Liposome-encapsulated oxymorphone prevents hyperalgesia for 7 days in a rat model of neuropathic pain

A delayed‐release formulation of liposome‐encapsulated oxymorphone (LEO) was produced using a novel dehydration–rehydration technique. Preparations were standardized spectrophotometrically against a known concentration of the drug. The purpose of this study was to test the analgesic properties of LEO in a rat model of neuropathic pain. Sprague–Dawley rats were divided into control (non‐neuropathic) and test (neuropathic) groups. Control and test groups were administered one SC injection of (i) vehicle liposomes (negative control treatment); (ii) liposome‐encapsulated morphine, 2.8 mg kg^?1 (positive control treatment); or (iii) LEO, 1.2 mg kg^?1. All treatments were administered after baseline thermal withdrawal latencies (TWL) were determined (9.2 ± 0.39 seconds (mean ± SEM)). Test groups then underwent sciatic ligation to induce neuropathic pain. TWL were determined in all six groups (n = 8) daily for 1 week. In a separate group of age‐matched rats, blood (0.3 mL from the jugular vein) and urine (1–2 mL via metabolism cages) were collected daily for 7 days after administration of LEO (1.2 mg kg^?1). TWL did not change in the control rats given liposome‐encapsulated sucrose or morphine. There was a small increase (p = 0.04) in TWL in control rats given LEO, likely as a result of the relatively higher dose of oxymorphone compared with morphine based on receptor affinity. TWL in test rats given blank liposomes decreased significantly (p < 0.001) by day 4 (7.1 ± 0.5 seconds), with a maximal decrease by day 7 (5.1 ± 0.36 seconds), indicating development of full hyperalgesia. In contrast, rats given liposome‐encapsulated morphine or oxymorphone had no change in TWL at day 4, indicating that these preparations prevented hyperalgesia after a single injection. This treatment effect persisted through day 7. Serum concentrations of oxymorphone after a single injection of LEO peaked at 4 hours (6.8 ± 0.82 ng mL^?1) and were detectable through day 4 (0.98 ± 0.003 ng mL^?1), while urine concentrations of drug were detectable through day 7. This result suggests that oxymorphone metabolites might have been responsible for the protracted analgesic response. The encapsulation efficiency of oxymorphone using this novel technique was approximately 96%. In conclusion, liposome encapsulation of oxymorphone proved to be an efficient mechanism to provide a delayed‐release formulation of this opioid. This single dose of subcutaneously administered liposome‐encapsulated oxymorphone was effective in preventing hyperalgesia for 7 days in this animal model of neuropathic pain.     

Laser acupuncture for acute inflammatory, visceral and neuropathic pain relief: An experimental study in the laboratory rat

Laser acupuncture is defined as the stimulation of traditional acupuncture points with low-intensity, non-thermal laser irradiation. We explored the clinical efficacy of a very low level diode laser wavelength 670 nm (Biolite LP020, RGM, Genoa, Italy), used to stimulate acupoints ST36 Zu San Li and TH5 Waiguan, on well-established experimental models of acute and persistent pain in the rat, e.g. acute inflammatory pain, muscle pain, visceral pain and neuropathic pain. We report the anti-edema and anti-hyperalgesia effects of laser acupuncture in models of acute inflammatory pain, e.g. CFA-induced inflammation and myofascial pain. We also indicate that spontaneous pain and thermal hyperalgesia are reduced in a neuropathic pain model, e.g. axotomy. On the contrary, no effects due to laser-acupuncture were observed on disconfort indices in a model of visceral pain, e.g. cystitis due to cyclophosphamide. We thus provide evidences that acupoints stimulation using a very low intensity laser irradiation can control pain and edema in specific experimental conditions.     

