Objective—To test the hypothesis that butorphanol or morphine induces antinociception with minimal respiratory depression in conscious red-eared slider turtles.
Design—Prospective crossover study.
Animals—37 adult male and female red-eared slider turtles (Trachemys scripta).
Procedures—Antinociception (n = 27 turtles) and respiratory (10 turtles) experiments were performed. Infrared heat stimuli were applied to the plantar surface of turtle limbs. Thermal withdrawal latencies were measured before and at intervals after SC administration of physiologic saline (0.9% NaCl) solution, butorphanol tartrate (2.8 or 28 mg/kg [1.27 or 12.7 mg/lb]), or morphine sulfate (1.5 or 6.5 mg/kg [0.68 or 2.95 mg/lb]). Ventilation was assessed in freely swimming turtles before and after SC administration of saline solution, butorphanol (28 mg/kg), or morphine (1.5 mg/kg).
Results—For as long as 24 hours after injection of saline solution or either dose of butorphanol, thermal withdrawal latencies among turtles did not differ. Low- and high-dose morphine injections increased latencies significantly by 8 hours. Ventilation was not altered by saline solution administration, was temporarily depressed by 56% to 60% for 1 to 2 hours by butorphanol (28 mg/kg) administration, and was significantly depressed by a maximum of 83 ± 9% at 3 hours after morphine (1.5 mg/kg) injection. Butorphanol and morphine depressed ventilation by decreasing breathing frequency.
Conclusions and Clinical Relevance—Although widely used in reptile species, butorphanol may not provide adequate antinociception for invasive procedures and caused short-term respiratory depression in red-eared slider turtles. In contrast, morphine apparently provided antinociception but caused long-lasting respiratory depression.
OBJECTIVE To determine the clinical features, treatment, and outcomes of treatment for oral and cutaneous squamous cell carcinoma (SCC) in avian species.
DESIGN Retrospective case series with nested cohort study.
ANIMALS 87 client-owned birds of various species with histologically confirmed SCC of the skin or oral cavity.
PROCEDURES Clinicians entered case information through an online survey tool. Data were collected regarding patient signalment, concurrent conditions, treatments, adverse effects, and clinical outcomes. Relationships were examined between complete excision and partial or complete response. Survival analysis was performed to compare outcomes among groupings of therapeutic approaches.
RESULTS Only 7 of 64 (11%) birds for which full outcome data were available had complete remission of SCC; 53 (83%) had progressive disease, were euthanized, or died of the disease. The unadjusted OR for partial or complete response following complete tumor excision (vs other treatment approaches) was 6.9 (95% confidence interval [CI], 1.8 to 25.8). Risk of death was 62% lower (hazard ratio, 0.38; 95% CI, 0.19 to 0.77) for birds that underwent complete excision versus conservative treatment. Median survival time from initial evaluation for birds receiving complete excision was 628 days (95% CI, 210 to 1,008 days), compared with 171 days (95% CI, 89 to 286 days) for birds receiving monitoring with or without conservative treatment. Birds receiving any other additional treatment had a median survival time of 357 days (95% CI, 143 to 562 days).
CONCLUSIONS AND CLINICAL RELEVANCE For birds with SCC, complete excision was the only treatment approach significantly associated with complete or partial response and increased survival time.
To evaluate the thermal antinociceptive effects of hydromorphone hydrochloride after IM administration to orange-winged Amazon parrots (Amazona amazonica).
8 healthy adult parrots (4 males and 4 females).
In a randomized crossover study, each bird received hydromorphone (0.1, 1, and 2 mg/kg) and saline (0.9% NaCl) solution (1 mL/kg; control) IM, with a 7-day interval between treatments. Each bird was assigned an agitation-sedation score, and the thermal foot withdrawal threshold (TFWT) was measured at predetermined times before and after treatment administration. Adverse effects were also monitored. The TFWT, agitation-sedation score, and proportion of birds that developed adverse effects were compared among treatments over time.
