nmpЖурнал им. Н.В. Склифосовского «Неотложная медицинская помощь»Russian Sklifosovsky Journal "Emergency Medical Care"2223-90222541-8017“N.V. Sklifosovsky Research Institute for Emergency Medicine”10.23934/2223-9022-2025-14-4-724-737nmp-2284Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESРоль внеклеточной дНК среди предикторов госпитальной летальности у пациентов с септическим шокомThe Role of Extracellular DNA Among Predictors of Hospital Mortality in Patients with Septic Shockhttps://orcid.org/0009-0005-2827-2176ГриненкоМ. С.GrinenkoM. S.

Гриненко Марина Сергеевна, врач анестезиолог-реаниматолог отделения общей реанимации ГБУЗ «ГКБ им. С.С. Юдина ДЗМ»

115446, Москва, Коломенский пр-д, д. 4

Marina S. Grinenko, Anesthesiologist-Resuscitator, General Intensive Care Department

Kolomenskiy proezd 2/1, bldg. 1 proezd 4, Moscow, 115446

grinenko898@mail.ruhttps://orcid.org/0000-0003-2581-3051ЗаиграевИ. А.ZaigraevI. A.

Заиграев Иван Андреевич, врач-терапевт ГБУЗ «ГКБ им. С.С. Юдина ДЗМ», младший научный сотрудник отдела фундаментальных и клинических проблем тромбоза при неинфекционных заболеваниях ФГБУ «НМИЦ ТПМ» МЗ РФ

115446, Москва, Коломенский пр-д, д. 4,

121552, Москва, пер. Петроверигский, д. 10, стр. 3

Ivan A. Zaigraev, Physician, S.S. Yudin City Clinical Hospital; Junior Researcher, Department of Fundamental and Clinical Problems of Thrombosis in Non-Communicable Diseases, National Medical Research Center for Therapy and Preventive Medicine

Kolomenskiy proezd 2/1, bldg. 1 proezd 4, Moscow, 115446,

Petroverigsky lane 10, bldg. 3, Moscow, 121552

zaigraevivan2002@yandex.ruhttps://orcid.org/0000-0001-7222-0537КротенкоН. П.KrotenkoN. P.

Кротенко Николай Петрович, врач анестезиолог-реаниматолог, кандидат медицинских наук, заведующий общей реанимацией ГБУЗ «ГКБ им. С.С. Юдина ДЗМ», доцент кафедры анестезиологии и реаниматологии им. профессора Е.А. Дамир ФГБОУ ДПО РМАНПО МЗ РФ

115446, Москва, Коломенский пр-д, д. 4,

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Nikolay P. Krotenko, Anesthesiologist-Resuscitator, Candidate of Medical Sciences, Head, General Intensive Care Department, S.S. Yudin City Clinical Hospital; Associate Professor, Department of Anesthesiology and Resuscitation named after Professor E.A. Damir, Russian Medical Academy of Continuous Professional Education

Kolomenskiy proezd 2/1, bldg. 1 proezd 4, Moscow, 115446,

Barricade Str. 2/1, bldg. 1, Moscow, 125993

npkrotenko@gmail.comhttps://orcid.org/0000-0002-5725-3805АфанасьеваМ. И.AfanasievaM. I.

Афанасьева Марина Ильинична, научный сотрудник 

121552, Москва, ул. Академика Чазова, д. 15а

Marina I. Afanasieva, Researcher

Petrovka Str. 25, bldg. 2, Moscow, 107031

miafanasieva.cardio@yandex.ruhttps://orcid.org/0009-0005-4083-1030ДороненковаА. А.DoronenkovaA. A.

Дороненкова Анастасия Алексеевна, врач-анестезиолог-реаниматолог 

115446, Москва, Коломенский пр-д, д. 4

Anastasia A. Doronenkova, Anesthesiologist-Resuscitator

Kolomenskiy proezd 2/1, bldg. 1 proezd 4, Moscow, 115446

kaymashnikovastasy@gmail.comhttps://orcid.org/0000-0002-6353-2552ИгнатенкоО. В.IgnatenkoO V.

Игнатенко Ольга Викторовна   врач анестезиолог-реаниматолог, кандидат медицинских наук, заместитель главного врача по анестезиологии и реаниматологии ГБУЗ «ГКБ им. С.С. Юдина ДЗМ», доцент кафедры анестезиологии и реаниматологии им. профессора Е.А. Дамир ФГБОУ ДПО РМАНПО МЗ РФ

115446, Москва, Коломенский пр-д, д. 4,

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1,

107031, Москва, ул. Петровка, д. 25, стр. 2

Olga V. Ignatenko, Anesthesiologist-Resuscitator, Candidate of Medical Sciences, Deputy Chief Physician for Anesthesiology and Resuscitation, S.S. Yudin City Clinical Hospital; Associate Professor, Department of Anesthesiology and Resuscitation named after Professor E.A. Damir, Russian Medical Academy of Continuous Professional Education

Kolomenskiy proezd 2/1, bldg. 1 proezd 4, Moscow, 115446,

Barricade Str. 2/1, bldg. 1, Moscow, 125993,

Petrovka Str. 25, bldg. 2, Moscow, 107031

 

ovignatenko@gmail.comhttps://orcid.org/0000-0001-8886-7175КричевскийЛ. А.KrichevskyiL. A.

