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Hintergrund und aktueller Einsatz von Adjuvanzien für die Regionalanästhesie

Aus der Forschung in die evidenzbasierte Patientenversorgung

Background and current use of adjuvants for regional anesthesia

From research to evidence-based patient treatment

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Zusammenfassung

Die Entdeckung der lokalanästhetischen Wirkung durch Blockade der Natriumionenkanäle war ein Meilenstein in der Anästhesie, die jedoch schon bald ihre Limitierung durch z. T. lebensbedrohliche toxische Wirkungen der Lokalanästhetika (LA) erfuhr. Durch Entwicklung neuartiger LA, aber auch durch Hinzunahme sog. Adjuvanzien wurde versucht, diese lebensbedrohlichen Wirkungen einzuschränken. Der vorliegende Beitrag hat zum Ziel, Hintergrund und aktuellen Stand der Anwendung dieser Adjuvanzien zur Regionalanästhesie zu betrachten. Durch Zusatz von Adrenalin, Clonidin oder Dexmedetomidin – jedoch nur als einmalige Gabe – kommt es zu einer schnelleren Anschlagzeit, einer längeren Wirkdauer und einer intensiveren neuronalen Blockade der Regionalanästhesie. Die Vorteile einer zusätzlichen Gabe von Natriumbikarbonat sind dagegen relativ gering und klinisch eher vernachlässigbar. Obwohl in der Literatur Belege für eine Verbesserung und Verlängerung der analgetischen Wirkung nach axonaler Gabe von Opioiden gefunden werden, sind zentrale Nebenwirkungen und eine systemische Wirkung nicht sicher ausgeschlossen. Die z. T. vorkommenden lokalanästhetischen Wirkungen der Opioide sind nicht immer klar abgrenzbar von den opioidrezeptorspezifischen Wirkungen. Mechanistische Untersuchungen postulieren eine funktionelle Kopplung von Opioidrezeptoren eher nach Störungen der axonalen Integrität des Nerven, nicht jedoch im intakten peripheren Nerv. Neuere Untersuchungen identifizieren Glukokortikoid- und Mineralokortikoidrezeptoren bevorzugt auf peripheren schmerzleitenden Nervenfasern. Dies geht einher mit zahlreichen klinischen Berichten einer deutlichen Verlängerung der lokalanästhetischen Wirkung. Neben bekannten genomischen Effekten, die sich über eine Änderung der Genexpression schmerzunterhaltender Proteinstrukturen ergeben, werden auch immer mehr schnell einsetzende, nichtgenomische Wirkungen der Steroide diskutiert, denen eine Veränderung intrazellulärer Signalwege zugrunde liegt. Zusammenfassend stehen dem Anästhesisten neue Erkenntnisse und Ergebnisse klinischer Studien zur Adjuvanzienapplikation im Rahmen der Regionalanästhesie zur Verfügung, die in der Bewertung ihres möglichen Einsatzes zur Schmerztherapie eines jeden individuellen Patienten Berücksichtigung finden sollten.

Abstract

The discovery of the local anaesthetic effect by blocking sodium ion channels was a milestone in anaesthesia but was soon limited by sometimes life-threatening toxic effects of the local anaesthetics. By developing novel local anaesthetics and also by adding so-called adjuvants, attempts have been made to limit these life-threatening events. This article focuses on the historic background and the current state of the use of these adjuvants for regional anaesthesia. Adding epinephrine, clonidine or dexmedetomidine, but only as a single dose, results in a faster onset, longer duration of action and increased intensity of neuronal blockade of regional anaesthesia. The benefits of adding sodium bicarbonate, on the other hand, are relatively minor and, therefore, clinically negligible. Although increasing evidence in the literature suggests an improvement and prolongation of the analgesic effect after axonal administration of opioids, which can also be given continuously, systemic effects are not fully ruled out due to the increased incidence of central side effects. The partial local anaesthetic effects of opioids cannot always be distinguished from opioid receptor-specific effects. Mechanistic studies postulate a functional coupling of opioid receptors in injured rather than in intact peripheral nerves. Recent studies have identified glucocorticoid and mineralocorticoid receptors predominantly on peripheral nociceptive nerve fibers. This is consistent with numerous clinical reports of a marked prolongation of the local anaesthetic effect. In addition to the known genomic effects of steroids that occur via a change in gene expression of pain-sustaining protein structures, faster non-genomic effects are also discussed, which occur via a change in intracellular signaling pathways. In summary, new insights into mechanisms and novel results from clinical trials will help the anaesthesiologist in the decision to use adjuvants for regional anaesthesia which, however, requires to weigh the individual patient’s benefits against the risks.

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  1. Klinik für Anästhesiologie mit S. op. Intensivmedizin, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland

    M. Schäfer, S. A. Mousa, M. Shaqura & S. Tafelski

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  1. M. Schäfer
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  2. S. A. Mousa
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  3. M. Shaqura
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  4. S. Tafelski
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Correspondence to M. Schäfer.

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M. Schäfer, S.A. Mousa, M. Shaqura und S. Tafelski geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag nimmt Bezug auf Studien, die an Tieren und an Patienten vorgenommen wurden. Für beides gab es ethische Einwilligungen über die entsprechenden autorisierten Gremien (Tierschutzbehörden und Ethikkommissionen). Abb. 1–4 zeigen immunhistochemische Anfärbungen von tierischen Gewebeschnitten.

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Schäfer, M., Mousa, S.A., Shaqura, M. et al. Hintergrund und aktueller Einsatz von Adjuvanzien für die Regionalanästhesie. Anaesthesist 68, 3–14 (2019). https://doi.org/10.1007/s00101-018-0522-6

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  • DOI: https://doi.org/10.1007/s00101-018-0522-6

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