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Российский медико-биологический вестник
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ Том 31, № 1, 2023 имени академика И. П. Павлова
УДК 617.52-002-02:616.314
DOI: https://doi.org/10.17816/PAVL0VJ106281
Синдром системного воспалительного ответа и сывороточный прокальцитонин при одонтогенной инфекции челюстно-лицевой области
A. A. Кабанова1 И. О . Походенько-Чудакова2, С. А. Кабанова1
1 Витебский государственный ордена Дружбы народов медицинский университет, Витебск, Республика Беларусь;
2 Белорусский государственный медицинский университет, Минск, Республика Беларусь
АННОТАЦИЯ
Введение. Синдром системного воспалительного ответа (ССВО) представляет собой прогрессирующий патофизиологический процесс, который может быть вызван различными клиническими предшествующими событиями, включая локальную или генерализованную инфекцию или неинфекционный воспалительный процесс, в т ч одонтогенный
Цель. Оценить наличие ССВО и уровня прокальцитонина в крови у пациентов с одонтогенной инфекцией челюстно-лицевой области .
Материалы и методы. Проспективное обсервационное исследование (n = 158) выполнено в 2015-2018 гг . Группа пациентов включала 61 (39,0 %) женщину и 97 (61,0%) мужчин в возрасте 34 (28-47) года . Контрольную группу составили 50 здоровых добровольцев: 25 (50,0%) мужчин, 25 (50,0%) женщин (р > 0,05), возраст — 30 (34-39) лет (р > 0,05) . Пациенты были разделены на три группы: 1 группа (n = 96) — пациенты с острым гнойным одонтогенным остеомиелитом челюсти, осложненным флегмоной одного клетчаточного пространства, 2 группа (n = 36) — пациенты с острым гнойным одонтогенным остеомиелитом челюсти, осложненным флегмоной 2-4-х клетчаточных пространств, 3 группа (n = 26) — пациенты с острым гнойным одонтогенным остеомиелитом челюсти, осложненным флегмоной дна полости рта . На основании результатов общего анализа крови, измерения температуры тела, частоты дыхания и частоты сердечных сокращений определялось наличие ССВО . Также в крови пациентов определялся уровень прокальцитонина
Результаты. Случаи развития флегмоны одного клетчаточного пространства ССВО были выявлены у 9% пациентов, при флегмоне 2-4-х пространств — у 36%, случаи флегмоны дна полости рта — у 80%; p (группа 1/ группа 2) = 0,002, p (группа 1/группа 3) < 0,001, p (группа 2/группа 3) = 0,001. Уровень прокальцитонина крови в группе здоровых добровольцев составил 0,009 (0,006-0,018) пг/мл . Все группы пациентов имели достоверно более высокий уровень прокальцитонина крови по сравнению с группой здоровых добровольцев: 1 группа — 0,034 (0,019-0,050) пг/мл, U = 23, р = 0,01; 2 группа — 0,1 1 (0,06-0,24) пг/мл, U = 12, р = 0,003; 3 группа — 0,41(0,30-1,15) пг/мл, U = 17, р < 0,001.
Заключение. Одонтогенная инфекция челюстно-лицевой области может сопровождаться развитием ССВО . Поиск значимых диагностических критериев развития жизнеугрожающих состояний должен быть продолжен
Ключевые слова: синдром системного воспалительного ответа; прокальцитонин; одонтогенная инфекция; челюстно-лицевая область
Для цитирования:
Кабанова A.A., Походенько-Чудакова И.О., Кабанова С.А. Синдром системного воспалительного ответа и сывороточный прокальцитонин при одонтогенной инфекции челюстно-лицевой области // Российский медико-биологический вестник имени академика И. П. Павлова. 2023. Т. 31, № 1. С. 119-125. D0I: https://doi.org/10.17816/PAVL0VJ106281
Рукопись получена: 14.04.2022
Рукопись одобрена: 22 . 09 . 2022
Опубликована:31. 03 . 2023
© Эко-Вектор, 2023 Все права защищены
ORIGINAL STUDY ARTICLES 120 -
DOI: https://doi.org/10.17816/PAVL0VJ106281
Systemic Inflammatory Response Syndrome and Serum Procalcitonin in Odontogenic Maxillofacial Infection
Arina A. Kabanova1 Irina 0 . Pokhoden'ko-Chudakova2, Svetlana A. Kabanova1
1 Vitebsk State Order of Peoples' Friendship Medical University, Vitebsk, Belarus;
2 Belarusian State Medical University, Minsk, Belarus
ABSTRACT
INTRODUCTION: The systemic inflammatory response syndrome (SIRS) is a progressive, pathophysiological process which may be caused by a variety of clinical precursor events including local or generalized infection, or non-infective inflammatory process
AIM: To determine the development of systemic inflammatory response syndrome (SIRS) and serum procalcitonin level in patients with odontogenic infection of the maxillofacial area .