Pharmacokinetics of oxymorphone in cats

Siao, K. T., Pypendop, B. H., Stanley, S. D., Ilkiw, J. E. Pharmacokinetics of oxymorphone in cats. J. vet. Pharmacol. Therap. 34 , 594–598. This study reports the pharmacokinetics of oxymorphone in spayed female cats after intravenous administration. Six healthy adult domestic shorthair spayed female cats were used. Oxymorphone (0.1 mg/kg) was administered intravenously as a bolus. Blood samples were collected immediately prior to oxymorphone administration and at various times up to 480 min following administration. Plasma oxymorphone concentrations were determined by liquid chromatography–mass spectrometry, and plasma oxymorphone concentration–time data were fitted to compartmental models. A three‐compartment model, with input in and elimination from the central compartment, best described the disposition of oxymorphone following intravenous administration. The apparent volume of distribution of the central compartment and apparent volume of distribution at steady state [mean ± SEM (range)] and the clearance and terminal half‐life [harmonic mean ± jackknife pseudo‐SD (range)] were 1.1 ± 0.2 (0.4–1.7) L/kg, 2.5 ± 0.4 (2.4–4.4) L/kg, 26 ± 7 (18–38) mL/min.kg, and 96 ± 49 (62–277) min, respectively. The disposition of oxymorphone in cats is characterized by a moderate volume of distribution and a short terminal half‐life.     

A comparison of ketorolac with flunixin, butorphanol, and oxymorphone in controlling postoperative pain in dogs.

Ketorolac tromethamine, a nonsteroidal anti-inflammatory analgesic, was compared with flunixin and butorphanol for its analgesic efficacy and potential side effects after laparotomy or shoulder arthrotomy in dogs. Sixty-four dogs were randomly assigned to receive butorphanol 0.4 mg/kg body weight (BW) (n = 21), flunixin 1.0 mg/kg BW (n = 21), or ketorolac 0.5 mg/kg BW (n = 22), in a double blind fashion. The analgesic efficacy was rated from 1 to 4 (1 = inadequate, 4 = excellent) for each dog. The average scores after laparotomy were ketorolac, 3.4; flunixin, 2.7; and butorphanol, 1.6. After shoulder arthrotomy, the average scores were ketorolac, 3.5; flunixin, 3.0; and butorphanol, 1.4 (5/11 dogs). As butorphanol was unable to control pain after shoulder arthrotomy, oxymorphone, 0.05 mg/kg BW, replaced butorphanol in a subsequent group of dogs and had a score of 2.0 (6/11 dogs). Serum alanine aminotransferase and creatinine were significantly elevated above baseline at 24 hours postoperatively in dogs receiving flunixin. One dog in each group developed melena or hematochezia. One dog receiving ketorolac had histological evidence of gastric ulceration. We concluded that ketorolac is a good analgesic for postoperative pain in dogs.     

Naloxone reversal of oxymorphone effects in dogs

Oxymorphone was administered IV to dogs 4 times at 20-minute intervals (total dosage, 1 mg/kg of body weight, IV) on 2 separate occasions. Minute ventilation, mixed-expired carbon dioxide concentration, arterial and mixed-venous pH and blood gas tensions, arterial, central venous, pulmonary arterial, and pulmonary wedge pressures, and cardiac output were measured. Physiologic dead space, base deficit, oxygen transport, and vascular resistance were calculated before and at 5 minutes after the first dose of oxymorphone (0.4 mg/kg) and at 15 minutes after the first and the 3 subsequent doses of oxymorphone (0.2 mg/kg). During 1 of the 2 experiments in each dog, naloxone was administered 20 minutes after the last dose of oxymorphone; during the alternate experiment, naloxone was not administered. In 5 dogs, naloxone was administered IV in titrated dosages (0.005 mg/kg) at 1-minute intervals until the dogs were able to maintain sternal recumbency, and in the other 5 dogs, naloxone was administered IM as a single dose (0.04 mg/kg). Naloxone (0.01 mg/kg, IV or 0.04 mg/kg, IM) transiently reversed most of the effects of oxymorphone. Within 20 to 40 minutes after IV naloxone administration and within 40 to 70 minutes after IM naloxone administration, most variables returned to the approximate values measured before naloxone administration. The effects of oxymorphone outlasted the effects of naloxone; cardiovascular and pulmonary depression and sedation recurred in all dogs. Four hours and 20 minutes after the last dose of oxymorphone, alertness, responsiveness, and coordination improved in all dogs after IM administration of naloxone. Cardiac arrhythmia, hypertension, or excitement was not observed after naloxone administration.     

