Assessing the efficacy of perioperative carprofen administration in dogs undergoing surgical repair of a ruptured cranial cruciate ligament

Twenty-one otherwise healthy dogs that presented for surgical repair of a ruptured cranial cruciate ligament were blindly and randomly given either carprofen (2.2 mg/kg body weight, orally) or a placebo beginning 12 hours preoperatively and continuing every 12 hours for a total of three doses. The patients were assessed for postoperative pain using a subjective pain score and given oxymorphone (0.1 mg/kg body weight, intramuscularly) every four hours if the pain score was 2 or greater. Blood samples were also collected to determine serum cortisol levels. There was a significant increase in serum cortisol levels in the immediate postoperative period in both the placebo group and the carprofen group (p less than 0.05). There was no significant difference in the percentage of increase in serum cortisol levels between the two groups. No correlation was evident between the serum cortisol levels and the corresponding pain scores in either group. This subjective method of assessing postoperative pain was not accurate and should not be relied upon for determination of postoperative analgesic administration. Perioperative oral administration of carprofen did not appear to be effective in controlling postoperative pain in these patients.     

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.     

Accuracy and optimization of force platform gait analysis in Labradors with cranial cruciate disease evaluated at a walking gait

OBJECTIVE: To determine the combination of ground reaction forces (GRFs) that best discriminates between lame and non-lame dogs. To compare the sensitivity of force platform gait analysis and visual observation at detecting gait abnormalities in Labradors after surgery for rupture of the cranial cruciate ligament (CCL). ANIMALS: All dogs were adult Labrador Retrievers: 17 free of orthopedic and neurologic abnormalities, 100 with unilateral CCL rupture, and 131 studied 6 months after surgery for unilateral CCL injury, 15 with observable lameness. PROCEDURE: Dogs were walked over a force platform with GRF recorded during the stance phase. Analytic properties of force platform gait analysis were calculated for several combinations of forces. The probability of visual observation detecting a gait abnormality was compared with that of force platform gait analysis. RESULTS: We determined that a combination of peak vertical force (PVF) and falling slope were optimal for discriminating sound and lame Labradors. After surgery, many dogs (75%) with no observable lameness failed to achieve GRFs consistent with sound Labradors. CONCLUSION: A force platform is an accurate method of assessing lameness in Labradors with CCL rupture and is more sensitive than visual observation. Assessing lameness with a combination of GRFs is better than using univariate GRFs. CLINICAL RELEVANCE: Therapies for stifle lameness can be accurately and objectively evaluated using 2 vertical ground reaction forces obtained from a force platform.     

Force plate gait analysis to assess limb function after tibial tuberosity advancement in dogs with cranial cruciate ligament disease

OBJECTIVE: To assess functional outcome in dogs with cranial cruciate ligament (CrCL) disease after tibial tuberosity advancement (TTA) using force plate gait analysis, and to evaluate parameters potentially influencing outcome. STUDY DESIGN: Prospective clinical study. ANIMALS: Consecutive clinical patients (n = 37) with CrCL-deficient stifles (n = 40). METHODS: The stifle joints were examined arthroscopically prior to TTA. Meniscal release was not performed if the medial meniscus was intact. Open medial arthrotomy and partial meniscectomy were performed in the presence of meniscal tears. Vertical ground reaction forces were measured preoperatively and at follow-up examinations four to 16 months postoperatively (mean: 5.9 months). The ground reaction forces of a group of 65 healthy dogs were used for the comparison. The potential effects of clinical parameters on functional outcome were evaluated statistically. RESULTS: Complete CrCL rupture was identified in 28 joints, and partial CrCL rupture in 12 joints. The medial meniscus was damaged in 21 stifles. Vertical ground reaction forces were significantly higher at follow-up (P < 0.01), but remained significantly lower than those of control dogs (P < 0.01). Complications were identified in 25% of joints, and the dogs with complications had significantly lower peak vertical forces at follow-up than the dogs without complications (P = 0.04). Other clinical parameters did not influence outcome. CONCLUSIONS: Tibial tuberosity advancement significantly improved limb function in dogs with CrCL disease, but did not result in complete return to function. Complications adversely affected functional outcome. CLINICAL SIGNIFICANCE: A return to a function of approximately 90% of normal can be expected in dogs with CrCL disease undergoing TTA.     

