Comparison of the sedative effects of alfaxalone and methadone with or without midazolam in dogs.

This blinded, randomized, prospective study evaluated the sedative and physiologic effects of a combination of alfaxalone and methadone with or without midazolam in adult dogs. Sixteen dogs received methadone (0.5 mg/kg body weight) and alfaxalone (1 mg/kg body weight), either with or without midazolam (0.5 mg/kg body weight), by intramuscular injection. Quality of sedation, heart rate, respiratory rate, systolic arterial pressure, rectal temperature, arterial oxygen saturation of hemoglobin, and dose of alfaxalone required for endotracheal intubation were recorded. Sedation score increased over time in both groups; however, dogs premedicated with methadone and alfaxalone appeared significantly less sedated than dogs premedicated with midazolam at 15, 20, and 25 minutes post-injection (P = 0.04). Dogs receiving methadone and alfaxalone were almost 5 times more likely to show excitement than those receiving midazolam (P = 0.03). We concluded that adding midazolam to an intramuscular combination of methadone and alfaxalone cannot be recommended in healthy dogs.

Comparaison des effets sédatifs de l'alfaxalone et de la méthadone avec ou sans midazolam chez le chien. Cette étude prospective randomisée à l'aveugle a évalué les effets sédatifs et physiologiques d'une association d'alfaxalone et de méthadone avec ou sans midazolam chez le chien adulte. Seize chiens ont reçu par voie intramusculaire (IM) méthadone (0,5 mg/kg) et alfaxalone (1 mg/kg) (MA) ou méthadone et alfaxalone à les même dosages plus midazolam (0,5 mg/kg) (MMA). La qualité de la sédation, la fréquence cardiaque, la fréquence respiratoire, la pression artérielle systolique, la température rectale, la saturation artérielle en oxygène de l'hémoglobine et la dose d'alfaxalone requise pour l'intubation endotrachéale ont été enregistrées. Le score de sédation augmentait avec le temps dans les deux groupes, cependant, les chiens ayant reçu la combinaison MMA semblaient significativement moins sous sédation que les chiens ayant reçu la combinaison MA 15, 20, et 25 minutes après l'injection (P = 0,04). Les chiens recevant MMA étaient presque cinq fois plus susceptibles de montrer de l'excitation que ceux recevant du MA (P = 0,03). Nous avons conclu que l'ajout de midazolam à une combinaison IM de méthadone et d'alfaxalone ne peut pas être recommandé chez les chiens en santé.(Traduit par les auteurs).

Neuromuscular blocking effects of vecuronium in dogs with autosomal-recessive centronuclear myopathy.

OBJECTIVE: To evaluate the potency of vecuronium and duration of vecuronium-induced neuromuscular blockade in dogs with centronuclear myopathy (CNM). ANIMALS: 6 Labrador Retrievers with autosomal-recessive CNM and 5 age- and weight-matched control dogs. PROCEDURES: Dogs were anesthetized on 2 occasions (1-week interval) with propofol, dexmedetomidine, and isoflurane. Neuromuscular function was monitored with acceleromyography and train-of-four (TOF) stimulation. In an initial experiment, potency of vecuronium was evaluated by a cumulative-dose method, where 2 submaximal doses of vecuronium (10 µg/kg each) were administered IV sequentially. For the TOF's first twitch (T1), baseline twitch amplitude and maximal posttreatment depression of twitch amplitude were measured. In the second experiment, dogs received vecuronium (50 µg/kg, IV) and the time of spontaneous recovery to a TOF ratio (ie, amplitude of TOF's fourth twitch divided by amplitude of T1) ≥ 0.9 and recovery index (interval between return of T1 amplitude to 25% and 75% of baseline) were measured. RESULTS: Depression of T1 after each submaximal dose of vecuronium was not different between groups. Median time to a TOF ratio ≥ 0.9 was 76.7 minutes (interquartile range [IQR; 25th to 75th percentile], 66.7 to 99.4 minutes) for dogs with CNM and 75.0 minutes (IQR, 47.8 to 96.5 minutes) for controls. Median recovery index was 18.0 minutes (IQR, 9.7 to 23.5 minutes) for dogs with CNM and 20.2 minutes (IQR, 8 to 25.1 minutes) for controls. CONCLUSIONS AND CLINICAL RELEVANCE: For the study dogs, neither potency nor duration of vecuronium-induced neuromuscular blockade was altered by CNM. Vecuronium can be used to induce neuromuscular blockade in dogs with autosomal-recessive CNM.