Centrally administered verapamil prevents the autonomic reaction to visceral pain in sheep

The significant role of voltage gated calcium channels (VGCC) L-type antagonists used concomitantly with opioids in attenuation of clinical pain has been confirmed. The aim of this study was to evaluate the effect of centrally administered verapamil on behavior and biochemical parameters in sheep that have undergone experimental duodenal distension (DD) and to determine whether verapamil exerts any anti-nociceptive effects under these conditions. The study was carried out using 24 mature crossbred ewes, each weighing 38-43 kg. Verapamil, a VGCC blocker, was administered through an intracerebroventricular cannula at the following doses: 0.25, 0.5, 1.0 and 2.0 mg in toto. Ten minutes later experimental DD was conducted by insertion and the distension of rubber balloon (containing 40 ml of warm water) inserted into sheep duodenum. After 5 min of mechanical DD the following reactions were then observed: the significant increase in behavioral pain responses, i.e. tachycardia, hyperventilation, inhibition of reticulo-ruminal contractions (70% approximately, during 15 min), an increase of plasma catecholamine concentration (over 7-fold increase of epinephrine during 2 h following DD, 2-times norepinephrine and ±80% increase of dopamine). Verapamil infusion administered 10 min prior to DD decreased intensity of visceral pain responses, such as: behavioral changes, tachycardia, hyperventilation, inhibition of the reticulo-rumen motility and efficiently prevented the appearance of catecholamine release. These data demonstrated that the development and persistence of duodenal hyperalgesia depends on the activation of Ca²⁺ ion flux leading to neurotransmitters release and modulation of membrane excitability. The observed antinociceptive action of VGCCs type-L blockers suggests that these channels play a crucial role in the modulation of acute visceral hyperalgesia in sheep.     

Colonic mast cell infiltration in rats with TNBS-induced visceral hypersensitivity

Colonic mucosal mast cells are implicated in the pathogenesis of visceral hypersensitivity associated with irritable bowel syndromes. This study was designed to investigate the roles of mucosal mast cells in development of an experimental visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats. TNBS, when injected into the proximal colon through laparotomy, produced a significant decrease in pain threshold of the distal colon to mechanical distention, indicating a visceral hypersensitivity. In the proximal colon that was directly insulted by TNBS, mucosal necrosis and extensive inflammatory cell infiltration were observed with concomitant increase in tissue myeloperoxide (MPO) activity. In the distal colon where distention stimuli were applied, the number of mucosal mast cells significantly increased following TNBS treatment, although neither mucosal injury nor increase in tissue MPO activity was observed. In an organ culture, spontaneous release of a mucosal mast cell-specific protease (RMCP-2) from the distal colon tissue of TNBS-treated rats was significantly larger than that of sham animals. Furthermore, TNBS-induced visceral hypersensitivity was significantly suppressed by subcutaneous pretreatment with a mast cell stabilizer doxantrazole in a dose-dependent manner. These findings suggest that prominent colonic mast cell infiltration associated with an enhanced spontaneous mediator release is responsible, at least partly, for development of visceral hypersensitivity induced by TNBS in rats.     

Effect of buprenorphine on the cardiovascular and respiratory response to visceral pain in conscious rabbits

