Einfluss von Morphin, Butorphanol und Levomethadon in unterschiedlicher Dosierung auf den thermischen nozizeptiven Schwellenwert bei Pferden

 

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Zusammenfassung

Gegenstand und Ziel: In der Pferdemedizin stehen verschiedene Opioide zur Behandlung von Schmerzen zur Verfügung. Es gibt jedoch wenig Information zu einem direkten Vergleich der analgetischen Effektivität, Wirkdauer und Nebenwirkungen der einzelnen Substanzen. Ziel dieser Studie war die Evaluierung gebräuchlicher Dosierungen von Morphin, Butorphanol und Levomethadon sowie die Evaluierung der analgetischen Effektivität dieser Opioide in einer höheren Dosierung mithilfe der Thermostimulation beim Pferd. Material und Methoden: Bei den Probanden handelte es sich um acht klinisch allgemeingesunde Tiere. Es wurde ein thermischer Reiz gesetzt und eine zuvor definierte Abwehrreaktion des Pferdes als Endpunkt gewertet. Nach Bestimmung von Nullwerten erhielten alle Pferde in einem randomisierten „Cross-over“-Studiendesign ein Plazebo (P = isotone Kochsalzlösung) sowie in jeweils zwei Dosierungen Morphin (M_{0,1 =} 0,1 mg/kg; M_0,2 = 0,2 mg/kg), Butorphanol (B_0,1 = 0,1 mg/kg; B_0,2 = 0,2 mg/kg) und Levomethadon (L_0,1 = 0,1 mg/kg; L_0,2 = 0,2 mg/kg) mit 14-tägiger Auswaschzeit. Die Messungen erfolgten nach 10, 30, 60, 90, 120, 180, 240, 300, 360, 420, 540 und 1350 Minuten. Neben dem thermischen Schwellenwert wurden Verhalten und Darmmotorik überprüft. Ergebnisse: Zu signifikant erhöhten Schwellenwerten kam es in den Gruppen M_0,2 (240 min), B_0,1 (90 min), B_0,2 (90 min), L_0,1 (60 min) und L_0,2 (300 min). Verhaltensänderungen in Form von Drangwandern, Lippenspiel, Kopfzucken, erhöhtem Muskeltonus, Zittern, Ataxie oder Leerkauen traten auf. Ferner kam es in allen Gruppen zu einer Reduzierung der Darmgeräusche und einem verzögerten Kotabsatz. Schlussfolgerung und klinische Relevanz: Levomethadon führte dosisabhängig zu einer lang anhaltenden Analgesie, während mit Butorphanol keine Verstärkung der Analgesie in der höheren Dosierung zu erreichen war. Ein Ceiling-Effekt liegt hier nahe. Morphin hatte nur in der hohen Dosis einen nachweisbaren analgetischen Effekt. Weitere Studien sind notwendig, um für den Einsatz von Levomethadon und Morphin beim Pferd eine fundierte Dosisempfehlung zu erarbeiten.

Summary

Objective: Various opioids are available for use in equine medicine. Studies directly comparing their analgesic effects and side effects are rare. Therefore, the aim of this study was to compare the antinociceptive effect and the duration of analgesia of two different doses of morphine, butorphanol and levomethadone in horses. Material and methods: Eight adult, healthy horses were used for this randomized, placebo-controlled, blinded cross-over trail. Each horse received placebo (P = 0.9% saline) and morphine (M_0.1 = 0.1 mg/kg; M_0.2 = 0.2 mg/ kg), butorphanol (B_0.1 = 0.1 mg/kg; B_0.2 = 0.2 mg/kg) and levomethadone (L_0.1 = 0.1 mg/kg; L_0.2 = 0.2 mg/kg) in a low and a high dose and with a wash-out period of 14 days. Thermal thresholds were determined by incremental contact heat applied to the skin at the withers. Single stimulations were performed 15 minutes prior and 10, 30, 60, 90, 120, 180, 240, 300, 360, 420, 540 and 1350 minutes after treatment. Threshold values, gastrointestinal auscultation score and horses’ behavior were recorded. Data were analyzed with analysis of variance for repeated measurements (p < 0.05). Results: In group M_0.1, changes in thermal thresholds did not reach significance. Thermal threshold increased significantly in the groups M_0.2, B_0.1, B_0.2, L_0.1 and L_0.2 for 240, 90, 90, 60 and 300 minutes, respectively. Behavioural changes, increased locomotion and decreased bowel sounds as well as delayed time until defecation were noticed in all groups. Conclusions: Levomethadone induced a dose-dependent increase and prolongation of analgesia, whereas with butorphanol there was no difference between dosages regarding duration and intensity of analgesia. Morphine provided detectable analgesia only in the high dose of 0.2 mg/kg. Clinical relevance: Levomethadone and morphine in the low dose (0.1 mg/kg) produced only minor and short lived anti-nociception and further studies are necessary to give a profound dose recommendation for the use of these drugs in horses.

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