Use of pressure platform gait analysis in cats with and without bilateral onychectomy

OBJECTIVE: To determine peak vertical force (PVF) and vertical impulse (VI) in cats that had or had not undergone bilateral forelimb onychectomy. ANIMALS: 26 healthy adult cats. PROCEDURE: Onychectomized cats (n = 13) had undergone surgery more than 6 months prior to the study. The PVF and VI were collected from all limbs of each cat with a 2-m pressure platform walkway. Cats were allowed to walk at a comfortable velocity, and acceleration was restricted to +/- 0.5 m/s2. Five valid trials were recorded for each cat with all trials collected in a single 1-hour session. All forces were normalized to and expressed as a percentage of the cat's body weight. RESULTS: Gait data were successfully collected in all cats. No significant difference was found for PVF or VI between cats that had or had not had onychectomy. Limb loads were greater in forelimbs than hind limbs for all trials. Mean PVF and VI in the forelimbs of cats in the nononychectomy group were 56.41% and 18.85%, respectively. Mean PVF and VI in the hind limbs of cats in the nononychectomy group were 50.22% and 14.56%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Gait analysis was successfully performed in cats with a pressure platform walkway. The absence of differences in PVF and VI between the 2 groups of cats suggests that bilateral forelimb onychectomy did not result in altered vertical forces measured more than 6 months after surgery in cats.     

Effect of surgical technique on limb function after surgery for rupture of the cranial cruciate ligament in dogs

OBJECTIVE: To determine the outcome and effect of surgical technique on limb function after surgery for rupture of the cranial cruciate ligament (RCCL) and injury to the medial meniscus in Labrador Retrievers. STUDY DESIGN: Prospective clinical study. ANIMALS: 131 Labrador Retrievers with unilateral RCCL and injury to the medial meniscus and 17 clinically normal Labrador Retrievers. PROCEDURE: Affected dogs had partial or complete medial meniscectomy and lateral suture stabilization (LSS), intracapsular stabilization (ICS), or tibial plateau leveling osteotomy (TPLO). Limb function was measured before surgery and 2 and 6 months after surgery. Treated dogs were evaluated to determine the probability that they could be differentiated from clinically normal dogs and tested to determine the likelihood that they achieved improvement. RESULTS: No difference was found between LSS or TPLO groups, but dogs treated with ICS had significantly lower ground reaction forces at 2 and 6 months. Compared with clinically normal dogs only, 14.9% of LSS-, 15% of ICS-, and 10.9% of TPLO-treated dogs had normal limb function. Improvement was seen in only 15% of dogs treated via ICS, 34% treated via TPLO, and 40% treated via LSS. CONCLUSIONS AND CLINICAL RELEVANCE: Surgical technique can influence limb function after surgery. Labrador Retrievers treated via LSS, ICS, or TPLO for repair for of RCCL and medial meniscal injury managed with partial or complete meniscectomy infrequently achieve normal function. Results of LSS and TPLO are similar and superior to ICS.     

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.     

Nitric oxide metabolite production in the cranial cruciate ligament, synovial membrane, and articular cartilage of dogs with cranial cruciate ligament rupture

OBJECTIVE: To measure concentrations of nitric oxide metabolites (nitrite-nitrate [NOt]) in cartilage, synovial membrane, and cranial cruciate ligament (CCL) in dogs and evaluate associations with osteoarthritis in dogs with CCL rupture. ANIMALS: 46 dogs with CCL rupture and 54 control dogs without joint disease. PROCEDURE: Tissue specimens for histologic examination and explant culture were harvested during surgery in the CCL group or immediately after euthanasia in the control group; NOt concentrations were measured in supernatant of explant cultures and compared among dogs with various degrees of osteoarthritis and between dogs with and without CCL rupture. RESULTS: Osteoarthritic cartilage had significantly higher NOt concentration (1,171.6 nmol/g) than did healthy cartilage (491.0 nmol/g); NOt concentration was associated with severity of macroscopic and microscopic lesions. Synovial membrane NOt concentration did not differ between dogs with and without CCL rupture. Ruptured CCL produced less NOt than did intact ligaments. In control dogs, NOt concentrations were similar for intact ligaments (568.1 nmol/g) and articular cartilage (491.0 nmol/g). Synthesis of NOt was inhibited substantially by coincubation with inhibitors. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that NOt in canine joint tissues originates from the inducible nitric oxide synthase pathway. Nitric oxide metabolite production in cartilage was greater in dogs with osteoarthritis than in healthy dogs and was associated with lesion severity, suggesting that nitric oxide inhibitors may be considered as a treatment for osteoarthritis. The CCL produces substantial concentrations of NOt; the importance of this finding is unknown.     

