Sedative and physiological effects of low-dose intramuscular alfaxalone in rabbits.

To evaluate sedative and physiological effects of low dose intramuscular (IM) alfaxalone, six healthy rabbits were administered single IM doses of alfaxalone at 1mg/kg (IM1), 2.5 mg/kg (IM2.5), or 5 mg/kg (IM5) with a minimum of 7-day washout period. Sedative effects were subjectively evaluated using a composite measure scoring system (maximum sedation score of 16) and pulse rate, respiratory rate, non-invasive blood pressure, and percutaneous oxygen-hemoglobin saturation were measured before and after IM alfaxalone. Loss of righting reflex (LRR) was achieved in all rabbits after IM2.5 and IM5 treatments but in only three rabbits after IM1 treatment. Median (interquartile range) times to LRR were 16 min (15-17), 6 min (6-6), and 4 min (4-4), and median durations of LRR were 0.5 min (0-7), 22.5 min (19-27), and 53 min (48-58) after IM1, IM2.5, and IM5 treatments, respectively. The duration of LRR after IM5 treatment was significantly longer than those after IM1and IM2.5 treatments (P<0.01). Median value of total sedation scores peaked at 10 min [score 3.5 (3-4)], from 10 min [score 13.5 (12-14)] to 15 min [score 13.5 (12-14)], and from 10 min [score 15 (12-15)] to 15 min [score 15 (14-15)] after IM1, IM2.5, and IM5 treatments, respectively. No rabbit showed circulatory depression and apnea although respiratory rate decreased after IM 2.5 and IM5 treatments. In conclusion, alfaxalone produced a dose-dependent sedative effect and a deep sedation was achieved by alfaxalone at 2.5 mg/kg IM in rabbits.

Effect of sevoflurane anesthesia on neuromuscular blockade produced by rocuronium infusion in dogs.

This study evaluated the effect of sevoflurane anesthesia on neuromuscular blockade with rocuronium in dogs. Six healthy beagle dogs were anesthetized four times with a minimum 14-day washout period. On each occasion, the dogs were administered 1.25-, 1.5-, 1.75-, or 2.0-fold of the individualized minimum alveolar concentration (MAC) of sevoflurane and received an infusion of rocuronium (0.5 mg/kg followed by 0.2 mg/kg/hr) for 120 min. Neuromuscular function was monitored with acceleromyography and train-of-four (TOF) stimulation of the left hind limb. Time to achieve TOF count 0 (onset time), time from the onset of neuromuscular blockade to the reappearance of TOF count 4 (blockade period), and time from the onset of rocuronium infusion to attaining a 70 or 90% TOF ratio (TOFR70 or TOFR90) were recorded. There were no significant differences in the onset time, blockade period, and plasma rocuronium concentration between the sevoflurane MAC multiples. The TOFR70 and TOFR90 were dose-dependently prolonged with the sevoflurane MAC multiples. There were significant differences in the TOFR70 and TOFR90 between the 1.25 sevoflurane MAC (median: 55 and 77.5 min, respectively) and 1.75 sevoflurane MAC (122.0 and 122.6 min; P=0.020 and P=0.020, respectively), 1.25 sevoflurane MAC and 2.0 sevoflurane MAC (126.0 and 131.4 min; P=0.020 and P=0.020), and 1.5 sevoflurane MAC (97.5 and 121.3 min) and 2.0 sevoflurane MAC (P=0.033 and P=0.032). In dogs, sevoflurane anesthesia produced dose-dependent prolongation of recovery from neuromuscular blockade produced by rocuronium.

Influence of sevoflurane anesthesia with mechanical ventilation and fluid-therapy on distribution of subcutaneously administered robenacoxib in dogs.

