This study assessed the feasibility of measuring tiludronate in horses using a minimally invasive bone biopsy technique. Eight horses were treated with intravenous (IV) tiludronate [1 mg/kg bodyweight (BW)], either once (n = 4) or twice, 28 d apart (n = 4). The horses that were treated once were euthanized on days 1, 43, 57, or 92 and those that were treated twice, were euthanized on days 112, 154, 194, or 364. Bone samples were taken bilaterally from each horse at 4 sites: the third metacarpal bone (MCIII), the 13th rib (R13), the tuber coxae (TC), and the cuboid bone (CB). Test samples were taken with a 5-mm diameter dental drill, while larger reference samples were taken with an osteotome. The concentrations of tiludronate were measured by high performance liquid chromatography (HPLC) with ultraviolet (UV) detection. The TC was the easiest site to sample, and no technical difficulties were encountered for extraction and measurement. Drill sampling at the MCIII was difficult. Moreover, both the extraction and measurement caused technical problems and results were unreliable in most cases (93%). Drill samples obtained from the R13 were very small and access to the CB required considerable dissection, which would not be feasible in vivo. Forty-six percent and 36% of the tiludronate measurements performed on the R13 and CB samples, respectively, were unreliable. The ratio of tiludronate concentrations ranged from 73% to 185% (median: 118%) in the TC, 65% to 208% (median: 81%) in the R13, and 26% to 110% (median: 57%) in the CB. In all but 1 horse, the highest concentrations of tiludronate were found in the TC. It was concluded that bone biopsies performed at the TC were adequate for measuring tiludronate in horses and should be considered in future for repeated measurements over time in living animals.

Objective-To determine plasma concentrations and behavioral, antinociceptive, and physiologic effects of methadone administered via IV and oral transmucosal (OTM) routes in cats. Animals-8 healthy adult cats. Procedures-Methadone was administered via IV (0.3 mg/kg) and OTM (0.6 mg/kg) routes to each cat in a balanced crossover design. On the days of drug administration, jugular catheters were placed in all cats under anesthesia; a cephalic catheter was also placed in cats that received methadone IV. Baseline measurements were obtained greater than 90 minutes after extubation, and methadone was administered via the predetermined route. Heart and respiratory rates were measured; sedation, behavior, and antinociception were evaluated, and blood samples were collected for methadone concentration analysis at predetermined intervals for 24 hours after methadone administration. Data were summarized and evaluated statistically. Results-Plasma concentrations of methadone were detected rapidly after administration via either route. Peak concentration was detected 2 hours after OTM administration and 10 minutes after IV administration. Mean +/- SD peak concentration was lower after OTM administration (81.2 +/- 14.5 ng/mL) than after IV administration (112.9 +/- 28.5 ng/mL). Sedation was greater and lasted longer after OTM administration. Antinociceptive effects were detected 10 minutes after administration in both groups; these persisted greater than 2 hours after IV administration and greater than 4 hours after OTM administration. Conclusions and Clinical Relevance-Despite lower mean peak plasma concentrations, duration of antinociceptive effects of methadone was longer after OTM administration than after IV administration. Methadone administered via either route may be useful for perioperative pain management in cats.

Objective—To determine effects of a continuous rate infusion of lidocaine on the minimum alveolar concentration (MAC) of sevoflurane in horses. Animals—8 healthy adult horses. Procedures—Horses were anesthetized via IV administration of xylazine, ketamine, and diazepam; anesthesia was maintained with sevoflurane in oxygen. Approximately 1 hour after induction, sevoflurane MAC determination was initiated via standard techniques. Following sevoflurane MAC determination, lidocaine was administered as a bolus (1.3 mg/kg, IV, over 15 minutes), followed by constant rate infusion at 50 μg/kg/min. Determination of MAC for the lidocaine-sevoflurane combination was started 30 minutes after lidocaine infusion was initiated. Arterial blood samples were collected after the lidocaine bolus, at 30-minute intervals, and at the end of the infusion for measurement of plasma lidocaine concentrations. Results—IV administration of lidocaine decreased mean ± SD sevoflurane MAC from 2.42 ± 0.24% to 1.78 ± 0.38% (mean MAC reduction, 26.7 ± 12%). Plasma lidocaine concentrations were 2,589 ± 811 ng/mL at the end of the bolus; 2,065 ± 441 ng/mL, 2,243 ± 699 ng/mL, 2,168 ± 339 ng/mL, and 2,254 ± 215 ng/mL at 30, 60, 90, and 120 minutes of infusion, respectively; and 2,206 ± 329 ng/mL at the end of the infusion. Plasma concentrations did not differ significantly among time points. Conclusions and Clinical Relevance—Lidocaine could be useful for providing a more balanced anesthetic technique in horses. A detailed cardiovascular study on the effects of IV infusion of lidocaine during anesthesia with sevoflurane is required before this combination can be recommended.

This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.