Objective  To evaluate the effect of buprenorphine administration on the cardiovascular and respiratory responses to noxious colorectal distension in conscious rabbits.
Study design  Prospective experimental trial.
Animals  Fifteen healthy, young adult New Zealand white rabbits (eight female).
Methods  Experiments were performed on conscious rabbits that were instrumented with intraabdominal arterial and venous catheters, and diaphragmatic and abdominal electromyographic electrodes. Colorectal distension was achieved by inflation of an acutely placed colorectal balloon catheter until mean arterial pressure increased 10–15 mmHg. Buprenorphine (0.06 mg) or saline was administered intravenously prior to, or during colorectal distension. Arterial blood pressure, heart rate, respiratory rate, abdominal electromyographic activity, and intra-balloon pressure were monitored.
Results  In the absence of colorectal distension, buprenorphine increased arterial blood pressure and decreased respiratory rate but did not change heart rate. Colorectal distension increased arterial blood pressure and heart rate, and decreased respiratory rate. The increase in arterial blood pressure associated with colorectal distension was attenuated following preemptive buprenorphine, but was not changed by buprenorphine administered during distension.
Conclusions and clinical relevance  If cardiovascular changes reflect the intensity of noxious stimulation, then these results support the preemptive administration of buprenorphine for visceral analgesia.     

Evaluation of client-specific outcome measures and activity monitoring to measure pain relief in cats with osteoarthritis

BACKGROUND: There are no validated systems for measuring pain from osteoarthritis in cats. HYPOTHESIS: Owner subjective assessments and an activity monitor (AM) can be used to detect pain in cats with osteoarthritis and to assess efficacy of treatments. ANIMALS: Thirteen cats older than 10 years old, with owner-assessed decreases in activity, painful arthritic joints, and clinically normal blood work were included and evaluated for 3 weeks. METHODS: A collar-mounted AM measured activity and a client-specific outcome measure (CSOM) questionnaire characterized the severity of impairment. Overall global quality of life was also evaluated for each treatment. In weeks 2 and 3, meloxicam (0.1 mg/kg, day 1; 0.05 mg/kg, days 2-5) or a placebo was administered in a blinded, randomized, cross-over manner to test the assessment systems. RESULTS: The cats had a median of 4 arthritic appendicular joints. Activity counts for the week when cats (complete data on activity; n=9) were administered meloxicam were significantly higher than at baseline (P = .02) but not after placebo (P = .06). Baseline activity counts were not significantly different from placebo (P = .6). The CSOM data (n=13) showed that owners considered their cats to be more active on meloxicam compared with baseline (P = .001) and placebo (P < .004), and more active on placebo than at baseline (P < .01). Global quality of life improved significantly with meloxicam (P < .042). CONCLUSIONS AND CLINICAL IMPORTANCE: Both an AM and a CSOM system can detect behavior associated with pain relief in cats that are arthritic. Objective activity data might allow subjective assessment systems to be validated for use in clinical studies.     

Comparison of histamine release induced by morphine and oxymorphone administration in dogs

Cardiovascular effects (vasodilatation, hypotension) of morphine administration have been attributed to central actions and peripheral histamine release. In the study reported here, we compared plasma histamine (Hm) concentrations after morphine sulfate and oxymorphone HCl administration in conscious dogs. Five healthy adult dogs (mean body weight, 10.1 kg) were randomly administered morphine (2 mg/kg of body weight, IV) or oxymorphone (0.2 mg/kg, IV) by a 5-second bolus injection at weekly intervals. Venous blood samples (5 ml) were collected from jugular veins before and at 1, 2, 5, 15, 30, and 60 minutes after drug administration. Behavioral changes were recorded. Plasma was analyzed by a radioenzymatic technique, using purified histamine N-methyltransferase as an enzyme catalyst (sensitivity of assay, 40 pg Hm/ml). Mean base-line Hm value for all dogs was 0.55 ng/ml. The mean Hm value was significantly higher (P less than 0.05) than the base-line value at 1, 2, 5, 15, and 60 minutes after morphine administration (531.4, 251.0, 113.0, 31.5, and 1.0 ng of Hm/ml, respectively), but there were no significant increases in histamine values from base-line values at any time after oxymorphone administration. All dogs given morphine and 1 dog given oxymorphone showed excitatory behavior; 2 dogs given morphine and 3 dogs given oxymorphone salivated profusely.     