Compared with the mean TFWT for the control treatment, the mean TFWT was significantly increased at 0.5, 1.5, and 3 hours and 1.5, 3, and 6 hours after administration of the 1- and 2-mg/kg hydromorphone doses, respectively. Significant agitation was observed at 0.5, 1.5, and 3 hours after administration of the 1 - and 2-mg/kg hydromorphone doses. Other adverse effects observed after administration of the 1- and 2-mg/kg doses included miosis, ataxia, and nausea-like behavior (opening the beak and moving the tongue back and forth).
CONCLUSIONS AND CLINICAL RELEVANCE
Although the 1- and 2-mg/kg hydromorphone doses appeared to have antinociceptive effects, they also caused agitation, signs of nausea, and ataxia. Further research is necessary to evaluate administration of lower doses of hydromorphone and other types of stimulation to better elucidate the analgesic and adverse effects of the drug in psittacine species.
To identify an oral dose of grapiprant for red-tailed hawks (RTHAs; Buteo jamaicensis) that would achieve a plasma concentration > 164 ng/mL, which is considered therapeutic for dogs with osteoarthritis.
6 healthy adult RTHAs.
A preliminary study, in which grapiprant (4 mg/kg [n = 2], 11 mg/kg , or 45 mg/kg ) was delivered into the crop of RTHAs from which food had been withheld for 24 hours, was performed to obtained pharmacokinetic data for use with modeling software to simulate results for grapiprant doses of 20, 25, 30, 35, and 40 mg/kg. Simulation results directed our selection of the grapiprant dose administered to the RTHAs in a single-dose study. Plasma grapiprant concentration, body weight, and gastrointestinal signs of RTHAs were monitored.
On the basis of results from the preliminary study and simulations, a grapiprant dose of 30 mg/kg was used in the single-dose study. The geometric mean maximum observed plasma concentration of grapiprant was 3,184 ng/mL, time to maximum plasma grapiprant concentration was 2.0 hours, and the harmonic mean terminal half-life was 17.1 hours. No substantial adverse effects were observed.
CONCLUSIONS AND CLINICAL RELEVANCE
Although the single dose of grapiprant (30 mg/kg) delivered into the crop achieved plasma concentrations > 164 ng/mL in the RTHAs, it was unknown whether this concentration would be therapeutic for birds. Further research that incorporates multidose assessments, safety monitoring, and pharmacodynamic data collection is warranted on the use of grapiprant in RTHAs from which food was withheld versus not withheld.
Describe the pharmacokinetics of grapiprant administered orally with food to red-tailed hawks (RTHAs; Buteo jamaicensis) and compare the results with previously described grapiprant pharmacokinetics administered without food in this species.
6 healthy adult RTHA (3 males, 3 females) under human care.
A single dose of grapiprant (30 mg/kg) was given orally to RTHAs, followed by force-feeding. Blood samples were obtained at 14 time points for 120 hours postgrapiprant administration. Plasma concentrations of grapiprant were measured via tandem liquid chromatography-mass spectrometry. Nonparametric superimposition using pharmacokinetic modeling software used plasma concentrations to calculate simulations of grapiprant plasma concentrations for 30 mg/kg administered orally with food every 12 hours.
The arithmetic mean maximum plasma concentration was 405.8 ng/mL, time to maximum plasma concentration was 16 hours, and harmonic mean terminal half-life was 15.6 hours. Simulations determined 30 mg/kg every 12 hours could attain minimum effective concentrations (> 164 ng/mL) reported in dogs for a sustained period of approximately 20 hours.
Grapiprant plasma concentrations were achieved above the canine therapeutic concentrations within 16 hours postmedication. Mean concentrations were maintained for approximately 20 hours. Simulations support a dosing frequency of 12-hour intervals with food reaching minimum effective concentrations established for canines, although it is unknown whether these plasma concentrations are therapeutic for birds. Bioaccumulation was not noted on simulations secondary to increased grapiprant administration. Further research including multidose assessments at this current dose with food, in vitro pharmacological characterization, and pharmacodynamic studies in this species are warranted.
