Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery

OBJECTIVE: To compare the safety and efficacy of preoperative administration of meloxicam with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery. ANIMALS: 36 dogs undergoing laparotomy, splenectomy, or cystotomy. PROCEDURE: Dogs were randomly assigned to 1 of 3 groups. In the first part of the study, dogs were given a single dose of meloxicam, ketoprofen, or a placebo, and buccal mucosal bleeding times were measured. In the second part of the study, dogs were given meloxicam, ketoprofen, or butorphanol prior to surgery. Dogs in the butorphanol group received a second dose immediately after surgery. Pain scores (1 to 10) were assigned hourly for 20 hours after surgery and used to determine an overall efficacy score for each dog. Dogs with a pain score > or =3 were given oxymorphone for pain. Dogs were euthanatized 8 days after surgery, and gross and histologic examinations of the liver, kidneys, and gastrointestinal tract were conducted. RESULTS: Overall efficacy was rated as good or excellent in 9 of the 12 dogs that received meloxicam, compared with 9 of the 12 dogs that received ketoprofen and only 1 of the 12 dogs that received butorphanol. No clinically important hematologic, biochemical, or pathologic abnormalities were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preoperative administration of meloxicam is a safe and effective method of controlling postoperative pain for 20 hours in dogs undergoing abdominal surgery; the analgesic effects of meloxicam were comparable to those of ketoprofen and superior to those of butorphanol.     

Analgesic effect of pre-operative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy

The analgesic, bleeding, and renal effects of dogs pre‐medicated with etodolac with and without butorphanol were evaluated. Twenty‐four 1‐year‐old healthy dogs, weighing 19 ± 3 kg (mean ± SD) were randomly assigned to four treatment groups (n = 6): control (C), etodolac (E), butorphanol (B), and etodolac with butorphanol (EB). Etodolac (12–14 mg kg^?1 PO) was given 1 hour before propofol induction and isoflurane maintenance anesthesia. Butorphanol (0.4 mg kg^?1 IV) was given immediately following endotracheal intubation. Control dogs received only propofol (8 mg kg^?1 to effect) and isoflurane anesthesia. All dogs were mechanically ventilated to maintain Pe ′CO₂ between 35 and 45 mm Hg (4.7–6.0 kPa). Lactated Ringer's solution was given at 10 mL kg^?1 hour^?1 during anesthesia. Plasma cortisol concentrations were assessed 1 day prior to surgery (baseline), immediately prior to anesthesia induction, and every 30 minutes until 5 hours following extubation, and 1 day after surgery. Total duration of anesthesia was 50 minutes and total surgery duration was 30 minutes. Isoflurane concentration area under the curve (AUC) over time during the anesthesia was compared among treatment groups. Buccal mucosal bleeding time (BMBT) was assessed 1 day before E administration and during surgery. Urine GGT to urine creatinine ratio, BUN, and plasma creatinine were taken daily from 1 day before to 3 days after surgery. Behavioral pain scores (numerical rating scale) were assessed by two observers blinded to the treatment during the 5‐hour recovery period at 30 minute intervals until 3 hours, and again at 5 hours after extubation. All data were analyzed using anova . Multiple comparisons were performed if the anova was significant. Alpha value was set at 0.05. Plasma cortisol concentrations significantly increased from time of extubation in all the treatment groups. They did not return to the baseline until 5, 2.5, 1.5, and 1.5 hours after extubation in the C, B, E, and EB groups, respectively. Isoflurane AUC was not significantly different among treatment groups. Dogs treated with EB had significantly less behavioral pain than all other groups throughout the 5‐hour recovery period. No significant difference was found between treatment groups or within treatment groups over time in BMBT, or any renal variables. This study demonstrated that (i) pre‐operative administration of E provides profound analgesia during the post‐operative period without renal or bleeding side‐effects in dogs undergoing OHE; and (ii) a combination of butorphanol–etodolac provides the best analgesic effect during the post‐operative period based on the behavioral pain score.     