Кричевский Лев Анатольевич, профессор, врач анестезиолог-реаниматолог, доктор медицинских наук, заведующий отделением анестезиологии и реанимации № 2 ГБУЗ «ГКБ им. С.С. Юдина ДЗМ», заведующий кафедрой анестезиологии и реаниматологии им. профессора Е.А. Дамир ФГБОУ ДПО РМАНПО МЗ РФ

115446, Москва, Коломенский пр-д, д. 4,

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Lev A. Krichevskyi, Professor, Anesthesiologist-Resuscitator, Doctor of Medical Sciences, Head, Department of Anesthesiology and Resuscitation No. 2, S.S. Yudin City Clinical Hospital; Professor, Head, Department of Anesthesiology and Resuscitation named after Professor E.A. Damir, Russian Medical Academy of Continuous Professional Education

Kolomenskiy proezd 2/1, bldg. 1 proezd 4, Moscow, 115446,

Barricade Str. 2/1, bldg. 1, Moscow, 125993

levkrich72@gmail.comhttps://orcid.org/0009-0007-8277-063XМарышеваА. Н.MaryshevaA. N.

Марышева Анастасия Николаевна, врач анестезиолог-реаниматолог отделения общей реанимации

115446, Москва, Коломенский пр-д, д. 4

Anastasia N. Marysheva, Anesthesiologist-Resuscitator, General Intensive Care Department

Kolomenskiy proezd 2/1, bldg. 1 proezd 4, Moscow, 115446

miss.marysheva@yandex.ruhttps://orcid.org/0009-0006-8106-8091АбдуллинЕ. Т.AbdullinE. T.

Абдуллин Евгений Тимурович, младший научный сотрудник

121552, Москва, ул. Академика Чазова, д. 15а

Evgeny T. Abdullin, Junior Researcher

Petrovka Str. 25, bldg. 2, Moscow, 107031

abdullin97@gmail.comhttps://orcid.org/0000-0001-5105-0313ПокровскийН. С.PokrovskyiN. S.

Покровский Николай Сергеевич, младший научный сотрудник

121552, Москва, ул. Академика Чазова, д. 15а

Nikolay S. Pokrovskyi, Junior Researcher

Petrovka Str. 25, bldg. 2, Moscow, 107031

nspokrovsky@gmail.comГБУЗ «Городская клиническая больница им. С.С. Юдина ДЗМ»РоссияS.S. Yudin Moscow City HospitalRussian FederationГБУЗ «Городская клиническая больница им. С.С. Юдина ДЗМ»; ФГБУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» МЗ РФРоссияS.S. Yudin Moscow City Hospital; National Medical Research Center for Therapy and Preventive MedicineRussian FederationГБУЗ «Городская клиническая больница им. С.С. Юдина ДЗМ»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» МЗ РФРоссияS.S. Yudin Moscow City Hospital; Russian Medical Academy of Continuous Professional EducationRussian FederationФГБУ «Национальный медицинский исследовательский центр кардиологии им. акад. Е.И. Чазова» МЗ РФРоссияFederal Research and Clinical Center of Intensive Care Medicine and RehabilitologyRussian FederationГБУЗ «Городская клиническая больница им. С.С. Юдина ДЗМ»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» МЗ РФ; ФГБНУ «Федеральный научно-клинический центр реаниматологии и реабилитологии»РоссияS.S. Yudin Moscow City Hospital; Russian Medical Academy of Continuous Professional Education;Russian Federation202530012026144724737Copyright © Гриненко М.С., Заиграев И.А., Кротенко Н.П., Афанасьева М.И., Дороненкова А.А., Игнатенко О.В., Кричевский Л.А., Марышева А.Н., Абдуллин Е.Т., Покровский Н.С., 20262026Гриненко М.С., Заиграев И.А., Кротенко Н.П., Афанасьева М.И., Дороненкова А.А., Игнатенко О.В., Кричевский Л.А., Марышева А.Н., Абдуллин Е.Т., Покровский Н.С.Grinenko M.S., Zaigraev I.A., Krotenko N.P., Afanasieva M.I., Doronenkova A.A., Ignatenko O.V., Krichevskyi L.A., Marysheva A.N., Abdullin E.T., Pokrovskyi N.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.jnmp.ru/jour/article/view/2284Цель

Цель. Исследовать роль вкДНК (внеклеточной ДНК) как независимого предиктора летальности у пациентов с септическим шоком, а также определить фенотип больных, уровень вкДНК которых ассоциирован с высокой госпитальной летальностью.

