Imagine this clinical scenario: you create an analgesic protocol for your clinic to ensure rabbits entering your care receive the best treatment available. Your research indicates meloxicam is the analgesic of choice as in comparison to opioids it has a reduced risk of gut stasis, which is a life-threatening complication in rabbits. Meloxicam also has a palatable oral form for easy administration.
You have heard that the minimum suggested dose of 0.2mg/kg may not provide adequate analgesia, and you are unsure if the higher dose of 1mg/kg would be a safe standard protocol. What is the evidence comparing 1mg/kg and 0.2mg/kg of oral meloxicam for significant changes in pain behaviour, and kidney and liver biochemical analytes?
The evidence
Five studies were critically appraised: four investigated safety at each dose rate of meloxicam and two investigated analgesic efficacies. Two were randomised controlled trials and three were prospective clinical trials, which are study designs that can provide strong evidence if performed correctly.
The two prospective clinical trials investigated the efficacy of meloxicam as an analgesic in rabbits based on plasma concentrations; 1 mg/kg of meloxicam achieved plasma concentrations considered therapeutic in dogs and humans. Both trials demonstrated repeatable results, with no rabbit developing significant abnormal changes in liver and kidney biochemical analytes. However, the therapeutic plasma concentration for rabbits is currently unknown, as the use of meloxicam is currently off label with no clinical trials conducted on rabbits. Therefore, the best available evidence is through behavioural pain studies.
Only two studies analysed pain behaviour in rabbits receiving meloxicam at 0.2mg/kg and 1mg/kg. In one study, there were significant differences in behaviour between the low (0.2mg/kg), medium (0.6mg/kg) and high (1mg/kg) groups, with the medium and high doses of meloxicam providing significantly more effective analgesia. Normal behaviour was displayed at a greater frequency as the dose increased, including searching behaviour, interaction with the environment and standing. However, the 1 mg/kg dose was only assessed for the first day post-operatively, before the dosage decreased to 0.5mg/kg for two days. Inactive pain behaviour, remaining motionless in response to pain, was present at every tested dose, indicating that a daily dosage above 1mg/kg may be required to achieve complete analgesia on the first day after surgery.
The other study demonstrated that a 0.2mg/kg dose rate was deemed inadequate based on faecal corticosterone metabolites, an accepted non-invasive, indirect method of assessing stress in animals that indicates the presence of significant pain.
A further study found the meloxicam-treated group (at a dose of 0.2mg/kg) had a faster return to baseline food consumption compared to those treated with buprenorphine or bupivacaine. The authors suggested that this indicated a greater level of analgesia. However, it is unclear whether food consumption is a reliable indicator of pain in rabbits.
Further studies indicate that 1mg/kg of meloxicam is safe in healthy, young rabbits. One study, not included in the critical appraisal, demonstrated the safety of meloxicam up to 1.5mg/kg for five days in rabbits, with no significant changes in biochemical analytes. Another excluded study noted no toxic effects after a single dose of 20 mg/kg of meloxicam in rabbits, although the method deciding this was unexplained.
Conclusion
Based on the current evidence, it appears beneficial to choose the higher recommended daily dose of 1mg/kg when using meloxicam for analgesia in rabbits. The limited number of studies available indicate that 0.2mg/kg meloxicam alone may be an ineffective analgesic in rabbits post-operatively. However, the overall evidence on analgesic efficacy is weak due to limited behavioural data and inconclusive results. There is moderate evidence for the safety of meloxicam in healthy rabbits for both doses.
The subjects are unlikely to be representative of the expected clinical population, as they were mostly healthy, young rabbits from a breed uncommonly used as pets. This could impact the applicability of the evidence in clinical practice.
Research on the therapeutic plasma concentration of meloxicam in rabbits would be useful. Further research should investigate pain behaviour at a dose rate of 1mg/kg or greater, potentially considering more frequent dosing.
The full Knowledge Summary can be read in RCVS Knowledge’s open access journal Veterinary Evidence.
