Research PaperComparison of perioperative racemic methadone, levo‐methadone and dextromoramide in cats using indicators of post‐operative pain
Introduction
Fear of adverse behavioural responses to opioid drugs, e.g. excitement, has resulted in effective analgesic treatment being withheld from cats (Woiwode 1962; Davis & Donnelly 1986; Hansen & Hardie 1993). Other concerns include the potential for opioid drugs to cause respiratory depression (Dohoo and Dohoo, 1996a, Dohoo and Dohoo, 1996b). These substances are also subject to drug‐control legislation and so, are unappealing to general practitioners. Nevertheless, it is being increasingly appreciated that opioid agonists can be used safely in cats, and that they appear to be effective in treating moderate‐to‐severe post‐operative pain.
Methadone is a synthetic OP3 agonist of the diphenylpropylamine class, and has pharmacological properties similar to morphine (Reisine & Pasternak 1996). It exists as one of the two enantiomers (Kristensen et al. 1996), which may result in significant pharmacological differences; indeed, the administration of chiral mixtures of drugs may be comparable to the simultaneous use of two agents with different pharmacodynamic and pharmacokinetic properties (Ariens, 1984, Ariens, 1986). The levo‐rotatory enantiomer (levo‐methadone) displays higher affinity for the OP3 receptor than the dextro‐rotatory molecule (Booth 1988; Kristensen et al. 1996; Reisine & Pasternak 1996), and is 10–50 times more potent as an analgesic (Kristensen et al. 1995). Levo‐methadone is available for veterinary use (l‐Polamivet, Hoechst AG, Frankfurt, Germany) and contains 2.5 mg mL−1 of the levo‐rotatory isomer in addition to 0.125 mg mL−1 fenpipramide. The latter is an atropine‐like compound, which partially offsets opioid‐induced vagal tone (Amman 1952). Dextromoramide is a synthetic morphine derivative, which also exists as one of the two enantiomers (Krüger & Orth 1959). The dextro‐rotatory isomer is a more potent analgesic and is structurally related to levo‐methadone (Forth et al. 1987). It is one of the few OP3 agonists used by veterinary practitioners in Switzerland, and its effects are known mainly from its use in dogs. Woiwode (1962) reported excitation (uncontrolled movements and enhanced aggression) in cats given 3 mg IM.
The experience of post‐operative pain is variable, and treatment aims at rendering pain sensation as tolerable as possible (Thurmon et al. 1996). The evaluation of pain is difficult, as objective criteria have not been defined (Smith et al. 1996). Changes in physiological variables (heart rate (HR), respiratory rate (RR), blood pressure), as well as biochemical indicators (epinephrine, norepinephrine cortisol and β‐endorphins), can be influenced by other factors (Taborsky et al. 1982; Benson 1995; Smith et al. 1996). However, observing spontaneous behavioural signs, indicative of pain, combined with a qualitative assessment of response to wound palpation, facilitates the evaluation of the effectiveness of analgesia (Waterman & Kalthum 1992).
The present study was undertaken to (i) objectively evaluate the sedative effects of three opioid agonist drugs in cats with respect to their usefulness for pre‐anaesthetic medication and post‐operative analgesia and (ii) to identify objective and subjective indicators of post‐operative pain in cats after ovariectomy.
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Materials and methods
Ninety client‐owned female cats, judged to be healthy on the basis of physical examination, were studied. They were fasted for 12 hours before induction of anaesthesia, and water was withheld for at least 30 minutes. The animals were observed undisturbed within their cage before pre‐anaesthetic medication, and their RR and behaviour were recorded. They were then spoken to, the cage door was opened and their pulse rate was taken. Body position, and responses to stimulation and behaviours were
Results
Population data were homogenous in terms of age and mass. The mean (±SD) mass of cats studied (n = 90) was 3.1 (2.1–4.5) kg and mean age was 14.6 (6.0–84.0) months. Various breeds were represented. Of the original 90 animals studied, 14 were excluded from analysis for exceeding the predetermined maximum duration of surgery (30 minutes), pregnancy or excessive aggressive/uncooperative behaviour before pre‐anaesthetic medication. All operations (from skin incision to placement of last suture)
Discussion
The drug doses used in the current study may not have been equianalgesic, which would explain some of the differences observed. The doses of racemic methadone (0.6 mg kg−1) and levo‐methadone (0.3 mg kg−1) used were higher than those cited elsewhere (0.1–0.2 mg kg−1, Brearley 1994; Paddleford 1999; 0.5 mg kg−1, Dobromylskyj 1993), as it was thought that this may have increased the likelihood of producing behavioural effects. The dextromoramide dose chosen was based on the lowest value
Acknowledgement
We would like to thank Dr Streuli AG, Uznach, Switzerland for partially sponsoring this study.
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