A comparison of methods for evaluation of pain and distress after orthopaedic surgery in horses

Post operative pain was evaluated in 13 horses subjectively and by measuring pre-defined behavioural and physiological variables. Twelve of the horses had undergone painful orthopaedic surgery and one had developed post anaesthetic myopathy and nerve damage after radiological examination under general anaesthesia. Venous blood samples were collected for catecholamine, ß-endorphin and cortisol assays before premedication and up to 72 h after surgery. No differences were seen in head position, ground pawing or use of the operated leg between the pre-and post anaesthetic periods. The subjective pain score was higher at 4 h after anaesthesia than the pre-operative score. Mean plasma ß-endorphin concentration increased above pre-operative values at 6 and 12 h after anaesthesia. Anaesthesia and surgery did not change mean plasma cortisol concentration, but it was lower in samples collected at 48 and 72 h. There was considerable individual variation in plasma catecholamine concentrations. At some time points the plasma concentration of catecholamines was higher than before premedication, but the maximal concentrations for adrenaline, noradrenaline and dopamine did not occur simultaneously. Heart rate was increased at 2 and 4 h, and abdominal sounds were decreased at 2 h. Packed cell volume was decreased in samples taken 2 to 12 h after anaesthesia. There was poor correlation between all the parameters measured in the study The subjective pain score and the plasma ß-endorphin concentration correlated with each other at several time points, but not during the immediate post operative period.     

Lower gastric ulcerogenic effect of suxibuzone compared to phenylbutazone when administered orally to horses

The objective was to compare the gastrointestinal and general toxicity of suxibuzone (SBZ) to that of phenylbutazone (PBZ) when administered orally in horses. Fifteen healthy horses were allocated to three treatment groups. One group received a high dose of PBZ for two weeks; the second group was given an equimolecular dosage of SBZ; and a third group received placebo. Horses were daily monitored, and blood samples were collected before and during the study. On day 18, complete post-mortem examinations were performed.One horse treated with PBZ showed clinical signs of NSAID toxicosis. Small oral ulcers were also detected in other two horses from the PBZ group and in two horses from the SBZ group. There were no statistical differences in the blood parameters among groups. Ulcers in the stomach's glandular mucosa were observed in all horses of the PBZ group, while only two horses of the SBZ group showed ulcerations. PBZ horses had a significant higher ulcerated area, and gastric ulcers were significantly deeper than those in the SBZ and placebo groups. No other lesions were found in any other tissue. In conclusion, SBZ causes significantly lower gastric ulcerogenic effect than PBZ when administered orally at equimolecular doses in horses.     

Pharmacopuncture Analgesia Using Flunixin Meglumine Injection into the Acupoint GV1 (Ho Hai) After Elective Castration in Horses

The study evaluated the effect of a 1/10 dose of flunixin meglumine administered into the governing vessel 1 (GV1) acupoint in horses that underwent castration. Twenty animals received 0.02 mg/kg detomidine intravenously, followed by 2.2 mg/kg ketamine and 0.1 mg/kg diazepam by the same route, and also a local anesthesia with 30 mL lidocaine. As postoperative analgesia, the animals received 1.1 mg/kg flunixin meglumine IV (FIV) or 0.11 mg/kg flunixin meglumine into the GV1 acupoint (FGV). Behavioral parameters were assessed 12 hours before the procedure (baseline) and at 4, 6, 12, and 24 hours after surgery; physiological parameters were measured at baseline and at 2, 4, 6, 8, 10, 12, 16, and 24 hours after surgery. The groups did not differ regarding pain scores. Heart rate was higher in the FIV group than in the FGV group 2 hours after surgery (46 ± 5.2 bpm vs. 37 ± 8.2 bpm); gut sounds decreased at 2, 4, and 6 hours in both groups. The temperature showed a decrease after 2 hours compared with baseline in the FGV group, and the systolic blood pressure was higher in the FGV group than in the FIV group at 8 hours (158 ± 18.1 mmHg vs. 134 ± 14.5 mmHg), 10 hours (157 ± 15.5 mm Hg vs. 130 ± 11.5 mmHg), and 12 hours (151 ± 18.7 mmHg vs. 134 ± 15.8 mmHg). Pharmacopuncture was as effective as conventional dose and route of flunixin meglumine in horses that underwent elective castration under those conditions.     

