау Yшiн iш ;уысы к;ысымыньщ мониторингiнiн мацызы туралы айгак;тайды. 1шек eтiмсiздiгiнiн алгашк;ы тэулшшде прокальцитониннщ кенеттен есу1 жэне осы биомаркердщ жт iшек eтiмсiздiгiнiн даму динамикасында б1ртшдеп есу1 бактериалды транслокацияньщ децгежн керсетед1 жэне жайылган септикальщ ас;ынулардын дамуын болжай алады. .
Негiзгi свздер: ц^рсащштк цысым, прокальцитонин, тэжiрибе, бактериалды транслокация, аш iшек втiмсiздiгi.
Динамика внутрибрюшного давления и уровня прокальцитонина в крови при кишечной непроходимости в эксперименте
Ж.М. Койшибаев1, Л.М. Койшибаева2, М.Х. Кузбаков2, Б. Серик3, М.Т. Культенова3
1Актюбинский медицинский центр, Актобе, Казахстан
2Актюбинский медицинский колледж имени героя Советского Союза Маншук Маметовой, Актобе, Казахстан
зЗападно-Казахстанский Медицинский Университет, Актобе, Казахстан
Представлены результаты экспериментального исследования динамики внутрибрюшного давления и прокальцитонина при тонкокишечной непроходимости.
Цель: изучить динамику показателей внутрибрюшного давления и уровень прокальцитонина сыворотки крови в динамике развития острой тонкокишечной непроходимости в эксперименте.
Методы. Проведено экспериментальное исследование на 131 белых беспородных крысах, поделенных на 2 группы: 1-ая с моделью острой обтурационной тонкокишечной непроходимости, 2-ая - группа сравнения ^ат-операция). Изучены динамика биомаркеров бактериальной транслокации в сыворотке крови и показатели внутрибрюшного давления на 1, 3, 5, 7 сутки развития острой кишечной непроходимости.
Результаты. По результатам исследования отмечается статистически значимое увеличение прокальцитонина более чем в 5 раз (р<0,05) уже с 1-х суток с достижением максимальных значений на 5 сутки. А также значимое повышение внутрибрюшного давления на 3, 7 сутки эксперимента (р<0,007) и по сравнению с группой сравнения.
Выводы. Полученные экспериментальные данные свидетельствуют о важности мониторинга внутрибрюшного давления для диагностики осложнений острой кишечной непроходимости, поскольку патологическое влияние повышенного внутрибрюшного давления зависит от длительности его воздействия и выраженности. Резкое повышение прокальцитонина в первые сутки кишечной непроходимости и постепенное нарастание этого биомаркера в динамике развития острой кишечной непроходимости отражает уровень бактериальной транслокации и может служить предиктором развития генерализованных септических осложнений.
Ключевые слова: внутрибрюшное давление, прокальцитонин, эксперимент, бактериальная транслокация, тонкокишечная непроходимость.
Introduction. Acute intestinal obstruction (AIO) for many years is an urgent and complex issue of emergency abdominal surgery in which the risk of purulent - septic complications is very high. According to available sources
mortality from AIO is from 1.95 to 25% [1, 2, 3]. One of the reasons for the development of septic complications is a syndrome of intra-abdominal hypertension, the main component of which is abdominal hypertension. Increas-
Dynamics of intra-abdominal pressure and procalcitonin level in the blood in intestinal obstruction:
ing the pressure in the abdominal cavity reduces blood flow in the superior mesenteric artery and, as a result, the blood supply to the mucous membrane of the gastrointestinal tract is disrupted with the possible development of necrosis of all layers of the intestinal wall. It leads to a decrease in the barrier function of the intestine and excessive bacterial colonization, which consists in pathological contamination of the small intestine by resistant and various bacterial populations, similar in composition (quantitative and qualitative) to the microflora of the colon and feces [4, 5, 6, 7]. Thus it ultimately leads to the translocation of bacteria into the systemic circulation, the development and progression of septic complications.