Материал и методы

Материал и методы. В проспективное одноцентровое обсервационное пилотное исследование включили пациентов старше 18 лет с клинической картиной септического шока (критерии Sepsis-3), поступивших в период август 2023 — май 2024 года в отделение интенсивной терапии ГБУЗ «ГКБ им. С.С. Юдина ДЗМ».

Результаты

Результаты. Итоговое число пациентов, включённых в исследование, составило n=52 (64% мужчин, 36% женщин) в возрасте 52,1±17,3 года, с тяжестью состояния по шкалам SOFA 10±4 и APACHE II 22±7 баллов соответственно. Концентрация вкДНК составила 3041 (876; 7815,0) нг/мл. Для вкДНК была определена статистически значимая связь с 28-дневной летальностью (AUC 0,69, 95% ДИ — доверительный интервал [0,54, 0,84], р=0,031), а также выявлена отрезная точка концентрации (более 1893 нг/мл), при которой отношение шансов (ОШ) вероятности смертельного исхода в стационаре соответствовало 4,3 (95% ДИ [1,3, 15,1], р=0,03). Зависимость риска развития смертельного исхода от концентрации вкДНК (не более 1893 или более 1893 нг/мл), оценённая с помощью лог-ранк критерия Мантеля–Кокса, была статистически значима (р=0,028). Медиана срока наступления смерти в группе вкДНК более 1893 нг/мл составила 7 дней, а при уровне вкДНК не более 1893 нг/мл — 11 дней. Независимыми предикторами концентрации вкДНК более 1893 нг/мл у больных с септическим шоком были уровень лактата смешанной венозной крови (ОШ 2,0; 95% ДИ [1,02, 3,92], р=0,044) и сумма баллов по шкале SOFA (ОШ 1,23; 95% ДИ [1,02, 1,47], р=0,029).

Заключение

Заключение. Исследование продемонстрировало, что внеклеточная ДНК является независимым предиктором летальности при септическом шоке, выявлена её пороговая концентрация, связанная со значительным повышением вероятности наступления смертельного исхода, которая может быть рассмотрена как лабораторный ориентир при определении показаний для её экстракорпоральной элиминации. Также определены маркёры значимого повышения концентрации вкДНК в кровотоке, что может служить инструментом для её косвенной оценки в режиме ˝Point of care˝.

Выводы 1

Выводы 1. Внеклеточная ДНК является независимым предиктором летальности у пациентов с септическим шоком. 2. Внеклеточную ДНК можно рассматривать как потенциальную мишень для экстракорпоральной терапии. 3. Пороговая концентрация внеклеточной ДНК, рассматриваемая как возможный лабораторный ориентир для инициации экстракорпоральной терапии — 1893 нг/мл. 4. Независимыми предикторами концентрации внеклеточной ДНК более 1893 нг/мл у больных с септическим шоком были уровень лактата смешанной венозной крови и количество баллов по шкале SOFA.

Introduction

Introduction. Extracellular DNA (exDNA) is a well-known but poorly understood mediator of sepsis. The aim was to investigate the role of exDNA as an independent predictor of mortality and as a marker of unfavorable clinical phenotype for patients with septic shock.

Material and methods

Material and methods. The patients over the age of 18 with septic shock (Sepsis-3 criteria) who were admitted to the intensive care unit of the S.S. Yudin City Clinical Hospital between August 2023 and May 2024 were included in a prospective observational study.

Results

Results. Total of fifty-two patients (64% men, 36% women) aged 52.1 ± 17.3 years, with severity of the condition on the SOFA score 10±4 and APACHE II score — 22±7 were included. The exDNA concentration was 3041 (876–7815.0) ng/ml. For exDNA, a significant (p=0,031) association with 28-day mortality was determined (AUC 0.69, 95% CI (0.54–0.84)), and a cut-off point >1893 ng/ml was identified, at which the OR of the hospital death corresponded to 4.3 (95% CI 1.3–15.1, p=0.03). The dependence of the risk of death on the concentration of exDNA (<1893 or >1893 ng/ml), estimated using the Mantel-Cox log-rank test, was statistically significant (p=0.028). The median survival time in the exDNA group >1893 ng/ml was 7 days, and for exDNA levels <1893 ng/ml — 11 days. Independent predictors of exDNA concentrations >1893 ng/ml in patients with septic shock were the level of mixed venous blood lactate (OR 2.0; 95% CI [1.02, 3.92], p=0.044) and SOFA score (OR 1.23; 95% CI [1.02, 1.47], p=0.029).

Conclusion

Conclusion. The exDNA level is an independent predictor of mortality in septic shock. Its cut-off point of 1893 ng/ml could be considered as an indication for extracorporeal elimination of exDNA. Point of care laboratory markers of a significant increase in the blood concentration of exDNA were also identified and could be considered as a guide to an intensive care.

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The authors declare that there are no conflicts of interest present.