Plasma and serum concentrations of phenylbutazone and oxyphenbutazone in racing Thoroughbreds 24 hours after treatment with various dosage regimens

The plasma and serum concentrations of phenylbutazone (PBZ) and oxyphenbutazone were measured in 158 Thoroughbred horses after various doses of PBZ wer given. All horses were competing or training at racetracks in various parts of the country. All horses used in the study had not been given PBZ 24 hours before they were placed on a specific dosage schedule. Samples were collected 24 hours after the last PBZ administration. Four grams of PBZ were given daily by stomach tube, paste, or tablet for 3 days. On day 4, 24 hours before sample collection, an IV dose of 2 g of PBZ was given, regardless of the dose and method of administration. The 24-hour PBZ plasma concentrations were 3.51, 6.13, and 6.40 micrograms/ml, respectively. After 2 g of PBZ was administered IV daily for 4 days, the plasma PBZ concentration was 4.16 g/ml; after a single 2-g IV administration, the serum concentration was 0.87 g/ml. Concentrations of oxyphenbutazone were 3.35 (stomach tube), 4.29 (paste), 3.60 (tablet), 3.65 (4-day IV), and 1.11 g/ml (single IV). A significant relationship was not found between the serum and the urinary concentrations at this 24-hour measurement. Split samples sent to various laboratories confirmed the stability of high-performance liquid chromatography as a method of analysis.     

Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy

A randomized, controlled, blinded clinical trial was performed to determine whether butorphanol administered by continuous rate infusion (CRI) for 24 hours after abdominal surgery would decrease pain and surgical stress responses and improve recovery in horses. Thirty-one horses undergoing exploratory celiotomy for abdominal pain were randomly assigned to receive butorphanol CRI (13 microg/kg/h for 24 hours after surgery; treatment) or isotonic saline (control). All horses received flunixin meglumine (1.1 mg/kg IV q12h). There were no significant differences between treatment and control horses in preoperative or operative variables. Treatment horses had significantly lower plasma cortisol concentration compared with control horses at 2, 8, 12, 24, 36, and 48 hours after surgery. Mean weight loss while hospitalized was significantly less for treatment horses than control horses, whether expressed as total decrease in body weight (13.9+/-3.4 and 27.9+/-4.5 kg, respectively) or as a percentage decrease in body weight (2.6+/-0.7 and 6.3+/-1.1%, respectively). Treatment horses were significantly delayed in time to first passage of feces (median times of 15 and 4 hours, respectively). Treatment horses had significantly improved behavior scores during the first 24 hours after surgery, consistent with the conclusion that they experienced less pain during that time. Butorphanol CRI during the immediate postoperative period significantly decreased plasma cortisol concentrations and improved recovery characteristics in horses undergoing abdominal surgery.     

Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses

OBJECTIVE: To assess effects of treatment with phenylbutazone (PBZ) or a combination of PBZ and flunixin meglumine in horses. ANIMALS: 24 adult horses. PROCEDURE: 13 horses received nonsteroidal antiinflammatory drugs (NSAIDs) in a crossover design. Eleven control horses were exposed to similar environmental conditions. Treated horses received PBZ (2.2 mg/kg, PO, q 12 h, for 5 days) and a combination of PBZ and flunixin meglumine (PBZ, 2.2 mg/kg, PO, q 12 h, for 5 days; flunixin meglumine, 1.1 mg/kg, IV, q 12 h, for 5 days). Serum samples were obtained on day 0 (first day of treatment) and day 5, and total protein, albumin, and globulin were measured. RESULTS: 1 horse was euthanatized with severe hypoproteinemia, hypoalbuminemia, and colitis during the combination treatment. Comparisons revealed no significant difference between control horses and horses treated with PBZ alone. There was a significant difference between control and treated horses when administered a combination of PBZ and flunixin meglumine. Correction for horses with values >2 SDs from the mean revealed a significant difference between control horses and horses administered the combination treatment, between control horses and horses administered PBZ alone, and between horses receiving the combination treatment and PBZ alone. Gastroscopy of 4 horses revealed substantial gastric ulcers when receiving the combination NSAID treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of the study indicates the need for caution when administering a combination NSAID treatment to horses because the detrimental effects may outweigh any potential benefits.     

Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum

OBJECTIVE: To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. ANIMALS: 18 horses. PROCEDURES: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed. RESULTS: Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects. CONCLUSIONS AND CLINICAL RELEVANCE: Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.     