OBJECTIVE To evaluate the thermal antinociceptive effects and pharmacokinetics of hydromorphone hydrochloride after IM administration to cockatiels (Nymphicus hollandicus).
ANIMALS 16 healthy adult cockatiels.
PROCEDURES During the first of 2 study phases, each cockatiel received each of 4 treatments (hydromorphone at doses of 0.1, 0.3, and 0.6 mg/kg and saline [0.9% NaCl] solution [0.33 mL/kg; control], IM), with a 14-day interval between treatments. For each bird, foot withdrawal to a thermal stimulus was determined following assignment of an agitation-sedation score at predetermined times before and for 6 hours after each treatment. During the second phase, a subset of 12 birds received hydromorphone (0.6 mg/kg, IM), and blood samples were collected at predetermined times for 9 hours after drug administration. Plasma hydromorphone concentration was determined by liquid chromatography–mass spectrometry. Noncompartmental analysis of sparse data was used to calculate pharmacokinetic parameters.
RESULTS Thermal withdrawal response did not differ among the 4 treatment groups at any time. Agitation-sedation scores following administration of the 0.3-and 0.6-mg/kg doses of hydromorphone differed significantly from those treated with saline solution and suggested the drug had a sedative effect. Plasma hydromorphone concentrations were > 1 ng/mL for 3 to 6 hours after drug administration in all birds.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IM administration of hydromorphone at the evaluated doses did not increase the thermal withdrawal threshold of cockatiels despite plasma drug concentrations considered therapeutic for other species. Further research is necessary to evaluate the analgesic effects of hydromorphone in cockatiels.
OBJECTIVE To evaluate thermal antinociceptive effects and pharmacokinetics of buprenorphine hydrochloride after IM administration to cockatiels (Nymphicus hollandicus).
ANIMALS 16 adult (≥ 2 years old) cockatiels (8 males and 8 females).
PROCEDURES Buprenorphine hydrochloride (0.3 mg/mL) at each of 3 doses (0.6, 1.2, and 1.8 mg/kg) and saline (0.9% NaCl) solution (control treatment) were administered IM to birds in a randomized within-subject complete crossover study. Foot withdrawal response to a thermal stimulus was determined before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were also determined. For the pharmacokinetic analysis, buprenorphine (0.6 mg/kg) was administered IM to 12 of the birds, and blood samples were collected at 9 time points ranging from 5 minutes to 9 hours after drug administration. Samples were analyzed with liquid chromatography–mass spectrometry. Pharmacokinetic parameters were calculated with commercial software.
RESULTS Buprenorphine at 0.6, 1.2, and 1.8 mg/kg did not significantly change the thermal foot withdrawal response, compared with the response for the control treatment. No significant change in agitation-sedation scores was detected between all doses of buprenorphine and the control treatment. Plasma buprenorphine concentrations were > 1 ng/mL in all 4 birds evaluated at 9 hours.
CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine at the doses evaluated did not significantly change the thermal nociceptive threshold for cockatiels or cause sedative or agitative effects. Additional studies with other pain assessments and drug doses are needed to evaluate the analgesic and adverse effects of buprenorphine in cockatiels and other avian species.
To determine the pharmacokinetics of amantadine after oral administration of single and multiple doses to orange-winged Amazon parrots (Amazona amazonica).
12 adult orange-winged Amazon parrots (6 males and 6 females).
A single dose of amantadine was orally administered to 6 birds at 5 mg/kg (n = 2), 10 mg/kg (2), and 20 mg/kg (2) in a preliminary trial. On the basis of the results, a single dose of amantadine (10 mg/kg, PO) was administered to 6 other birds. Two months later, multiple doses of amantadine (5 mg/kg, PO, q 24 h for 7 days) were administered to 8 birds. Heart rate, respiratory rate, behavior, and urofeces were monitored. Plasma concentrations of amantadine were measured via tandem liquid chromatography–mass spectrometry. Pharmacokinetic parameter estimates were determined via noncompartmental analysis.