Objective--To determine whether joint lavage performed simultaneously with IV regional limb perfusion (IVRLP) reduces the effectiveness of IVRLP and to compare 2 types of tourniquets used for this procedure in horses. Animal--11 adult horses. Procedures--2 groups of 6 horses were tested by use of a pneumatic or an Esmarch tourniquet (1 horse was tested twice [once in each group]). Standing IVRLP with amikacin (500 mg) was performed for 30 minutes. Simultaneously, the metacarpophalangeal joint was lavaged with 2 L of lactated Ringer's solution and the egress fluids were collected. Samples of the distal interphalangeal joint synovial fluid and blood from the digital and jugular veins were collected at set time intervals. Amikacin concentrations in all fluids were determined via fluorescence polarization immunoassay. Results--Less amikacin was measured in the systemic circulation with the Esmarch tourniquet than with the pneumatic tourniquet. Amikacin concentrations in the synovial fluid from the distal interphalangeal joints of the Esmarch tourniquet group ranged from 45.1 to 1,968 μg/mL and in the pneumatic tourniquet group ranged from 1.7 to 92.3 μg/mL after 30 minutes of IVRLP. Total loss of amikacin in the egress fluids from the joint lavage ranged from < 1.36 to 7.72 mg for the Esmarch tourniquet group and from < 1.20 to 1.75 mg for the pneumatic tourniquet group. Conclusions and Clinical Relevance--On standing horses, IVRLP performed simultaneously with joint lavage resulted in negligible loss of amikacin in the egress lavage fluids. The Esmarch tourniquet was more effective in preventing loss of amikacin from the distal portion of the limb, easier to use, and less expensive than the pneumatic tourniquet.

Objective—To evaluate whether guaifenesin can prevent adverse anesthetic induction events caused by propofol and whether a guaifenesin-propofol induction combination has brief cardiovascular effects commensurate with rapid drug washout. Animals—8 healthy adult horses. Procedures—Guaifenesin was administered IV for 3 minutes followed by IV injection of a bolus of propofol (2 mg/kg). Additional propofol was administered if purposeful movement was detected. Anesthesia was maintained for 2 hours with isoflurane or sevoflurane at 1.2 times the minimum alveolar concentration with controlled normocapnic ventilation. Normotension was maintained via a dobutamine infusion. Plasma concentrations of propofol and guaifenesin were measured every 30 minutes. Results—Mean ± SD guaifenesin and propofol doses inducing anesthesia in half of the horses were 73 ± 18 mg/kg and 2.2 ± 0.3 mg/kg, respectively. No adverse anesthetic induction events were observed. By 70 minutes, there was no significant temporal change in the dobutamine infusion rate required to maintain normotension for horses anesthetized with isoflurane or sevoflurane. Mean plasma guaifenesin concentrations were 122 ± 30µM, 101 ± 33µM, 93 ± 28µM, and 80 ± 24µM at 30, 60, 90, and 120 minutes after anesthetic induction, respectively. All plasma propofol concentrations were below the limit of quantitation. Conclusions and Clinical Relevance—Guaifenesin prevented adverse anesthetic induction events caused by propofol. Guaifenesin (90 mg/kg) followed by propofol (3 mg/kg) should be sufficient to immobilize > 99% of calm healthy adult horses. Anesthetic drug washout was rapid, and there was no change in inotrope requirements after anesthesia for 70 minutes.

Objective—To determine the pharmacokinetics of tramadol and its metabolites O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) in adult horses. Animals—12 mixed-breed horses. Procedures—Horses received tramadol IV (5 mg/kg, over 3 minutes) and orally (10 mg/kg) with a 6-day washout period in a randomized crossover design. Serum samples were collected over 48 hours. Serum tramadol, ODT, and NDT concentrations were measured via high-performance liquid chromatography and analyzed via noncompartmental analysis. Results—Maximum mean ± SEM serum concentrations after IV administration for tramadol, ODT, and NDT were 5,027 ± 638 ng/mL, 0 ng/mL, and 73.7 ± 12.9 ng/mL, respectively. For tramadol, half-life, volume of distribution, area under the curve, and total body clearance after IV administration were 2.55 ± 0.88 hours, 4.02 ± 1.35 L/kg, 2,701 ± 275 h•ng/mL, and 30.1 ± 2.56 mL/min/kg, respectively. Maximal serum concentrations after oral administration for tramadol, ODT, and NDT were 238 ± 41.3 ng/mL, 86.8 ± 17.8 ng/mL, and 159 ± 20.4 ng/mL, respectively. After oral administration, half-life for tramadol, ODT, and NDT was 2.14 ± 0.50 hours, 1.01 ± 0.15 hours, and 2.62 ± 0.49 hours, respectively. Bioavailability of tramadol was 9.50 ± 1.28%. After oral administration, concentrations achieved minimum therapeutic ranges for humans for tramadol (> 100 ng/mL) and ODT (> 10 ng/mL) for 2.2 ± 0.46 hours and 2.04 ± 0.30 hours, respectively. Conclusions and Clinical Relevance—Duration of analgesia after oral administration of tramadol might be < 3 hours in horses, with ODT and the parent compound contributing equally.

