Analgesic efficacy and pharmacokinetics of combinations of morphine, dexmedetomidine and maropitant in dogs : a thesis presented in partial fulfilment of the requirement for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand
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Date
2020
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Massey University
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Abstract
Multimodal analgesia is gaining popularity in veterinary medicine. It is an approach that involves the administration of two or three classes of analgesic drugs with different modes of actions to enhance the analgesic effects and lower the adverse effects associated with high dose of a single drug. In a series of experiments conducted in this thesis, the combinations of morphine, dexmedetomidine and maropitant were evaluated using different pain models with the aim of using them in a multimodal strategy in dogs undergoing ovariohysterectomy or other surgical procedures.
Firstly, a pilot study evaluating the efficacy of combinations of the test drugs was performed using a hot-plate test and tail-flick test in rats. The combination of morphine and maropitant showed a significantly higher (p < 0.0001) tail-flick latency compared to all other treatment groups indicating a supra-additive effect of spinal analgesia between morphine and maropitant.
A pharmacokinetic study to investigate the disposition of the test drug combinations after intramuscular (IM) administration in dogs under anaesthesia was conducted. The results showed that the elimination half-life of morphine was higher and the clearance rate was lower when combined with dexmedetomidine compared to morphine and maropitant combination or morphine alone at higher doses. This effect may have a clinical advantage of prolonging the dosing interval of morphine.
A study to evaluate and compare the analgesic efficacy of the combination of morphine, dexmedetomidine and maropitant in dogs undergoing ovariohysterectomy was conducted. The study showed that dogs receiving the combination of morphine and dexmedetomidine had significantly lower (p < 0.05) pain scores, obtained by the short form of the Glasgow composite measure pain scale and visual analogue pain scale, in the postoperative period. All dogs that received dexmedetomidine showed arrhythmia and second-degree heart block immediately after IM administration.
Finally, the efficacy of the test drug combinations was evaluated using changes in electroencephalographic indices of nociception (median frequency, spectral edge frequency and total power) in anaesthetised dogs subjected to a noxious electrical stimulus. The combination of morphine and dexmedetomidine showed a significantly lower change in the post stimulation median and spectral edge frequencies compared to all other treatment groups. The dogs receiving dexmedetomidine also demonstrated arrhythmia and second-degree heart block.
In conclusion, the combination of morphine and dexmedetomidine showed a superior analgesic effect compared to morphine alone at higher dose and appeared to be the most effective combination among other combinations of morphine, dexmedetomidine and maropitant. The cardiovascular changes produced by the test drugs may be clinically insignificant in fit and healthy dogs. In future, the efficacy of the combination of morphine, dexmedetomidine and maropitant at other different doses rates and ratios should also be evaluated.
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Veterinary anesthesia, Analgesics, Effectiveness, Pharmacokinetics, Dogs, Surgery