Effect of Medetomidine, Dexmedetomidine, and Their Reversal with Atipamezole on the Nociceptive Withdrawal Reflex in Beagles

Abstract

The objectives were: (1) to compare the antinociceptive activity of dexmedetomidine and medetomidine, and (2) to investigate its modulation by atipamezole. This prospective, randomized, blinded experimental trial was carried out on eight beagles. During the first session, dogs received either medetomidine (MED) (0.02 mg kg−1 intravenously (IV)] or dexmedetomidine (DEX) [0.01 mg kg−1 IV), followed by either atipamezole (ATI) (0.1 mg kg−1) or an equivalent volume of saline (SAL) administered intramuscularly 45 min later. The opposite treatments were administered in a second session 10–14 days later. The nociceptive withdrawal reflex (NWR) threshold was determined using a continuous tracking approach. Sedation was scored (0 to 21) every 10 min. Both drugs (MED and DEX) increased the NWR thresholds significantly up to 5.0 (3.7–5.9) and 4.4 (3.9–4.8) times the baseline (p = 0.547), at seven (3–11) and six (4–9) minutes (p = 0.938), respectively. Sedation scores were not different between MED and DEX during the first 45 min (15 (12–17), p = 0.67). Atipamezole antagonized sedation within 25 (15–25) minutes (p = 0.008) and antinociception within five (3–6) minutes (p = 0.008). Following atipamezole, additional analgesics may be needed to maintain pain relief.

Efficacy and Safety of Dexmedetomidine Premedication in Balanced Anesthesia: A Systematic Review and Meta-Analysis in Dogs

“…As for the safety, dogs experienced lower HR and higher SAP and MAP with dexmedetomidine at 30 min after premedication; however, none needed treatment for bradycardia and hypertension [ 42 ]. Using low doses of atipamezole was an approach for treating dexmedetomidine-induced bradycardia in general anesthesia, which may also reduce arterial blood pressure via α-2 adrenoceptor blockade [ 43 , 44 ]. For the most part, dexmedetomidine is safe and effective for small animals with ASA 1 and ASA 2 physical status, as well as some irritable animals and even wildlife.…”

Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles

“…Approximately 1 h before the start of the session, EMLA cream (Aspen Pharma Schweiz GmbH) was applied over the cephalic veins, covered with a plastic film and wrapped in an occlusive bandage. A 20-or 22-gauge catheter (Group ATI, Antisedan, 5 mg/mL; Orion Corporation; 0.1 mg/kg) was administered intramuscularly 45 min after the medetomidine or dexmedetomidine injection (Siegenthaler et al, 2020) (Table 1).…”

“…The first treatment was randomly assigned (see above); the other drug was administered in the second experimental session (Table 1). Approximately 1 h before the (Group ATI, Antisedan, 5 mg/mL; Orion Corporation; 0.1 mg/kg) was administered intramuscularly 45 min after the medetomidine or dexmedetomidine injection (Siegenthaler et al, 2020) (Table 1).…”

“…Although some studies found the effects of the two products similar (Gómez‐Villamandos et al, 2006; Granholm et al, 2007), others documented clinical differences. The same dose of dexmedetomidine provided stronger (Raszplewicz et al, 2013) or more prolonged (Siegenthaler et al, 2020) sedation when administered within the racemate than when administered alone. However, the subjective reaction to pinching was reduced for a slightly longer duration when dexmedetomidine was administered alone rather than with the racemate (Kuusela et al, 2000).…”

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and also has analgesic properties (Siegenthaler et al, 2020). It can be administered as a single enantiomer, or as a racemic mixture together with levomedetomidine [(S)-(−)-medetomidine] ("medetomidine").

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