Robenacoxib is a novel nonsteroidal anti-inflammatory drug approved for dogs. The present study aimed to evaluate influences of sevoflurane anesthesia on the distribution of robenacoxib in dogs. Ten healthy beagle dogs (1 to 11 years old, 9.3 to 14.3 kg body weight, 6 males and 4 females) were subcutaneously administered robenacoxib (2 mg/kg) under conscious condition or sevoflurane anesthesia inhaled a 1.3-fold predetermined individual minimum alveolar concentration of sevoflurane at a 28-day interval. The dogs under sevoflurane anesthesia were also mechanically ventilated and received fluid-therapy. On each occasion, serum samples were collected from the dogs before and at 5, 15, 30, 60, 120, 180, and 240 min after the robenacoxib administration. Serum robenacoxib concentration was measured by a liquid chromatography-tandem mass spectrometry. Maximum serum concentration of robenacoxib (Cmax) was 2.2 µg/ml [range: 1.2-4.6] (median [range: minimum-maximum]) and time of Cmax (Tmax) was 90 min [range: 60-120] in the conscious dogs. In the sevoflurane-anesthetized dogs, the Cmax significantly declined (1.3 µg/ml [range: 0.8-1.4], P=0.008) and Tmax was delayed (120 min [range: 120-240], P=0.018) compared with those in the conscious dogs. The serum robenacoxib concentration at 240 min (C240) decreased to 0.5 µg/ml [range: 0.2-0.9] in the conscious dogs, while it remained higher in the sevoflurane-anesthetized dogs (1.0 µg/ml [range: 0.3-1.4], P=0.011). In conclusion, the anesthetic procedure with sevoflurane, mechanically ventilated, and received fluid-therapy might affect the pharmacokinetics of subcutaneously administered robenacoxib in dogs.

Interaction between maropitant and carprofen on sparing of the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs.

Maropitant, a neurokinin-1 receptor antagonist, may provide analgesic effects by blocking pharmacological action of substance P. Carprofen is a non-steroidal anti-inflammatory drug commonly used for pain control in dogs. The purpose of this study was to evaluate the effect of a combination of maropitant and carprofen on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs. Six healthy adult beagle dogs were anesthetized with sevoflurane four times with a minimum of 7-day washout period. On each occasion, maropitant (1 mg/kg) alone, carprofen (4 mg/kg) alone, a combination of maropitant (1 mg/kg) and carprofen (4 mg/kg), or saline (0.1 ml/kg) was subcutaneously administered at 1 hr prior to the first electrical stimulation for the sevoflurane MAC-BAR determination. The sevoflurane MAC-BAR was significantly reduced by maropitant alone (2.88 ± 0.73%, P=0.010), carprofen alone (2.96 ± 0.38%, P=0.016) and the combination (2.81 ± 0.51%, P=0.0003), compared with saline (3.37 ± 0.56%). There was no significant difference in the percentage of MAC-BAR reductions between maropitant alone, carprofen alone and the combination. The administration of maropitant alone and carprofen alone produced clinically significant sparing effects on the sevoflurane MAC-BAR in dogs. However, the combination of maropitant and carprofen did not produce any additive effect on the sevoflurane MAC-BAR reduction. Anesthetic premedication with a combination of maropitant and carprofen may not provide any further sparing effect on anesthetic requirement in dogs.

Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol (KMP-TIVA) in horses undergoing surgery.

Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol drug combination (KMP-TIVA) were determined in 5 Thoroughbred horses undergoing surgery. The horses were anesthetized with intravenous administration (IV) of ketamine (2.5 mg/kg) and midazolam (0.04 mg/kg) following premedication with medetomidne (5 µg/kg, IV) and artificially ventilated. Surgical anesthesia was maintained by controlling propofol infusion rate (initially 0.20 mg/kg/min following an IV loading dose of 0.5 mg/kg) and constant rate infusions of ketamine (1 mg/kg/hr) and medetomidine (1.25 µg/kg/hr). The horses were anesthetized for 175 ± 14 min (range from 160 to 197 min). Propofol infusion rates ranged from 0.13 to 0.17 mg/kg/min, and plasma concentration (Cpl) of propofol ranged from 11.4 to 13.3 µg/ml during surgery. Cardiovascular measurements during surgery remained within clinically acceptable ranges in the horses (heart rate: 33 to 37 beats/min, mean arterial blood pressure: 111 to 119 mmHg, cardiac index: 48 to 53 ml/kg/min, stroke volume: 650 to 800 ml/beat and systemic vascular resistance: 311 to 398 dynes/sec/cm(5)). The propofol Cpl declined rapidly after the cessation of propofol infusion and was significantly lower at 10 min (4.5 ± 1.5 µg/ml), extubation (4.0 ± 1.2 µg/ml) and standing (2.4 ± 0.9 µg/ml) compared with the Cpl at the end of propofol administration (11.4 ± 2.7 µg/ml). All the horses recovered uneventfully and stood at 74 ± 28 min after the cessation of anesthesia. KMP-TIVA provided satisfactory quality and control of anesthesia with minimum cardiovascular depression in horses undergoing surgery.