Cardiopulmonary effects of medetomidine, oxymorphone, or butorphanol in selegiline-treated dogs

OBJECTIVES: To determine if chronic selegiline HCl administration affects the cardiopulmonary response to medetomidine, oxymorphone, or butorphanol in dogs. STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Twenty-eight adult, random source, hound dogs weighing 21-33 kg. METHODS: Dogs were assigned to the following treatment groups: selegiline + medetomidine (MED; n = 6); placebo + MED (n = 6), selegiline + oxymorphone (OXY; n = 6); placebo + OXY (n = 6); selegiline + butorphanol (BUT; n = 7) or placebo + BUT (n = 6). Nine dogs were treated with two of the three pre-medicants. Dogs were treated with selegiline (1 mg kg(-1) PO, q 24 hours) or placebo for at least 44 days prior to pre-medicant administration. On the day of the experiment, arterial blood for blood gas analysis, blood pressure measurements, ECG, cardiac ultrasound (mM-mode, 2-D, and continuous wave Doppler), and behavioral observations were obtained by blinded observers. An IV injection of MED (750 micro g m(-2)), OXY (0.1 mg kg(-1)) or BUT (0.4 mg kg(-1)) was given. Cardiopulmonary and behavioral data were collected at 1, 2, 5, 15, 30, and 60 minutes after injection. RESULTS: Selegiline did not modify responses to any of the pre-medicant drugs. Medetomidine caused a significant decrease in heart rate (HR), cardiac output (CO), and fractional shortening (FS). Mean arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP) were increased. Level of consciousness and resistance to restraint were both decreased. Oxymorphone did not affect MAP, CO, CVP, or SVR, but RR and PaCO(2) were increased. Level of consciousness and resistance to restraint were decreased. BUT decreased heart rate at 1 and 5 minutes. All other cardiovascular parameters were unchanged. BUT administration was associated with decreased arterial pH and increased PaCO(2). BUT decreased level of consciousness and resistance to restraint. CONCLUSIONS AND CLINICAL RELEVANCE: Although pre-medicants themselves altered cardiopulmonary and behavioral function, selegiline did not affect the response to medetomidine, oxymorphone, or butorphanol in this group of normal dogs.     

Anti-nociceptive efficacy of carprofen, levomethadone and buprenorphine for pain relief in cats following major orthopaedic surgery

A placebo-controlled, randomized blind study was conducted in cats (n = 60) after fracture repair to compare the analgesic effects as well as the side-effects of carprofen, buprenorphine and levomethadone during a 5-day treatment. Cats with severe shock symptoms or increases in blood urea nitrogen (BUN) and creatinine were excluded from the study. The cats were randomly assigned to four groups (n= 15). In group 1, carprofen was administered upon extubation at an initial dose of 4 mg/kg body weight, followed by one-third of that dose three times daily on days 2 to 5. In group 2, buprenorphine was administered in a single dose of 0.01 mg/kg body weight upon extubation and subsequently every 8 h. Levomethadone (group 3) was applied according to the same scheme at a dosage of 0.3 mg/kg body weight each time. The placebo (group 4) was given at the same time intervals as the opioids. Examinations were carried out prior to anaesthesia, between 30 min and 8 h after extubation, and on the following 4 days, 1 h after administration of the analgesics or the placebo as well as 1 h before the next administration. Pain and sedation evaluation was carried out with a visual analogue system (VAS) and with the aid of a numerical estimation scale (NRS). Pain was also scored by measuring mechanical nociceptive threshold of traumatized tissue. Plasma glucose and cortisol concentration, heart rate, respiration rate, blood pressure and body temperature were measured. Furthermore, a complete blood count and clinical chemistry including BUN, creatinine, alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), arterial blood pressure (AP), total protein and electrolytes of the cats were checked on the day of admission as well as on the last day of this study (day 5). Defaecation and urination as well as wound healing were monitored. On the basis of the mechanical nociceptive threshold of the traumatized tissue, concentrations of plasma glucose and cortisol and pain assessment using NRS and VAS, carprofen was found to have better anti-nociceptive efficacy when compared with the two opioid analgesics, while the analgesic effect of levomethadone was similar to that of buprenorphine. However, the carprofen group also showed comparably high median NRS and VAS pain scores in addition to occasional broad deviations from the group mean on the first post-operative treatment day. Sedative effects were detected for buprenorphine and levomethadone; in addition, symptoms of central excitation were noted with levomethadone. There was no indication of any clinically relevant respiratory depressive or cardiovascular effects, nor of any undesired renal, gastrointestinal or hepatic effects of the analgesics applied. However, the somewhat insensitive examination methods did not permit sufficient evaluation of side-effects, particularly on the gastrointestinal tract and the kidneys. It was found that carprofen and buprenorphine were well-tolerated analgesics for a 5-day administration in the cat, whereas levomethadone caused central excitation in some cases in the dosage scheme used here. However, it was apparent that none of the tested analgesics induced sufficient analgesia in the post-operative phase. For this reason, suitable methods must be found to improve analgesia, particularly in the immediate post-operative phase.     

