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.     

Comparison of ketoprofen and carprofen administered prior to orthopedic surgery for control of postoperative pain in dogs.

OBJECTIVE: To compare analgesic and adverse effects of ketoprofen and carprofen when used to control pain associated with elective orthopedic surgeries in dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 93 client-owned dogs: 46 undergoing reconstruction of the cranial cruciate ligament, 47 undergoing femoral head and neck excision, and 15 control dogs anesthetized for radiographic procedures. PROCEDURE: Dogs undergoing surgery were randomly given ketoprofen, carprofen, or saline (0.9% NaCl) solution, SC, prior to surgery. Pain score and serum cortisol concentration were recorded for 12 hours after surgery for all dogs. When pain score was > or = 7, oxymorphone was administered i.m. Bleeding time was measured prior to and during surgery. RESULTS: The proportion of dogs that required oxymorphone was significantly higher for the carprofen and placebo groups than for the ketoprofen group. Pain score for the placebo group was significantly higher than for the ketoprofen and carprofen groups, 2, 8, and 9 hours after surgery. Cortisol concentration was significantly higher for the placebo group than for the carprofen group at 4 and 6 hours after surgery. Significant differences were not detected between ketoprofen and carprofen groups with respect to pain score and cortisol concentration. Bleeding time was significantly longer for the ketoprofen group than for the other groups during surgery. One dog treated with ketoprofen developed a hematoma at the surgical site. CONCLUSIONS AND CLINICAL RELEVANCE: Ketoprofen and carprofen given prior to surgery were effective for postoperative pain relief in dogs. However, ketoprofen should not be used when noncompressible bleeding may be a problem.     

Effect of perioperative oral carprofen on postoperative pain in dogs undergoing surgery for stabilization of ruptured cranial cruciate ligaments

A randomized, placebo-controlled, parallel study was conducted to investigate the effectiveness of oral carprofen for the control of postoperative pain in dogs undergoing knee surgery for stabilization of ruptured cranial cruciate ligaments. Dogs were randomly assigned to treatment with carprofen (n = 10) or placebo (n = 9). Pain was assessed at 1, 2, 4, 6, 24, and 48 hours and 10 and 21 days postoperatively. Eight of 10 dogs treated with carprofen and five of nine dogs treated with placebo were given at least one dose of morphine as rescue therapy. The mean relative dose of morphine given at 1 hour (P =.01) and 24 hours (P =.02) after surgery was greater for dogs treated with carprofen than for dogs given a placebo. There were no significant postoperative differences in cortisol levels or any measured variable. It appears that the scoring system used was not sensitive enough to detect differences in pain between a known analgesic and a placebo.     

Long-term treatment with carprofen of 805 dogs with osteoarthritis

The pain-relieving effect of carprofen and tolerance to the drug were investigated in 805 dogs that were lame as a result of osteoarthritis. The dogs were of different breeds, ages and bodyweights and of both sexes, and were selected from 51 veterinary clinics. Each dog was treated orally by its owner with 4 mg/kg carprofen for 84 consecutive days. Twenty-four dogs were removed from the study because of side effects, and 55 left the study for reasons unrelated to the treatment. The condition of the dogs and the benefit of the treatment were evaluated by the veterinary surgeons and the owners after 14 days, and at the end of the period of treatment, when 194 of the dogs (26.7 per cent) were no longer lame, and 357 (49.2 per cent) had improved. The period for which the dogs had been lame before entering the study significantly (P<0.01) affected the results and the rate of improvement. Too much exercise during the 84 days of treatment caused some dogs to relapse.     

Effect of carprofen on hemostatic variables in dogs

OBJECTIVE: To evaluate the effect of carprofen on hemostatic variables in clinically normal dogs. ANIMALS: 12 clinically normal Labrador Retrievers. PROCEDURE: 10 dogs (6 females, 4 males) received carprofen (2.2 mg/kg of body weight, PO, q 12 h) for 5 days. Two dogs (untreated control group; 1 female, 1 male) did not receive carprofen. Hemostatic variables (platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, platelet aggregation, and bleeding time) were assessed for all dogs prior to treatment, on day 5 of treatment, and 2 and 7 days after discontinuation of the drug (days 7 and 12). Serum biochemical variables and Hct were assessed prior to treatment and on days 5 and 12. RESULTS: In dogs receiving carprofen, platelet aggregation was significantly decreased, and onset of aggregation was significantly delayed on days 5, 7, and 12, compared with pretreatment values. Activated partial thromboplastin time was significantly increased on days 5, 7, and 12 over pretreatment values in treated dogs, but values remained within reference ranges. Significant differences were not detected in buccal mucosal bleeding time, other serum biochemical and hemostatic variables, or Hct, compared with pretreatment values and the internal control group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of carprofen for 5 days causes minor but not clinically important alterations in hemostatic and serum biochemical variables in clinically normal Labrador Retrievers. Carprofen is commonly used to treat osteoarthritis and chronic pain in dogs, but prior to this study, its effect on platelet aggregation and hemostatic variables was unknown.     

