Evaluation of the muscular relaxant effect of dexmedetomidine or medetomidine in cats
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- Scrollavezza, P., Tambella, A.M., Vullo, C. et al. Vet Res Commun (2009) 33: 213. doi:10.1007/s11259-009-9271-y
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The alpha2 adrenoceptor agonist medetomidine (MED) is an equal racemic mixture of two enantiomers, dexmedetomidine (DEX) and levomedetomidine (LEV); the LEV enantiomer is generally considered to be pharmacologically inactive, whereas the DEX enantiomer is active (Virtanen et al. 1988; MacDonald et al. 1991; Savola and Virtanen 1991). Clinical studies in dogs and cats have shown that the pharmacodynamic effects of DEX are twice as potent as the MED racemic mixture, therefore DEX is administered at half the dose of MED for sedation; as for MED, the sedative and analgesic effects of DEX are antagonised by atipamezole (Cullen 1996; Ansah et al. 1998, 2000; Kuusela et al. 2000; Mendes et al. 2003; Granholm et al. 2006). DEX has been approved for clinical use in dogs and cats in Italy since 2008, and we immediately started to use it for dog and cat sedation. The sedation effect of DEX in the dog is similar to that of MED, whereas the muscular relaxant effect in the cat was lower than that of MED. The aim of this study was to evaluate and compare the muscular relaxant effects in cats following treatment with DEX or MED at bioequivalent doses.
Materials and methods
Eighteen cats, of different weight, breed and sex, ASA I or ASA II, after owners’ written consent, were randomly allocated to receive an intramuscular injection of either MED 0.1 mg/kg (n = 9) or DEX 0.05 mg/kg (n = 9). The animals were conducted to the Veterinary Hospital of the Veterinary Medicine Faculty, University of Camerino for admit to surgery. Before administration and 10, 15, 20 and 30 minutes after injection, muscular relaxation was assessed by an investigator blinded to the identity of the agent used, who measured the eye position, relaxation of the jaw and the tongue, and pedal reflex according to a predefined scale. The eye position scale was divided into three scores (1 = normal position of eye and normal palpebral reflex; 2 = rotated eye and normal palpebral reflex; 3 = rotated eye and absence of palpebral reflex). The relaxation of the jaw and the tongue were divided into four scores (1 = normal; 2 = moderate jaw tone and tongue difficult to extend; 3 = limited muscular tone, tongue not difficult to extend and not possible to retract; 4 = very limited muscular tone, tongue easy to take out and impossible to retract). The pedal reflex was given four scores (1 = normal; 2 = easy to arouse but with slow reaction; 3 = increased stimulus required to arouse; 4 = absent). In each animal the scores from the different scales were added to obtain a numeric value of the muscular relaxation. During the 30 minutes of monitoring no drugs or stimulation were given to animals. Data were examined by means of ANOVA for continuous variables and values of P < 0.05 were considered statistically significantly different.
Demographic distribution was similar between DEX and MED treatments with respect to age, weight and sex. No side effects were observed after DEX and MED administration and the following anaesthetic administration allowed surgery to be performed. Time to lateral recumbency after administration of MED (4.0–7.0 minutes) was also not significantly different from that observed after administration of DEX (4.0–8.0 minutes). The mean values for muscular relaxation, eye position, jaw and tongue relaxation and pedal reflex were similar in both groups before administration of MED or DEX. However, the same parameters were significantly different after administration of MED and DEX: 8 vs 7 after 10 minutes, 10 vs 8 after 15 minutes, 11 vs 10 after 20 minutes and 10 vs 9 after 30 minutes, respectively. The mean muscular relaxation scores for MED were significantly greater than for DEX following administration for any time-point: P < 0.05 at 10 minutes, P < 0.01 at 15, 20, and 30 minutes. The peak muscular relaxation effect for both alpha2 treatments was observed at approximately 20 minutes.
The alpha2 adrenoceptor agonist MED has been used for sedation in dogs and cats for a long time (Stenberg et al. 1987; Vähä-Vahe 1989). DEX is the active enantiomer of racemic MED. DEX shows a higher affinity for alpha2 receptors compared with MED and it has gained greater interest as a sedative over MED in human anaesthesiology because it has a low affinity for alpha1 receptors and because it reduces stress, does not change the haemodynamic parameters or decrease plasma levels of adrenaline and noradrenaline (Aho et al. 1992). Also in Veterinary Medicine, the use of DEX on dogs and cats seems better than MED. The low alpha1 adrenoceptor affinity of DEX avoids arrhythmias mediated by catecholamines. Moreover, the dose of DEX to metabolize is administered at half the corresponding bioequivalent dose of MED (Kuusela et al. 2000; Granholm et al. 2006, 2007). Low doses of LEV produce anti-sedative and anti-analgesic effects (Kuusela et al. 2001). However, side effects were observed when DEX is used at high doses. In fact, it is observed that sedation and analgesia induced by DEX, unlike MED, reach a ceiling effect beyond which further dosages decrease sedation level (Schwinn et al. 1991; Ansah et al. 2000) and that LEV, 50% of MED, also produces signs of sedation or analgesia (Doze et al. 1989; Savola and Virtanen 1991).
From the present study we can conclude that administration of a high dose of MED (0.08 mg/kg) in the cat is more suitable for deep sedation than a bioequivalent dose of DEX (0.04 mg/kg), such as that recommended from leaflet of Dexdomitor, the commercial name of DEX.