Sedative effects of hydromorphone or oxymorphone with or without acepromazine in dogs

Hydromorphone is an agonist opioid with potency approximately five times that of morphine and half that of oxymorphone. The purpose of this study was to compare hydromorphone with oxymorphone, with or without acepromazine, for sedation in dogs, and to measure plasma histamine before and after drug administration. Ten dogs received IM hydromorphone (H; 0.2 mg kg^?1), oxymorphone (O; 0.1 mg kg^?1), hydromorphone with acepromazine (H; 0.2 mg kg^?1, A; 0.05 mg kg^?1) or oxymorphone with acepromazine (O; 0.1 mg kg^?1, A; 0.05 mg kg^?1) in a randomized Latin‐square design. Sedation score, heart rate, respiratory rate, blood pressure, and SpO₂ were recorded at baseline and every 5 minutes after drug administration up to 25 minutes. Plasma histamine was measured at baseline and at 25 minutes post‐drug administration. Data were analyzed with repeated measures anova . Mean ± SD body weight was 21.62 ± 1.54 kg. Mean ± SD age was 1.07 ± 0.19 years. Sedation score was significantly greater for OA after 5 minutes than O alone (4.1 ± 3.5 versus 1.9 ± 1.5) and for HA after 15 minutes than H alone (8.6 ± 2.9 versus 5.9 ± 2.5). There was no significant difference in sedation between H and O at any time point. There was no significant difference between groups at any time with respect to heart rate, respiratory rate, blood pressure or SpO₂. Mean ± SD plasma histamine (nM ml^?1) for all groups was 1.72 ± 2.69 at baseline and 1.13 ± 1.18 at 25 minutes. There was no significant change in plasma histamine concentration in any group. Hydromorphone is effective for sedation in dogs and does not cause measurable increase in histamine. Sedation with hydromorphone is enhanced by acepromazine.     

Cardiovascular effects of epidurally administered oxymorphone and an oxymorphone-bupivacaine combination in halothane-anesthetized dogs

OBJECTIVE: To evaluate cardiovascular effects of epidurally administered oxymorphone (OXY) and an OXY-bupivacaine combination (O/B) in halothane-anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: In a randomized crossover design study, dogs were anesthetized with halothane and given OXY, O/B, and saline solution (SAL). Eucapnia and end-tidal halothane concentration of 1.2% were established. Heart rate (HR), systemic and pulmonary arterial pressures, central venous pressure (CVP), and cardiac output were measured at baseline and 5, 15, 30, 45, 60, and 75 minutes after treatment. At 90 minutes, glycopyrrolate was administered IV, and measurements were repeated at 95 minutes. Cardiac index (CI), stroke volume, stroke index, systemic vascular resistance (SVR), and left ventricular work were calculated. End-tidal halothane concentration was decreased to 0.8% from 17 to 45 minutes and to 0.5% from 47 to 95 minutes for OXY and O/B, whereas for SAL, it was maintained at 1.5 and 1.2%, respectively. Samples were obtained at 0, 2, 5, 15, 30, 45, 60, and 95 minutes for measurement of serum opiate concentration and comparison with values after IM administration of OXY. RESULTS: HR decreased, but CVP and SVR increased in response to OXY and O/B. These changes were reversed after IV administration of glycopyrrolate, resulting in significant increase in CI, compared with that in response to SAL. Serum opiate concentration increased markedly and peaked within 15 minutes after OXY and O/B administration but did not differ from values after IM administration. CONCLUSIONS: Epidural administration of OXY results in rapid systemic uptake and decreased HR. Glycopyrrolate administration improves HR, resulting in improved CI at equipotent halothane concentrations.     