MATERIALS AND METHODS: The prospective observational study evaluated on 158 medical patients from 2015 to 2018 at the Department of maxillofacial surgery, Faculty of Stomatology, Vitebsk state medical University . The patients were divided into 3 groups: 1 group (96 people) had acute purulent odontogenic osteomyelitis of mandible complicated by the cellulitis of one space cellular spaces, group 2 (36 patients) had acute purulent odontogenic osteomyelitis of mandible complicated by the cellulitis of 2-4 cellular spaces, group 3 (26 people) — had acute purulent odontogenic osteomyelitis of the mandible complicated by Ludwig's angina . Blood tests of all patients were performed . Based on the blood test, breath rate, heart rate and body temperature SIRS was determined .
RESULTS: Acute odontogenic osteomyelitis, complicated by cellulitis, is characterized by the development of SIRS . In case of one cellular space cellulitis SIRS developed in 9. 0% of patients, in case of 2-4 cellular spaces cellulitis — in 36 . 0%, in case of Ludwig's angina — in 80 . 0% . PCT blood level in healthy group was 0 . 009 (0 . 006-0 . 018) pg/ml . All patients' groups had significantly higher PCT blood level compared with the healthy group: 1 group — 0 . 034 (0 . 019-0 . 050) pg/ml, U = 23, p = 0 . 01; 2 group — 0 .1 1 (0. 06-0 . 24) pg/ml, U =12, p = 0 . 003; 3 group — 0 . 41 (0 . 30-1.15) pg/ml, U = 17, p < 0 . 001.
CONCLUSION: Odontogenic maxillofacial infection is accompanied by SIRS . The search for significant diagnostic criteria for the development of life-threatening conditions should continue
Keywords: systemic inflammatory response syndrome; procalcitonin; odontogenic infectious; maxillofacial area
For citation:
Kabanova AA, Pokhoden'ko-Chudakova 10, Kabanova SA. Systemic Inflammatory Response Syndrome and Serum Procalcitonin in Odontogenic Maxillofacial Infection. I. P. Pavlov Russian Medical Biological Herald. 2023;31(1):119-125. DOI: https://doi.org/10.17816/PAVL0VJ106281
Received: 14.04.2022 Accepted: 22 . 09 . 2022 Published: 31. 03 . 2023
e c o • v e c t o r cc) Eco-Vector, 2023
All rights reserved
LIST OF ABBREVIATIONS
CRP — C-reactive protein PCT — procalcitonin
qSOFA — quick Sequential Organ Dysfunction Score SIRS — systemic inflammatory response syndrome SOFA — Sequential Organ Dysfunction Score
INTRODUCTION
The systemic inflammatory response syndrome (SIRS) is a progressive, pathophysiological process which may be caused by a variety of clinical precursor events including local or generalized infection, or non-infective inflammatory process SIRS is the first phase of the systemic host response to injury or infection, and is defined as occurring in any patient with any two or more of the four clinical criteria: body temperature over 38°C or under 36°C, heart rate greater than 90 beats/minute, respiratory rate greater than 20 breaths/minute or partial pressure of CO2 less than 32 mmHg, leucocyte count greater than 12,000 or less than 4,000/microliter or over 10% immature forms or bands . More than two decades ago, the combination of infection and SIRS was defined as sepsis [1]. However, subsequent research revealed that sepsis is not an exclusively proinflammatory condition; rather, it may involve early anti-inflammatory responses [2] Moreover, SIRS criteria were found to be too sensitive and insufficiently specific to identify infected patients at risk for a complicated course [3] The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Task Force recently redefined sepsis . Sepsis is accordingly viewed as a «life threatening organ dysfunction caused by a dysregulated host response to infection» [4] . The Sequential Organ Dysfunction Score (SOFA) was proposed as the most suitable modality in diagnosing sepsis However, for frontline clinicians, the SOFA score was not useful as a quick bedside screening tool to identify sepsis due to the inclusion of laboratory markers which may take time . Thus, the taskforce proposed quick SOFA (qSOFA) that only includes 3 easily obtainable bedside parameters for quick identification of sepsis [5] .