Clinical efficacy and pharmacokinetics of carprofen in the treatment of dogs with osteoarthritis

Six medium to large breed dogs with osteoarthritis were treated with 2 mg/kg of racemic carprofen, mixed with their morning feed, daily for 28 days. The treatment significantly (P < 0.01) reduced their mean lameness score, measured on a visual analogue scale, and there was a trend (P = 0.11) for the peak vertical forces exerted on a forceplate to be increased in the most severely affected limb. The plasma concentration-time relationships of the S(+) and R(-) enantiomers were studied for 24 hours after the first dose and after seven days and 28 days. There were no significant differences between the mean pharmacokinetic parameters measured on the three occasions, suggesting that carprofen was not accumulated and that tolerance to the drug did not develop. Although the pharmacokinetic parameters of the S(+) and R(-) enantiomers were generally very similar, there were wide variations both between and within dogs.     

Effectiveness of the homeopathic preparation Zeel compared with carprofen in dogs with osteoarthritis

The authors compared the symptomatic effectiveness of a complex homeopathic preparation Zeel (1-3 tablets orally per day depending on body weight) to carprofen (4 mg/kg body weight) in dogs (n=68) aged >1 yr diagnosed with osteoarthritis in a multicenter, prospective, observational open-label cohort study in 12 German veterinary clinics. The active treatment period was 56 days. Symptomatic effectiveness, lameness, stiffness of movements, and pain on palpation were evaluated by treating veterinarians and owners. Clinical signs of osteoarthritis improved significantly (P<0.05) at all time points (days 1, 28, and 56) with both therapies. At the end of the treatment period, effectiveness was comparable in both groups. Both treatment regimens were well tolerated with only three treatment-related adverse events, all in the carprofen group.     

Development of a scale to evaluate postoperative pain in dogs

OBJECTIVE: To design and evaluate a scale for measurement of postoperative pain in dogs. DESIGN: Randomized, blinded, prospective study, with positive- and negative-control groups. ANIMALS: 36 dogs undergoing general anesthesia for ovariohysterectomy and 12 dogs undergoing general anesthesia without surgery. PROCEDURE: A pain assessment scale was developed for dogs, which incorporated physiologic data (heart and respiratory rates) and behavioral responses (response to palpation, activity, mental status, posture, and vocalization). This pain scale was then applied to a study in which dogs were allocated to 2 groups, depending on the type of medication administered (acepromazine maleate only or acepromazine and butorphanol) before induction of general anesthesia. The 36 dogs that had ovariohysterectomy were allocated to 3 groups, members of which received butorphanol, carprofen, or no analgesic after surgery. Dogs were scored for signs of pain and videotaped at 0, 1, 2, 4, 6, 8, 12, and 18 hours after surgery by an assessor who was blinded to the groups. Results were analyzed for significant differences in pain scores for single categories and total pain scores among groups. Video segments were scrambled and then scored by a second external assessor to test the repeatability of the results, using the pain assessment scale. RESULTS: Mean total pain scores were significantly different between the group of dogs that underwent general anesthesia only and each group of dogs that underwent general anesthesia and surgery. Pain scores for the analgesic-treatment groups reflected the known onset and duration of action of the analgesic used. Agreement between the internal and external assessors was excellent and indicated high precision between the 2 assessors for the population of dogs as a whole. CLINICAL IMPLICATIONS: Behavioral and physiologic measurements can be used reliably to evaluate degree of pain in dogs during the postoperative period and their response to analgesics.     

Renal effects of carprofen and etodolac in euvolemic and volume-depleted dogs

Objective-To determine the effects of carprofen and etodolac on renal function in euvolemic dogs and dogs with extracellular fluid volume depletion induced via administration of furosemide. Animals-12 female Beagles. Procedures-Dogs received a placebo, furosemide, carprofen, etodolac, furosemide and carprofen, and furosemide and etodolac. The order in which dogs received treatments was determined via a randomization procedure. Values of urine specific gravity, various plasma biochemical variables, glomerular filtration rate (GFR [urinary clearance of creatinine]), and renal plasma flow (urinary clearance of para-aminohippuric acid) were determined before and after 8 days of drug administration. A washout time of approximately 12 days was allowed between treatment periods. Results-Administration of furosemide, furosemide and carprofen, and furosemide and etodolac caused changes in urine specific gravity and values of plasma biochemical variables. Administration of carprofen or etodolac alone did not have a significant effect on renal plasma flow or GFR. Concurrent administration of furosemide and carprofen or furosemide and etodolac caused a significant decrease in GFR. After 12-day washout periods, mean values of GFR were similar to values before drug administration for all treatments. Conclusions and Clinical Relevance-Results indicated GFR decreased after 8 days of concurrent administration of furosemide and carprofen or furosemide and etodolac to dogs. Administration of preferential cyclooxygenase-2 inhibitors to dogs with extracellular fluid volume depletion or to dogs treated with diuretics may transiently impair renal function.     

