The aim of this study was to evaluate the respiratory and hemodynamic effects of a low-dose dexmedetomidine infusion [1mg/kg body weight (BW) per hour], with or without a loading dose (1 mg/kg BW), in dogs under isoflurane anesthesia. Thirty dogs were premedicated with methadone [0.3 mg/kg BW intramuscular (IM)], induced with propofol intravenous (IV) and maintained with isoflurane (1.3% to 1.4%) under mechanical ventilation. Animals were randomly assigned to 3 intravenous (IV) treatments (n = 10): 1 mg/kg BW dexmedetomidine, followed by 1 mg/kg BW per hour (group BI); or saline solution bolus, followed by either an infusion of 1 mg/kg BW per hour dexmedetomidine (group I) or saline solution (group C). The infusions were interrupted after 30 minutes. Respiratory system static compliance (Cstat) and respiratory system resistance (Rrs), partial pressure of oxygen/fractional inspired oxygen ratio (PaO(2)/FIO(2)), intrapulmonary shunt (Fshunt), and cardiac output (CO) were determined 5 minutes before the bolus (BASELINE), at the end of the bolus (BOLUS), and at 15 (T15), 30 (T3(0)), and 45 minutes (T45) intervals. In group BI, Cstat and PaO(2)/FiO(2) were higher at T15 and T3(0) than at BASELINE in the same group and than group C at the same times. In group I, the same parameters at T30 were higher than at BASELINE and than group C at the same time. In group BI, Rrs and Fshunt were lower than at BASELINE and than group C at the same time. In group I, the same parameters at T30 were lower than at BASELINE and those of group C at the same time. Cardiac output (CO) at T30 was higher in groups BI and I than in group C. The results of this study showed that low-dose dexmedetomidine infusion improves oxygenation and respiratory system mechanics and has a stabilizing hemodynamic effect in dogs anesthetized with isoflurane and mechanically ventilated.

OBJECTIVE: To assess the analgesic efficacy of an IV constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination in calves undergoing umbilical herniorrhaphy. ANIMALS: 20 weaned Holstein calves with umbilical hernias. PROCEDURES: Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). The assigned CRI was begun after anesthesia induction. A pain-scoring system and incisional algometry were used to assess pain, and blood samples were obtained to measure serum cortisol concentration at predetermined times for 120 hours after CRI initiation. RESULTS: Mean pain scores did not differ significantly between the MLK and control groups at any time. Mean algometry score for the MLK group was significantly greater (calves were less responsive to pressure) than that for the control group at 4 hours after CRI initiation. Mean cortisol concentration decreased over time for both groups and was significantly greater for the MLK group than the control group at 1, 4, and 18 hours after CRI initiation. CONCLUSIONS AND CLINICAL RELEVANCE: A CRI of MLK provided adequate postoperative analgesia to calves that underwent umbilical herniorrhaphy. However, the technical support required for CRI administration limits its use to hospital settings. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols and withdrawal intervals.

OBJECTIVE To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in guinea pigs (Cavia porcellus). ANIMALS 8 healthy adult guinea pigs (4 sexually intact females and 4 sexually intact males). PROCEDURES In a crossover study, hydromorphone (0.3 mg/kg) was administered once IM (epaxial musculature) or IV (cephalic catheter) to each guinea pig at a 1-week interval (2 treatments/guinea pig). Blood samples were collected before and at predetermined intervals after drug administration via a vascular access port. Plasma hydromorphone concentrations were determined by liquid chromatography–tandem mass spectrometry. Noncompartmental analysis of data was used to calculate pharmacokinetic parameters. RESULTS Mean ± SD clearance and volume of distribution for hydromorphone administered IV were 52.8 ± 13.5 mL/min/kg and 2.39 ± 0.479 L/kg, respectively. Mean residence time determined for the IV and IM administration routes was 0.77 ± 0.14 hours and 0.99 ± 0.34 hours, respectively. The maximum observed plasma concentration following IM administration of hydromorphone was 171.9 ± 29.4 ng/mL. No sedative effects were observed after drug administration by either route. CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetic data indicated that hydromorphone at a dose of 0.3 mg/kg may be administered IV every 2 to 3 hours or IM every 4 to 5 hours to maintain a target plasma concentration between 2 and 4 ng/mL in guinea pigs. Hydromorphone had high bioavailability after IM administration. Further research is necessary to evaluate the effects of other doses and administration routes and the analgesic effects of hydromorphone in guinea pigs.