There has been widespread debate about the sensitivity and specificity of SIRS and SOFA in recognising sepsis and multiple organ dysfunction syndrome since the new criteria have been introduced qSOFA was thought to be more specific while SIRS was more sensitive [6] It has also been reported that SIRS was more accurate in predicting an established infection [7] .
Numerous laboratory tests are available for determine the risk of multiple organ dysfunction syndrome (e g using procalcitonin (PCT), C-reactive protein (CRP), fibrinogen, or tumor necrosis factor-a levels, leukocyte index, albumin or cholesterol levels, etc . ) [8, 9] .
Odontogenic infection is one of the most common diseases, accounting for 60% of reason for dental
consultation with the dentist The severity of the infection depends on multiple factors, such as the virulence of the bacteria, the systemic state of the patient and the anatomical spaces affected [10] .
Odontogenic infection with fulminant progression that lead to severe, sometimes life-threatening complications like sepsis, airway obstruction, fasciitis, tissue necrosis, acute respiratory distress syndrome, thrombosis, mediastinitis, and multiorgan dysfunction syndrome are rare, but require extensive interdisciplinary collaboration especially with specialists for anesthesiology and intensive care medicine [11] .
To improve the diagnosis and treatment methods for systemic inflammatory reactions to odontogenic infection, special attention should be paid to the search of new early criteria for organ dysfunction
PCT is a precursor of calcitonin and is synthesized by C-cells of the thyroid gland In addition, PCT is formed as a result of a reaction to endotoxins and as a result of a mediated response to bacterial infections . PCT has the highest sensitivity and specificity for predicting systemic bacterial inflammation . PCT levels are associated with the severity of bacterial infections and may also be useful in determining the initiation and duration of antibiotic treatment by measuring PCT PCT analysis can be performed within 1 hour so that a patient's systemic infection status can be quickly determined and treatment initiated [12].
The aim of this study is to determine the systemic inflammatory response syndrome (SIRS) and procalcitonin blood level in patients with odontogenic infection of the maxillofacial area
MATERIALS AND METHODS
The prospective observational study (2015-2018) evaluated on 158 patients at the Department of Maxillofacial Surgery, Faculty of Stomatology of Vitebsk State Medical University . The Ethics Committee of VSMU has approved this study according to the protocol
Patient group included 61 (39 . 0%) females and 97 (61. 0%) males with age 34 (28-47) years .
Control group consisted of 50 healthy volunteers: 25 (50. 0%) — male, 25 (50. 0%) — female, age — 30 (34-39) years . There was no a significant difference between patient and healthy volunteers by age and sex (p > 0 . 05) . The inclusion criteria in the study for the patients: - diagnosis — acute odontogenic osteomyelitis of the jaw, complicated by cellulitis;
- the age over 18 years;
- availability of voluntary informed consent to participate in the study
The exclusion criteria:
- the age less than 18 years;
- pregnancy;
- concomitant diseases in the acute stage;
- presence of a history of alcohol abuse and drug use;
- lack of voluntary informed consent .
The patients were divided into 3 groups:
- 1 group (n = 96) had acute purulent odontogenic osteomyelitis of mandible complicated by the cellulitis of one cellular space;
- 2 group (n = 36) had acute purulent odontogenic osteomyelitis of mandible complicated by the cellulitis of 2-4 cellular spaces;
- 3 group (n = 26) — had acute purulent odontogenic osteomyelitis of the mandible complicated by Ludwig's angina
All patients underwent a clinical examination, which included: subjective methods and objective methods (physical and special) The treatment of the patients was complex and included tooth extraction, incision and drainage, general anti-inflammatory therapy according to standard protocol Antecubital venous blood was drawn before admission for the measurement of white blood cell counts and PCT concentrations Based on the blood test (leucocytes count), breath rate, heart rate and body temperature of the patients SIRS was determined
SIRS was defined by the satisfaction of any two of the criteria:
- body temperature over 38°C or under 36°C;
- heart rate greater than 90 beats/minute;
- respiratory rate greater than 20 breaths/minute or partial pressure of C02 less than 32 mmHg;
- leucocyte count greater than 12,000 or less than 4,000/ microliters or over 10% immature forms or bands [13].
