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- Author or Editor: Eugene P. Steffey x
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OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug.
ANIMALS 11 Thoroughbred horses enrolled in a fitness training program.
PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed.
RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration.
CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.
Objective—To develop a method for surgical placement of a commercial microsensor intracranial pressure (ICP) transducer and to characterize normal ICP and cerebral perfusion pressures (CPP) in conscious adult horses.
Animals—6 healthy castrated male adult horses (1 Holsteiner, 1 Quarter Horse, and 4 Thoroughbreds).
Procedure—Anesthesia was induced and maintained by use of isoflurane as the sole agent. Catheters were inserted percutaneously into the jugular vein and carotid artery. A microsensor ICP transducer was inserted in the subarachnoid space by means of right parietal craniotomy. The burr hole was then sealed with bone wax, the surgical incision was sutured, and the transducer was secured in place. Measurements were collected 1 hour after horses were able to stand during recovery from anesthesia.
Results—Mean ± SD values for ICP and CPP were 2 ± 4 and 102 ± 26 mm Hg, respectively.
Conclusion and Clinical Relevance—This report describes a relatively facile technique for obtaining direct and accurate ICP measurements for adult horses. The ICP values obtained in this study are within reference ranges established for other species and provide a point of reference for the diagnosis of abnormal ICP in adult horses. (Am J Vet Res 2002;63:1252–1256)
Objective—To test the hypothesis that isofluraneanesthetized horses during controlled ventilation and spontaneous ventilation exhibit temporal changes in cerebral hemodynamics, as measured by intracranial pressure and cerebral perfusion pressure, that reflect temporal changes in systemic arterial pressure.
Animals—6 healthy adult horses.
Procedure—Horses were anesthetized in left lateral recumbency with 1.57% isoflurane in O2 for 5 hours in 2 experiments by use of either controlled ventilation (with normocapnia) or spontaneous ventilation (with hypercapnia) in a randomized crossover design. Intracranial pressure was measured with a subarachnoid strain-gauge transducer. Carotid artery pressure, central venous pressure, airway pressures, blood gases, and minute ventilation also were measured.
Results—Intracranial pressure during controlled ventilation significantly increased during constant dose isoflurane anesthesia and thus contributed to decreasing cerebral perfusion pressure. Intracranial pressure was initially higher during spontaneous ventilation than during controlled ventilation, but this difference disappeared over time; no significant differences in cerebral perfusion pressures were observed between horses that had spontaneous or controlled ventilation.
Conclusions and Clinical Relevance—Cerebral hemodynamics and their association with ventilation mode are altered over time in isoflurane-anesthetized horses and could contribute to decreased cerebral perfusion during prolonged anesthesia. (Am J Vet Res 2003;64:1444–1448)
Objective—To measure the effects of isoflurane end-tidal concentration and mode of ventilation (spontaneous vs controlled) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in horses.
Animals—6 adult horses of various breeds.
Procedure—Anesthesia was induced and maintained with isoflurane in O2 in 6 healthy, unmedicated, adult horses. Using a subarachnoid strain gauge transducer, ICP was measured. Blood gas tensions and carotid artery pressures also were measured. Four isoflurane doses were studied, corresponding to the following multiples of the minimum alveolar concentration (MAC): 1.0 MAC, 1.2 MAC, 1.4 MAC, and 1.6 MAC. Data were collected during controlled ventilation and spontaneous ventilation at each dose.
Results—Increasing isoflurane end-tidal concentration induced significant dose-dependent decreases in mean arterial pressure (MAP) and CPP but no change in ICP. Hypercapnic spontaneous ventilation caused significant increases in MAP and ICP, compared with normocapnic controlled ventilation; no change in CPP was observed.
Conclusion and Clinical Relevance—Hypercapnia likely increases cerebral blood flow (CBF) by maintaining CPP in the face of presumed cerebral vasodilation in healthy anesthetized horses. The effect of isoflurane dose on CBF, however, remains unresolved because it depends on the opposinginfluences of a decrease in CCP and cerebral vasodilation. (Am J Vet Res 2003;64:21–25)
Objective—To determine pharmacokinetics and selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys.
Animals—6 adult male rhesus monkeys.
Procedure—Fentanyl (8 mg/kg of body weight, IV) was administered to 6 monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and esophageal temperature were kept constant, and ventilation was mechanically assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and fentanyl concentrations were determined before and for 8 hours after administration of fentanyl. Pharmacokinetics of fentanyl were derived by use of noncompartmental methods based on statistical moment theory.
Results—Heart rate and mean arterial pressure decreased transiently following fentanyl administration. Maximal decreases were observed 5 to 15 minutes after administration. Arterial pH, PaCO2, and PaO2 ranged from 7.46 ± 0.04 to 7.51 ± 0.05 units, 29.2 ± 3 to 34.6 ± 4.4 mm Hg, and 412.6 ± 105.3 to 482.9 ± 71.2 mm Hg, respectively. The clearance, volume of distribution area, volume of distribution steady state, mean residence time, area under the curve, elimination rate constant, and half-life were 32.5 ± 2.48 ml/kg/min, 9.04 ± 1.91 L/kg, 7.0 ± 1.2 L/kg, 218.5 ± 35.5 min, 0.247 ± 0.019 mg/ml/min, 0.004 ± 0.001/min, and 192.0 ± 33.5 min, respectively.
Conclusions and Clinical Relevance—Transient but potentially clinically important decreases in heart rate and mean arterial pressure were observed following fentanyl administration. Distribution and clearance data were similar to those reported for dogs and humans. (Am J Vet Res 2000;61:931–934)
Objective—To compare anesthesia-related events associated with IV administration of 2 novel micellar microemulsion preparations (1% and 5%) and a commercially available formulation (1%) of propofol in horses.
