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.
29 April 2022 in Journal of Veterinary Pharmacology and Therapeutics
The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45 min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC-MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%-56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl-1) and central and peripheral volumes of distribution (V-1, V-2). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs.
1 November 2020 in Veterinary Anaesthesia and Analgesia
Pelicans (Pelecanus spp.) are commonly kept in captivity in open display, necessitating regular use of deflighting techniques. Feather follicle extirpation using a diode laser is an irreversible deflighting method that requires immobilization through general anesthesia. This case series reports on the use of an injectable balanced anesthesia protocol integrating multimodal analgesia for this short surgical procedure in 12 Dalmatian pelicans (Pelecanus crispus) housed in a zoological institution. The protocol involved administering a combination of medetomidine (0.03–0.04 mg/kg), butorphanol (0.3–0.4 mg/kg), and ketamine (3–4 mg/kg) (MBK) in a single syringe via intramuscular injection, preceded by subcutaneous administration of meloxicam (0.5 mg/kg). Vital variables were monitored through a combination of clinical assessments and equipment-based methods, and Korbel's reflex scores (KRS) were determined. No additional anesthetic agents were required with the intermediate and higher dosages, and atipamezole was administered at the end for reversal. This combination of drugs provided sufficient depth of anesthesia for the 30-min procedures, comprehending clinical examination, preparation, surgery, and venous blood sampling. The procedure was successful in all subjects, with no complications observed. Based on the present observations, it is recommended to use the higher end of the dose ranges to ensure adequate muscle relaxation and absence of response to noxious stimuli. This corresponded to a mean KRS score of 5.