Intravenous continuous infusion of lidocaine for treatment of equine ileus

OBJECTIVE: To determine if intravenous lidocaine is useful and safe as a treatment for equine ileus. Study DESIGN: Prospective double-blinded placebo-controlled trial. STUDY POPULATION: Horses (n = 32) with a diagnosis of postoperative ileus (POI) or enteritis and that had refluxed >20 L or had been refluxing for >24 hours. METHODS: Refluxing horses were administered lidocaine (1.3 mg/kg intravenously [IV] as a bolus followed by a 0.05 mg/kg/min infusion) or saline (0.9% NaCl) solution placebo for 24 hours. Variables evaluated included volume and duration of reflux, time to 1st fecal passage, signs of pain, analgesic use, heart rate and arrhythmias, respiratory rate, temperature, days of hospitalization, outcome (survival to discharge), and complications. RESULTS: Of the lidocaine-treated horses, 65% (11/17) stopped refluxing within 30 hours (mean+/-SD, 15.2+/-2.4 hours) whereas 27% (4/15) of the saline-treated horses stopped within 30 hours. Fecal passage was significantly correlated with response to treatment; horses that responded to lidocaine passed feces within 16 hours of starting the infusion. Compared with placebo treatment, lidocaine treatment resulted in shorter hospitalization time for survivors, equivalent survival to discharge, no clinically significant changes in physical or laboratory variables, and no difference in the rate of incisional infections, jugular thrombosis, laminitis, or diarrhea. Muscle fasciculations occurred in 3 lidocaine-treated horses (18%). CONCLUSION: IV lidocaine significantly improved the clinical course in refluxing horses with minimal side effects. CLINICAL RELEVANCE: At the infusion rate studied, IV lidocaine is safe and should be considered for the treatment of equine ileus.     

Ketorolac Is Not More Effective Than Flunixin Meglumine or Phenylbutazone in Reducing Foot Pain in Horses

The objective was to compare the analgesic efficacy of ketorolac tromethamine (KT) and two other nonsteroidal anti-inflammatory drugs (NSAIDs), including flunixin meglumine (FM) and phenylbutazone (PB), using a heart bar shoe (HBS) model of reversible foot lameness in horses. Nine adult horses were used in a blinded, randomized, placebo-controlled crossover study. After induction of left front limb lameness using a modified HBS model, one of three NSAIDs (KT, 2.0 mg/kg IV; FM, 1.1 mg/kg IV; PB, 4.4 mg/kg IV) or saline (placebo) was administered IV as a single dose. Lameness was assessed every 30 minutes for 2 hours, then every hour up to 12 hours using both a lameness grading scale (lameness score; LS) and a body-mounted inertial sensor system (lameness locator; LL). High-performance liquid chromatography and mass spectrometry were used to measure plasma drug concentration at various time points. There was no difference in percent reduction of LS or LL value between KT and any other group, or between FM and placebo. The PB group showed a significantly higher percentage in LS reduction than the placebo and FM groups. The mean percent reduction in LL value was greater for the PB group than that for the placebo and FM groups. Plasma drug concentration was similar among horses for each drug at each time point, with drug concentrations decreasing over time. Thus, variation in plasma drug concentration did not influence lameness reduction for any drug. Ketorolac tromethamine was not superior to FM or PB in reducing lameness using a HBS model.     

Systemic effects of a prolonged continuous infusion of ketamine in healthy horses

Background: Ketamine as continuous rate infusion (CRI) provides analgesia in hospitalized horses. Objective: Determine effects of prolonged CRI of ketamine on gastrointestinal transit time, fecal weight, vital parameters, gastrointestinal borborygmi, and behavior scores in healthy adult horses. Animals: Seven adult Thoroughbred or Thoroughbred cross horses, with permanently implanted gastric cannulae. Methods: Nonblinded trial. Random assignment to 1 of 2 crossover designed treatments. Ketamine (0.55 mg/kg IV over 15 minutes followed by 1.2 mg/kg/h) or lactated Ringer's solution (50 mL IV over 15 minutes followed by 0.15 mL/kg/h) treatments. Two hundred 3 × 5 mm plastic beads administered by nasogastric tube before drug administration. Every 2 hours vital parameters, behavior scores recorded, feces collected and weighed, and beads retrieved. Every 6 hours gastrointestinal borborygmi scores recorded. Study terminated upon retrieval of 180 beads (minimum 34 hours) or maximum 96 hours. Nontransit time data analyzed between hours 0 and 34. Results: No significant (P < .05) differences detected between treatments in vital signs or gastrointestinal borborygmi. Significant (P = .002) increase in behavior score during ketamine infusion (0.381) from hours 24–34 compared with placebo (0). Ketamine caused significant delay in passage of 25, 50, and 75% of beads (ketamine = 30.6 ± 5.3, 41.4 ± 8.4, 65.3 ± 13.5 hours versus placebo = 26.8 ± 7.9, 34.3 ± 11.1, 45.8 ± 19.4 hours), and significant (P < .05) decrease in fecal weight from hours 22 (12.6 ± 3.2 versus 14.5 ± 3.8 kg) through 34 (18.5 ± 3.9 versus 12.8 ± 6.4 kg) of infusion. Conclusions and Clinical Importance: Ketamine CRI delayed gastrointestinal transit time in healthy horses without effect on vital parameters.     