PCT in blood serum was determined by the enzyme immunoassay using a universal photometer and ELISA kits manufactured by Vector-Best, Russia
Statistical data analysis was performed using the Statistica application spreadsheet package (Version 10-Index, license No . STA9999K347156W, Stat Soft Inc . , USA) and Excel (Microsoft, USA) In the case of a non-normal distribution of a trait, the median (Me), the lower 25th (LQ), and the upper 75th quartile (UQ) were calculated . The Mann-Whitney (U) test was used to assess statistical significance between unrelated groups For multiple comparisons of independent groups, the Kruskal-Wallis test was used A p value < 0 05 was found to be statistically significant . Correlation analysis was performed using the Spearman method
RESULTS
Patients with acute odontogenic osteomyelitis of the jaw, complicated by cellulitis of one cellular space, were characterized by the following combinations of SIRS signs: two of the four signs of SIRS were detected in 4 (4 0%) patients, three out of four — in 3 (3 0%), four signs were identified in 2 (2 0%) patients In total, in subgroup 1 of the comparison group, the presence of SIRS signs was revealed in 9 (9 0%) patients
Patients with acute odontogenic osteomyelitis of the jaw, complicated by cellulitis of 2-4 cellular spaces, were characterized by the following combinations of SIRS signs: two of the four signs of SIRS were detected in 1 (3 . 0%) patient, three out of four — in 10 (28 0%), four signs were identified in 2 (6 0%) patients In total, in the subgroup 2 the presence of SIRS signs was revealed in 13 (36 0%) patients
Patients with acute odontogenic osteomyelitis of the jaw, complicated by Ludwig's angina, were characterized by the following combinations of SIRS signs: two of the four signs of SIRS were detected in 4 (15 . 0%) patients, three out of four — in 10 (38 0%), four signs were detected in 7 (27 0%) patients In total, in the subgroup 3, the presence of one of the pairs of SIRS signs was detected in 21 patients (80 0%, Figure 1). Comparison of the SIRS frequency between groups of patients allowed us to establish that the differences were statistically significant: p (group 1/group 2) = 0 . 002, p (group 1/ group 3) < 0 . 001, (group 2/group 3) = 0 . 001.
90 80 70 60 50 40 30 20 10 O
SO
36
9
i^m
Cellulitis of one cellular space Cellulitis of 2-4 cellular space Ludwig's angina
■ % Systemic Inflammatory Response Syndrome
Fig. 1. Presence (%) of SIRS at the patients with odontogenic infection.
Notes: SIRS — systemic inflammatory response syndrome; p (group 1/group 2) = 0.002, p (group 1/group 3) < 0.001, (group 2/group 3) :
0.001.
PCT blood level in healthy group was 0 .009 (0 .006-0 . 018) pg/ml. All patients' groups had significantly higher PCT blood level compared with the healthy group: 1 group — 0 . 034 (0 . 019-0 . 050) pg/ml, U = 23, p = 0 . 01; 2 group — 0 .1 1 (0 . 06-0 . 24) pg/ml, U =12, p = 0 . 003; 3 group — 0 . 41 (0 . 30-1.15) pg/ml, U = 17, p < 0 . 001.
DISCUSSION
Odontogenic maxillofacial infections have a high potential to progress to systemic infections If these infections cannot be brought under control, they can cause bacteremia, bacterial endocarditis, mediastinitis, cavernous sinus thrombosis, suppurative jugular vein thrombophlebitis, arterial carotid erosion, maxillary sinusitis, osteomyelitis, and deep neck infections [14]. One of the most important tasks for the oral and maxillofacial surgeon called to evaluate a patient presenting with a maxillofacial infection is to rapidly assess him or her and determine the severity of the infection
Rangel-Fausto, et al published a prospect survey of patients admitted to a tertiary hospital, which revealed that 68% of hospital admissions of surveyed units met the criteria for SIRS SIRS progression was as follows: 26% developed sepsis, 18% developed severe sepsis, and 4% developed septic shock within 28 days of hospitalization Mortality rates were 7% (SIRS), 16% (sepsis), 20% (severe sepsis), and 46% (septic shock) Pittet, et al also showed that control group patients had the lowest time of hospitalization, while SIRS patients, as well as patients who had sepsis and severe sepsis required, respectively, and on a progressive basis, longer hospitalization SIRS is a disease that can and must be combated when diagnosed early, as its evolution is dangerous to the patient and can have fatal damage [15].
Among patients in the J . Byers, et al . audit of Scottish medical centers 16% of the patients with maxillofacial infection met the criteria for SIRS on admission [16]. In our study 80% cases of Ludwig's angina and only 9% cases of one space cellulitis characterized by SIRS
PCT is a biomarker of systemic bacterial infection and may not rise in strictly localized infectious process like appendicitis or pyelonephritis [17] . Regardless of severity, localized infection can lead to systemic infection, and PCT is the only statistically significant laboratory marker that differs between patients with systemic infection and localized infection The mean PCT values on admission were 7 . 24 ng/mL (range, 0 . 09-37 .15 ng/mL) and 0 . 40 ng/mL (range, 0 . 02-4. 94 ng/mL) in the sepsis group and non-sepsis group, respectively The procalcitonin values between the two groups showed a significant difference (p < 0 . 05) [12] .
