Заместительная терапия препаратами антитромбина в комплексном лечении сепсиса

Purpose — to assess the efficacy of supplementation therapy for antithrombin deficiency in the combined treatment of sepsis.Materials and methods. A prospective-retrospective study of the efficacy of supplementation therapy for antithrombin deficiency during sepsis was carried out; 90 patients were examined. The patients were split into two groups whether antithrombin deficiency correction was or was not undertaken. The composite outcome — the incidence of cardiovascular complications as of day 28 from the therapy commencement — was chosen as the primary endpoint of the study. The secondary endpoints of the study were prevalence of adverse events as of day 28 from the therapy commencement and 180-day mortality.Results. There was no difference between the groups either in respect of 28-day mortality or composite outcome. Analysis of secondary endpoints revealed that in the group of patients who received antithrombin supplementation therapy, the risk of development of an acute renal injury was significantly lower on day 28 and 180 from therapy commencement: OR 3.5 [95% CI 1.05–11.66] at P=0.04 and OR 2.92 [95% CI 1.02–8.31] at P=0.045, respectively.Conclusion. Correction of antithrombin level to activity level ‘over 61%’ is associated with decreased incidence degree III acute kidney failure (KDIGO).Цель работы — оценить эффективность применения заместительной терапии недостаточности антитромбина при комплексном лечении сепсиса.Материал и методы. Провели проспективно — ретроспективное исследования эффективности заместительной терапии недостаточности антитромбина при сепсисе; обследованы 90 пациентов. В зависимости от того, проводили ли коррекцию недостаточности антитромбина, пациентов разделили на две группы. Первичной точкой исследования выбрали композитный исход — частоту развития осложнений со стороны сердечно-сосудистой системы через 28 дней после начала лечения. Вторичные точки исследования — частота развития неблагоприятных событий на 28 день от начала лечения и 180 дневная летальность.Результаты. Группы не различались между собой ни по 28-дневной летальности, ни по композитному исходу. При анализе вторичных точек выявили, что в группе пациентов получавших заместительную терапию антитромбином, риск развития острого почечного повреждения был существенно ниже на 28 и 180 сутки от начала лечения: OR 3,5 [95% CI 1,05–11,66] при р=0,04 и OR 2,92 [95% CI 1,02–8,31] при р=0,045, соответственно.Заключение. Коррекция уровня антитромбина до уровня активности «более 61%» ассоциирована со снижением частоты развития острой почечной недостаточности III cт. (KDIGO)

Adaptive Phage Therapy in the Treatment of Patients with Recurrent Pneumonia (Pilot Study)

Aim. To evaluate the safety and efficacy of the adaptive phage therapy technique in patients with recurrent pneumonia in neurological critical care.Material and methods. The clinical study included 83 chronically critically ill patients with severe brain damage. The bacteriophage cocktail selected against specific hospital strains was administered by inhalation to 43 patients. The control group included 40 patients who received conventional antimicrobial therapy. The changes in clinical, laboratory and instrumental parameters, levels of biomarkers, microbiological and PCR tests of bronchoalveolar lavage fluid were assessed, including those in the «phage therapy with antibiotics» (n=29) and «phage therapy without antibiotics» (n=14) subgroups.Results. The groups were comparable in terms of basic parameters (age, sex, diagnosis, organ dysfunction according to APACHE II, use of vasoactive drugs) and the level of airway colonization with antibioticresistant bacterial strains. Good tolerability and absence of clinically significant side effects were observed during inhaled administration of the bacteriophage cocktail. Computed tomography on day 21 showed a significant reduction in lung damage in patients who received bacteriophages. Patients treated with bacteriophages without antibiotics had significantly lower need for mechanical ventilation. The mortality rate on day 28 did not differ significantly and was 4.7% (2/43) in the bacteriophage-treated group vs 5% (2/40) in the control group.Conclusion. The first experience of using the adaptive phage therapy technique in chronically critically ill patients in neurological intensive care demonstrated the safety of inhalational administration of the bacteriophage cocktail. The efficacy of the technique was confirmed by the treatment results obtained in the phage therapy group, which were not inferior to those in the group with conventional antibiotic therapy, while several clinical and laboratory parameters tended to improve even in patients who received bacteriophages and did not receive antibiotics

