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

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

Altres ajuts: Canadian Institutes of Health Research (CIHR, FDN-143302); General Research Fund (14104419), Research Grant Council, Hong Kong SAR, China; National Health and Medical Research Council, Funding Schemes (NHMRC Project Grant 1162362), Australia; McMaster University Department of Medicine Career Research Award and a Physicians' Services Incorporated (PSI) Foundation Mid-Career Clinical Research Award.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. Methods: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018

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. Methods The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration ClinicalTrials.gov NCT03505723. Registered on 23 April 2018

Volatile and Intravenous Anesthetics for Brain Protection in Cardiac Surgery: Does the Choice of Anesthesia Matter?

Postoperative neurologic complications have a significant effect on morbidity, mortality, and long-term disability in patients undergoing cardiac surgery. The etiology of brain injury in patients undergoing cardiac surgery is multifactorial and remains unclear. There are several perioperative causative factors for neurologic complications, including microembolization, hypoperfusion, and systemic inflammatory response syndrome. Despite technologic advances and the development of new anesthetic drugs, there remains a high rate of postoperative neurologic complications. Moreover, despite the strong evidence that volatile anesthesia exerts cardioprotective effects in patients undergoing cardiac surgery, the neuroprotective effects of volatile agents remain unclear. Several studies have reported an association of using volatile anesthetics with improvement of biochemical markers of brain injury and postoperative neurocognitive function. However, there is a need for additional studies to define the optimal anesthetic drug for protecting the brain in patients undergoing cardiac surgery

The use of levosimendan in cardiac surgery: an update after the LEVO-CTS, CHEETAH and LICORN trials in the light of clinical practice

Levosimendan is a calcium sensitizer and ATP-dependent potassium channel opener which exerts sustained hemodynamic, symptomatic and organ-protective effects. It is registered for the treatment of acute heart failure, and when inotropic support is considered appropriate. In the past fifteen years, levosimendan has been widely used in clinical practice, and has also been tested in clinical trials to stabilize at-risk patients undergoing cardiac surgery. Recently, three randomized, placebo-controlled, multicenter studies (LICORN, CHEETAH and LEVO-CTS) have been published reporting on the peri-operative use of levosimendan in patients with compromised cardiac ventricular function. Taken together, many smaller trials conducted in the past suggested beneficial outcomes with levosimendan in peri-operative settings. In contrast, the latest three studies were neutral or inconclusive. In order to understand the reasons for such dissimilarity, a group of experts from Austria, Belgium, Finland, France, Germany, Italy, Switzerland, and Russia, including investigators from the three most recent studies, met to discuss the study results in the light of both the previous literature and current clinical practice. Despite the fact that the null hypothesis could not be ruled out in the recent multicenter trials, we conclude that levosimendan can still be viewed as a safe and effective inodilator in cardiac surgery.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited