Cardiovascular and sedation reversal effects of intramuscular administration of atipamezole in dogs treated with medetomidine hydrochloride with or without the peripheral α2-adrenoceptor antagonist vatinoxan hydrochloride

Abstract

OBJECTIVE To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467). ANIMALS 8 purpose-bred, 2-year-old Beagles. PROCEDURES A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 μg/kg) or MED mixed with 400 μg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 μg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis. RESULTS Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole–treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA. CONCLUSIONS AND CLINICAL RELEVANCE Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol, on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

“…The gastrointestinal distress may have influenced the cardiovascular variables after atipamezole administration. By contrast, the increases in HR and CI were much larger than those recorded in a previous study (Turunen et al 2019). However, the effect may have been exaggerated by the atipamezole dose administered, which should have been adjusted according to the timing of previously administered medetomidine.…”

“…Subsequently, recovery characteristics before and after atipamezole administration were assessed. Atipamezole interacts favourably with vatinoxan when used to reverse medetomidineinduced sedation (Turunen et al 2019). However, there are no reports of the interaction of atipamezole and vatinoxan with ketamine.…”

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“…Außerdem sollte bei Bedarf eine zusätzliche Schmerzbehandlung erfolgen, da die Analgesie kürzer als die sedierende Wirkung sein kann [10]. Obwohl die Erholung von der Sedierung mit dem α 2 -Rezeptorantagonisten Atipamezol 30 min nach Zenalpha ® schneller und vollständiger als nach alleiniger Medetomidin-Behandlung mit Atipamezol erfolgte [12], ist die routinemäßige Verabreichung von Atipamezol aufgrund der raschen Erholung von der Zenalpha ® -Sedierung nicht angezeigt [10]. Grund hierfür ist, dass nach intramuskulärer Gabe von Atipamezol bei 50 % der Hunde eine Tachykardie beobachtet wurde [10].…”