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Sidney Lanteigne
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Sidney LanteigneAdministrator
Asked: November 22, 20222022-11-22T20:25:01+00:00 2022-11-22T20:25:01+00:00

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  • 2

Ketamin

Der Wirkstoff Ketamin ist ein Narkose- und Schmerzmittel, das aktuell wegen seiner sehr schnell eintretenden antidepressiven Wirkung an Bedeutung gewonnen hat. In dieser Indikation ist sein Enantiomer Esketamin der erste Arzneistoff mit neuem Wirkmechanismus.

Ketamin: Übersicht

Anwendung
Wirkmechanismus
Dosierung
Nebenwirkungen
Wechselwirkungen
Kontraindikation
Schwangerschaft/Stillzeit
Verkehrstüchtigkeit
ATC Code
  • N01AX03 – Ketamin
Ketamin

Anwendung

Ketamin besitzt folgende Indikationen:

  • Einleitung und Durchführung einer Allgemeinanästhesie ggf. in Kombination mit Hypnotika
  • Supplementierung bei Regionalanästhesien
  • Anästhesie und Analgesie in der Notfallmedizin
  • Behandlung des therapieresistenten Status asthmaticus
  • Analgesie bei intubierten Patienten

In den USA steht Patienten esketaminhaltiges Nasenspray (Spravato™) gegen therapieresistente Depressionen zur Verfügung (Esketamin ist das (S)-Enantiomer von Ketamin). Im Gegensatz zu klassischen Antidepressiva tritt der antidepressive Effekt bereits innerhalb weniger Tage ein, so dass der Wirkstoff auch bei akuten Schüben geeignet ist.

Anwendungsart

Der Wirkstoff Ketamin ist als Injektionslösung auf dem deutschen Markt verfügbar. In den USA ist Esketamin als Nasenspray zugelassen.

Wirkmechanismus

Ketamin ist ein chiraler Wirkstoff, der nicht kompetitiv antagonistisch an glutamatergen NMDA-Rezeptoren wirkt.

In Konzentrationen innerhalb des klinischen Dosisbereichs beeinflusst Ketamin eine Vielzahl von zellulären Prozessen:

  • Blockade von NMDA-Kanälen
  • Blockade von hyperpolarisationsaktivierten zyklischen Nukleotidkanälen (HCN1)
  • Blockade von nikotinischen Acetylcholin-Ionenkanälen
  • Delta-und Mu-Opioid-Agonismus und Opioid-Potenzierung
  • Cyclisches Guanosinmonophosphat-System (cGMP)
  • AMPA-Rezeptoren
  • Metabotrope Glutamatrezeptoren (mGluR)
  • Reduktion der cholinergen Neuromodulation
  • Erhöhte Freisetzung aminerger Neuromodulatoren (Dopamin und Noradrenalin), Neurosteroide, L-Typ-Ca2+-Kanäle

Neben der bekannten NMDA-Blockade hat Ketamin Einfluss auf eine Vielzahl von intrazellulären neuronalen Prozessen. Die hypnotischen Effekte beruhen vermutlich auf einer Kombination der sofortigen Kanalblockade von NMDA- und HCN1-Kanälen. Im Gegensatz dazu resultieren die anhaltenden antidepressiven Wirkungen wahrscheinlich aus nachgeschalteten Effekten – wie etwa einer aktivitätsbedingten Zunahme der strukturellen synaptischen Konnektivität. Die analgetischen Wirkungen von Ketamin scheinen sowohl eine kurzfristige als auch eine langfristige Beeinflussung der Zellfunktion zu sein. Wahrscheinlich werden seine unmittelbaren analgetischen Wirkungen vorwiegend durch eine Kombination aus Opioidsensibilisierung und aminerger Nozizeption vermittelt, wohingegen die Hemmung von neuropathischem Schmerz auf einer Kombination von sofortiger rezeptorvermittelter Wirkung und Initiierung länger anhaltender Zellsignalkaskaden beruht.

Antidepressive Wirkung

Es wird postuliert, dass Ketamin in niedrigen Dosen die Glutamat-Neurotransmission durch Zunahme der Glutamat-Freisetzung und der AMPA-Rezeptorexpression erhöht. Dies führt zu einer sekundär erhöhten BDNF-Freisetzung und damit zu einer Aktivierung von mTOR. Über einen komplexen Signalweg kommt es dann zu einer erhöhten synaptischen Proteinexpression (GluR1) sowie Insertion und Dichte von Synapsen, was zu einer erhöhten strukturellen Konnektivität zwischen Neuronen -insbesondere im präfrontalen Kortex- führt.

Dosierung

Allgemeinanästhesie

Zur Einleitung werden i. v. 1 – 2 mg Ketamin/kg KG bzw. i. m. 4 – 8 mg Ketamin/kg KG appliziert; zur Aufrechterhaltung der Narkose wird im Allgemeinen alle 10 – 15 Minuten die halbe Initialdosis bei Bedarf nachinjiziert.