Analgesic efficacy of butorphanol and morphine in bearded dragons and corn snakes

OBJECTIVE: To test the hypothesis that administration of butorphanol or morphine induces antinociception in bearded dragons and corn snakes. DESIGN: Prospective crossover study. ANIMALS: 12 juvenile and adult bearded dragons and 13 corn snakes. PROCEDURES: Infrared heat stimuli were applied to the plantar surface of bearded dragon hind limbs or the ventral surface of corn snake tails. Thermal withdrawal latencies (TWDLs) were measured before (baseline) and after SC administration of physiologic saline (0.9% NaCl) solution (equivalent volume to opioid volumes), butorphanol tartrate (2 or 20 mg/kg [0.91 or 9.1 mg/lb]), or morphine sulfate (1, 5, 10, 20, or 40 mg/kg [0.45, 2.27, 4.5, 9.1, or 18.2 mg/lb]). RESULTS: For bearded dragons, butorphanol (2 or 20 mg/kg) did not alter hind limb TWDLs at 2 to 24 hours after administration. However, at 8 hours after administration, morphine (10 and 20 mg/kg) significantly increased hind limb TWDLs from baseline values (mean +/- SEM maximum increase, 2.7+/-0.4 seconds and 2.8+/-0.9 seconds, respectively). For corn snakes, butorphanol (20 mg/kg) significantly increased tail TWDLs at 8 hours after administration (maximum increase from baseline value, 3.0+/-0.8 seconds); the low dose had no effect. Morphine injections did not increase tail TWDLs at 2 to 24 hours after administration. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with doses used in most mammalian species, high doses of morphine (but not butorphanol) induced analgesia in bearded dragons, whereas high doses of butorphanol (but not morphine) induced analgesia in corn snakes.     

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.     

Comparison of preoperative carprofen and postoperative butorphanol as postsurgical analgesics in cats undergoing ovariohysterectomy

OBJECTIVE: To compare carprofen to butorphanol, with regard to postsurgical analgesic effects, duration of analgesia, and adverse side effects. STUDY DESIGN: Blinded, randomized clinical study. ANIMALS: Seventy-one cats, 0.5-5 years of age, weighing 3.24 +/- 0.61 kg, undergoing ovariohysterectomy (OHE). METHODS: Cats were premedicated with subcutaneous atropine (0.04 mg kg(-1)), acepromazine (0.02 mg kg(-1)), and ketamine (5 mg kg(-1)). Anesthesia was induced with ketamine (5 mg kg(-1)) and diazepam (0.25 mg kg(-1)) given intravenously, and maintained with isoflurane. There were three treatment groups: group C (4 mg kg(-1) carprofen SC at induction), group B (0.4 mg kg(-1) butorphanol SC at end of surgery), and group S (0.08 mL kg(-1) of sterile saline SC at induction and end of surgery). Behavioral data were collected using a composite pain scale (CPS), prior to surgery (baseline) and 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours post-surgery. Interaction scores were analyzed separately. Cats with CPS scores >12 received rescue analgesia (meperidine, 4 mg kg(-1), intramuscular). RESULTS: Sixty cats completed the study. The CPS scores did not differ significantly between groups C and B at any time period. CPS scores for groups B and C were significantly increased for 12 hours post-surgery, and in group S for 20 hours. Both group C and B CPS scores were significantly lower than group S in this 20-hour postoperative period, except at 4 hours (B and C) and at 3 and 8 hours (B alone). Interaction scores for group C returned to preoperative baseline 4 hours after surgery, while both groups B and S remained increased for at least 24 hours post-surgery. Nine cats required meperidine. CONCLUSION: In this study, carprofen provided better postsurgical analgesia than butorphanol. Clinical relevance Neither drug completely abolished pain, however preoperative carprofen provided better pain control compared with postoperative butorphanol in the 24-hour period following OHE surgery in cats.     

Efficacy and safety of preoperative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy

Eighteen dogs undergoing ovariohysterectomy were premedicated with etodolac, butorphanol, or their combination. Various parameters, such as blood pressure, isoflurane requirements, behavioral pain scores, plasma cortisol concentration, plasma glucose concentration, and mucosal bleeding time, were assessed. The integrated plasma cortisol values were significantly lower in the etodolac and etodolac with butorphanol groups. Dogs receiving etodolac and butorphanol had the lowest behavioral pain scores from extubation until the end of monitoring. Isoflurane concentration over time (area under the curve), buccal mucosal bleeding time, and indices of renal function were not significantly different among the treatment groups.     

