Neues bei der Therapie intrazerebraler Blutungen

Zusammenfassung

Seit Veröffentlichung der DGN-Leitlinie zur Behandlung intrazerebraler Blutungen (ICB) im Jahr 2012 und der ESO-Leitlinie im Oktober 2014 sind einige neue Studien publiziert worden. Wir fassen hier die wesentlichen Ergebnisse dieser Untersuchungen zusammen, diskutieren die Konsequenzen für die zukünftige Therapie und mögliche Implikationen für weitere klinische Studien. Übergeordnetes Ziel ist es, im Rahmen der Behandlung von intrazerebralen Blutungen eine Nachblutung und sekundäre Hirnschädigungen zu vermeiden. Bei Patienten mit spontaner ICB wird die Sterblichkeit und Behinderung durch die Behandlung auf einer Stroke Unit (im Vergleich mit nicht spezialisierten Einheiten) gesenkt. Die 3 großen Blutdruckstudien (ATACH, INTERACT, INTERACT-II) konnten aufzeigen, dass eine Senkung des systolischen Blutdrucks unter 140 mmHg (innerhalb einer Stunde) bei akuter ICB (innerhalb von 6 Stunden nach Symptombeginn) nicht mit einer erhöhten Sterblichkeit oder Morbidität einhergeht und deshalb als sicher eingestuft werden kann.

Nach der STICH-1- und STICH-2-Studie kann die chirurgische Evakuation von ICB nicht als Routinemaßnahme empfohlen werden. Lediglich bei Patienten mit einem Glasgow Coma Scale Score von 9–12 könnte eine frühe Operation unter bestimmten Bedingungen sinnvoll sein. Bei begleitendem akutem obstruktiven Hydrocephalus sollte (bei supra- und infratentorieller ICB) die Anlage einer externen Ventrikeldrainage (EVD) erfolgen. Die Frage, ob die Kombination einer EVD und intrathekaler Thrombolyse einen klinischen Nutzen hat, wird gegenwärtig in der CLEAR-III-Studie prospektiv untersucht. Bei der Entfernung der EVD sollte die vorübergehende Anwendung einer lumbalen Drainage erwogen werden, die zu einer Reduktion der Shunt-Anlage und einem besseren klinischen Ergebnis führen kann. Die CLOTS-3-Studie zeigte, dass intermittierende pneumatische Kompressionsstrümpfe zur Thrombose-Prophylaxe bei Schlaganfall wirksam sind und insbesondere Patienten mit ICB davon profitieren.

Zur Behandlung von Antikoagulantien assoziierten ICB liegen 2 kürzlich veröffentlichte große retrospektive multizentrische Studien vor. Erstmals konnten Zielwerte zur schnellen und suffizienten Normalisierung der Gerinnung (INR<1,3 innerhalb 4 Stunden) identifiziert werden, welche mit einer reduzierten Rate an Nachblutungen assoziiert waren. Unklar bleibt allerdings, mit welchem Agens dies am besten erreicht werden kann. Weiterhin unklar bleibt ob, wie und ggfs. wann eine erneute Antikoagulation wieder aufgenommen werden soll. Im Folgenden wollen wir in diesem Zusammenhang auch auf die direkten nicht Vitamin-K-OAK (NOAC) eingehen und den aktuellen Stand zu den Antidots vorstellen.

Abstract

Since the DGN guidelines for ICH in 2012 and the ESO guidelines in October 2014 became available, various clinical trials supporting available data have been published. The results of these trials are summarized and the consequences for future treatment and clinical trials are discussed. The paramount aim in the treatment of ICH is to prevent hematoma expansion and to avoid secondary brain damage. Acute stroke unit care reduces death and dependency for patients with ICH in comparison with care in a general ward. The three blood-pressure trials (ATACH, INTERACT, INTERACT-II) demonstrated that in acute ICH, intensive blood pressure reduction (systolic target<140 mmHg in<1 h) within 6 h of onset is safe. Following the results of STICH 1 and 2 trials, there is no evidence to support routine surgical intervention to improve outcome after supratentorial ICH in comparison with conservative management, but early surgery may be beneficial for patients with a GCS score 9–12. In case of associated obstructive hydrocephalus in patients with supra- and infratentorial ICH, it seems reasonable to apply an external ventricular drain (EVD). The ongoing RCT CLEAR III investigates if the combination of EVD with intraventricular thrombolysis compared with EVD with placebo improves outcome. Before removal of EVD, a transient use of a lumbar drainage should be considered, in order to reduce the need for shunt surgery and improve outcome. The CLOTS-3 trial showed that intermittent pneumatic compression is useful for the prevention of proximal deep vein thrombosis in stroke patients, and that patients with ICH seem to benefit at least as much as patients with ischemic stroke. Recently, 2 large retrospective multicenter trials on treatment of ICH associated with oral anticoagulation were published. For the first time, INR values for fast and sufficient INR reversal (< 1.3 within 4 h) could be identified and were associated with lower rates of hematoma enlargement. It remains unclear which agent is best to reach this aim. Furthermore, it is not clear how and when re-anticoagulation should be performed. In this context, we address to the non-vitamin K oral anticoagulants (NOAC) and present the current status of the NOAC antidotes.

Schlüsselwörter

intrazerebrale Blutungen - Blutungsprogression - chirurgische Interventionen - Thromboseprophylaxe - Antikoagulanzien

Keywords

intracerebral hemorrhage - hematoma expansion - surgical interventions - thrombosis prevention - anticoagulants

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