Objective: To determine whether therapeutic concentrations of levetiracetam can be achieved in cats and to establish reasonable IV and oral dosing intervals that would not be associated with adverse effects in cats. Animals: 10 healthy purpose-bred cats. Procedures: In a randomized crossover study, levetiracetam (20 mg/kg) was administered orally and IV to each cat. Blood samples were collected 0, 10, 20, and 40 minutes and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after administration. Plasma levetiracetam concentrations were determined via high-performance liquid chromatography. Results: Mean ± SD peak concentration was 25.54 ± 7.97 μg/mL. The mean y-intercept for IV administration was 37.52 ± 6.79 μg/mL. Half-life (harmonic mean ± pseudo-SD) was 2.95 ± 0.95 hours and 2.86 ± 0.65 hours for oral and IV administration, respectively. Mean volume of distribution at steady state was 0.52 ± 0.09 L/kg, and mean clearance was 2.0 ± 0.60 mL/kg/min. Mean oral bioavailability was 102 ± 39%. Plasma drug concentrations were maintained in the therapeutic range reported for humans (5 to 45 μg/mL) for at least 9 hours after administration in 7 of 10 cats. Only mild, transient hypersalivation was evident in some cats after oral administration. Conclusions and Clinical Relevance: Levetiracetam (20 mg/kg) administered orally or IV to cats every 8 hours should achieve and maintain concentrations within the therapeutic range for humans. Levetiracetam administration has favorable pharmacokinetics for clinical use, was apparently tolerated well, and may be a reasonable alternative antiepileptic drug in cats.

Objective--To establish a computed tomography (CT)-angiography protocol and measure the diameters of major arteries in parrots. Animals--13 Hispaniolan Amazon parrots (Amazona ventralis). Procedures--16-slice CT scanning was used to measure the apparent diameter of the ascending aorta, abdominal aorta, pulmonary arteries, and brachiocephalic trunk. Before scanning, all birds underwent ECG and echocardiographic assessment and were considered free of detectable cardiovascular diseases. Each bird was anesthetized, and a precontrast helical CT scan was performed. Peak aortic enhancement was established with a test bolus technique via dynamic axial CT scan over a predetermined single slice. An additional bolus of contrast medium was then injected, and a helical CT-angiography scan was performed immediately afterward. Arterial diameter measurements were obtained by 2 observers via various windows before and after injection, and intra- and interobserver agreement was assessed. Results--Reference limits were determined for arterial diameter measurements before and after contrast medium administration in pulmonary, mediastinal, and manual angiography windows. Ratios of vertebral body diameter to keel length were also calculated. Intraobserver agreement was high (concordance correlation coefficients ≥ 0.95); interobserver agreement was medium to high (intraclass correlation coefficients ≥ 0.65). Conclusions and Clinical Relevance--CT-angiography was safe and is of potential diagnostic value in parrots. We recommend performing the angiography immediately after IV injection of 3 mL of iohexol/kg. Arterial diameter measurements at the described locations were reliable.

Objective—To compare cardiovascular effects of sevoflurane alone and sevoflurane plus an IV infusion of lidocaine in horses. Animals—8 adult horses. Procedures—Each horse was anesthetized twice via IV administration of xylazine, diazepam, and ketamine. During 1 anesthetic episode, anesthesia was maintained by administration of sevoflurane in oxygen at 1.0 and 1.5 times the minimum alveolar concentration (MAC). During the other episode, anesthesia was maintained at the same MAC multiples via a reduced concentration of sevoflurane plus an IV infusion of lidocaine. Heart rate, arterial blood pressures, blood gas analyses, and cardiac output were measured during mechanical (controlled) ventilation at both 1.0 and 1.5 MAC for each anesthetic protocol and during spontaneous ventilation at 1 of the 2 MAC multiples. Results—Cardiorespiratory variables did not differ significantly between anesthetic protocols. Blood pressures were highest at 1.0 MAC during spontaneous ventilation and lowest at 1.5 MAC during controlled ventilation for either anesthetic protocol. Cardiac output was significantly higher during 1.0 MAC than during 1.5 MAC for sevoflurane plus lidocaine but was not affected by anesthetic protocol or mode of ventilation. Clinically important hypotension was detected at 1.5 MAC for both anesthetic protocols. Conclusions and Clinical Relevance—Lidocaine infusion did not alter cardiorespiratory variables during anesthesia in horses, provided anesthetic depth was maintained constant. The IV administration of lidocaine to anesthetized nonstimulated horses should be used for reasons other than to improve cardiovascular performance. Severe hypotension can be expected in nonstimulated horses at 1.5 MAC sevoflurane, regardless of whether lidocaine is administered.