Effects of phenylbutazone on bone activity and formation in horses

OBJECTIVE: To determine the effects of phenylbutazone (PBZ) on bone activity and bone formation in horses. ANIMALS: 12 healthy 1- to 2-year-old horses. PROCEDURES: Biopsy was performed to obtain unicortical bone specimens from 1 tibia on day 0 and from the contralateral tibia on day 14. Fluorochromic markers were administered IV 2 days prior to and on days 0, 10, 15, and 25 after biopsy was performed. Six horses received PBZ (4.4 mg/kg of body weight, PO, q 12 h) and 6 horses were used as controls. All horses were euthanatized on day 30 and tissues from biopsy sites, with adjacent cortical bone, were collected. Osteonal density and activity, mineral apposition rate (MAR), and percentage of mineralized tissue filling the biopsy-induced defects in cortical bone were assessed. Serum samples from all horses were analyzed for bone-specific alkaline phosphatase activity and concentration of PBZ. RESULTS: MAR was significantly decreased in horses treated with PBZ. Regional acceleratory phenomenon was observed in cortical bone in both groups but was significantly decreased in horses treated with PBZ. Osteonal activity was similar at all time points in all horses. In control horses, percentage of mineralized tissue filling the cortical defects was significantly greater in defects present for 30 days, compared with defects present for 14 days. Differences in percentage of mineralized tissue were not detected in horses treated with PBZ. CONCLUSIONS AND CLINICAL RELEVANCE: PBZ decreased MAR in cortical bone and appeared to decrease healing rate of cortical defects in horses.     

Preemptive Analgesia,Including Morphine,Does Not Affect Recovery Quality and Times in Either Pain-Free Horses or Horses Undergoing Orchiectomy

Recovery quality and times from general anesthesia in horses may be influenced by surgery, analgesia with morphine or combinations of both. Twenty-three adult healthy horses were enrolled in this prospective experimental trial in a clinical setting and were randomly allocated to one of the following groups: anesthesia only (GA; n = 6), preemptive analgesia and anesthesia (GAA; n = 5), anesthesia and castration (GC; n = 6), or preemptive analgesia, anesthesia, castration, and intraoperative local analgesia (GCA; n = 6). All horses were sedated with intramuscular (IM) xylazine (0.5 mg/kg). Anesthesia was induced with intravenous (IV) guaifenesin (100 mg/kg) and thiopental (5 mg/kg) and maintained with isoflurane in oxygen. Animals in groups with preemptive analgesia received IM morphine (0.2 mg/kg) and dipyrone (10 mg/kg) and IV flunixin meglumine (1.0 mg/kg) immediately before sedation. Recoveries from general anesthesia were rope-assisted. Recovery scores (from 8 [excellent recovery] to 70 [worst recovery]) and times were compared between groups, using a one-way analysis of variance followed by a Tukey's test (P < .05). Mean ± standard deviation (SD) and range recovery scores were 22 ± 14 (8–45), 9 ± 2 (8–12), 14 ± 5 (8–22), and 12 ± 1 (10–13) in groups GA, GAA, GC, and GCA, respectively. Mean ± SD times to stand in minutes were 21 ± 10, 18 ± 7, 33 ± 12, and 35 ± 21 in groups GA, GAA, GC and GCA, respectively. No statistically significant differences were found for any of the variables. Neither preoperative administration of analgesics, including morphine, nor castration interfered with the recovery qualities and times in horses undergoing general anesthesia. Preemptive morphine did not worsen anesthetic recovery quality in horses.     

Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs

OBJECTIVE: To compare preoperative administration of meloxicam and butorphanol to perioperative administration of butorphanol alone for control of postoperative signs of pain in dogs. ANIMALS: 40 client-owned dogs scheduled for surgical repair of a cranial cruciate ligament rupture. PROCEDURE: Group-1 dogs received butorphanol (0.2 mg/kg, IV) and meloxicam (0.2 mg/kg, IV) just prior to surgery. Group-2 dogs received butorphanol just prior to surgery (0.2 mg/kg, IV) and at incision closure (0.1 mg/kg, IV). Pain assessment began 1 to 2 hours before surgery and from extubation until 24 hours after surgery by obtaining the following measurements: the visual analog scale (VAS) score, cumulative pain score (CPS), adjusted cumulative pain score, modified cumulative pain score, and the adjusted modified cumulative pain score (AMCPS). Serum cortisol concentration was measured between 12 to 24 and between 1 to 2 hours prior to surgery, and at 30 minutes, and 1, 2, 4, 8, 18, and 24 hours after extubation. RESULTS: No significant differences between treatment groups were observed in CPS or VAS score. At 8, 9, 10, and 11 hours after extubation, meloxicam-butorphanol-treated dogs had a significantly lower AMCPS, compared with butorphanol-alone-treated dogs. Total serum cortisol concentration (area under the curve) during the measurement period was significantly lower in meloxicam-butorphanol-treated dogs, compared with butorphanol-alone treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative single dose administration of meloxicam-butorphanol is equivalent to or slightly better than the administration of 2 perioperative doses of butorphanol for the control of postoperative signs of pain in dogs.     

Analgesic comparison of meloxicam or ketoprofen for orthopedic surgery in dogs

OBJECTIVE: To compare the safety and efficacy of 2 analgesic protocols (preoperative meloxicam or intraoperative ketoprofen administration) during the first 24 hours after orthopedic surgery in dogs. STUDY DESIGN: Double-blind, prospective randomized clinical trial. ANIMALS: Sixty client-owned dogs. METHODS: Dogs with surgical orthopedic disorders were randomly separated into 2 groups: 30 dogs were administered 0.2 mg/kg meloxicam intravenously (IV) immediately before induction and 30 dogs were administered 2 mg/kg ketoprofen IV, 30 minutes before the end of surgery. Pain was assessed with a visual analog scale (VAS) and a cumulative pain score (CPS) preoperatively and at 30 minutes, 1, 2, 3, 4, 6, 8, and 24 hours after extubation. Selected serum biochemical variables were measured before and 24 hours after surgery and, buccal mucosal bleeding time (BMBT) and whole blood clotting time (WBCT) were measured before and 8 hours after surgery. Dogs were anesthetized with propofol and maintained on halothane in oxygen. Any complications were documented for 7 days after surgery. Results were compared between the 2 groups for significant differences in VAS scores (2-sample t-test) and in CPS (Wilcoxon's 2-sample test). Moreover, results were analyzed for significant differences in area under the curve (AUC) for VAS (2-sample t-test) and CPS (Wilcoxon's 2-sample test) among groups. To assess the effects of treatments on biochemical and coagulation functions, pre- and postoperative mean values of BMBT and WBCT were compared within both treatment groups (paired t-tests) and between both groups (2-sample t-test). RESULTS: No significant differences in pain response or coagulation were found between meloxicam- and ketoprofen-treated dogs. In both groups, alkaline phosphatase and alanine aminotransferase concentrations were significantly increased compared with baseline. No serious complications occurred. CONCLUSIONS: Preoperative administration of meloxicam is a safe and effective method of controlling postoperative pain for up to 24 hours in dogs undergoing orthopedic surgery. CLINICAL RELEVANCE: Analgesia after administration of preoperative meloxicam was comparable with administration of ketoprofen at the end of the surgery.     