Animals—9 healthy horses.
Procedures—On 3 occasions, each horse was anesthetized with 1 of the 3 propofol formulations (1% or 5% microemulsion or 1% commercial preparation). All horses received xylazine (1 mg/kg, IV), and anesthesia was induced with propofol (2 mg/kg, IV). Induction and recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and at intervals following anesthesia for quantification of clinicopathologic variables.
Results—Compared with the commercial formulation, the quality of anesthesia induction in horses was slightly better with the micellar microemulsion formulas. In contrast, recovery characteristics were qualitatively and quantitatively indistinguishable among treatment groups (eg, time to stand after anesthesia was 34.3 ± 7.3 minutes, 34.1 ± 8.8 minutes, and 39.0 ± 7.6 minutes in horses treated with the commercial formulation, 1% microemulsion, and 5% microemulsion, respectively). During recovery from anesthesia, all horses stood on the first attempt and walked within 5 minutes of standing. No clinically relevant changes in hematologic and serum biochemical analytes were detected during a 3-day period following anesthesia.
Conclusions and Clinical Relevance—Results suggest that the micellar microemulsion preparation of propofol (1% or 5%) has similar anesthetic effects in horses, compared with the commercially available lipid propofol formulation. Additionally, the micellar microemulsion preparation is anticipated to have comparatively low production costs and can be manufactured in various concentrations.
Objective—To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine.
Animals—8 healthy horses (mean ± SEM age, 6.6 ± 1.0 years; mean body weight, 551 ± 50 kg).
Procedures—Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration.
Results—Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation.
Conclusions and Clinical Relevance—Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period.
Objective—To evaluate the use of xylazine and ketamine for total IV anesthesia in horses.
Procedure—Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, IV), guaifenesin (75 mg/kg, IV), and ketamine (2 mg/kg, IV). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (µg/kg/min) and X and K represent xylazine and ketamine, respectively: X35+K90 with 100% inspired oxygen (O2), X35+K120-O2, X35+K150-O2, X70+K90-O2, K150-O2, and X35+K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated.
Results—Heart rate and cardiac index were higher and total peripheral resistance lower in K150-O2 and X35+K120-air groups. The mean arterial pressure was highest in the X35+K120-air group and lowest in the K150-O2 group (125 ± 6 vs 85 ± 8 at 20 minutes, respectively). Mean PaO2 was lowest in the X35+K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-O2 (23 ± 6 minutes and 33 ± 8 minutes, respectively) and longest for those receiving X70+K90-O2 (58 ± 28 minutes and 69 ± 27 minutes, respectively).
Conclusions and Clinical Relevance—Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses. (Am J Vet Res 2005;66:1002–1007)
Objective—To establish the route of infusion (IV or intraosseous) that results in the highest concentration of amikacin in the synovial fluid of the tibiotarsal joint and determine the duration of peak concentrations.
Procedure—Regional perfusion of a limb on 15 horses was performed. Amikacin sulfate was infused into the saphenous vein or via intraosseous infusion into the distal portion of the tibia (1 g in 56 ml of lactated Ringer's solution) or proximal portion of the metatarsus (1 g of amikacin in 26 ml of lactated Ringer's solution). Amikacin concentrations were measured in sequential samples from tibiotarsal joint synovial fluid and serum. Samples were obtained immediately prior to release of the tourniquet and 0.5, 1, 4, 8, 12, and 24 hours after the tourniquet was released. Radiographic contrast material was infused into the same locations as the antibiotic perfusate to evaluate distribution in 6 other horses.
Results—Infusion into the saphenous vein produced the highest concentration of amikacin in the tibiotarsal joint, compared with the distal portion of the tibia (mean ± SE, 701.8 ± 366.8 vs 203.8 ± 64.5 µg/ml, respectively). Use of a lower volume of diluent in the proximal portion of the metatarsus produced a peak value of 72.2 ± 23.4 µg/ml.
Conclusions and Clinical Relevance—For regional perfusion of the tarsus, IV infusion is preferred to intraosseous infusion, because higher concentrations are achieved in the synovial fluid, and the procedure is easier to perform. (Am J Vet Res 2002;63:374–380).
Objective—To evaluate sevoflurane as an inhalation anesthetic for thoracotomy in horses.
Animals—18 horses between 2 and 15 years old.
Procedure—4 horses were used to develop surgical techniques and were euthanatized at the end of the procedure. The remaining 14 horses were selected, because they had an episode of bleeding from their lungs during strenuous exercise. General anesthesia was induced with xylazine (1.0 mg/kg of body weight, IV) followed by ketamine (2.0 mg/kg, IV). Anesthesia was maintained with sevoflurane in oxygen delivered via a circle anesthetic breathing circuit. Ventilation was controlled to maintain PaCO2 at approximately 45 mm Hg. Neuromuscular blocking drugs (succinylcholine or atracurium) were administered to eliminate spontaneous breathing efforts and to facilitate surgery. Cardiovascular performance was monitored and supported as indicated.
Results—2 of the 14 horses not euthanatized died as a result of ventricular fibrillation. Mean (± SD) duration of anesthesia was 304.9 ± 64.1 minutes for horses that survived and 216.7 ± 85.5 minutes for horses that were euthanatized or died. Our subjective opinion was that sevoflurane afforded good control of anesthetic depth during induction, maintenance, and recovery.
Conclusions and Clinical Relevance—Administration of sevoflurane together with neuromuscular blocking drugs provides stable and easily controllable anesthetic management of horses for elective thoracotomy and cardiac manipulation. (Am J Vet Res 2000;61:1430–1437)