Arginin-Vasopressin im septischen und vasodilatatorischen Schock

Zusammenfassung

Die derzeitige Therapie des septischen/vasodilatorischen Kreislaufversagens umfasst die Volumentherapie sowie die Infusion inotroper und vasoaktiver Substanzen. Noradrenalin ist dabei das Vasokonstringens der ersten Wahl und führt bei den meisten Patienten zu einer Stabilisierung des Schockzustandes. Dennoch stellt das irreversible Kreislaufversagen, bei dem die konventionelle hämodynamische Therapie versagt, die häufigste Todesursachen von Patienten mit schwerer Sepsis und septischem Schock dar. Bei solchen fortgeschrittenen, Katecholamin-refraktären Schockzuständen führte Arginin-Vasopressin (AVP) wiederholt zu einem Anstieg des mittleren arteriellen Blutdrucks, einer Reduktion toxisch-hoher Noradrenalin Dosen sowie zu weiteren positiven hämodynamischen, endokrinologischen und renalen Veränderungen. Obwohl AVP in früheren klinischen Untersuchungen und in einzelnen Tieruntersuchungen negative inotrope Effekte hatte, führt eine kontinuierliche niedrig-dosierte AVP-Infusion bei Patienten mit fortgeschrittenem septischen/vasodilatorischen Schock nur bei hyperdynamen Kreislaufverhältnissen zu einem Abfall des Cardiac Index. Negative Auswirkungen auf die Darmzirkulation und die systemische Mikrozirkulation können nicht ausgeschlossen werden, wurden allerdings in der klinischen Praxis noch nicht an einem grossen Kollektiv in einer prospektiven Studie bestätigt. Nebenwirkungen einer zusätzlichen AVP Therapie im septischen/vasodilatorischen Schock sind ein Anstieg des Gesamtbilirubins, sowie ein Abfall der Thrombozytenzahlen. Ein vorübergehender Anstieg der hepatischen Transaminasen unter AVP Therapie ist wahrscheinlich meist in Zusammenhang mit vorausgehenden hypotensiven Episoden zu bringen. Wichtige Punkte, die bei der Anwendung von AVP als "rescue vasopressor" im septischen/vasodilatorischen Schock beachtet werden müssen, sind: 1) Infusion von AVP nur in fortgeschrittenen Schockzuständen, bei denen eine konventionelle Therapie nicht zur Kreislaufstabilisierung ausreicht (z.B. Noradrenalin-Dosierungen >0,5-0,6 μg/kg/min), 2) Sicherstellung einer Normovolämie, 3) Infusion von AVP ausschliesslich in Kombination mit Noradrenalin, 4) strikte Vermeidung von Bolusinjektionen sowie Steigerungen der kontinuierlichen Dosierungen >4 IU/h. Die Auswirkungen einer zusätzlichen AVP Therapie auf die Mortalität im fortgeschrittenen septischen/vasodilatorischen Schock wird derzeit in einer grossen Multicenter Studie in Nordamerika und Australien untersucht.

Abstract

Current therapy of septic/vasodilatory cardiovascular failure includes volume resuscitation and infusion of inotropic and vasopressor agents. Norepinephrine is the first-line vasoconstrictor, and can stabilize hemodynamic variables in most patients. Nontheless, irreversible cardiovascular failure which is resistant to conventional hemodynamic therapies still is the main cause of death in patients with severe sepsis and septic shock. In such advanced, catecholamine-resistant shock states, arginine-vasopressin (AVP) has repeatedly caused an increase in mean arterial blood pressure, a decrease in toxic norepinephrine-dosages, as well as further beneficial hemodynamic, endocrinologic and renal effects. Although AVP exerted negative inotropic effects in previous clinical trials and in selected animal experiments, a continuous low-dose AVP infusion during advanced septic/vasodilatory shock caused a decrease in cardiac index only in patients with a hyperdynamic circulation. Adverse effects on gastrointestinal circulation and the systemic microcirculation can not be excluded, but have not yet been confirmed in clinical prospective trials. Negative side effects of a supplementary AVP therapy are an increase in total bilirubin concentrations, and a decrease in platelet count. A transient increase in hepatic transaminases during AVP infusion is most likely related to preceding hypotensive episodes. Important points which must be considered when using AVP as a "rescue vasopressor" in septic/vasodilatory shock states are: 1) AVP infusion only in advanced shock states that can not be adequately reversed by conventional hemodynamic therapy (e.g. norepinephrine >0,5-0,6 μg/kg/min), 2) presence of normovolemia, 3) AVP infusion only in combination with norepinephrine, 4) strict avoidance of bolus injections and dosages >4 IU/h. Effects of a supplementary AVP infusion in advanced vasodilatory shock on survival are currently examined in a large, prospective multicenter trial in North America and Australia.

Schlüsselwörter

arginin vasopressin - septischer schock - vasodilatorischer schock - noradrenalin - nebenwirkungen

Key words

arginine vasopressin - septic shock - vasodilatory shock - norepinephrine - side effects

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