Multicentre,controlled, randomised and blinded field study comparing efficacy of suxibuzone and phenylbutazone in lame horses

Reasons for performing study: In horses, it has been demonstrated that suxibuzone (SBZ) has a lower gastric ulcerogenic effect than phenylbutazone (PBZ). However, no field trials have been reported comparing the efficacy of the drugs in alleviating lameness. Objectives: To compare the therapeutic effect of SBZ to that of PBZ when administered orally in lame horses. Acceptability of both products was also compared. Methods: Lame horses (n = 155) were used in a multicentre, controlled, randomised and double‐blinded clinical trial. Horses were treated orally with either SBZ or PBZ at equivalent therapeutic dosages. PBZ was given to 79 horses at a dose of 4.4 mg/kg bwt/12 h for 2 days, followed by 2.2 mg/kg bwt/12 h for 6 days. SBZ was given to 76 horses at 6.6 mg/kg bwt/12 h for 2 days, followed by 3.3 mg/kg bwt/12 h for 6 days. Efficacy of treatments was evaluated by clinicians in equine practices according to lameness progression throughout the study. Product ingestion was checked daily to evaluate product acceptability. Results: Although SBZ showed a statistically significant tendency to have a better efficacy than PBZ (Odds ratio = 2.7; P = 0.016), significance dissipated once the analysis was adjusted for some imbalanced baseline covariates, confirming that they were actually related to the apparent advantage of SBZ over PBZ. Product acceptability was significantly higher in the SBZ group than in the PBZ group (96.1% vs. 77.2%; P = 0.001). Conclusions: SBZ and PBZ did not show significant differences in alleviating lameness in horses. However, SBZ had better product acceptability when administered orally with some food. Potential relevance: SBZ is a good therapeutic alternative to PBZ in horses since there is no significant difference in alleviating lameness between the 2 therapies.     

Comparison of perioperative racemic methadone, levo-methadone and dextromoramide in cats using indicators of post-operative pain

OBJECTIVE: To compare three opioid agonist drugs for perioperative analgesia in cats. STUDY DESIGN: Prospective, blind, controlled, randomised trial. ANIMALS: Ninety client-owned cats, weighing 3.1 (2.1-4.5) kg, aged 14.6 (6.0-84.0) months, were studied. METHODS: Seventy-six cats, scheduled for ovariectomy, received either 0.6 mg kg(-1) racemic methadone, 0.3 mg kg(-1) levo-methadone, 0.05 mg kg(-1) dextromoramide or a saline placebo IM. Behaviour and body position were assessed and scored 20 minutes later by a single 'blinded' observer. Anaesthesia was induced with propofol and maintained with halothane. Heart rate (HR), respiratory rate (RR), Fe'CO2 and SpO2 were recorded during anaesthesia. Post-operatively, pain was categorised as absent, moderate or severe, on the basis of appearance, behaviour and response to palpation of the surgical wound (pain score). Appearance, pain scores and physiological variables were monitored every 30 minutes, for a duration of 4 hours. Differences between time-dependent continuous variables were analysed using mixed models for repeated measurements. Differences in categorical, time-dependent variables were analysed using chi2-tests. Significance was set at p < or = 0.05. RESULTS: There were no significant changes in appearance after pre-anaesthetic medication. After surgery, there was no association between appearance and pain score with HR or RR. The assessment of pain depended on comparison with the placebo group, by comparing animals' reactions to wound palpation. Sixteen of the 18 cats in the placebo group and 14 of the 19 cats in the dextromoramide group showed signs of moderate-to-severe pain after surgery. In the levo-methadone group (n = 20), one animal showed pain after 60 minutes and two after 120 minutes. One cat in the racemic methadone group (n = 19) showed pain signs and behavioural changes at 60 minutes. Compared to the two methadone groups, 'rescue' analgesia was required more often in cats treated with dextromoramide or saline. CONCLUSION AND CLINICAL RELEVANCE: Dextromoramide (0.05 mg kg(-1)) was ineffective, while racemic methadone (0.6 mg kg(-1)) and levo-methadone (0.3 mg kg(-1)) provided effective analgesia in cats following ovariectomy, without behavioural, respiratory or cardiovascular side effects.     

Pharmacokinetics of phenylbutazone given intravenously or orally in mature Holstein bulls

Six mature Holstein bulls were each given 10 mg of phenylbutazone (PBZ)/kg of body weight, PO. Of the 6 bulls, 3 were given 10 mg of PBZ/kg by rapid IV administration 4 weeks later. Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling (sum of exponential functions). The harmonic mean of the biologic half-life of PBZ was 62.6 +/- 12.9 hours after oral administration and 61.6 +/- 7.2 hours after IV administration. The mean residence time was 94.61 +/- 8.44 hours and 90.49 +/- 8.93 hours for oral and IV administration, respectively. The mean total body clearance was 0.0015 +/- 0.0003 L/h/kg, with the mean apparent volume of distribution 0.134 +/- 0.021 L/kg. Mean bioavailability was 73 +/- 2% after oral administration. Phenylbutazone was adequately absorbed from the gastrointestinal tract in bulls. The apparent volume of distribution was small, indicating that PBZ distributed mainly into plasma and extracellular fluid. The total body clearance was also small, which accounted for the long half-life of PBZ in bulls.     