Cyclooxygenases 1 and 2 inhibition and analgesic efficacy of dipyrone at different doses or meloxicam in cats after ovariohysterectomy

ObjectiveTo evaluate the cyclooxygenases (COX) inhibition, adverse effects and analgesic efficacy of dipyrone or meloxicam in cats undergoing elective ovariohysterectomy.Study designProspective, blinded, randomized, clinical study.AnimalsA total of 30 healthy young cats.MethodsThe cats were randomly assigned to three postoperative groups: D25 (dipyrone 25 mg kg^?1 every 24 hours), D12.5 (dipyrone 12.5 mg kg^?1 every 12 hours) and M (meloxicam 0.1 mg kg^?1 every 24 hours). In the first 24 hours, the drugs were administered intravenously (IV), and then orally for 6 (dipyrone) or 3 days (meloxicam). Prostanoids thromboxane B₂ and prostaglandin E₂ concentrations served as indicators of COX activity and, with physiological variables and pain and sedation scores, were measured for 24 hours after first analgesic administration. Rescue analgesia (tramadol, 2 mg kg^?1 IV) was provided if Glasgow feline composite measure pain scale (CMPS-Feline) ≥5. Laboratory tests included symmetric dimethylarginine and adverse effects were evaluated regularly up to 7 and 10 days after surgery, respectively. Parametric and nonparametric data were analyzed with two-way anova and Kruskal-Wallis tests, respectively (p < 0.05).ResultsIn the first half hour after analgesic administration, COX-1 activity was close to zero and remained significantly lower than before drug administration for 24 hours in all groups. The inhibition of COX-2 activity was significant for 30 minutes in all groups and up to 4 hours in group M. No alterations in laboratory tests or significant adverse effects were observed. Pain scores and need for rescue analgesia did not differ statistically among groups.ConclusionsDipyrone at both doses and meloxicam provided a nonselective inhibition of COX-1 and -2 activities and effective analgesia without causing significant adverse effects or laboratory tests alterations.Clinical relevanceDipyrone at both doses provides equally effective analgesia without causing adverse effects in cats undergoing ovariohysterectomy.     

Comparison of transdermal administration of fentanyl versus intramuscular administration of butorphanol for analgesia after onychectomy in cats

OBJECTIVE: To compare postoperative discomfort assessed by subjective pain score and plasma cortisol concentrations in cats undergoing onychectomy that received analgesia by use of transdermal fentanyl (TDF) patches or an i.m. injection of butorphanol. DESIGN: Randomized prospective clinical trial. ANIMALS: 22 client-owned cats weighing 2.2 to 5 kg (4.84 to 11 lb) undergoing onychectomy. PROCEDURE: Researchers were blinded to which cats received a TDF patch (25 microg/h) 18 to 24 hours prior to surgery or an i.m. injection of butorphanol (0.2 mg/kg (0.09 mg/lb]) at the time of sedation, immediately following extubation, and at 4-hour intervals thereafter for 12 hours. Clinical variables, plasma cortisol concentration, and pain scores were evaluated and recorded 24 hours prior to surgery, at extubation, and 2, 4, 8, 12, 24, 36, and 48 hours after surgery. RESULTS: The TDF group had a lower pain score than the butorphanol group only at 8 hours after surgery. Both groups had significantly lower mean plasma cortisol concentrations 0, 24, 36, and 48 hours after surgery, compared with mean plasma cortisol concentrations prior to surgery. No significant differences in appetite or response to handling the feet were observed between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Our data did not reveal a difference in pain relief between administration of TDF and butorphanol. Plasma cortisol concentrations were not different between groups. Fentanyl appeared to provide equivalent analgesia to butorphanol in cats undergoing onychectomy. The primary advantage of using a TDF patch is that repeated injections are not required.     

