Plasma concentrations and sedative effects of a dexmedetomidine, midazolam, and butorphanol combination after transnasal administration in healthy rabbits

Abstract

Plasma concentrations of dexmedetomidine (D = 0.1 mg/kg), midazolam (M = 2 mg/kg), and butorphanol (B = 0.4 mg/kg) were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) after their simultaneous (DMB) transnasal (TN) administration to healthy rabbits. Time-dependent changes in sedation and antinociception were evaluated by measuring a sedation score based on rabbit's posture, loss of the righting, palpebral and pedal withdrawal reflexes and by instrumental monitoring of rectal temperature, heart rate, arterial blood pressure, pulse-oximetry, and capnometry. The peak plasma concentration (Cmax ) of each drug was reached within 5 min (Tmax ) from DMB-TN administration along with deep sedation and analgesia. Such effects subsided after 45 min into a moderate sedation and analgesia lasting for additional 15 min. All rabbits awakened spontaneously and uneventfully 90 min after DMB-TN administration. During the anesthetic procedure, arterial blood pressure markedly decreased and respiratory depression ensued requiring oxygen supplementation. The results of this study show that all three molecules of the DMB combination were absorbed through the TN route, inducing deep sedation and analgesia suitable for minor surgical procedures. Such combination should be used with caution in rabbits bearing cardiovascular or respiratory diseases because of its ability to induce hypotension and respiratory depression.

Comparison of two injectable anaesthetic protocols in Egyptian fruit bats(Rousettus aegyptiacus)undergoing gonadectomy

“…In the present study, this association produced high-quality immobilization with rapid and smooth induction. Anaesthesiologic protocols including the association of alpha-2 adrenergic agonists, opioids and benzodiazepines have already been described in veterinary medicine in several species [28,29] Tuval and colleagues (2018), the dosages and total volumes of drugs used in this study were considerably lower, probably also due to the different route of administration. In our study, IM administration was performed in the thigh muscles; no behaviour referable to muscle soreness or pain was observed following injection or during recovery phase, and no bats had difficulty in flying following the procedure.…”

“…In the present study, this association produced high-quality immobilization with rapid and smooth induction. Anaesthesiologic protocols including the association of alpha-2 adrenergic agonists, opioids and benzodiazepines have already been described in veterinary medicine in several species [28,29]. As regards bats, only Tuval and colleagues (2018) have compared different subcutaneous combinations of medetomidine, MDZ and opioids in R. aegyptiacus with no apparent morbidity and mortality.…”

Influences of Gender on Intravenous Nalbuphine Actions After Major Abdominal Surgery: A Multicenter Study

“…Interestingly, butorphanol produced higher analgesic efficacy in men in the cold-water stimulus pain model [ 18 ]. Importantly, clearance of butorphanol has been shown to be lower in women compared to men, raising the possibility that pharmacokinetic differences may play a role [ 34 , 35 ]. Finally, studies on gender difference with the use of nalbuphine have been previously scanty and were done with single doses in somatic pain models [ 6 ].…”

Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol and antagonism by atipamezole in rabbits

“…The anesthetic duration of 90 min seems to be a long time period for injectable anesthesia compared to our data. Santangelo et al reported that the transnasally administered anesthetic mixture of dexmedetomidine (DXM): 0.1 mg + MID: 2 mg + BUT: 0.4 mg/kg caused deep sedation and analgesia suitable for minor surgical procedures in rabbits [24]. DXM is an alpha 2 -adrenergic receptor agonist and has a double potency of an equal dose of MED [5].…”