Antinociceptive activity of pre- versus post-operative intra-articular bupivacaine in goats undergoing stifle arthrotomy

ObjectiveTo evaluate the peri-operative analgesic efficacy of intra-articular bupivacaine administered before or after stifle arthrotomy.Study designProspective, randomized, blind, placebo-controlled experimental trial.AnimalsThirty-nine healthy goats.MethodsThe goats were allocated randomly to one of three intra-articular treatment groups: group PRE (bupivacaine before and saline after surgery), group POST (saline before and bupivacaine after surgery) and group CON (saline before and after surgery). Anaesthesia was maintained with a constant end-tidal sevoflurane of 2.5%. Intra-operatively heart rate (HR), respiratory rate and mean arterial blood pressure (MAP) after critical surgical events (CSE) were recorded and compared with pre-incision values. Propofol requirements to maintain surgical anaesthesia were recorded. Flunixin was administered for 5 days. Post-operative pain assessment at 20 minutes, 2 hours, 4 hours after recovery and on day 2 and 3 included a multidimensional pain score (MPS), a lameness score and mechanical nociceptive threshold (MNT) testing. Rescue analgesia consisted of systemic opioids. Data were analysed using Kruskal–Wallis, Mann–Whitney, Friedman or chi-square tests as appropriate.ResultsIntra-operatively, group PRE had lower HR and MAP at several CSEs than groups POST/CON and required less propofol [0 mg kg^?1 (0–0 mg kg^?1)] than group POST/CON [0.3 mg kg^?1 (0–0.6 mg kg^?1)]. Post-operatively, group POST had significantly higher peri-articular MNTs than groups PRE and CON up to 4 hours after recovery. No treatment effect was detected for MPS, lameness scores and rescue analgesic consumption at any time point.Conclusions and clinical relevancePre-operative intra-articular bupivacaine provided notable intra-operative analgesia in goats undergoing stifle arthrotomy but did not reduce post-operative pain. Post-operative intra-articular bupivacaine provided a short lasting reduction of peri-articular hyperalgesia without affecting the requirements for systemic analgesia. Multimodal perioperative pain therapy is recommended to provide adequate analgesia for stifle arthrotomy in goats.     

Synovial fluid bupivacaine concentrations following single intra‐articular injection in normal and osteoarthritic canine stifles

Intra‐articular bupivacaine helps alleviate pain in animals receiving joint surgery, but its use has become controversial as ex vivo studies have illuminated the potential for chondrotoxicity. Such studies typically involve cell cultures incubated in solutions containing high bupivacaine concentrations for long durations. The aim of this study was to measure the actual synovial fluid bupivacaine concentrations after intra‐articular injection. Eight healthy beagles with normal stifles and 22 large and giant‐breed dogs with stifle osteoarthritis (OA) were treated with a single intra‐articular injection of bupivacaine (1 mg/kg) into a stifle. Joint fluid samples were taken from the treated stifle immediately after injection and 30 min after injection and analyzed for bupivacaine concentrations. Immediately after injection, the median bupivacaine concentrations in normal and OA stifles were 3.6 and 2.5 mg/mL, respectively. Thirty minutes after injection, bupivacaine concentrations in normal and OA stifles were 0.4 and 0.6 mg/mL, respectively. These results provide insight into the pharmacokinetics of bupivacaine after injection into a joint. Given its immediate dilution and rapid drop in synovial fluid concentration, bupivacaine is unlikely to damage chondrocytes when administered as a single intra‐articular injection.     

Effect of caudal epidural xylazine on intraoperative distress and post-operative pain in Holstein heifers

Objective To compare the effects of caudal epidural xylazine versus saline on tolerance of paravertebral nerve block and flank surgery and on post‐operative pain in heifers used for a veterinary student training laboratory. Study design Randomized controlled prospective study. Animals Fourteen one‐year‐old, nongravid, healthy Holstein heifers, weighing 360 ± 5 kg. Methods Xylazine (0.05 mg kg^?1) or 0.9% saline (5 mL) was injected using a caudal epidural technique to seven heifers undergoing a flank surgery. Nerve block of the right paravertebral fossa was performed using equal parts of lidocaine 2% and bupivacaine 0.5%. Heart and respiratory rates, rectal temperature, rumination frequency, and appetite were recorded before and at 4, 8, and 24 hours after surgery. Scores were recorded for: tolerance of local anesthesia injections (pre‐operatively), sedation, ataxia and distress (intraoperatively, every 30 minutes), and pain (4, 8, and 24 hours post‐operatively). Results The animals reaction to local anesthetic injection was judged to be less in the xylazine group by both an experienced observer (p < 0.001) and student surgeons (p < 0.01). The xylazine group required less local anesthetic (82.9 ± 13.8 mL) versus the saline group (108.4 ± 19.6 mL, p = 0.035). Intraoperatively, xylazine heifers were more sedated at all times (p‐values from <0.001 to 0.017), were more ataxic for the first 1.5 hours (p‐values from <0.001 to 0.026), and lower in distress at all times (p‐values from <0.001 to 0.007). No difference in post‐operative pain or physiologic variables was found, except immediately post‐operatively, rectal temperature was higher in the xylazine group (39.5 ± 0.3 °C) than in the saline group (38.6 ± 0.2 °C, p < 0.001). Conclusion and clinical relevance Compared with epidural saline, caudal epidural xylazine reduced distress of anesthetic injection and surgical manipulation in heifers and an improvement in animal well‐being was apparent. This effect may have been as a result of sedation. Pre‐operative epidural xylazine did not appear to improve post‐surgical analgesia in our study.     