Synovial membrane changes after experimental transection of the cranial cruciate ligament in dogs

Degenerative joint disease and inflammation of the synovial membrane were produced in the left stifle of 16 dogs by severing the cranial cruciate ligament. Arthrotomy only was performed on the right stifle. Synovial membrane from these joints was histologically examined at 1, 2, 8, and 13 weeks after surgical operation. Similar tissue was obtained from 4 healthy dogs for comparison. Inflammatory changes in the synovium of the left stifle progressed with time and were prominent at 8 weeks postoperatively; subsynovial fibrosis was greatest at 13 weeks. Inflammation of the synovial membrane and subsynovial tissue was characterized by synovial cell hypertrophy and hyperplasia, plasma cell and lymphocyte infiltration, and increased vascularization of the subsynovial region.     

Kinematic gait analysis of the hind limb after tibial plateau levelling osteotomy and cranial tibial wedge osteotomy in ten dogs

This study identifies and compares the kinematic gait changes occurring in tibial plateau levelling osteotomy (TPLO) and cranial tibial wedge osteotomy (CTWO) limbs after transection of the cranial cruciate ligament (CrCL). Ten, healthy, adult beagle dogs were assigned to TPLO (five dogs) and CTWO (five dogs) groups. Hind limb kinematics were assessed, while dogs were trotted at speeds ranging from 2.0 to 2.3 m/s. The animals were evaluated preoperatively (prior to TPLO and CTWO surgery) and at both 8 and 12 weeks after surgery. Two-dimensional evaluation was synchronized to obtain the three-dimensional coordinates using the APAS motion analysis software. Gait patterns were assessed by measuring stifle, tibiotarsal joint angles and stifle joints angular velocity. Stifle and tibiotarsal joint functions were not affected by TPLO surgery, but stifle and tibiotarsal joint angles were changed, following CTWO surgery, compared with their preoperative values. The angular velocity patterns of CTWO were characterized by increased stifle joint extension velocity from the middle to end swing phase and decrease in the peak velocities (flexion) during swing phase. None of these changes was observed in the stance phase after the CTWO surgery. These kinematic results showed that dogs that underwent a CTWO procedure were more likely to have significantly hyperextended gait patterns of the swing phase postoperatively than the dogs that had a TPLO procedure for repair of a ruptured CrCL.     

Morphology, histology and functional anatomy of the canine cranial cruciate ligament

Morphologically the canine cranial cruciate ligament can be divided into a cranio-medial and caudo-lateral component which perform reciprocal functions at all angles of flexion of the stifle joint. Histologically the main constituents of these two components are bundles of longitudinally orientated collagen fibre. The results of the study of the effect of partial and total sectioning of the cranial cruciate ligament on the "anterior-draw" movement implied that the relatively minor degree of movement, elicited following sectioning of either of the components of the ligament, would not be detected under clinical conditions. For joint instability to be clinically detectable most of the ligament must have ruptured, or the intact portion must have undergone degenerative or disruptive changes.     

Pre- and postoperative force plate analysis of dogs with experimentally transected cranial cruciate ligaments treated using tibial plateau leveling osteotomy

Objective— Quantitative and objective assessment of hindlimb kinetics after cranial cruciate ligament (CrCL) transection and subsequent stifle stabilization using the tibial plateau leveling osteotomy (TPLO) in normal dogs.
Study Design— In vivo experimental biomechanical evaluation.
Animals— Six healthy adult foxhounds.
Methods— Dogs were screened by orthopedic and radiographic examination before study entry. Force plate analysis of gait was measured before extirpation of the right CrCL and TPLO and again at 8 and 18 weeks after surgery.
Results— There was a significant decrease in peak vertical forces (PVFs) and vertical impulse (VI) of the treated hindlimb at 8 weeks when compared with preoperative and 18-week measurements. When compared with preoperative values, there was no significant difference in 18 week PVF and VI in dogs that had TPLO.
Conclusion— TPLO can restore kinetic measures of limb function at 18-weeks after surgery when compared with preoperative values after experimental transection of the CrCL in dogs.
Clinical Relevance— TPLO induces lameness that returns to near normal at 18 weeks. The severity and duration of lameness was similar to that reported for other experimental models of stifle instability repaired by different techniques.     

Endoscopy of the gastroduodenal mucosa after carprofen, meloxicam and ketoprofen administration in dogs

Endoscopy was undertaken to examine the gastroduodenal mucosa of 24 healthy dogs after seven days and again after 28 days of oral non-steroidal anti-inflammatory drug (NSAID) administration. The dogs were divided into four groups. One group received ketoprofen (1 mg/kg every 24 hours), one group carprofen (2 mg/kg every 12 hours for seven days followed by 2 mg/kg every 24 hours), a third group meloxicam suspension (0·2 mg/kg every 24 hours), and the last group gelatin (one capsule every 24 hours). Serum biochemical and complete blood count parameters did not change significantly after NSAID administration. Gastroduodenal lesions were observed in 17 dogs, but in all cases these were mild to moderate. The dogs receiving gelatin or carprofen showed the fewest and the least severe lesions, although there was no statistically significant difference between the three test drugs and the control group (P 0–05). None of the dogs showed any clinical signs related to the gastrointestinal lesions.     

