Fentanyl Plasma Concentrations after Application of a Transdermal Patch in Three Different Locations to Refine Postoperative Pain Management in Rabbits.

Valentina Mirschberger,Anja Heider,Helene Rohrbach,Christian Von Deimling,Claudia Spadavecchia,Stephan Zeiter

doi:10.3390/ani10101778

Valentina Mirschberger, Anja Heider + Show 4 more

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https://doi.org/10.3390/ani10101778

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Abstract

Simple SummaryFentanyl patches offer “stress free” postoperative pain management in rabbits. It has been shown that fentanyl uptake is dependent on exogenous and endogenous factors of the area where the patch is applied. The purpose of the study was to investigate three different locations (neck, inner and outer surface of the ear) to obtain reliable fentanyl plasma concentrations above those previously shown to be analgesic. The fentanyl plasma concentration was measured at several time points after patch application. In addition, the practicability of the proposed methods was evaluated. The group with application on the neck had the fastest uptake and equal to or over the analgesic plasma concentration for up to 72 h. The outer surface of the ear had slightly slower uptake and shorter analgesic duration whereas fentanyl uptake at the inner surface of the ear was insufficient to provide plasma analgesic concentration. The preparation of the neck proved to be the most laborious because of the thin and dense fur and the removal of the patch resulted in erythema. In conclusion, depending on how long potent analgesia is required, either the neck or the outer surface of the ear are suitable for patch application enabling “stress free” and reliable postoperative analgesia in rabbits.Transdermal patches allow a noninvasive and “stress free” analgesia in rabbits. As fentanyl uptake is dependent on exogenous and endogenous factors of the area where the patch is applied, this study investigated three different locations (neck, inner and outer surfaces of the ear) for fentanyl patch application to provide adequate and reliable fentanyl plasma concentrations above those previously shown to be analgesic. Fentanyl plasma concentration was measured at different time points (3, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120 h) and rabbits were assessed for their general conditions and treatment-related side effects. Practicability of the proposed methods was evaluated. Following patch application on the neck, fentanyl plasma concentrations equal to or above the analgesic value were measured in all rabbits between 6 and 72 h. Comparable concentrations were reached between 9 and 48 h in all animals for the outer ear surface. However, for the inner ear surface, analgesic concentrations were not reached, even if practicability was considered the best for this location. Preparation of the neck skin was judged as the most cumbersome due to the clipping of the dense fur and patch removal resulted in erythema. In summary, the application of the fentanyl patch on the neck and outer ear surface allowed the reach of reliable plasma concentrations above the analgesic threshold in rabbits. When applied on the neck, fentanyl patches provided the longest duration of analgesic plasma concentrations, whereas patch application and removal were easier on the outer ear surface.

Highlights

Rabbits are commonly used as animal models in biomedical research, e.g., orthopedic studies concerning bone healing, cartilage repair and infection studies [1,2,3]
One rabbit was excluded from the study and subsequently replaced due to CNS symptoms occurring application
The aim of the study was to determine fentanyl plasma concentrations in rabbits from patches applied at three different locations with the final aim to refine analgesia

Summary

Introduction

Rabbits are commonly used as animal models in biomedical research, e.g., orthopedic studies concerning bone healing, cartilage repair and infection studies [1,2,3]. In these experimental studies, the animals often undergo invasive surgeries which require systemic analgesia for several days. The administration of systemic analgesia in invasive experimental studies involving rabbits increased significantly from 16% (1995–997) to 50% (2005–2007) [4,5]. Despite improvement in the last 20 years it is reported that pain management is still inadequate for pet rabbits [6]. The most commonly used drug was buprenorphine as the first-line therapy over this period [4]

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