Dauerinfusion

Alternativ kann Ketamin als Dauerinfusion in einer Dosierung von 1 – 6 mg Ketamin/kg KG und Stunde verabreicht werden. Bei Polytrauma und Patienten in schlechtem Allgemeinzustand ist eine Dosisreduktion erforderlich.

Supplementierung einer Regionalanästhesie

Zur Supplementierung einer Regionalanästhesie werden nach Bedarf 0,25 – 0,5 mg Ketamin/kg KG appliziert.

Anästhesie in der Notfallmedizin

Zur Anästhesie in der Notfallmedizin werden i. v. 0,25 – 0,5 mg Ketamin/kg KG bzw. i. m. 0,5 – 1,0 mg Ketamin/kg KG appliziert.

Therapieresistenter Status asthmaticus

Zur Behandlung des therapieresistenten Status asthmaticus werden i. v. 1 – 2 mg Ketamin/kg KG, bei Bedarf bis 5 mg Ketamin/kg KG appliziert.

Analgesie bei intubierten Intensivpatienten

Für die Analgesie bei intubierten Intensivpatienten werden im Allgemeinen 0,5 mg Ketamin/kg KG als Bolus mit einer anschließenden Dauerinfusion von 0,4 – 1,0(-3,0) mg Ketamin/kg KG und Stunde bei gleichzeitiger Anwendung eines Benzodiazepins appliziert. Eine Behandlungsdauer von 4 – 6 Wochen sollte nicht überschritten werden.

Nebenwirkungen

Sehr häufig (≥ 1/10) treten unter der Anwendung mit Ketamin folgende Nebenwirkungen auf:

  • Aufwachreaktionen, z. B. lebhafte Träume, inklusive Albträume, Schwindel und motorische Unruhe
  •  Anstieg des Blutdrucks und der Herzfrequenz (Ein Anstieg von 20 % über den Ausgangswert ist häufig).

Wechselwirkungen

Für die Anwendung von Ketamin bestehen folgende Wechselwirkungen:

  • Hypnotika, speziell Benzodiazepine oder Neuroleptika ► Verlängerung der Wirkdauer, aber auch Abschwächung der Nebenwirkungen
  • Aminophyllin ► Absenkung der Krampfschwelle
  • Schilddrüsenhormone sowie direkt oder indirekt wirkenden Sympathomimetika ► Auftreten einer arteriellen Hypertonie und einer Tachykardie
  • Nichtdepolarisierender Muskelrelaxantien ► Wirkung kann verlängert sein.
  • Halothan ► Die anästhetische Wirkung von Halothan wird verstärkt, so dass niedrigere Halothan-Dosen ausreichend sein können. Bei gleichzeitiger Anwendung von Ketamin und Halothan kann sich das Risiko erhöhen, durch die zusätzliche Gabe von Epinephrin Herzrhythmusstörungen auszulösen.

Kontraindikation

Ketamin darf nicht angewendet werden bei:

  • Überempfindlichkeit gegen Ketamin
  • Schlecht eingestelltem oder nicht behandeltem Bluthochdruck (arterielle Hypertonie – systolischer/diastolischer Blutdruck über 180/100 mmHg in Ruhe).
  • Präeklampsie und Eklampsie
  • Nicht oder ungenügend behandelter Hyperthyreose
  • Situationen, die einen muskelentspannten Uterus erfordern, z. B. drohende Uterusruptur, Nabelschnurvorfall

Schwangerschaft/Stillzeit

Tierexperimentelle Studien haben Hinweise auf eine Reproduktionstoxizität gezeigt. Über eine Anwendung in der Schwangerschaft und Stillzeit liegen bisher keine ausreichenden Erfahrungen vor. Ketamin sollte daher in den ersten 3 Monaten der Schwangerschaft und in der Stillzeit nicht angewendet werden.

Da Ketamin die Plazenta passiert, muss bei Dosen von mehr als 2 mg/kg KG i. v. mit einer Atemdepression des Neugeborenen gerechnet werden. Zum Übergang von Ketamin in die Muttermilch existieren keine Daten.

Verkehrstüchtigkeit

Verkehrstüchtigkeit und Bedienen von Maschinen

Mindestens 12 Stunden nach einer Narkose mit Ketamin darf der Patient nicht aktiv am Straßenverkehr teilnehmen, eine Maschine bedienen oder ohne sicheren Halt arbeiten. Der Patient sollte sich nur in Begleitung nach Hause begeben und keinen Alkohol zu sich nehmen.

Weitere Informationen sind der jeweiligen Fachinformation zu entnehmen.

Wirkstoff-Informationen

Molare Masse:
237.73 g·mol-1
Mittlere Halbwertszeit:
ca. 3.0 H
Q0-Wert:
1.0
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