ОПРЕДЕЛЕНИЕ УРОВНЯ АНТИТРОМБИНА ПОЗВОЛЯЕТ ПРОГНОЗИРОВАТЬ КЛИНИЧЕСКИЕ ИСХОДЫ СЕПСИСА

Antithrombin is one of the key regulating factors of homeostasis, which activity significantly reduces in SIRS.The objective of the study: to investigate possibility and feasibility to test antithrombin level in blood plasma in order to predict treatment outcomes in patients with sepsis.Subjects. The level of antithrombin was tested in 83 patients by the start and at the peak of the disease. Predictive value was compared for antithrombin tests, some other parameters of coagulogram, and clinical severity scales in sepsis.Results. On the 5th day of the disease, the most significant predictors of the unfavorable outcome of sepsis were identified: fibrinogen level (Odds ratio – 2.42 [0.92–6.33]; p = 0.0722); and antithrombin level (Odds ratio – 26.4 [8.02 86.86]; p < 0.0001).Pair-wise comparison of ROC-curves of fibrinogen and antithrombin at the final point of the study demonstrated differences between areas under curve (AUC), which made 0.337 [95% CI 0.154–0.520] with p = 0.0003, which confirmed the assumption of the high predictive value of antithrombin level. With the cut-off point at ≤ 61% this test demonstrated the sensitivity and specificity of 79% and 88% respectively.Conclusion: In order to predict severity and potential outcome of sepsis, it is recommended to test antithrombin level at the peak of the disease.Антитромбин (АТ) является одним из ключевых факторов-регуляторов гемостаза, активность которого существенно снижается при SIRS.Цель работы: изучить возможность и целесообразность определения уровня AT в плазме крови для прогнозирования результатов лечения септических больных.Методы. У 83 больных сепсисом определяли содержание АТ в начале и на пике заболевания. Проведено сравнение прогностических возможностей определения уровня АТ, некоторых других показателей коагулограммы и клинических шкал оценки тяжести состояния при сепсисе.Результаты. На 5-е сут заболевания выявлены наиболее значимые предикторы неблагоприятного исхода сепсиса: уровень фибриногена (Odds ratio – 2,42 [0,92–6,33]; p = 0,0722); уровень АТ (Odds ratio – 26,4 [8,02 86,86]; p < 0,0001).Попарное сравнение ROC-кривых фибриногена и АТ в конечной точке исследования показало различие между площадями AUC (Area Under Curve), которое составило 0,337 [95%-ный ДИ 0,154–0,520] при p = 0,0003, что подтвердило предположение о высокой значимости теста с АТ. С точкой отсечения ≤ 61% данный тест продемонстрировал соотношение чувствительности и специфичности 79 и 88% соответственно.Вывод. Для прогнозирования тяжести течения и вероятного исхода сепсиса рекомендуется определение уровня АТ в период «разгара» заболевания

Адаптивная фаготерапия пациентов с рецидивирующими пневмониями (пилотное исследование)