Effects of postoperative administration of ketoprofen or carprofen on short- and long-term results of femoral head and neck excision in dogs

OBJECTIVE: To determine whether postoperative administration of ketoprofen or carprofen had any effects on short- or long-term results of femoral head and neck excision (FHNE) in dogs. DESIGN: Prospective randomized controlled trial. ANIMALS: 40 client-owned, large-breed dogs undergoing FHNE and 15 healthy large-breed dogs used as controls for hip joint angle measurements and force plate analyses. PROCEDURE: Dogs undergoing FHNE were treated with ketoprofen, carprofen, or a placebo for 21 days after surgery. Hip joint abduction and extension angles were measured at the end of surgery and 120 days later. Lameness scores were assigned, and force plate analyses were performed on days 3, 15, and 120. RESULTS: There were no significant differences among treatment groups in regard to hip joint angles or lameness scores. Force plate analysis revealed that dogs in all 3 treatment groups bore consistently less weight on the operated limb than did control dogs for the duration of the study. Dogs receiving ketoprofen had greater peak propulsive force at a walk on day 3 and greater peak vertical force at a walk on day 15 than did dogs receiving the placebo. Treatment of an acute condition and preservation of the lesser trochanter, but not postoperative analgesic administration, were positively associated with ground reaction forces on day 120. Owners of 12 of 31 dogs indicated that the dog's gait worsened for a few days after discontinuation of analgesic administration. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of ketoprofen or carprofen after surgery was not associated with long-term results of FHNE, probably because of the impact of other factors. Because some owners noticed worsening of the lameness following cessation of analgesic administration in the present study, it is possible that longer administration would have improved long-term results.     

Clinical evaluation of firocoxib and carprofen for the treatment of dogs with osteoarthritis

A double-blind, randomised, controlled, multicentre field study was conducted to compare the safety and efficacy of firocoxib chewable tablets and carprofen tablets in 218 dogs with osteoarthritis. Firocoxib is a non-steroidal anti-inflammatory drug with more than 350-fold selectivity in dogs for the inducible isoform of the enzyme cyclo-oxygenase-2. The efficacy, tolerance and ease of administration of firocoxib (5 mg/kg/day) and carprofen (4 mg/kg/day) were assessed by the owners and the attending veterinarians during 30 days of treatment. The efficacy was assessed in terms of the dogs' overall scores at the end of the treatment, based on the veterinarians' assessment of lameness, pain on manipulation/palpation, range of motion, and joint swelling; 92.5 per cent of the dogs treated with firocoxib and 92.4 per cent of the dogs treated with carprofen had improved. The reduction in lameness in the dogs treated with firocoxib was significantly greater than in the dogs treated with carprofen. The owners' evaluations were that 96.2 per cent of the dogs treated with firocoxib and 92.4 per cent of the dogs treated with carprofen had improved, and this difference was statistically significant.     

Comparison of carprofen and pethidine as postoperative analgesics in the cat

The postoperative analgesia and sedation in cats given carprofen (4·0 mg/kg bodyweight by subcutaneous injection preoperatively) was compared to that in cats given pethidine (3·3 mg/kg bodyweight by intramuscular injection postoperatively) in a controlled, randomised, blinded, multicentre clinical trial. Further dosing with the particular analgesic was allowed if a cat was exhibiting unacceptable pain. In total, 57 carprofen cases and 59 pethidine cases were evaluated. Significantly fewer cats in the carprofen group required additional doses of analgesic, and mean pain scores were significantly lower from four hours after ovariohysterectomy, and at 18 to 24 hours after castration, compared to the pethidine group. In conclusion, carprofen provided as good a level of postoperative analgesia as pethidine, but of a longer duration (at least 24 hours) and was well tolerated. It thus provides an option for 'pre-emptive analgesia' in cats about to undergo surgery.     

The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal

This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period.     