C Bertolus, et al made conclusion from their study that serum PCT concentrations usually remain in the low range in facial odontogenic cellulitis and seem to have a
limited added value for risk stratification [18] . According to our data patients with acute odontogenic osteomyelitis complicated by cellulitis had significantly higher PCT blood level compared with the healthy group
CONCLUSION
Thus, the development of odontogenic infectious diseases of the maxillofacial region is accompanied by a systemic inflammatory response syndrome . In case of one cellular space cellulitis systemic inflammatory response syndrome was revealed in 9. 0% of patients, in case of 2-4 cellular spaces cellulitis — in 36 . 0%, in case of Ludwig's angina — in 80 . 0% . Comparison of the systemic inflammatory response syndrome frequency between subgroups of patients allowed us to establish that the systemic inflammatory response syndrome was associated with infection severity Correlation between the presence of systemic inflammatory response syndrome and the procalcitonin level in the blood serum can be evaluated as informative procalcitonin criteria for patient's condition aggravation
To prevent the development of severe complications of maxillofacial infection it is necessary to take into account the localization, prevalence of the process, as well as the appearance of laboratory markers of generalization . The search for significant diagnostic criteria for the development of life-threatening conditions should continue . According to the results of our studies, the level of procalcitonin in the blood serum, as indicator correlating with the development of systemic inflammatory response syndrome, may be promising in this regard, which requires further research
ADDITIONALLY
Funding. This study was not supported by any external sources of funding.
Conflict of interests. The authors declare no conflicts of interests. Acknowledgment. The authors are grateful to the staff of the Laboratory of the Vitebsk State Medical University for their help in conducting the study.
Contribution of the authors: А. A. Kabanava — research concept and design, text writing, processing of the material, writing the text; I. O. Pokhoden'ko-Chudakova — research design and editing; S. A. Kabanava — collection and processing of material, statistical processing, writing the text. The authors confirm the correspondence of their authorship to the ICMJE International Criteria. AH authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work.
Финансирование. Автор заявляет об отсутствии внешнего финансирования при проведении исследования.
Конфликт интересов. Автор заявляет об отсутствии конфликта интересов.
Благодарность. Авторы выражают благодарность коллективу научно-исследовательской лаборатории Витебского государственного медицинского университете за помощь в проведении исследования. Вклад авторов: Кабанова А. А. — концепция и дизайн исследования, написание текста, обработка материала, написание текста; Походенько-Чудакова И. О. — дизайн исследования и редактирование; Кабано-
ва С. А. — сбор и обработка материала, статистическая обработка, написание текста. Авторы подтверждают соответствие своего авторства международным критериям 1Си (все авторы внесли существенный вклад в разработку концепции и подготовку статьи, прочли и одобрили финальную версию перед публикацией).
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ОБ АВТОРАХ
*Кабанова Арина Александровна, д.м.н., доцент; ORCID: https://orcid.org/0000-0002-0121-1 139; eLibrary SPIN: 8930-3890; е-mail: arinakabanova@mail.ru
Походенько-Чудакова Ирина Олеговна, д.м.н., профессор; ORCID: https://orcid.org/0000-0002-0353-0125; eLibrary SPIN: 9486-9067; е-mail: ip-c@yandex.ru
Кабанова Светлана Алексеевна, к.м.н., доцент; ORCID: https://orcid.org/0000-0001-8165-7570; eLibrary SPIN: 4916-6722; e-mail: chlx.vgmu@mai.ru
AUTHOR'S INFO
*Arina A. Kabanova, MD, Dr. Sci. (Med.), Associate Professor; ORCID: https://orcid.org/0000-0002-0121-1139; eLibrary SPIN: 8930-3890; e-mail: arinakabanova@mail.ru
Irina O. Pokhoden'ko-Chudakova, MD, Dr. Sci. (Med.), Professor; ORCID: https://orcid.org/0000-0002-0353-0125; eLibrary SPIN: 9486-9067; e-mail: ip-c@yandex.ru
Svetlana A. Kabanova, MD, Cand. Sci. (Med.), Associate Professor; ORCID: https://orcid.org/0000-0001-8165-7570; eLibrary SPIN: 4916-6722; e-mail: chlx.vgmu@mai.ru
* Автор, ответственный за переписку / Corresponding author
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