Comparison of carprofen and butorphanol as post-surgical analgesics in cats

Post‐operative pain management by a single subcutaneous (SC) injection of carprofen has been found to be effective in cats and dogs. This clinical study compared the analgesic properties of injectable carprofen and butorphanol in 71 healthy cats (0.5–5 years, mean weight 3.24 ± 0.61 kg) undergoing ovariohysterectomy. Cats were randomly assigned to three groups: Group C received carprofen 4 mg kg^?1 SC at intubation and sterile saline 0.08 mL kg^?1 SC at extubation; Group B received sterile saline 0.08 mL kg^?1 SC at intubation and butorphanol 0.4 mg kg^?1 SC at extubation; Group S received sterile saline 0.08 mL kg^?1 SC at intubation and extubation. All cats were pre‐medicated with atropine (0.04 mg kg^?1 SC), acepromazine (0.02 mg kg^?1 SC), ketamine (5 mg kg^?1 SC), and induced IV with ketamine (5 mg kg^?1) and diazepam (0.25 mg kg^?1). Serum biochemistry values were taken at 24 and 48 hours post‐surgically and compared to a pre‐surgical baseline. Behavioral data were collected by a blinded investigator prior to surgery (baseline) and 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours post‐surgery; the data were compiled into composite pain scores on a scale from 0 to 21 and complemented by visual analogue scores (VAS). Scoring was based on changes in behavior, posture, vocalization, and response to interactive stimulation. Cats with pain scores >12 were considered to be moderately painful, received meperidine (4 mg kg^?1 IM), and were excluded from further statistical analyses. Sixty of 71 cats completed the study. Anesthetic time was 88.5 ± 21.8 minutes (mean ± SD). Meperidine was given to one cat in C, three in B, and five in S. There were no significant differences in biochemistry values. There were no significant differences in pain scores between C and B at any time period; B and C pain scores were significantly lower than S at 1, 2, 12, 16, and 20 hours post‐operatively, and C lower than S at 3 and 8 hours post‐surgery. Pain scores decreased over the 24‐hour study in all groups; the greatest decrease in each group was between 4 and 8 hours post‐operatively. In this study, carprofen provided post‐surgical analgesia comparable to butorphanol.     

Liposome-encapsulated doxorubicin (Doxil) and doxorubicin in the treatment of vaccine-associated sarcoma in cats

The purpose of this randomized, multicenter study was to evaluate the toxicity and efficacy of liposome-encapsulated doxorubicin (LED) and doxorubicin (DOX) in the treatment of feline vaccine-associated sarcoma (VAS). Cats were divided according to their disease status into a microscopic arm (no evidence of gross disease) and a macroscopic arm (evidence of gross disease). Each arm was randomized to receive either LED (1-1.5 mg/kg i.v. q3 weeks) or DOX (1 mg/kg i.v. q3 weeks). Thirty-three cats were entered in the macroscopic arm of the study with an overall response rate of 39% (5 complete response and 8 partial response) and a median time to progression of 84 days. Response rates were not different between LED and DOX. Seventy-five cats were entered into the microscopic arm. When compared to a similar historical control population treated with surgery alone, the cats receiving chemotherapy had a prolonged median disease-free interval (388 days versus 93 days). No difference in efficacy was detected between LED and DOX. LED at 1.5 mg/kg induced delayed nephrotoxicosis in 23%, necessitating a decrease in the recommended dosage to 1 mg/kg, and cutaneous toxicosis in 21.7% of treated cats. This study showed that both DOX and LED are efficacious in the treatment of VAS and should be considered in the treatment of this tumor.