Renal effects of carprofen administered to healthy dogs anesthetized with propofol and isoflurane

OBJECTIVE: To evaluate renal effects of carprofen in healthy dogs following general anesthesia. DESIGN: Randomized clinical trial. ANIMALS: 10 English hound dogs (6 females and 4 males). PROCEDURE: Dogs were randomly assigned to control (n = 5) or carprofen (5) groups. Anesthesia was induced with propofol (6 to 8 mg/kg [2.7 to 3.6 mg/lb] of body weight, i.v.) and maintained with isoflurane (end-tidal concentration, 2.0%). Each dog underwent two 60-minute anesthetic episodes with 1 week between episodes, and mean arterial blood pressure was maintained between 60 and 90 mm Hg during each episode. Dogs in the carprofen group received carprofen (2.2 mg/kg [1 mg/lb], p.o.) at 9:00 AM and 6:00 PM the day before and at 7:00 AM the day of the second anesthetic episode. Glomerular filtration rates (GFR) were determined during each anesthetic episode by use of renal scintigraphy. Serum creatinine and BUN concentrations and the urine gamma-glutamyltransferase-to-creatinine concentration (urine GGT:creatinine) ratio were determined daily for 2 days before and 5 days after general anesthesia. RESULTS: Significant differences were not detected in BUN and serum creatinine concentrations, urine GGT:creatinine ratio, and GFR either between or within treatment groups over time. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not significantly alter renal function in healthy dogs anesthetized with propofol and isoflurane. These results suggest that carprofen may be safe to use for preemptive perioperative analgesia, provided that normal cardiorespiratory function is maintained.     

Effects of carprofen, meloxicam and deracoxib on platelet function in dogs

ObjectiveTo determine effects of anti-inflammatory doses of COX-2 selective NSAIDs carprofen, meloxicam, and deracoxib on platelet function in dogs and urine 11-dehydro-thromboxane B2.Study designRandomized, blocked, crossover design with a 14-day washout period.AnimalsHealthy intact female Walker Hounds aged 1–6 years and weighing 20.5–24.2 kg.MethodsDogs were given NSAIDs for 7 days at recommended doses: carprofen (2.2 mg kg^?1, PO, every 12 hours), carprofen (4.4 mg kg^?1, PO, every 24 hours), meloxicam (0.2 mg kg^?1, PO, on the 1st day then 0.1 mg kg^?1, PO, every 24 hours), and deracoxib (2 mg kg^?1, PO, every 24 hours). Collagen/epinephrine and collagen/ADP PFA-100 cartridges were used to evaluate platelet function before and during and every other day after administration of each drug. Urine 11-dehydro-thromboxane B₂ was also measured before and during administration of each drug.ResultsAll NSAIDs significantly prolonged PFA-100 closure times when measured with collagen/epinephrine cartridges, but not with collagen/ADP cartridges. The average duration from drug cessation until return of closure times (collagen/epinephrine cartridges) to baseline values was 11.6, 10.6, 11 and 10.6 days for carprofen (2.2 mg kg^?1 every 12 hours), carprofen (4.4 mg kg^?1 every 24 hours), meloxicam and deracoxib, respectively.Conclusions and clinical relevanceOral administration of some COX-2 selective NSAIDs causes detectable alterations in platelet function in dogs. As in humans, PFA-100 collagen/ADP cartridges do not reliably detect COX-mediated platelet dysfunction in dogs. Individual assessment of platelet function is advised when administering these drugs prior to surgery, particularly in the presence of other risk factors for bleeding.     

Comparison of carprofen and meloxicam for 72 hours following ovariohysterectomy in dogs

OBJECTIVE: To compare the peri- and post-operative (72 hours) analgesic effects of injectable and orally administered carprofen and meloxicam for ovariohysterectomy in dogs. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Forty-three dogs undergoing elective ovariohysterectomy. MATERIALS AND METHODS: Dogs were randomly assigned to receive pre-operative carprofen, meloxicam or sterile saline by subcutaneous injection. Pre-anaesthetic medication was intramuscular acepromazine (0.02 mg kg(-1)) and methadone (0.2 mg kg(-1)). Anaesthesia was induced with either thiopentone or propofol injected to effect, and maintained with isoflurane in oxygen. Visual analogue scores (VAS) for pain and sedation were recorded at 1, 2, 3, 4 and 6 hours following tracheal extubation. Oral medication with the same treatment was continued post-operatively for 3 days, with VAS scores for pain being recorded before, and 2 hours after treatment on each day. Differences between group age, body mass, duration of general anaesthesia, time from treatment injection to tracheal extubation and time from treatment injection to first oral treatment were analysed using one-way analysis of variance and Kruskal-Wallis test. Visual analogue scores for pain and sedation were analysed using a re-randomization method. The significance level was set at p < 0.05. RESULTS: Meloxicam-treated subjects had lower mean VAS than the control group at 2 and 6 hours following tracheal extubation. Control group VAS were more varied than meloxicam scores (at 6 hours) and carprofen scores (at 3 and 6 hours). On the first post-operative day, pre- to post-treatment VAS scores decreased significantly after meloxicam. On day 3, scores in the meloxicam-treated group were significantly lower than control values after treatment. Changes in pre- to post-treatment VAS were greater in animals receiving either meloxicam or carprofen compared with those given saline. CONCLUSIONS AND CLINICAL RELEVANCE: Both carprofen and meloxicam provided satisfactory analgesia for 72 hours following ovariohysterectomy in dogs.