Research Paper
Comparison of perioperative racemic methadone, levo‐methadone and dextromoramide in cats using indicators of post‐operative pain

https://doi.org/10.1111/j.1467-2987.2004.00148.xGet rights and content

Abstract

Objective

To compare three opioid agonist drugs for perioperative analgesia in cats.

Study design

Prospective, blind, controlled, randomised trial.

Animals

Ninety client‐owned cats, weighing 3.1 (2.1–4.5) kg, aged 14.6 (6.0–84.0) months, were studied.

Methods

Seventy‐six cats, scheduled for ovariectomy, received either 0.6 mg kg−1 racemic methadone, 0.3 mg kg−1 levo‐methadone, 0.05 mg kg−1 dextromoramide or a saline placebo IM. Behaviour and body position were assessed and scored 20 minutes later by a single ‘blinded’ observer. Anaesthesia was induced with propofol and maintained with halothane. Heart rate (HR), respiratory rate (RR), Feco2 and SpO2 were recorded during anaesthesia. Post‐operatively, pain was categorised as absent, moderate or severe, on the basis of appearance, behaviour and response to palpation of the surgical wound (pain score). Appearance, pain scores and physiological variables were monitored every 30 minutes, for a duration of 4 hours. Differences between time‐dependent continuous variables were analysed using mixed models for repeated measurements. Differences in categorical, time‐dependent variables were analysed using χ2‐tests. Significance was set at p ≤ 0.05.

Results

There were no significant changes in appearance after pre‐anaesthetic medication. After surgery, there was no association between appearance and pain score with HR or RR. The assessment of pain depended on comparison with the placebo group, by comparing animals’ reactions to wound palpation. Sixteen of the 18 cats in the placebo group and 14 of the 19 cats in the dextromoramide group showed signs of moderate‐to‐severe pain after surgery. In the levo‐methadone group (n = 20), one animal showed pain after 60 minutes and two after 120 minutes. One cat in the racemic methadone group (n = 19) showed pain signs and behavioural changes at 60 minutes. Compared to the two methadone groups, ‘rescue’ analgesia was required more often in cats treated with dextromoramide or saline.

Conclusion and clinical relevance

Dextromoramide (0.05 mg kg−1) was ineffective, while racemic methadone (0.6 mg kg−1) and levo‐methadone (0.3 mg kg−1) provided effective analgesia in cats following ovariectomy, without behavioural, respiratory or cardiovascular side effects.

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.

Section snippets

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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