Современные и потенциальные возможности применения левосимендана в лечении сердечной недостаточности и септического шока: обзор литературы

Левосимендан относят к классу препаратов — сенситизаторов кальция, который проявляет свои положительные инотропные эффекты за счет увеличения сродства тропонина С миокарда к кальцию без дополнительной потребности миокарда в кислороде, что выгодно отличает его от катехоламинов и присущих им негативных эффектов (ишемия миокарда, аритмии, вазоконстрикция, гипергликемия). В 2000 г. препарат был впервые применен для краткосрочного лечения декомпенсированной хронической сердечной недостаточности (ХСН). По прошествии более чем 20 лет клиническое применение левосимендана охватило довольно широкую область среди пациентов с патологией сердечно-сосудистой системы, и его использование вышло далеко за рамки первичных показаний. На текущий момент левосимендан исследован более чем в 200 рандомизированных исследованиях у пациентов с различными клиническими профилями: острая декомпенсация ХСН, прогрессирующая сердечная недостаточность, острый инфаркт миокарда, кардиогенный шок, терапия синдрома низкого сердечного выброса в кардиохирургии, периоперационное использование в детской кардиохирургии, септический шок, легочная гипертензия, правожелудочковая недостаточность, кардиомиопатия Такоцубо, пациенты с механическими устройствами поддержки кровообращения. В данном обзоре рассмотрены фармакологические особенности препарата и ключевые рандомизированные клинические исследования, посвященные использованию левосимендана у различных категорий пациентов, помимо официально рекомендованных показаний. Также в статье представлен краткий обзор текущих и запланированных рандомизированных исследований

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

Background: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes

РАССТРОЙСТВА ТРЕВОЖНО-ДЕПРЕССИВНОГО СПЕКТРА У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ ТРОМБОЭМБОЛИЧЕСКОЙ ЛЕГОЧНОЙ ГИПЕРТЕНЗИЕЙ В ОТДАЛЕННЫЕ СРОКИ ПОСЛЕ ОПЕРАЦИИ

