Septischer Schock und septische Kardiomyopathie

Abstract

Sepsis is a very frequent diagnosis in intensive care units. It is associated with a high mortality rate and often affects the cardiovascular system. Moreover, sepsis is the most common form of shock and is often also accompanied by acute organ failure such as myocardial dysfunction. Besides vasoplegia through decrease of systemic vascular resistance, an acute reduction of myocardial contractility and ventricular dilation are the typical signs of sepsis-induced myocardial dysfunction. With the increased availability of bedside transthoracic echocardiography over the last few years, the diagnosis of cardiomyopathy is verified much more frequently in septic patients. Given that the diagnosis is highly complex and characterized by different origins as well as diverse pathogens, it is difficult to make a prediction regarding a prognosis. However, research has shown that it is highly likely that absence of normokinesia will have a negative influence on the prognosis. The underlying pathophysiological mechanisms of sepsis-induced myocardial dysfunction are not completely understood. Infective toxin binding via toll-like receptors to different cell types (such as macrophages, endothelial cells and directly to cardiomyocytes), which leads to increased release of cytokines as well as the activation of the coagulation and the complement system. Additionally, the release of intracellular calcium is impaired and mitochondrial cell respiration is altered resulting in reduced contractility. Despite these findings in recent literature, a specific therapy of these cellular dysfunctions is so far not yet available. Patients should be treated according to both the procedures outlined by the Surviving Sepsis Campaign (especially with the early application of anti-infective therapy), and against acute heart failure, with the goal of normokinesia. Further studies are warranted to investigate the underlying mechanisms in more detail and potentially provide specific and targeted therapeutic approaches which would be of high clinical importance.

Kernaussagen

Sepsis und septischer Schock

• Die Sepsis ist eine häufige Erkrankung, die nach wie vor mit einer hohen Mortalität assoziiert ist.

• Der septische Schock ist die häufigste Schockform und geht nicht selten mit akuten Organdysfunktionen, u. a. auch des Herz-Kreislauf-Systems, einher.

Septische Kardiomyopathie

• Bei der septischen Kardiomyopathie nimmt der periphere vaskuläre Widerstand durch Vasoplegie ab. Außerdem ist eine akute rechts- und/oder linksventrikuläre Funktionseinschränkung mit Abnahme der Kontraktilität zu beobachten.

• Die Diagnose der septischen Kardiomyopathie wird häufiger gestellt, seitdem die transthorakale Echokardiografie zunehmend bettseitig verfügbar ist.

• Eine genaue Aussage über die Prognose ist bei der Komplexität des Krankheitsbildes kaum möglich, es ist jedoch davon auszugehen, dass sich Abweichungen von der normokinetischen Arbeit des Herzens negativ auswirken.

• Die zugrunde liegenden pathophysiologische Mechanismen sind bisher nicht abschließend geklärt. Infektive Toxine binden über Toll-like-Rezeptoren an Makrophagen, Endothelzellen und Kardiomyozyten selbst und vermitteln neben einer Zytokinfreisetzung (u. a. TNF-α, NFκB und Interleukin-1β) eine Aktivierung des Gerinnungs- und Komplementsystems (mit Koagulopathie und Apoptose) und eine verminderte intrazelluläre Kalziumfreisetzung sowie mitochondriale Modifikationen der Zellatmung. Über diese Mechanismen erklärt sich die akut eingeschränkte myokardiale Kontraktilität. Aus diesen Erkenntnissen der Studien der letzten Jahre konnten Hinweise auf den Vorteil einer Herzfrequenzmodulation nachgewiesen werden.

• Neben der Sepsis-Therapie der Surviving Sepsis Campaign (rasche Einleitung einer kausalen antibiotischen Therapie und supportiver Maßnahmen) könnten Ansätze der Herzinsuffizienztherapie (Betablocker, Kalzium-Sensitizer wie Levosimendan und neue Substanzgruppen wie I_f-Kanalblocker, z. B. Ivabradin, oder Myosin-Aktivatoren wie Omecamtiv) mit dem Ziel, normokinetische Zustände herzustellen, zum Einsatz kommen.

• Weitere Studien zur genaueren Aufdeckung der Pathophysiologie sowie das Ableiten kausaler, gezielter Therapieansätze der septischen Kardiomyopathie sind notwendig, um langfristig die Mortalität zu senken.

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