Dose range finding study for the efficacy of meloxicam administered prior to sodium urate-induced synovitis in cats.

OBJECTIVE: To determine the lowest efficacious dose of oral meloxicam for relieving pain in cats with a sodium urate (SU)-induced acute inflammatory synovitis. STUDY DESIGN: Randomized, blinded, controlled, and four-way crossover study. ANIMALS: Eight surgically neutered cats (four males, four females) paired according to sex. METHODS: Each pair of cats was treated with 0 (placebo), 0.025, 0.05, or 0.075 mg kg(-1) oral meloxicam once daily for 4 days prior to injection, into alternating stifles, of 1 mL of 20 mg mL(-1) SU crystals, beginning with the right stifle. Each cat received each of the four treatments, separated by at least 21 days. Analgesic efficacy was evaluated based on objective (e.g., pressure mat data total force, contact pressure, and contact area) and subjective (e.g., scores for Analgesia Scale [AS], Lameness Scale [LS], and Visual Analog Scale [VAS]) outcome measures for pain assessment. All outcome measures were recorded before and during 30 hours after SU injection. The pre-defined primary outcome measure was the area under the response-time curve (AUC(0-30) hours) of the total force of the injected limb. Data were analyzed by analysis of variance. A sequential test procedure was applied and the test sequence stopped in case of a nonsignificant result. RESULTS: Meloxicam at doses of 0.05 and 0.075 mg kg(-1) day(-1) PO was significantly different from placebo for the pre-defined primary outcome measure (i.e., AUC(0-30) hours of total force). All tested meloxicam doses were lower than placebo for the subjective outcome measures (i.e., AUC(0-30) hours of AS, LS, and VAS). CONCLUSIONS AND CLINICAL RELEVANCE: The lowest efficacious dose of meloxicam for relieving pain in cats with an SU-induced synovitis was 0.05 mg kg(-1) day(-1) PO according to the pre-defined primary outcome measure. However, lower doses may also be effective as seen in the subjective outcome measures.

Comparison of Etomidate, Benzocaine, and MS222 Anesthesia with and without Subsequent Flunixin Meglumine Analgesia in African Clawed Frogs (Xenopus laevis).

Often few alternative anesthetics for exotic species are available, due to the small numbers of these animals used in research. In this study, we evaluated the depth and duration of anesthesia in Xenopus laevis after their immersion in 3 doses of etomidate (15, 22.5, and 30 mg/L) and in 3 doses of benzocaine (0.1%, 0.5%, and 1%) compared with the 'gold standard,' tricaine methanesulfonate (MS222; 2 g/L). We then chose an optimal dose for each alternative anesthetic according to induction time, duration of surgical plane, and time to complete recovery. The optimal etomidate and benzocaine doses (22.5 mg/L and 0.1%, respectively) as well as the MS222 dose were then used to achieve a surgical plane of anesthesia, with the addition of flunixin meglumine (25 or 50 mg/kg) administered in the dorsal lymph sac at the completion of mock oocyte harvest. Efficacy of the analgesic was assessed at 1, 3, 6, and 24 h postoperatively by using acetic acid testing (AAT). Histology of the liver, kidney, and tissues surrounding the dorsal lymph sac was performed at day 3, 14, and 28 in each group of animals. Mild to moderate myocyte degeneration and necrosis were present in tissues surrounding the dorsal lymph sac at both flunixin meglumine doses after etomidate and benzocaine anesthesia. In addition, the 50-mg/kg dose of flunixin meglumine resulted in the death of 5 of the 12 frogs within 24 h, despite an otherwise uneventful anesthetic recovery. In conclusion, benzocaine and etomidate offer alternative anesthetic regimens, according to typical requirements for an anesthetic event. Flunixin meglumine at the 25-mg/kg dose provided analgesic relief at the latest time point during etomidate dosage and at all time points during benzocaine dosage, but further characterization is warranted regarding long-term or repeated analgesic administration.

Analgesic efficacy of preoperative administration of meloxicam or butorphanol in onychectomized cats.

OBJECTIVE: To determine analgesic efficacy and adverse effects of preemptive administration of meloxicam or butorphanol in cats undergoing onychectomy or onychectomy and neutering. DESIGN: Randomized controlled study. ANIMALS: 64 female and 74 male cats that were 4 to 192 months old and weighed 1.09 to 705 kg (2.4 to 15.5 lb). PROCEDURE: Cats received meloxicam (0.3 mg/kg [0.14 mg/lb], s.c.) or butorphanol (0.4 mg/kg [0.18 mg/lb], s.c.) 15 minutes after premedication and prior to anesthesia. A single blinded observer measured physiologic variables, assigned analgesia and lameness scores, and withdrew blood samples for each cat at baseline and throughout the 24 hours after surgery. Rescue analgesia (butorphanol, 0.4 mg/kg, i.v. or s.c.) or administration of acepromazine (0.025 to 0.05 mg/kg [0.011 to 0.023 mg/lb], i.v.) was allowed. RESULTS: Meloxicam-treated cats were less lame and had lower pain scores. Cortisol concentration was higher at extubation and lower at 1, 5, and 12 hours in the meloxicam-treated cats. Fewer meloxicam-treated cats required rescue analgesia at 3, 5, 12, and 24 hours after extubation. General impression scores were excellent or good in 75% of meloxicam-treated cats and 44% of butorphanol-treated cats. There was no treatment effect on buccal bleeding time; PCV and BUN concentration decreased in both groups, and glucose concentration decreased in meloxicam-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of meloxicam improved analgesia for 24 hours without clinically relevant adverse effects in cats that underwent onychectomy or onychectomy and neutering and provided safe, extended analgesia, compared with butorphanol.

