Wirkmechanismen der vasokonstriktiven Therapie der Ösophagusvarizenblutung

Zusammenfassung

Die Ösophagusvarizenblutung ist ein akuter Notfall mit hoher Sterblichkeitsrate, bei dem die schnelle Therapie mit einem vasokonstriktiven Medikament Leben retten kann, wenn die Expertise erfahrener Endoskopiker nicht sofort verfügbar ist. Vasokonstriktive Medikamente wie Terlipressin, Vasopressin, Somatostatin oder Octreotid sind nicht nur als Erstmaßnahme geeignet, sondern erhöhen als adjuvante Therapie die Erfolgsaussichten endoskopischer Maßnahmen. Als Arzneimittel behördlich zugelassen für diese Indikation sind nur die Wirkstoffe Terlipressin und Vasopressin, wobei Terlipressin wegen seiner besseren Wirksamkeit und Verträglichkeit zu bevorzugen ist. Während der Wirkmechanismus von Terlipressin auf die Blutstillung und auf die gestörten Kreislaufverhältnisse bekannt ist, sind die Wirkmechanismen von Somatostatin und Octreotid bislang unklar. Auch hat sich die Wirksamkeit von Somatostatin und Octreotid gegenüber Plazebo weniger deutlich ergeben als die von Terlipressin. Terlipressin kontrahiert die dilatierten splanchnischen Blutgefäße, so dass weniger Blut in die Portalvene fließt. Damit reduziert sich der portalvenöse Druck, die portokavalen Umgehungskreisläufe werden entlastet, der Druck in den Varizen wird reduziert und die Blutung wird gestillt. Zusätzlich korrigiert Terlipressin die zentrale und arterielle Hypovolämie und dämpft die erhöhte Aktivierung des Renin-Angiotensin-Aldosteron-Systems und des sympathischen Nervensystems. Konsequenzen sind die Entlastung des Herzens, eine bessere Durchblutung der Organe - Leber und Nieren eingeschlossen - sowie eine Verbesserung der hyperdynamen Kreislaufsituation und eine Erhöhung der Überlebensrate.

Abstract

Variceal bleeding is one of the most dramatic complications in gastroenterology and has a high mortality rate. Early treatment with vasoactive drugs can save lives when skilled endoscopists are not immediately available. Vasoactive drugs like terlipressin, somatostatin or octreotide are not only indicated as first-choice emergency treatment, but they also increase the success rate of endoscopic treatments. Whereas the efficacy and mechanisms of action of terlipressin to arrest haemorrhage and to improve the disturbed cardiovascular situation of cirrhotic patients, including those with hepatorenal syndrome, are well documented, the efficacy and mechanisms of action of somatostatin and octreotide remain unclear and uncertain. On account of its vasoconstrictive effects on the dilated splanchnic blood vessels, terlipressin reduces blood flow into the portal vein and, thus, reduces portal venous pressure and blood flow through porto-systemic shunts. As a consequence, variceal bleeding is arrested, central and arterial hypovolaemia is corrected, and activation of the renin-angiotensin-aldosterone system as well as the sympathetic nervous system is reduced, leading to lower intrahepatic and intrarenal resistance. The result is an improvement of organ perfusion - including perfusion of the kidneys and the liver - as well as an improvement of the hyperdynamic cardiovascular situation and a better survival rate. Whereas terlipressin has been shown to stimulate kidney function and to prolong survival time in patients with bleeding esophageal varices as well as those with hepatorenal syndrome, no such promising effects were observed with somatostatin or octreotide.

Schlüsselwörter

Hepatorenales Syndrom - hyperdynamer Blutkreislauf - Leberzirrhose - Octreotid - Ösophagusvarizenblutung - pharmakologische Wirkmechanismen - portale Hypertonie - Somatostatin - Terlipressin - zentrale Hypovolämie

Key words

Central hypovolaemia - hepatorenal syndrome - hyperdynamic circulation - liver cirrhosis - octreotide - esophageal varices bleeding - pharmacological mechanisms - portal hypertension - somatostatin - terlipressin

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