The effect of inflammation on the disposition of phenylbutazone in Thoroughbred horses

The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study ( n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg ( n = 5) or 4.4 mg/kg ( n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. Inflammation did not appear to affect the plasma kinetics or the urinary excretion of PBZ and its metabolites, oxyphenbutazone (OPBZ) or hydroxyphenylbutazone (OHPBZ) when PBZ was administered at 8.8 mg/kg. However, small but significant increases ( P <0.05) in total body clearance ( CL _B; 29.2 ± 3.9 vs. 43.8 ± 8.1 mL/ h-kg) and the volume of distribution, calculated by area ( V _d(area); 0.18 ± 0.05 vs. 0.25 ± 0.03 L/kg) or at steady-state ( V _d(SS); 0.17±0.04 vs. 0.25 ± 0.03 L/ kg), were obtained in horses after adjuvant injection, compared to controls, when PBZ was administered at 4.4 mg/kg which corresponded to relatively higher tissues concentrations and lower plasma concentrations (calculated) at the time of maximum peripheral PBZ concentration. Soft tissue inflammation also induced a significantly ( P <0.05) higher amount of OPBZ in the urine 18 h after PBZ administration but the total urinary excretion of analytes over 48 h was unchanged. These results have possible implications regarding the administration of PBZ to the horse close to race-day.     

Electroencephalographic and cardiovascular variables as nociceptive indicators in isoflurane-anaesthetized horses

OBJECTIVE: To evaluate Fourier-transformed electroencephalographic (EEG) variables, mean arterial blood pressure (MAP) and pulse rate as nociceptive indicators in isoflurane-anaesthetized horses. ANIMALS: Five standardbred and three Norwegian cold-blooded trotter stallions undergoing castration, aged 2-4 years, mass 378-538 kg. MATERIALS AND METHODS: All horses received intravenous (IV) detomidine (10 microg kg(-1) IV) and butorphanol (0.01 mg kg(-1) IV). Additional detomidine (4 microg kg(-1) IV) was administered in the induction area. Anaesthesia was induced with ketamine (2.5 mg kg(-1) IV) and diazepam (40 microg kg(-1) IV), and maintained for 30 minutes with isoflurane (end-tidal concentration of 1.4%) vaporized in oxygen. The electroencephalogram, MAP and pulse rate were recorded for 15 minutes, beginning 5 minutes before skin incision. Differences between the mean values of recordings taken before, and during surgery were calculated and tested for significant differences using a two-sided Student's t-test. RESULTS: A significant rise in MAP and a fall in pulse rate were found. No significant change was found in any EEG variable. CONCLUSION/CLINICAL relevance Of the variables evaluated, MAP seems to be the most sensitive and reliable indicator of nociception in isoflurane-anaesthetized horses.     

Efficacy of Epidural Morphine Versus Intravenous Morphine for Post-Thoractotomy Pain in Dogs

We compared the effects of epidural and intravenous morphine on analgesic effectiveness, vital signs, cortisol and catecholamine concentrations in dogs. Twelve healthy mongrel dogs undergoing experimental thora-cotomy under non-opioid general anaesthesia were randomly assigned to two groups: group A (n=6) received 0.15 mg/kg morphine epidurally, and group B (n=6) received 0.15 mg/kg morphine IV. Postoperatively, animals were observed hourly for the first 10 hours, then at 18 and 24 hours, and heart rate, systolic and diastolic blood pressure, respiratory rate and pain score were measured. Serum cortisol and plasma catecholamines were measured at 0, 2, 4, 8 and 24 hours postoperatively. Epidural morphine was associated with a significant reduction in pain, cortisol levels, systolic blood pressure (all p<.01) and heart rate (p<.05). There was a direct correlation between pain score, cortisol and catecholamine concentrations in each group; both were lower in the group receiving epidural morphine. Our data indicate that epidural morphine is safe, effective and provides an alternative approach for treatment of post-thoracotomy pain.