The kalaemic and neuromuscular effects of succinylcholine in centronuclear myopathy: A pilot investigation in a canine model.

BACKGROUND: Myopathies are generally considered to increase the risk for succinylcholine-induced hyperkalaemia and may affect the duration of action of neuromuscular blockers. Centronuclear (myotubular) myopathy (CNM) is congenital and produces various degrees of muscular weakness and associated complications such as respiratory failure. The effects of succinylcholine and the potentially lethal consequences of hyperkalaemia on patients with CNM are unknown due to its rarity. One source of information is the dog, as CNM occurs naturally in dogs. Because of its remarkable similarity with the disease in man, canine CNM can serve as a model to further our knowledge of the effects of succinylcholine. OBJECTIVES: We examined the kalaemic and neuromuscular effects of succinylcholine in dogs with and without autosomal-recessive CNM. DESIGN: A prospective, experimental study. SETTING: Anaesthesiology laboratory, College of Veterinary Medicine, Cornell University, New York, USA. PATIENTS: Six dogs with autosomal-recessive CNM and six control dogs. INTERVENTIONS: Dogs received succinylcholine 0.3 mg kg during isoflurane anaesthesia. MAIN OUTCOME MEASURES: Whole blood potassium concentration was measured 5 min before and after succinylcholine administration. Neuromuscular function was measured with acceleromyography and single twitch stimulation. RESULTS: All dogs recovered uneventfully from anaesthesia. The increase in potassium concentration [mean (SD)] following succinylcholine was similar between groups: CNM 0.5 (0.4) mmol l and control 0.7 (0.4) mmol l (P = 0.47). Recovery of the single twitch to 25, 75 and 90% was longer in the CNM group (all P < 0.001); 90% recovery took 35.5 (1.18) min for the CNM group and 23.3 (1.68) min for the control group. CONCLUSION: CNM did not exacerbate the increase in blood potassium that is ordinarily seen with succinylcholine. Recovery from succinylcholine was nearly 50% longer in dogs with CNM. Although our sample size is too small to evaluate the incidence of succinylcholine-induced hyperkalaemia, extrapolation of these findings suggests that increased duration of action should be expected if succinylcholine is given to a patient with autosomal-recessive CNM.

Observations of the potency and duration of vecuronium in isoflurane-anesthetized horses.

OBJECTIVE: To evaluate the potency and duration of three subparalyzing doses of vecuronium (VEC) in isoflurane-anesthetized horses. STUDY DESIGN: Prospective experimental study. ANIMALS: Thirteen healthy adult horses undergoing arthroscopic surgery. METHODS: During isoflurane anesthesia, horses received one of three doses of vecuronium (25, 50, or 100 µg kg(-1)). Neuromuscular transmission was monitored with acceleromyography (AMG) with train-of-four (TOF) stimulation of the radial nerve. Maximal depression of the first twitch (T1), and onset time were recorded for each dose. Recovery time to a TOF ratio >90% was also evaluated. RESULTS: Vecuronium 25 µg kg(-1) produced no observable T1 depression in four horses. VEC 50 µg kg(-1) (n = 5) produced a maximal T1 depression of [median (min, max)] 41 (20, 71) % in four horses, and no neuromuscular block was seen in the fifth. VEC 100 µg kg(-1) was given to four horses and produced a T1 depression of 73 (64, 78) %. Of the four horses in which VEC 50 µg kg(-1) produced a measurable neuromuscular block, three recovered spontaneously 43 (40, 52) minutes after VEC administration; a fourth subject received edrophonium to reverse residual block at the end of the surgery. Spontaneous recovery after VEC 100 µg kg(-1) occurred by 112 minutes in one horse, and had to be facilitated by edrophonium in the remaining three horses, more than 2 hours after VEC had been given. CONCLUSIONS AND CLINICAL RELEVANCE: A dose of 100 µg kg(-1) VEC in isoflurane anesthetized horses failed to produce complete paralysis. The partial neuromuscular block lasted at least 2 hours after this dose had been administered. Edrophonium was required to reverse the neuromuscular block in three of four horses. It is likely that more than 100 µg kg(-1) VEC would be necessary for complete neuromuscular blockade in horses, and that this dose will last >2 hours.