Anesthetic and cardiovascular effects of balanced anesthesia using constant rate infusion of midazolam-ketamine-medetomidine with inhalation of oxygen-sevoflurane (MKM-OS anesthesia) in horses.

The anesthetic sparring and cardiovascular effects produced by midazolam 0.8 mg/ml-ketamine 40 mg/ml-medetomidine 0.05 mg/ml (0.025 ml/kg/hr) drug infusion during sevoflurane in oxygen (MKM-OS) anesthesia was determined in healthy horses. The anesthetic sparring effects of MKM-OS were assessed in 6 healthy thoroughbred horses in which the right carotid artery was surgically relocated to a subcutaneous position. All horses were intubated and ventilated with oxygen using intermittent positive pressure ventilation (IPPV). The end-tidal concentration of sevoflurane (ET(SEV)) required to maintain surgical anesthesia was approximately 1.7%. Heart rate and mean arterial blood pressure averaged 23-41 beats/min and 70-112 mmHg, respectively. All horses stood between 23-44 min after the cessation of all anesthetic drugs. The cardiovascular effects of MKM-OS anesthesia were evaluated in 5 healthy thoroughbred horses ventilated using IPPV. Anesthesia was maintained for 4 hr at an ET(SEV) of 1.7%. Each horse was studied during left lateral (LR) and dorsal recumbency (DR) with a minimum interval between evaluations of 1 month. Cardiac output and cardiac index were maintained between 70-80% of baseline values during LR and 65-70% of baseline values during DR. Stroke volume was maintained between 75-85% of baseline values during LR and 60-70% of baseline values during DR. Systemic vascular resistance was not different from baseline values regardless of position. MKM-OS anesthesia may be useful for prolonged equine surgery because of its minimal cardiovascular depression in both of lateral and dorsal recumbency.

Axial correction of pes varus by transverse-opening wedge osteotomy and T-plate fixation with beta-tricalcium phosphate (beta-TCP) transplantation in dachshunds.

Axial correction was performed surgically in two miniature dachshunds presenting with lateral patellar dislocation and limping caused by pes varus. Pes varus had resulted from asymmetric closure of the physis of the distal tibia. Prior to surgery, osteotomy was simulated by measuring X-ray films to determine the distance required for the wedge opening. Transverse-opening wedge osteotomy was performed on the medial side of the distal tibia, and beta-tricalcium phosphate (beta-TCP) was inserted in a wedge shape into the area created by the cuneiform osteotomy. Finally, the tibia was fixed by a veterinary 1.5/2.0-mm T-plate. Both dogs were able to walk a few days after surgery, and the lateral dislocation of the patella normalized almost completely in about one month. At two months, X-ray films showed that the implant had remained in position without any dislocation, and the beta-TCP had fused with the surrounding bone.

Fixation to the canine bone of artificial implant with new surface structure.

Screw and laser (SL) column by making screw threads and forming small holes using laser irradiation on the base metal and conventional beads coating (BC) columns were embedded into the shaft of canine femurs, and compared the implant fixation to the host bone. The interfacial strength in SL columns was almost equivalent as BC columns, and bone-column contact rate was higher than BC columns significantly at twelve weeks after implantation. The newly devised SL surface had almost equivalent bone fixation strength comparable to the conventional BC surface. Also, this surface should provide a useful porous surface for use in artificial joints since there is no risk of surface structure detachment.