Abstract
Summary
Timing for the application and use of fentanyl patches for pre-emptive analgesia and sedation is crucial to obtain good clinical outcomes. Placement and timing is important to maximise clinical effect and apparent levels of analgesia.
Introduction
The use of sheep as preclinical models for the investigation of orthopaedic conditions is gaining momentum, the control of their pain is a significant ethical issue. The daily need for injecting non-steroidal anti-inflammatory drugs (NSAIDs) and/or the shorter acting opioids increases the demand for handling post-operatively which can increase animal distress and risk of human injury. NSAIDs can have a negative effect on bone healing, complicating results. Opioid analgesics have no impact on bone healing. Fentanyl patches have become another option for use in pain management. Pre-emptive analgesia helps reduce the demand on post-operative analgesic use. Fentanyl has the added benefit of producing mild sedation. This study evaluated the pharmacokinetics of fentanyl patches in sheep in an effort to maximise pre and post-surgical analgesia.
Methods
Eight sheep were divided into 2 groups of 4. Both groups had a 100µg/kg/hr fentanyl patch (Durogesic – Janssen, Sydney, Australia) applied to the clipped and cleaned skin of the antebrachium and were held in place with a light bandage. (A dose rate range of 1- 1.6µg/kg/hr was achieved). Group 1 had a second patch applied after 72 hours and group 2 had a second patch applied after 24 hours. Blood samples were taken at 0, 3, 6, 12, 24, 36, 48 and 72 hours post patch application. The blood was immediately spun down and the serum drawn off and frozen. Serum levels for fentanyl were measured using commercial ELISA kits and read using a spectrophotometer. Animal behaviour throughout the study was observed and recorded by trained staff (CC, JR).
Results
Six hours after the patch application, the sheep were relaxed and easily approachable. They stood calmly while blood was being drawn. This behaviour remained up to the 48 hour time point at which time cornering them in their pen became marginally more difficult, however they still stood calmly for the blood collection. By 72 hours, all sheep co-operation had dissipated. Peak blood levels of Fentanyl were reached by 12 hours post patch application. These levels were maintained with a relatively flat drug plateau for the prescribed 72 hours post application. No difference was found in the peak drug levels post application of the second patch between the two groups. There was no second higher peak in blood levels attained.
Discussion
This study quantified the drug absorption and elimination curves of fentanyl using a controlled application method in an effort to better apply and manage post-surgical analgesia in sheep used for orthopaedic studies. The results indicate that the application of fentanyl for pre-emptive surgical analgesia can be applied for the full duration of 72 hours prior to the application of the second patch at the time of surgery. No benefit regarding analgesia appears to be gained from changing the first patch after 24 hours as peak serum levels are not affected. However for peak sedation the second patch can be applied anytime from 6 to 48 hours. This analgesic regime is beneficial to the animal as well as its handling and management.