To date the existing methods for the determination of bacterial translocation (BT) often give false negative results and thus this makes it difficult to predict the development of generalized septic complications. Currently, one of the important directions of a more accurate and sensitive diagnosis is the determination of biomarkers of bacterial migration, which play the role of predictors of septic complications: one of which is Procalcitonin (PCT). In normal plasma concentration of PCT is below 0.1 ng /ml., but during severe bacterial infections it can be increased more than 100 ng / ml. A large number of studies on the definition PCT reliably indicate that this protein is an early inflammatory proteins, increase of which in the early stages of generalized infection development is a diagnostic and prognostic indicator of systemic inflammatory response and its complications. Average microbiological study of the blood in the early hours of bacteremia does not produce results, in contrast to the prior PCT whose value can be determined in the first 2-4 hours of the onset of the process [8, 9, 10].
Purpose of the research: to study the dynamics of Procalcitonin and intra-abdominal pressure during intestinal obstruction in the experiment.
Materials and Methods. The study was conducted on 131 white mongrel rats. They were divided into two groups: 1st group - 91 rats with acute small intestinal obstruction, 2nd - comparison group (sham-surgery) - 40 rats. In both groups of animals are equally divided into 4 groups depending on the time of observation (1, 3, 5 and 7 days).
In the group with AIO autopsy is made on the abdomen: 1 day -25 animals, day 3-25 animals, day 3-24 animals and day 7-17 animals. In the case of the progression
of acute intestinal obstruction 9 animals was excluded from experiment on the 5th and 7th day.
In comparison group (sham-surgery) the abdominal cavity is opened and sutured. The control opening of the abdominal cavity is performed: 1 day (10 animals), day 3 (10 animals), day 5 (10 animals) and day 7 (10 animals).
Animals are kept under standard vivarium conditions and in compliance with the International Regulations for bioethics proposed by international organizations and associations, including the Declaration of Helsinki of the World Medical Association (2013). The study design is approved by the decision of the Ethics Committee of KSMU (protocol № 98 dated 09.02.2016, the assigned number is 240). Derivation of animals from the experiment performed by exsanguination in a state of anesthesia, in accordance with the recommendations "AVMA Guidelines for the Euthanasia of Animals: 2013 Edition" [11].
Measurement of intra-abdominal pressure (IAP) is made up of modeling of AIO and sham-surgery, and also after the above-mentioned time intervals after the simulation the IAP is measured again. A device of original design is used for direct IAP measuring [12].
Also, under anesthesia, a blood sample is taken for immunological examination. Determination of PCT in blood serum was performed on an ELISA-robotic system Evolis (BioRad). The standard ELISA kit was used: ELISA Kit for Procalcitonin (PCT) SEA689Ra (sensitivity: 6.1 pg / ml).
To study enterohematic BT in the experiment, we developed a model of obstructive intestinal obstruction by applying plastic clips with a special clipper to the section of the small intestine 1.5 cm proximal to the ileocecal angle [13]. This model has the characteristics of apodactili-ty, sterility and reproducibility and maximally reflects the course of AIO in real conditions.