Aim. To evaluate the safety and efficacy of the adaptive phage therapy technique in patients with recurrent pneumonia in neurological critical care.Material and methods. The clinical study included 83 chronically critically ill patients with severe brain damage. The bacteriophage cocktail selected against specific hospital strains was administered by inhalation to 43 patients. The control group included 40 patients who received conventional antimicrobial therapy. The changes in clinical, laboratory and instrumental parameters, levels of biomarkers, microbiological and PCR tests of bronchoalveolar lavage fluid were assessed, including those in the «phage therapy with antibiotics» (n=29) and «phage therapy without antibiotics» (n=14) subgroups.Results. The groups were comparable in terms of basic parameters (age, sex, diagnosis, organ dysfunction according to APACHE II, use of vasoactive drugs) and the level of airway colonization with antibioticresistant bacterial strains. Good tolerability and absence of clinically significant side effects were observed during inhaled administration of the bacteriophage cocktail. Computed tomography on day 21 showed a significant reduction in lung damage in patients who received bacteriophages. Patients treated with bacteriophages without antibiotics had significantly lower need for mechanical ventilation. The mortality rate on day 28 did not differ significantly and was 4.7% (2/43) in the bacteriophage-treated group vs 5% (2/40) in the control group.Conclusion. The first experience of using the adaptive phage therapy technique in chronically critically ill patients in neurological intensive care demonstrated the safety of inhalational administration of the bacteriophage cocktail. The efficacy of the technique was confirmed by the treatment results obtained in the phage therapy group, which were not inferior to those in the group with conventional antibiotic therapy, while several clinical and laboratory parameters tended to improve even in patients who received bacteriophages and did not receive antibiotics.Цель. Оценка безопасности и эффективности технологии адаптивной фаготерапии в лечении пациентов с рецидивирующими пневмониями в нейрореаниматологии.Материал и методы. В клиническое исследование включили 83 пациента в хроническом критическом состоянии с тяжелым повреждением головного мозга. У 43 пациентов ингаляционно применили комплексный препарат бактериофагов, адаптированный к госпитальным штаммам данного учреждения. Группу сравнения сравнения составили пациенты (n=40), получавшие традиционную антибактериальную терапию. Оценивали динамику клинико-лабораторных, инструментальных показателей, биомаркеров, результаты микробиологических и ПЦР-исследований бронхо-альвеолярного лаважа, в том числе — раздельно в подгруппах «фаготерапия с антибиотиками» (n=29) и «фаготерапия без антибиотиков» (n=14).Результаты. Группы были сопоставимы по основным показателям (возраст, пол, диагноз, степень органных дисфункций по APACHE II, применение вазоактивных препаратов) и уровню бактериальной колонизации дыхательных путей антибиотикорезистентными штаммами. При ингаляционном введении комплексного препарата бактериофагов наблюдали хорошую переносимость, отсутствие клинически значимых побочных эффектов. По данным компьютерной томографии, к 21-му дню выявили значимое снижение степени повреждения легких. У пациентов, получавших лечение бактериофагами без антибиотиков, значимо снизилась потребность в проведении искусственной вентиляции легких. Летальность к 28-м сут. значимо не различалась: при фаготерапии — 2/43 (4,7%), в группе сравнения — 2/40 (5%).Заключение. Первый опыт применения технологии адаптивной фаготерапии в лечении хронических реанимационных пациентов в нейрореаниматологии продемонстрировал безопасность ингаляционного введения комплексного препарата бактериофагов. Эффективность технологии подтверждена результатами лечения, полученными в группе фаготерапии, которые не уступали таковым в группе с традиционной антибиотикотерапией, а ряд клинико-лабораторных показателей имел тенденцию к улучшению даже в случаях полного отказа от антибиотиков в пользу бактериофагов

Supplementation therapy with Antithrombin Drugs in the Combined Treatment of Sepsis

Purpose — to assess the efficacy of supplementation therapy for antithrombin deficiency in the combined treatment of sepsis.Materials and methods. A prospective-retrospective study of the efficacy of supplementation therapy for antithrombin deficiency during sepsis was carried out; 90 patients were examined. The patients were split into two groups whether antithrombin deficiency correction was or was not undertaken. The composite outcome — the incidence of cardiovascular complications as of day 28 from the therapy commencement — was chosen as the primary endpoint of the study. The secondary endpoints of the study were prevalence of adverse events as of day 28 from the therapy commencement and 180-day mortality.Results. There was no difference between the groups either in respect of 28-day mortality or composite outcome. Analysis of secondary endpoints revealed that in the group of patients who received antithrombin supplementation therapy, the risk of development of an acute renal injury was significantly lower on day 28 and 180 from therapy commencement: OR 3.5 [95% CI 1.05–11.66] at P=0.04 and OR 2.92 [95% CI 1.02–8.31] at P=0.045, respectively.Conclusion. Correction of antithrombin level to activity level ‘over 61%’ is associated with decreased incidence degree III acute kidney failure (KDIGO)

TESTING ANTITHROMBIN LEVEL ALLOWS PREDICTING A CLINICAL OUTCOME OF SEPSIS

Antithrombin is one of the key regulating factors of homeostasis, which activity significantly reduces in SIRS.The objective of the study: to investigate possibility and feasibility to test antithrombin level in blood plasma in order to predict treatment outcomes in patients with sepsis.Subjects. The level of antithrombin was tested in 83 patients by the start and at the peak of the disease. Predictive value was compared for antithrombin tests, some other parameters of coagulogram, and clinical severity scales in sepsis.Results. On the 5th day of the disease, the most significant predictors of the unfavorable outcome of sepsis were identified: fibrinogen level (Odds ratio – 2.42 [0.92–6.33]; p = 0.0722); and antithrombin level (Odds ratio – 26.4 [8.02 86.86]; p < 0.0001).Pair-wise comparison of ROC-curves of fibrinogen and antithrombin at the final point of the study demonstrated differences between areas under curve (AUC), which made 0.337 [95% CI 0.154–0.520] with p = 0.0003, which confirmed the assumption of the high predictive value of antithrombin level. With the cut-off point at ≤ 61% this test demonstrated the sensitivity and specificity of 79% and 88% respectively.Conclusion: In order to predict severity and potential outcome of sepsis, it is recommended to test antithrombin level at the peak of the disease