Russian Journal of Pediatric Surgery, Anesthesia and Intensive CareRussian Journal of Pediatric Surgery, Anesthesia and Intensive CareРоссийский вестник детской хирургии, анестезиологии и реаниматологии2219-40612587-6554Eco-Vector124210.17816/psaic1242Original Study ArticlesОригинальные исследованияResearch ArticleAlgorithm for predicting sepsis in newborns with respiratory pathology and perinatal lesions of the central nervous system on mechanical ventilationАлгоритм прогнозирования сепсиса у новорожденных с респираторной патологией и перинатальным поражением центральной нервной системы, находящихся на искусственной вентиляции легкихhttps://orcid.org/0000-0001-5530-21943120-7069PukhtinskayaMarina G.ПухтинскаяМарина Гаевна
Russian Federation

Dr. Sci. (Med.), Leading Researcher

д-р мед. наук, вед. научн. сотр.

puhmar@mail.ruhttps://orcid.org/0000-0002-9201-83338136-4128EstrinVladimir V.ЭстринВладимир Владимирович
Russian Federation

Dr. Sci. (Med.), Professor

д-р мед. наук, профессор

medinsur@aaanet.ruScientifically Research Institute of Obstetrics and Pediatrics, Rostov-on-Don State Medical UniversityНаучно-исследовательский институт акушерства и педиатрии, Ростовский государственный медицинский университет26052022240720221221191301603202225052022Copyright ©; 2022, Pukhtinskaya M.G., Estrin V.V.Copyright ©; 2022, Пухтинская М.Г., Эстрин В.В.2022Pukhtinskaya M.G., Estrin V.V.Пухтинская М.Г., Эстрин В.В.https://creativecommons.org/licenses/by-nc-nd/4.0https://rps-journal.ru/jour/article/view/1242

BACKGROUND: Predicting sepsis in ventilated neonates remains a challenge in neonatology.

AIM: To increase the efficiency of predicting sepsis diagnosis in newborns by developing a decision rule for its development based on decision trees.

MATERIALS AND METHODS: This clinical study retrospectively reviewed 200 full-term newborns with respiratory pathology that are admitted to the intensive care unit and are on mechanical ventilation without clinical signs of bacterial infection.

Upon admission to the department on days 1, 3–5, and 20, an enzyme-linked immunosorbent assay determined the plasma concentration of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, granulocyte colony-stimulating factor, soluble Fas ligand, fibroblast growth factors, and nitric oxide (NO), and immunophenotyping method determined CD3+CD19–, CD3–CD19+, CD3+CD4+, CD3+CD8+, CD69+, CD71+, CD95+, HLA–DR+, CD34+, CD14+, CD3–CD56+; lymphocytes expressing AnnexinV-FITC+PI–, and AnnexinV-FITC+PI+. The possibility of diagnosing sepsis upon intensive care unit admission was assessed by statistical cluster analysis of the total studied immunological criteria. The method of decision trees in the statistical environment R formed a diagnostic rule for predicting sepsis.

RESULTS: Visualization of the cluster analysis results of admitted patients did not exclude the presence of two clusters among them (with and without sepsis, which explain the 60.81% of the point variability).

Sepsis prediction rule are as follows: disease progression occurs if on day 1 CD95 is ≥16.8% and NO is ≤9.6 mkmol/l or CD95 is ≤16.8%, CD34 is ≤0.2%, CD69 is ≥4.12% or CD95 is ≤16.8%, CD34 is ≤0.2%, CD69 is ≤4.12%, and lymphocytes expressing AnnexinV-FITC+PI– is ≥12.3%. The diagnostic accuracy was 96.00%; sensitivity was 97.00%; specificity was 94.90%; the false-positive proportion of diagnoses was 5.10%; the false-negative proportion of diagnoses was 2.94%; the positive result accuracy was 95.19%; and the negative result was 96.88%. The disease was complicated by bacterial sepsis development on 4–5 days of observation in 45 newborns.

CONCLUSIONS: Significant importance in sepsis development belongs to the prevalence of altered immunocompetent cells over proliferation and endogenous synthesis of nitric oxide. The cumulative determination of CD95+, CD69+, AnnexinV-FITC+PI–, CD34+, and plasma nitric oxide concentration helped diagnose sepsis development at the preclinical stage. The obtained results indirectly confirm the relevance of studies on sepsis prevention and treatment by drug correction of apoptosis and inhaled NO.

Актуальность. Прогнозирование сепсиса у новорожденных, находящихся на искусственной вентиляции легких, по-прежнему остается сложной задачей неонатологии.

Цель — повышение эффективности прогнозирования сепсиса у новорожденных, находящихся на искусственной вентиляции легких, путем разработки решающего правила его развития методом деревьев принятия решений.

Материалы и методы. В ретроспективное клиническое исследование было включено 200 доношенных новорожденных с респираторной патологией, поступивших в отделение реанимации на искусственной вентиляции легких, без клинических признаков бактериального инфицирования. При поступлении в отделение, на 5-е и 20-е сутки определяли: методом иммуноферментного анализа — плазменную концентрацию IL-1β, IL-6, IL-8, TNF-α, G-CSF, s-Fas, FGF, NO; методом иммунофенотипирования — CD3+CD19–, CD3–CD19+, CD3+CD4+, CD3+CD8+, CD69+, CD71+, CD95+, HLA-DR+, CD34+, CD14+, CD3–CD56+; лимфоциты с экспрессией AnnexinV-FITC+PI–, AnnexinV-FITC+PI+. Методом кластерного анализа совокупности исследуемых иммунологических критериев оценена возможность диагностики сепсиса при поступлении в реанимацию. Методом деревьев принятия решений сформировано правило прогнозирования сепсиса.

Результаты. Визуализация результатов кластерного анализа поступивших пациентов не исключала наличие среди них двух кластеров (с наличием и отсутствием сепсиса — эти два компонента разъясняют 60,81 % точечной изменчивости).

Правило прогнозирования сепсиса: развитие заболевания происходит, если на первые сутки CD95 ≥ 16,8 % и NO ≤ 9,6 мкмоль/л или CD95 ≤ 16,8 % и CD34 ≤ 0,2 % и CD69 ≥ 4,12 % или CD95 ≤ 16,8 % и CD34 ≤ 0,2 % и CD69 ≤ 4,12% и лимфоциты с экспрессией AnnexinV-FITC+PI– ≥ 12,3 %. Точность диагностики 96,00 %; чувствительность 97,00 %; специфичность 94,90 %; ложноположительная доля диагнозов 5,10 %; ложноотрицательная доля диагнозов 2,94 %; точность положительного результата 95,19 %; точность отрицательного результата 96,88 %. На 4–5-е сутки наблюдения у 45 новорожденных заболевание осложнилось развитием бактериального сепсиса.

Выводы. Существенное значение в развитии сепсиса принадлежит превалированию альтерации иммунокомпетентных клеток над пролиферацией и эндогенному синтезу оксида азота. Совокупное определение CD95+, CD69+, AnnexinV-FITC+PI–, CD34+ и плазменной концентрации оксида азота позволяет диагностировать развитие сепсиса на доклинической стадии. Полученные результаты косвенно подтверждают актуальность исследований, посвященных профилактике и терапии сепсиса медикаментозной коррекцией апоптоза и ингаляционным оксидом азота.

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