Antinociceptive effects of hydromorphone, butorphanol, or the combination in cats

The goal of this study was to assess the antinociceptive activity of a single dose of hydromorphone or butorphanol and to examine the effect of their coadministration on thermal thresholds in cats. Thermal thresholds were measured after IM administration of hydromorphone (0.1 mg/kg), butorphanol (0.4 mg/kg), a combination of butorphanol and hydromorphone (0.4 and 0.1 mg/kg), or saline to each of 6 cats in a randomized, blinded, crossover study design. There were at least 12 days between treatments. Thermal thresholds were measured by a thorax-mounted thermal threshold-testing device specifically developed for cats. Thermal thresholds were measured before treatment, at varying intervals to 12 hours, and at 24 hours after treatments. Data were analyzed by an analysis of variance with a repeat factor of time. Dysphoria was associated with butorphanol administration but not with hydromorphone or hydromorphone-butorphanol combined administration. Vomiting was seen with hydromorphone but not with butorphanol or hydromorphone-butorphanol combined. The control treatment group was stable over time (P = .22; mean threshold, 40.1 degrees C). Thresholds were significantly (P < .05) higher than the control treatment between 15 and 165 minutes for butorphanol, between 15 and 345 minutes for hydromorphone, and between 15 and 540 minutes for hydromorphone-butorphanol combined. The addition of butorphanol to hydromorphone decreased the intensity of antinociception during the 1st 2 hours but extended the duration of observable antinociception from 5.75 to 9 hours. The present study suggests that the combination of butorphanol and a pure OP3 (mu) receptor agonist clinically does not produce increased analgesia and indeed may result in decreased analgesia.     

Evaluation of the clinical efficacy of meloxicam in cats with painful locomotor disorders.

The ability of two non-steroidal anti-inflammatory drugs to modify the clinical manifestations of pain associated with locomotor disease was assessed. Sixty-nine cats with acute or chronic locomotor disorders were recruited from 14 first opinion UK veterinary practices and randomly allocated to one of two treatment groups. Group A received meloxicam drops (0.3 mg/kg orally on day 1 followed by 0.1 mg/kg daily for four more consecutive days) and group B received ketoprofen tablets (1.0 mg/kg orally once daily for five days). Each cat underwent a full clinical examination before treatment, 24 hours after initiation of treatment and 24 hours after completion of treatment. General clinical parameters (demeanour and feed intake) and specific locomotor parameters (weightbearing, lameness, local inflammation and pain on palpation) were scored using a discontinuous scale scoring system. The two groups did not differ in terms of age, weight, gender distribution or duration of clinical signs; nor did they differ in terms of general clinical or specific locomotor scores pretreatment. Both treatment regimens resulted in a significant improvement in demeanour, feed intake and weightbearing, and a significant reduction in lameness, pain on palpation and inflammation. No significant difference was observed between the two treatment groups with respect to any of the parameters measured and both treatments were associated with minimal observed side effects. Meloxicam and ketoprofen were found to be effective analgesics and well tolerated in cats with acute or chronic locomotor disorders when administered for short-term treatment (five days) in such cases. However, meloxicam was assessed to be significantly more palatable than ketoprofen.     

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis

OBJECTIVE: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. ANIMALS: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. PROCEDURE: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. RESULTS: Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.     

Postoperative analgesic efficacy of meloxicam compared to tolfenamic acid in cats undergoing orthopaedic surgery

Objectives : To investigate the efficacy of meloxicam or tolfenamic acid administered preoperatively and postoperatively (five days in total) to cats undergoing surgical fracture repair. Methods : Eighty-eight otherwise healthy cats were matched according to fracture site and then randomly allocated to one of two groups, receiving 0·2 mg/kg meloxicam by subcutaneous injection (group M) or 1·5 to 3 mg/kg tolfenamic acid orally (group T) before anaesthesia. Analgesia was continued with 0.05 mg/kg oral meloxicam once daily or 1·5 to 3 mg/kg oral tolfenamic acid twice daily for four days postoperatively. Pain was assessed by a blinded observer using visual analogue scales and a functional limb score. The drug administrator assessed feed intake and palatability of the treatment. Results : Data from 66 cats were analysed. Visual analogue scale pain scores and functional limb scores decreased over time in both groups but were not significantly different between treatments. Feed intake was similar in both groups. Meloxicam was significantly more palatable than tolfenamic acid on all treatment days. Clinical Significance : Meloxicam and tolfenamic acid demonstrated comparable analgesia, without clinically observable side effects. Meloxicam may be associated with superior compliance in clinical practice due to the higher palatability and once daily treatment resulting in better ease of administration.     

Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats

Lehr, T., Narbe, R., Jöns, O., Kloft, C., Staab, A. Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats. J. vet. Pharmacol. Therap. 33 , 277–286. The objectives of these investigations were: first, to describe the pharmacokinetic properties of meloxicam in cats following single and multiple oral administration and secondly, to simulate different oral dosage regimes for meloxicam in cats after multiple dose administration to illustrate and evaluate those dosage regimes for the alleviation of inflammation and pain in cats. Six healthy domestic short hair cats were treated orally with various dosage regimes (0.05–0.2 mg/kg/day). Plasma samples were collected at predefined times and quantitatively analysed using liquid/liquid extraction followed by reverse phase HPLC with UV‐detection. Meloxicam plasma concentration data were analysed using the population pharmacokinetic approach (software: NONMEM). The final model was used to simulate different dosage regimes. The plasma concentration–time profiles of meloxicam in cats after oral single and multiple dose administration were best described by an open one‐compartment model with first‐order absorption and first‐order elimination. Pharmacokinetic parameters were estimated to be 0.00656 L/h/kg for the total apparent body clearance (CL/F), 0.245 L/kg for the apparent volume of distribution (V/F), 1.26 1/h for the absorption constant (K_A) and 25.7 h for the mean plasma terminal half‐life. Simulations showed that the median trough steady‐state concentrations of 228 ng/mL were reached after five, one or 6 days following a single initial dose of 0.05, 0.1 and 0.2 mg/kg each followed by 0.05 mg/kg/day.     

Analgesic effect of butorphanol in ponies following castration

Reasons for performing study: In the UK butorphanol has a marketing authorisation for administration to horses for sedation in combination with detomidine, and at a higher dose (0.1 mg/kg bwt), for the alleviation of pain. There is only a limited number of clinical studies designed to examine the analgesic effects of butorphanol administration following surgery. Objective: To investigate the effect of premedication with butorphanol on post operative pain following castration under general anaesthesia in ponies. Hypothesis: Ponies receiving butorphanol would experience less pain after castration than ponies that did not receive butorphanol. Methods: A randomised, observer blinded clinical study in which 20 ponies received butorphanol and detomidine (Group B) or detomidine alone (Group C). Anaesthesia was induced with ketamine and diazepam and open castration performed. Pain was assessed by one individual using a dynamic interactive visual analogue scale (DIVAS) 100 mm in length (0 = no pain, 100 mm the maximum possible pain for that procedure). ‘Rescue’ analgesia was administered when DIVAS >50 mm and was butorphanol i.v. On the second occasion DIVAS was >50 mm, flunixin was administered i.v. Data from the DIVAS were analysed using a Mann Whitney Test. Results: Only one animal did not require rescue analgesia after surgery (Group C). DIVAS were not significantly different between groups (P = 0.063). Conclusions and potential relevance: Castration is sufficiently painful that administration of a single preoperative dose of butorphanol does not provide adequate post operative analgesia.     

Changes in thermal threshold response in eight cats after administration of buprenorphine, butorphanol and morphine

Thermal thresholds were measured in eight cats after the intramuscular administration of morphine (0.2 mg/kg), buprenorphine (0.01 mg/kg) or butorphanol (0.2 mg/kg), doses commonly used in clinical practice; 0.9 per cent saline (0.3 ml) was injected as a control. Groups of six cats were used and each cat participated in at least two treatments, according to a randomised design. The investigator was blinded to the treatments. The thermal thresholds were measured with a testing device developed specifically for cats, and measurements were made before and five, 30, 45 and 60 minutes and two, four, six, 12 and 24 hours after the injections. There was no significant change in thermal threshold after the injection of saline. With butorphanol, the threshold was increased only at five minutes after the injection and was decreased two hours after the injection; with morphine it was increased from between four and six hours after the injection, and with buprenorphine it was increased from between four and 12 hours after the injection.