OBJECTIVE To describe the pharmacokinetics of morphine, lidocaine, and ketamine associated with IV administration of a constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination to calves undergoing umbilical herniorrhaphy. ANIMALS 20 weaned Holstein calves with umbilical hernias. PROCEDURES Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). For all calves, the CRI was begun after anesthesia induction. Blood samples were obtained immediately before and at predetermined times for 120 hours after initiation of the assigned treatment. Noncompartmental analysis was used to estimate pharmacokinetic parameters for the MLK group. RESULTS During the CRI, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine. Mean terminal half-life was 4.1, 0.98, and 1.55 hours and area under the concentration-time curve was 41, 14,494, and 7,426 h•μg/mL for morphine, lidocaine, and ketamine, respectively. After the CRI, the mean serum drug concentration at steady state was 6.3, 616.7, and 328 ng/mL for morphine, lidocaine, and ketamine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE During the CRI of the MLK solution, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine, likely owing to the fairly long half-life of morphine. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols.

Recumbency affects respiratory mechanics and oxygenation in anesthetized horses. Changes in pleural and abdominal pressures that can impair ventilation have not been described in all recumbencies. The objective of this study was to determine the effects of patient positioning on transdiaphragmatic pressure and selected hemodynamic variables. Horses were maintained under total intravenous general anesthesia with nasal oxygen supplementation. Transnasal balloon catheters in the stomach and thoracic esophagus were used to measure intrathoracic and gastric pressures in standing horses and in anesthetized horses positioned in right and left lateral recumbency, dorsal recumbency, reverse Trendelenburg position, and Trendelenburg position. Transdiaphragmatic pressure was calculated as the difference between gastric and intrathoracic pressures. Measurements of oxygen saturation (SpO(2)), heart rate, systolic, diastolic and mean arterial pressures, and respiratory rate were obtained every 5 minutes. When compared to dorsal recumbency, gastric expiratory pressure is decreased in the standing position. Thoracic expiratory pressure is decreased in standing and reverse Trendelenburg. Transdiaphragmatic expiratory pressure and SpO(2) are decreased in Trendelenburg. Heart rate is increased in reverse Trendelenburg. Systolic, diastolic, and mean arterial pressures are decreased in reverse Trendelenburg and increased in left lateral and right lateral recumbency. We found that there is wide variation in respiratory pressures between horses and positions and they are not predictive of associated changes in hemodynamic variables.

OBJECTIVE To evaluate the pharmacokinetics of hydromorphone hydrochloride after IM and IV administration to orange-winged Amazon parrots (Amazona amazonica). ANIMALS 8 orange-winged Amazon parrots (4 males and 4 females). PROCEDURES Hydromorphone (1 mg/kg) was administered once IM. Blood samples were collected 5 minutes and 0.5, 1.5, 2, 3, 6, and 9 hours after drug administration. Plasma hydromorphone concentrations were determined with liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated with a compartmental model. The experiment was repeated 1 month later with the same dose of hydromorphone administered IV. RESULTS Plasma hydromorphone concentrations were > 1 ng/mL for 6 hours in 8 of 8 and 6 of 7 parrots after IM and IV injection, respectively. After IM administration, mean bioavailability was 97.6%, and mean maximum plasma concentration was 179.1 ng/mL 17 minutes after injection. Mean volume of distribution and plasma drug clearance were 4.24 L/kg and 64.2 mL/min/kg, respectively, after IV administration. Mean elimination half-lives were 1.74 and 1.45 hours after IM and IV administration, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with rapid plasma clearance and a large volume of distribution after IV administration in orange-winged Amazon parrots. Drug elimination half-lives were short. Further pharmacokinetic studies of hydromorphone and its metabolites, including investigation of multiple doses, different routes of administration, and sustained-release formulations, are recommended.