Determination of the effective dosage of tiletamine–zolazepam–ketamine–xylazine,with or without methadone,in dogs

ObjectiveTo determine the effective dosage of the combination tiletamine–zolazepam–ketamine–xylazine (TKX), with or without methadone, in dogs.Study designProspective, randomized, experimental study.AnimalsA total of 29 dogs.MethodsDogs were randomly administered TKX (group TKX, n = 13) or combined with 0.3 mg kg^–1 of methadone (group TKXM, n = 16) intramuscularly. The TKX solution contained tiletamine (50 mg mL^–1), zolazepam (50 mg mL^–1), ketamine (80 mg mL^–1) and xylazine (20 mg mL^–1). The effective dosages for immobility in 50% and 95% of the population (ED₅₀ and ED₉₅) were estimated using the up-and-down method. Approximately 20 minutes after drug administration, a skin incision was performed and the response was judged as positive or negative if the dogs moved or did not move, respectively. The TKX volume for the subsequent dog in the same group was increased or decreased by 0.005 mL kg^–1 if the response of the previous dog was positive or negative, respectively. Heart and respiratory rates, and sedation/anesthesia scores (range 0–21) were recorded before and 15 minutes after drug administration.ResultsEstimated ED₅₀ and ED₉₅ (95% confidence intervals) were: TKX, 0.025 (0.020–0.029) and 0.026 (0.010–0.042) mL kg^–1; TKXM, 0.022 (0.018–0.025) and 0.033 (0.017–0.049) mL kg^–1. Median (interquartile range) scores for sedation/anesthesia were 17 (16–18) and 17 (15–20), and times until lateral recumbency were 5 (4–6) and 6 (4–10) minutes in TKX and TKXM, respectively (p > 0.05). In both groups heart and respiratory rates decreased, but values remained acceptable for anesthetized dogs.Conclusions and clinical relevanceThe results provide a guide for volumes of TKX and TKXM in dogs requiring restraint for minimally invasive procedures. Inclusion of methadone in the TKX combination did not influence ED₅₀.     

Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site

ObjectiveTo describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.Study designRandomized crossover experiment; prospective study.AnimalsEleven healthy adult horses between 6 and 20 years of age and weighing 487–592 kg.MethodsIn the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg^?1) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg^?1 SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.ResultsFollowing IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg^?1 minute^?1 and volume of distribution at steady-state was 3.16 ± 0.65 L kg^?1. Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.Conclusions and clinical relevanceBuprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.     

Postanesthetic hyperthermia in cats: a retrospective comparison between hydromorphone and buprenorphine

OBJECTIVE: To determine the prevalence of postanesthetic hyperthermia [rectal temperature >40 degrees C (104 degrees F)] in a clinical population of cats. STUDY DESIGN: Retrospective study. ANIMAL POPULATION: One hundred and twenty-five cats with an age range of 2 months to 16.1 years, and weighing 3.9 +/- 1.5 kg. MATERIALS AND METHODS: Data were obtained from the medical records of 125 cats that underwent general anesthesia. Information on perioperative rectal temperatures, breed, sex, weight, surgical procedure, anesthetic time, surgery time, anesthetic and analgesic drugs were retrieved. STATISTICAL ANALYSES: Five groups of cats were compared; group 1 (n = 15) received acepromazine and no opioids; group 2 (n = 17) received acepromazine and buprenorphine; group 3 (n = 19) received acepromazine, buprenorphine and ketoprofen; group 4 (n = 45) received acepromazine and hydromorphone and group 5 (n = 29) received acepromazine, hydromorphone and ketoprofen. Data conformed to a split-plot repeated measures analysis of variance and was analyzed using SAS PROC MIXED. Post hoc tests were by means of Bonferroni t-test; < or = 0.05 was considered significant. RESULTS: Rectal temperature was significantly decreased in all groups at the end of anesthesia. Rectal temperature was significantly elevated at 1, 1.5, 2, 3, 4 and 5 hours after the end of anesthesia in group 4, and at 2, 3 and 4 hours in group 5. Sixty-four percent of cats in group 4 and 69% in group 5 had rectal temperatures >40 degrees C (104 degrees F) at one or more times in the postanesthetic period. The highest temperature recorded was 42.5 degrees C (108.5 degrees F) in one cat in group 4. Mean rectal temperature did not exceed the preoperative temperature at any time during the postanesthetic period in group 1, 2 and 3 animals. CONCLUSIONS: This study indicates an association between hyperthermia and perioperative administration of hydromorphone in cats. CLINICAL RELEVANCE: When hydromorphone is used in cats their body temperature should be closely monitored.