Динамика органной дисфункции и маркеров воспаления у пациентов с септическим шоком при мультимодальной гемокоррекции: мультицентровое, рандомизированное, контролируемое исследование

АКТУАЛЬНОСТЬ: Септический шок считается наиболее серьезным осложнением в интенсивной медицине и сопровождается значительной летальностью. Экстракорпоральная гемокоррекция может улучшить результаты лечения пациентов с септическим шоком. ЦЕЛЬ ИССЛЕДОВАНИЯ: оценка влияния гемокоррекции с помощью мультимодального адсорбента «Эфферон ЛПС» на динамику органной дисфункции и маркеры воспаления у пациентов с септическим шоком. МАТЕРИАЛЫ И МЕТОДЫ: Мультицентровое рандомизированное контролируемое исследование проведено в четырех медицинских организациях города Москвы (НИИ СП им. Н.Ф. Склифосовского ДЗМ, ГКБ № 1 им. Н.И. Пирогова ДЗМ, ГКБ им. С.С. Юдина ДЗМ, ГКБ № 68 им. В.П. Демихова ДЗМ) с марта 2021 г. по май 2022 г. В исследование включены 58 пациентов (29 мужчин и 29 женщин) с септическим шоком. Рандомизацию проводили в соотношении 2:1 (гемоперфузия: контроль). Не позднее 24 ч после включения пациента в исследование выполняли процедуры селективной гемоперфузии или использовали стандартную терапию. Гемосорбцию с использованием «Эфферон ЛПС» проводили двукратно, с интервалом 24,5 (23,3–26,0) ч. РЕЗУЛЬТАТЫ: Применение селективного гемосорбента «Эфферон ЛПС» позволило уже через 72 ч снизить тяжесть органной дисфункции у пациентов с септическим шоком с 7 до 3 баллов по шкале SOFA (Sequential Organ Failure Assessment) за счет улучшения гемодинамики, респираторной и почечной функции. В отличие от контрольной группы, в группе «Эфферон ЛПС» уже через 72 ч значимо снижался уровень С-реактивного белка (СРБ) в 1,5 раза, прокальцитонина (ПКТ) — в 2,7 раза, интерлейкина-6 — в 2,3 раза. Тяжесть органной дисфункции значимо коррелировала с уровнем СРБ (r = 0,346) и ПКТ (r = 0,444). Длительность госпитализации выживших пациентов составила 16,1 и 30,1 дня в группе «Эфферон ЛПС» и контрольной группе соответственно (p = 0,032). Потребность в проведении заместительной почечной терапии у выживших к 3-м суткам значимо снижалась с 73,7 до 33,3 % только в группе «Эфферон ЛПС», но не в контрольной группе. ВЫВОДЫ: Применение селективного гемосорбента «Эфферон ЛПС» позволило уменьшить выраженность системного воспаления и значимо снизить тяжесть органной дисфункции у пациентов с септическим шоком за счет улучшения показателей гемодинамики, газообмена и почечной функции

Biomarkers of infection in the optimization of antibacterial therapy: justified expectations

Despite the continuous improvement of approaches to antimicrobial therapy and the emergence of new highly effective antibiotics, severe bacterial infections being a significant cause of morbidity and mortality remain a top of mind issue for clinicians. Immediate initiation of the effective antibiotic therapy is an essential component of the successful treatment of serious bacterial infections, and therefore, special attention should be paid to the timely diagnosis. Measurements of biomarkers of inflammation (C-reactive protein, procalcitonin, presepsin, proadrenomedullin) in combination with clinical evaluation are important at first for the diagnosis of bacterial infection, and after that these can help to assess the clinical response to therapy and determine the time-point of antibiotics withdrawal. This review presents the characteristics of the main markers of inflammation, discusses the situations when determination of biomarkers is appropriate, and also provides modern clinical recommendations and algorithms regarding the use of these diagnostic markers in the management of patients with bacterial infections

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy The SCARLET Randomized Clinical Trial

Importance: Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy. Objective: To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy. Design, Setting, and Participants: The SCARLET trial was a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study conducted in intensive care units at 159 sites in 26 countries. All adult patients admitted to one of the participating intensive care units between October 2012 and March 2018 with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, defined as an international normalized ratio greater than 1.40 without other known etiology and a platelet count in the range of 30 to 150 × 10 9/L or a greater than 30% decrease in platelet count within 24 hours, were considered for inclusion. The final date of follow-up was February 28, 2019. Interventions: Patients with sepsis-associated coagulopathy were randomized and treated with an intravenous bolus or a 15-minute infusion of thrombomodulin (0.06 mg/kg/d [maximum, 6 mg/d]; n = 395) or matching placebo (n = 405) once daily for 6 days. Main Outcome and Measures: The primary end point was 28-day all-cause mortality. Results: Among 816 randomized patients, 800 (mean age, 60.7 years; 437 [54.6%] men) completed the study and were included in the full analysis set. In these patients, the 28-day all-cause mortality rate was not statistically significantly different between the thrombomodulin group and the placebo group (106 of 395 patients [26.8%] vs 119 of 405 patients [29.4%], respectively; P =.32). The absolute risk difference was 2.55% (95% CI, -3.68% to 8.77%). The incidence of serious major bleeding adverse events (defined as any intracranial hemorrhage; life-threatening bleeding; or bleeding event classified as serious by the investigator, with administration of at least 1440 mL [typically 6 units] of packed red blood cells over 2 consecutive days) was 23 of 396 patients (5.8%) in the thrombomodulin group and 16 of 404 (4.0%) in the placebo group. Conclusions and Relevance: Among patients with sepsis-associated coagulopathy, administration of a human recombinant thrombomodulin, compared with placebo, did not significantly reduce 28-day all-cause mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT01598831

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy The SCARLET Randomized Clinical Trial

Importance: Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy. Objective: To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy. Design, Setting, and Participants: The SCARLET trial was a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study conducted in intensive care units at 159 sites in 26 countries. All adult patients admitted to one of the participating intensive care units between October 2012 and March 2018 with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, defined as an international normalized ratio greater than 1.40 without other known etiology and a platelet count in the range of 30 to 150 × 10 9/L or a greater than 30% decrease in platelet count within 24 hours, were considered for inclusion. The final date of follow-up was February 28, 2019. Interventions: Patients with sepsis-associated coagulopathy were randomized and treated with an intravenous bolus or a 15-minute infusion of thrombomodulin (0.06 mg/kg/d [maximum, 6 mg/d]; n = 395) or matching placebo (n = 405) once daily for 6 days. Main Outcome and Measures: The primary end point was 28-day all-cause mortality. Results: Among 816 randomized patients, 800 (mean age, 60.7 years; 437 [54.6%] men) completed the study and were included in the full analysis set. In these patients, the 28-day all-cause mortality rate was not statistically significantly different between the thrombomodulin group and the placebo group (106 of 395 patients [26.8%] vs 119 of 405 patients [29.4%], respectively; P =.32). The absolute risk difference was 2.55% (95% CI, -3.68% to 8.77%). The incidence of serious major bleeding adverse events (defined as any intracranial hemorrhage; life-threatening bleeding; or bleeding event classified as serious by the investigator, with administration of at least 1440 mL [typically 6 units] of packed red blood cells over 2 consecutive days) was 23 of 396 patients (5.8%) in the thrombomodulin group and 16 of 404 (4.0%) in the placebo group. Conclusions and Relevance: Among patients with sepsis-associated coagulopathy, administration of a human recombinant thrombomodulin, compared with placebo, did not significantly reduce 28-day all-cause mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT01598831