Investigation of the composition, turnover, and thermal properties of ruptured cranial cruciate ligaments of dogs

OBJECTIVE: To assess different components of the extracellular matrix with regard to their thermal properties, composition, and turnover in ruptured cranial cruciate ligaments (CCLs) of dogs, compared with components of intact CCLs from a breed predisposed to CCL failure. SAMPLE POPULATION: Ruptured CCLs obtained from 8 dogs of breeds predisposed to ruptured CCLs and intact CCLs from 12 cadaveric Labrador Retrievers. PROCEDURE: Ruptured and intact CCLs were analyzed for water content; collagen content and collagen cross-links were evaluated via hydroxyproline and amino-acid analyses, respectively. Glycosaminoglycan (GAG) content was analyzed via dimethylmethylene blue and uronic acid assays. Matrix metalloproteinases (MMPs)-2 and -9 and the tissue inhibitors of metalloproteinases (TIMPs)-1 and -2 were detected via gelatin SDS-PAGE zymography and reverse gelatin zymography. Thermal analysis of ligaments was performed by use of differential scanning calorimetry. RESULTS: Ruptured CCLs had significantly higher lamounts of immature cross-links, total and sulfated GAGs, and water content, compared with that of the intact ligaments. Compared with intact CCLs, concentration of pro-MMP-2 was significantly higher in ruptured CCLs; the maximum temperature of collagen denaturation was significantly lower in the ruptured CCLs. CONCLUSIONS AND CLINICAL RELEVANCE: The extracellular matrix of ruptured CCLs had an increased matrix turnover indicated by increased collagen and GAG synthesis, compared with that of intact CCLs. Although the extracellular matrix changes may have occurred before ligament rupture, it is possible that these observed changes may be part of a reparative process after rupture.     

Efficacy of oral calcium pentosan polysulphate for the treatment of osteoarthritis of the canine stifle joint secondary to cranial cruciate ligament deficiency

The efficacy of calcium pentosan polysulphate (CaPPS) as a slow-acting drug for the treatment of osteoarthritis of the canine stifle joint, secondary to cranial cruciate ligament deficiency, was tested in a double-blind, placebo-controlled clinical trial over a period of one year. Dogs with the deficiency were treated surgically, matched for bodyweight, and randomly assigned to treatment or placebo groups. Active treatment began six weeks postoperatively and consisted of 10 mg/kg CaPPS orally, once weekly for four weeks, repeated every 12 weeks. The outcome was assessed in terms of function by the dogs' owners, by the radiographical grading of the osteoarthritis, and by the measurement of total sulphated glycosaminoglycans and the 5D4 epitope of keratan sulphate in the synovial fluids of affected joints. There were no differences either in functional outcome or in the radiographical progression of osteoarthritis between the two groups. Fifty-four weeks after surgery, the concentration of 5D4 in synovial fluid (expressed as change from baseline values) had decreased significantly in the treatment group compared with the placebo group (P=0.03).     

Clinical efficacy of flunixin,carprofen and ketoprofen as adjuncts to the antibacterial treatment of bovine respiratory disease

Three non-steroidal anti-inflammatory drugs (NSAIDs), flunixin, ketoprofen and carprofen, were used in conjunction with ceftiofur, in the treatment of naturally occurring bovine respiratory disease. Sixty-six mixed-breed beef cattle weighing on average 197 kg met the inclusion criteria of pyrexia of at least 40 degrees C, an illness score indicating at least moderate illness and at least moderate dyspnoea. They were allocated randomly to four treatment groups. All the groups received ceftiofur for three days at a dose rate of 1.1 mg/kg by intramuscular injection, and three groups received, in addition, a single dose of either flunixin (2.2 mg/kg by intravenous injection) or ketoprofen (3 mg/kg by intravenous injection) or carprofen (1.4 mg/kg by subcutaneous injection). During the first 24 hours of the study, the pyrexia of the three groups treated with a NSAID was reduced significantly more than the pyrexia of the group treated with ceftiofur alone, and two and four hours after treatment the reduction in pyrexia was significantly greater in the groups treated with flunixin and ketoprofen than in the group treated with carprofen. There were no statistically significant differences between the four groups with respect to depression, illness scores, dyspnoea or coughing. There was less lung consolidation in the three groups treated with a NSAID than in the animals treated with ceftiofur alone, but the difference was significant only in the group treated with flunixin.