Statistical analysis was performed using the program IBM «SPSS Statistics 20.0» with calculating for each index the average value (M), standard deviation (SD), the confidence interval (CI). The significance of differences in groups between baseline values and values after the operation was determined using the Wilcoxon test for related groups between the group of AIO and the group Sham -used the Mann-Whitney test for independent groups and between the groups for different periods of observation - using Kruskal-Wallis test for k-independent groups. Differences were considered statistically significant at p
Table 1 - The average values of intra-abdominal pressure indicators in the comparison group (sham-surgery)
N
10 10 10 10
Before sham - surgery
After sham - surgery
Before - After*
For days **
M SD 95% CI M SD 95% CI k z P
1.63 0.43 -0.55 2.70 0.88 0.57 3.59 4.80 one -1.63 0,102
1.75 0.78 -1.85 7.35 2.75 1.85 -3.51 5.17 one -1.63 0,102
1.75 1.15 0.64 6.26 3.45 1.13 3.50 4.75 one -1.07 0,285
1.80 0.64 -14.30 10.01 2.85 1.91 -3.87 6.05 one -1.34 0.18
k x2 P
4 6.20 0,102
Remarks:
* - Wilcoxon test for two related groups
** - Kruskal-Wallis test for k-independent groups
IAP mm Hg
Figure 1 - The Dynamics of IAP compared with initial values in the control group (sham- surgery)
IAP mm Hg
Day
□ Before
□ After
Figure 2 - The Dynamics of IAP in comparison with the initial values in the group of AIO
<0.05.
Results. During the experiment, all animals were measured by laboratory IAP before surgery and after 1, 3, 5 and 7 hours. Data analysis showed (Table 1), that in the comparison group (sham-surgery) statistically significant difference of IAP is not observed in comparison with the initial values (p> 0,1), nor in the dynamics of observation for 7 days (p > 0,1) (Figure 1).
In the group with the AIO model there is a statistically significant increase in IAP compared with the initial values on days 1-7 (p <0.0001) (Figure 2).
The most pronounced differences with the initial value is observed on the 7th day - by 2.48 times (Table 2).
In the dynamics of AIO there is also a significant change in IAP per day (p < 0.05). So, if on the 3rd day IAP increased by 1.03 times as compared with 1 day, then on the 7th day this indicator increased by 1.2 times compared to the previous days, while on the 5th day there is a slight decrease in IAP.
When comparing AIO group with sham-group there is
a noticeable difference on day 1: IAP 4.8 times more than in the group of the animals with laparotomy, but without AIO model (p <0,001) (Table 3). In the future, the level of IAP for 3-7 days also remains higher than in the comparison group.
When determining PCT biomarker, confidence interval (95% CI) in intact animals was 45.7 - 77.7 pg / ml.
The average rate of PCT in sham - group is fixed in the first day at a level of 45.2 ± 20.4 pg / ml. In the group with ileus 5.4 times increase of this biomarker is observed compared with the comparison group (p < 0.05), which confirms a general picture of microorganisms circulating in the systemic circulation, respectively, the fact of BT (Table 4).
On the 3rd day in the control group a slight increase of biomarker is observed during the experimental period with achieving maximum numbers for 7th day.
In the study group, a gradual increase of PCT in blood serum is noted achieving the highest level on the fifth day of the experiment. 8.4 times increasing of the difference PCT indicators in the group with ileus compared with the Sham group (p = 0.08) (Table 4).
Table 2 - Average intra- abdominal pressure value indicators in the group of AIO
Day
1
3
5
N
25 25 24 7 17
Before the creation of the model
model AIO
Before - After*
For days !
M SD 95% CI M SD 95% CI k z P
1.85 0.57 1.61 2.09 4.20 1.42 3.59 4.80 one -4.02 <0.0001
1.97 0.94 1.58 2.36 4.34 2.01 3.51 5.17 one -4.38 <0.0001
2.13 0.92 1.74 2.52 4.12 1.48 3.50 4.75 one -4.04 <0.0001
2.00 0.55 1.66 2.34 4.96 1.81 3.87 6.05 one -3.2 0,001
k <2
4 7.65 0.05
Remarks:
* - Wilcoxon test for two related groups
** - Kruskal-Wallis test for k-independent groups
P
Table 3 - Comparison of IAP dynamics in the group of AIO and sham
Day IAP sham IAP AIO z P
M SD M SD
1 0.88 0.57 4.20 1.42 -2.7 0.001
3 2.75 1.85 4.34 2.01 -1.45 0.17
5 3.45 1.13 4.12 1.48 -0.66 0.53
7 2.85 1.91 4.96 1.81 -1.19 0.31
Dynamics of intra-abdominal pressure and procalcitonin level in the blood in intestinal obstruction: ...