HighlightsThe article presents the analysis of anxiety and depressive disorders in patients who were followed as outpatients after surgery for chronic thromboembolic pulmonary hypertension in the long term, taking into account the study during the COVID–19 pandemic.The prevalence of clinically pronounced anxiety disorders in the group was 10.9%, depression - 18.6%, a combination of anxiety-depressive disorders was noted in 10.3% of cases.Multifactorial analysis revealed that the development of severe anxiety disorders in patients with chronic thromboembolic pulmonary hypertension in the long term is associated with a complicated postoperative course. Independent risk factors for clinically pronounced depressive disorders in these patients were older age, a history of cerebral circulation disorders, as well as pronounced post-COVID-19 functional disorders. Aim. To study the frequency and severity of anxiety-depressive disorders in patients with chronic thromboembolic pulmonary hypertension (CTEPH) in the long term after pulmonary thromboendarterectomy and to identify factors affecting their development.Methods. 156 patients with CTEPH were examined in the long term after surgery using the generalized anxiety disorder (GAD) questionnaire GAD-7 and the Beck`s Depression Inventory. In patients who suffered COVID-19, a “Post-COVID-19 Functional Status scale” (PCFS) was used to measure functional status over time after COVID-19. Logistic regression analysis was used to identify predictors of clinically pronounced GAD and depression in the long-term period after surgery.Results. In patients with CTEPH, clinically significant GAD and depression in the long term after surgery were observed in 10.9 and 18.6% of cases, respectively. A combination of anxiety and depressive disorders was noted in 10.3% of patients. The development of GAD was associated with cardiopulmonary insufficiency in the early postoperative period (ОR 3,1; CI 1,2–13,8; p = 0,009). Clinically pronounced depression was associated with older age (ОR 1,3; CI 1,04–2,0; p = 0,02), chronic cerebral circulatory insufficiency (ОR 7,6; CI 1,8–17,5; p = 0,02) and pronounced post-COVID-19 functional neurological disorders according to the PCFS scale (ОR 6,7; CI 1,9–14,5; p = 0,007). The combination of clinically expressed anxiety and depression was correlated with older age (ОR 1,1; CI 1,02–1,3; p = 0,04).Conclusion. The prevalence of clinically pronounced GAD in the group was 10.9%, depression was 18.6%, and a combination of anxiety and depressive disorders was noted in 10.3% of patients. The development of clinically significant GAD is associated with a complicated course of cardiac surgery. Independent risk factors for clinically significant depression were older age, a history of cerebral circulatory disorders and pronounced post-COVID-19 functional neurological disorders.Основные положенияСтатья посвящена изучению тревожных и депрессивных расстройств у пациентов диспансерной группы наблюдения с хронической тромбоэмболической легочной гипертензией в отдаленные сроки после хирургического вмешательства с учетом проведения исследования в период пандемии COVID-19.Распространенность клинически выраженных тревожных расстройств в изучаемой группе составила 10,9%, депрессии – 18,6%, сочетание тревожно-депрессивных расстройств зарегистрировано в 10,3% случаев.Многофакторный анализ показал, что развитие выраженных тревожных расстройств у пациентов с хронической тромбоэмболической легочной гипертензией в отдаленные сроки после хирургического вмешательства ассоциировано с осложненным течением операции. Независимыми факторами риска клинически выраженных депрессивных расстройств у данных пациентов явились старший возраст, нарушения мозгового кровообращения в анамнезе, а также выраженные постковидные функциональные нарушения. Цель. Изучить частоту и тяжесть тревожно-депрессивных расстройств у пациентов с хронической тромбоэмболической легочной гипертензией (ХТЛГ) в отдаленные сроки после тромбэндартерэктомии из легочной артерии и выявить факторы, влияющие на их развитие.Материалы и методы. Обследовано 156 пациентов с ХТЛГ в отдаленные сроки после операции с помощью опросника генерализованного тревожного расстройства (ГТР) GAD-7 и шкалы депрессии Бека. У больных, перенесших COVID-19, проведена оценка по шкале постковидного функционального статуса (PCFS). С помощью логистического регрессионного анализа выявлены предикторы клинически выраженных ГТР и депрессии в отдаленный период после операции.Результаты. У больных ХТЛГ клинически значимые ГТР и депрессия в отдаленный период после операции наблюдались в 10,9 и 18,6% случаев соответственно. Сочетание тревожно-депрессивных расстройств отмечено у 10,3% пациентов. Развитие клиники ГТР ассоциировано с сердечно-легочной недостаточностью в раннем послеоперационном периоде (ОШ 3,1; ДИ 1,2–13,8; p = 0,009). Клинически выраженная депрессия ассоциирована с более старшим возрастом (ОШ 1,3; ДИ 1,04–2,0; p = 0,02), хронической недостаточностью мозгового кровообращения (ОШ 7,6; ДИ 1,8–17,5; p = 0,02) и выраженными постковидными нарушениями функционального статуса по шкале PCFS (ОШ 6,7; ДИ 1,9–14,5; p = 0,007). Сочетание клинически выраженной тревоги и депрессии взаимосвязано с более старшим возрастом (ОШ 1,1; ДИ 1,02–1,3; p = 0,04).Заключение. Распространенность клинически выраженных ГТР в изучаемой группе составила 10,9%, депрессии – 18,6%, сочетание тревожно-депрессивных расстройств зарегистрировано у 10,3% пациентов. Развитие клинически значимых ГТР ассоциировано с осложненным течением кардиохирургического вмешательства. Независимыми факторами риска клинически значимой депрессии явились старший возраст, нарушения мозгового кровообращения в анамнезе и выраженные постковидные функциональные нарушения

Tranexamic Acid in Patients Undergoing Noncardiac Surgery

BACKGROUND Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, −2.6 percentage points; 95% CI, −3.8 to −1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, −1.1 to 1.7; one-sided P=0.04 for noninferiority). CONCLUSIONS Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.

Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper

Peer reviewe

Tranexamic Acid in Patients Undergoing Noncardiac Surgery

BACKGROUND Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, −2.6 percentage points; 95% CI, −3.8 to −1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, −1.1 to 1.7; one-sided P=0.04 for noninferiority). CONCLUSIONS Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians’ opinions and routine practices to understand the clinicians’ response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to “do you agree” and “do you use”) showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location