Recent developments in nonsteroidal antiinflammatory drugs in cats.

Pain, particularly chronic pain, is an underestimated ailment in cats. Veterinarians tend to under-diagnose and under-treat pain in this aloof and stoic species. Until recently, there was only one analgesic (i.e., butorphanol) approved in the United States for use in cats; but many analgesics, particularly opioids, have been used extra-label for this purpose. Nonsteroidal antiinflammatory drugs (NSAIDs) have been used sparingly in cats because of safety concerns, which are less of an issue with the newer agents. Meloxicam is the only NSAID labeled for use in cats in the United States, but other agents are available in this country and are labeled for use in cats in other countries.

Pharmacokinetics and selected behavioral responses to butorphanol and its metabolites in goats following intravenous and intramuscular administration.

OBJECTIVE: To evaluate disposition of a single dose of butorphanol in goats after intravenous (IV) and intramuscular (IM) administration and to relate behavioral changes after butorphanol administration with plasma concentrations. DESIGN: Randomized experimental study. ANIMALS: Six healthy 3-year-old neutered goats (one male and five female) weighing 46.5 ± 10.5 kg (mean ± D). METHODS: Goats were given IV and IM butorphanol (0.1 mg kg-1) using a randomized cross-over design with a 1-week interval between treatments. Heparinized blood samples were collected at fixed intervals for subsequent determination of plasma butorphanol concentrations using an enzyme linked immunosorbent assay (ELISA). Pharmacokinetic values (volume of distribution at steady state [VdSS], systemic clearance [ClTB], extrapolated peak plasma concentration [C0] or estimated peak plasma concentration [CMAX], time to estimated peak plasma concentration [TMAX], distribution and elimination half-lives [t1/2], and bioavailability) were calculated. Behavior was subjectively scored. A two-tailed paired t-test was used to compare the elimination half-lives after IV and IM administration. Behavioral scores are reported as median (range). A Friedman Rank Sums test adjusted for ties was used to analyze the behavioral scores. A logit model was used to determine the effect of time and concentration on behavior. A value of p < 0.05 was considered significant. RESULTS: Volume of distribution at steady state after IV administration of butorphanol was 1.27 ± 0.73 L kg-1, and ClTB was 0.0096 ± 0.0024 L kg-1 minute-1. Extrapolated C0 of butorphanol after IV administration was 146.5 ± 49.8 ng mL-1. Estimated CMAX after IM administration of butorphanol was 54.98 ± 14.60 ng mL-1, and TMAX was 16.2 ± 5.2 minutes; bioavailability was 82 ± 41%. Elimination half-life of butorphanol was 1.87 ± 1.49 and 2.75 ± 1.93 hours for IV and IM administration, respectively. Goats became hyperactive after butorphanol administration within the first 5 minutes after administration. Behavioral scores for goats were significantly different from baseline at 15 minutes after IV administration and at 15 and 30 minutes after IM administration. Both time and plasma butorphanol concentration were predictors of behavior. Behavioral scores of all goats had returned to baseline by 120 minutes after IV administration and by 240 minutes after IM administration. Conclusions and Clinical Relevance The dose of butorphanol (0.1 mg kg-1, IV or IM) being used clinically to treat postoperative pain in goats has an elimination half-life of 1.87 and 2.75 hours, respectively. Nonpainful goats become transiently excited after IV and IM administration of butorphanol. Clinical trials to validate the efficacy of butorphanol as an analgesic in goats are needed.

Effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and mechanical threshold in goats.

OBJECTIVE: To evaluate the effects of medetomidine and its antagonism with atipamezole in goats. STUDY DESIGN: Prospective randomized crossover study with 1 week between treatments. ANIMALS: Six healthy 3-year-old neutered goats (three male and three female) weighing 39.1-90.9 kg (60.0 +/- 18 kg, mean +/- SD). METHODS: Goats were given medetomidine (20 microg kg(-1), IV) followed, 25 minutes later, by either atipamezole (100 microg kg(-1), IV) or saline. Heart and respiratory rate, rectal temperature, indirect blood pressure, and mechanical threshold were measured, and sedation and posture were scored and blood samples obtained to measure epinephrine, norepinephrine, free fatty acids, glucose, and cortisol concentrations at baseline (immediately before medetomidine), 5 and 25 minutes after medetomidine administration, and at 5, 30, 60, and 120 minutes after the administration of antagonist or saline. Parametric and nonparametric tests were used to evaluate data; p < 0.05 was considered significant. RESULTS: Medetomidine decreased body temperature, heart rate, and respiratory rate and increased mean arterial blood pressure, cortisol, and glucose. Recumbency occurred 89 +/- 50 seconds after medetomidine administration. All goats were standing 86 +/- 24 seconds after atipamezole administration whereas all goats administered saline were sedate and recumbent at 2 hours. Tolerance to compression of the withers and metacarpus increased with medetomidine. From 5 to 120 minutes after saline or atipamezole administration, there were differences in body temperature, glucose, and cortisol but none in heart rate or blood pressure. Three of the six goats receiving saline developed bloat; five of six urinated. After atipamezole, four of six goats developed piloerection and all goats were agitated and vocalized. CONCLUSION: At the doses used, atipamezole antagonized the effects of medetomidine on recumbency, sedation, mechanical threshold, and the increase in glucose. Atipamezole increased the rate of return of cortisol toward baseline, and prevented further decline in rectal body temperature. CLINICAL RELEVANCE: Atipamezole may be used to antagonize some, but not all effects of medetomidine.