Table 4 - Indicators of Procalcitonin (PCT) biomarker pg / ml on day 1,3,5 and 7
Day N sham 95% CI AIO 95% CI Z p
M SD M SD
day 1 10 45.2 20.4 5.4 - 95.8 25 245.2 265.8 12l.4 - 363.1 -1.92 0.05
day 3 10 58.4 11.9 28.4 - 165.3 25 264.4 2l6.3 141.9 - 38l.0 -0.94 0.41
day 5 10 61.l 22.6 41.6 - 265.1 24 51l.8 363.1 34l.9 - 68l.8 -1.08 0.08
day l 10 l5.0 11.6 29.0 - 1l9.0 1l 419.4 245.0 244.2 - 594.l -2.15 0.03
Table 5 - Comparison of PCT indicators in the main group for days
Day PCT k p
M SD 95% CI x
one 245.2 265.8 12l.4 - 363.1
3 264.4 2l6.3 141.9 - 38l.0 10.8 4 0,013
5 51l.8 363.1 34l.9 - 68l.8
l 419.4 245.0 244.2 - 594.l
Note - x2is the value of Kruskal-Wallis test for k-independent groups
On the 7th day ileus biomarker level slightly reduced by 19.1% compared with the PCT at day 5, but its level 5.6 times higher than in the control group (p < 0.03) (Table 4).
In the comparison group significant differences depending on the length of the postoperative period (sham -surgery) have been identified (x2= 2.57; p = 0,46).
There are significant differences between PCT level in the main group in different development periods of AIO (p = 0,013). Mainly, significant differences are observed between 1 and 5 days (z = -2,54; p = 0,011); 1 and 7 days (z = -2,20; p = 0,028) (Table 5).
Discussion
In the group with simulated intestinal obstruction even on the first day, a significant 4.8 times increase of IAP compared with the group sham (p <0,001) and remains higher than in the control group for 7 days.
In the dynamics of the development of AIO there is also a significant change in IAP per day (p < 0.05). A gradual increase in IAP indicators on days 1 and 3 and a slight decrease in indicators by 1.02 times on day 5 indicates the inclusion of compensatory mechanisms, including an increase in the compliance of the anterior abdominal wall. Because excessive further enhance IAP at 7 days 1.2 times there is a failure of compensatory mechanisms which ultimately leads to the development of hypoxia bodies by disrupting tissue perfusion and respiratory failure with high standing aperture and reduction in venous return to the right heart [14, 15].
Also, a significant variation in the PCT level on the 1st day of the AIO group with a gradual increase PCT in blood serum, as a response to an increase in the intestinal barrier permeability and massive translocation of microorganisms with reaching maximum numbers on the 5th day of the experiment compared with the initial parameters is considered a marker of the initial stage of bacteremia and microbial translocation according to published data [8, 16]. A dynamic decrease in PCT levels by 7 days is probably due to a decrease in reactivity and immune response to bacterial translocation, with a reduction in protective factors.
Conclusion. Monitoring of intra-abdominal pressure in the dynamics of acute intestinal obstruction in the experiment showed a statistically significant increase in intra-abdominal pressure, both in comparison with the initial values (p <0.0001), and with the comparison group (sham- surgery) (p = 0.001) during the entire observation period. The obtained experimental data indicate the need to monitor indicators of intra-abdominal pressure in acute intestinal obstruction as an early diagnosis and prompt treatment.
A study of the dynamics of Procalcitonin in acute intestinal obstruction showed that this marker, being a reliable indicator of the entry of gram-negative microorganisms into the bloodstream can effectively record the initial stages of translocation of microorganisms and can serve as a reliable early marker of bacterial migration and translocation in the initial period of acute small intestinal obstruction early septic complications of this pathology.
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