Mean ± SD maximum plasma concentration, time to maximum plasma concentration, half-life, and area under the concentration-versus-time curve from the last dose to infinity were 1,174 ± 186 ng/mL, 3.8 ± 1.8 hours, 23.2 ± 2.9 hours, and 38.6 ± 7.4 μg·h/mL, respectively, after a single dose and 1,185 ± 270 ng/mL, 3.0 ± 2.4 hours, 21.5 ± 5.3 hours, and 26.3 ± 5.7 μg·h/mL, respectively, at steady state after multiple doses. No adverse effects were observed.
CONCLUSIONS AND CLINICAL RELEVANCE
Once-daily oral administration of amantadine at 5 mg/kg to orange-winged Amazon parrots maintained plasma concentrations above those considered to be therapeutic in dogs. Further studies evaluating safety and efficacy of amantadine in orange-winged Amazon parrots are warranted.
Procedures—In each bird, a standardized osteotomy of 1 femur was performed and the fracture was immobilized with an intramedullary pin. Degree of postoperative pain was evaluated 6 times/d for 4 days by use of 3 methods: an electronic perch for assessment of weight-bearing load differential of the pelvic limbs, 4 numeric rating pain scales for assessment of pain (all of which involved the observer in the same room as the bird), and analysis of video-recorded (observer absent) partial ethograms for bird activity and posture. Measurements obtained were compared with data collected before the surgery to evaluate the ability of these methods to detect pain.
Results—The weight-bearing load differential was a sensitive, specific, reliable, and indirect measure of fracture-associated pain in the model used. Two of 4 tested pain scales (fractured limb position and subjective evaluation of degree of pain) were sensitive and specific for detecting pain and were reliable in a research setting. Interobserver reliability of the 4 pain scales was excellent. Partial ethograms were sensitive for identifying pain-associated behavior in pigeons, particularly during the first 2 days after surgery.
Conclusions and Clinical Relevance—The fracture pain model was reliable and reproducible and may be useful for experimental studies involving postsurgical pain in pigeons. Weight-bearing load differential was the most sensitive and specific means of determining degree of pain in pigeons during the first 4 days after hind limb fracture induction.
Objective—To determine the effects of meloxicam on values of hematologic and plasma biochemical analysis variables and results of histologic examination of tissue specimens of Japanese quail (Coturnix japonica).
Animals—30 adult Japanese quail.
Procedures—15 quail underwent laparoscopic examination of the left kidneys, and 15 quail underwent laparoscopic examination and biopsy of the left kidneys. Quail in each of these groups received meloxicam (2.0 mg/kg, IM, q 12 h; n = 10) or a saline (0.9% NaCl) solution (0.05 mL, IM, q 12 h; control birds; 5) for 14 days. A CBC and plasma biochemical analyses were performed at the start of the study and within 3 hours after the last treatment. Birds were euthanized and necropsies were performed.
Results—No adverse effects of treatments were observed, and no significant changes in values of hematologic variables were detected during the study. Plasma uric acid concentrations and creatine kinase or aspartate aminotransferase activities were significantly different before versus after treatment for some groups of birds. Gross lesions identified during necropsy included lesions at renal biopsy sites and adjacent air sacs (attributed to the biopsy procedure) and pectoral muscle hemorrhage and discoloration (at sites of injection). Substantial histopathologic lesions were limited to pectoral muscle necrosis, and severity was greater for meloxicam-treated versus control birds.
Conclusions and Clinical Relevance—Meloxicam (2.0 mg/kg, IM, q 12 h for 14 days) did not cause substantial alterations in function of or histopathologic findings for the kidneys of Japanese quail but did induce muscle necrosis; repeated IM administration of meloxicam to quail may be contraindicated.