Influences of carprofen and the experience of the surgeon on post-castration pain in lambs and young sheep

This study evaluated the influences of carprofen and the experience of the surgeon on post‐castration pain in lambs and young sheep castrated in the field. A total of 201, 1–6‐week‐old lambs with a mean body mass of 11.0 ± 2.4 kg (mean ± SD) were castrated after local application of 4 mL lidocaine (2%). Preoperatively lambs were given either 20 mg carprofen SC or an equal volume of saline in a randomized order. A further 34 sheep, aged 6 months, with a mean body mass of 36.0 ± 4.5 kg were castrated after local application of 7 mL lidocaine (2%). Preoperatively sheep received 2 mg kg^?1 carprofen SC or an equal volume of saline in a randomized order. Lidocaine was injected SC in front of, behind and into each spermatic cord. All surgery was performed using the same Burdizzo clamp (jaw 45 mm wide, handles 225 mm) either by students or experienced veterinary surgeons. Pain was assessed preoperatively and at 24, 48 and 72 hours after castration by two independent observers unaware of the treatment group. Observers scored pain using a visual analog scale (100 mm) after applying gentle pressure onto the scrotal region ( Thornton & Waterman‐Pearson 1999 ). Swelling of the scrotal region was scored as ‘severe’, ‘present but not severe’ and ‘not present’. The VAS scores were compared using a Mann–Whitney test, p < 0.05 was considered significant. Swelling was compared using Fisher's exact test. In lambs, no significant differences in pain scores between those treated with carprofen or saline were noted by either observer (p > 0.48) at any of the three assessment times. However, the number of lambs with severe or present swelling of the scrotal region was significantly lower in those receiving carprofen (8% versus 18%, p = 0.028). Lambs castrated by students showed significantly higher pain scores (23% versus 13%, p < 0.001 at 24 hours; 20% versus 13%, p = 0.0062 at 48 hours; 16% versus 10%, p = 0.0088 at 72 hours) and significantly more swelling (18% versus 8%, p = 0.0189) of the scrotal region than those castrated by veterinary surgeons. Young sheep receiving carprofen preoperatively had significantly lower pain scores (12 mm versus 25 mm, p = 0.037) 24 hours after surgery compared to sheep receiving saline. No scrotal swelling was obvious in sheep. Juvenile sheep but not lambs, receiving carprofen preoperatively showed reduced pain scores up to 24 hours after surgery. Carprofen reduced swelling of the scrotum in lambs. Lambs castrated by experienced surgeons scored lower VAS scores at all times and showed less swelling of the scrotal region.     

Evaluation of intraperitoneal and incisional lidocaine or bupivacaine for analgesia following ovariohysterectomy in the dog

Objective To determine if intraperitoneal (IP) and incisional (SC) lidocaine or bupivacaine provide analgesia following ovariohysterectomy (OHE). Study Design Prospective, randomized, controlled, blinded clinical trial. Animals Thirty dogs presenting to the Veterinary Teaching Hospital for elective OHE. Methods Dogs were pre‐medicated with acepromazine and butorphanol, induced with thiopental and maintained with isoflurane. They were randomly assigned to three groups: 10 received 8.8 mg kg^?1 2% lidocaine with epinephrine IP (LID); 10 received 4.4 mg kg^?1 0.75% bupivacaine IP (BUP); and 10 received 0.9% saline IP (SAL) upon completion of OHE. All IP doses were standardized to 0.88 mL kg^?1 with saline. An additional 2 mL of undiluted solution was placed SC prior to incisional closure. Dogs were scored at 0.5, 1, 2, 3, 6, 8 and 18 hours post‐extubation by one observer. Dogs were evaluated using a visual analogue scale (VAS) for pain and sedation, and a composite pain scale (CPS) that included physiologic and behavioral variables. Dogs were treated with 0.22 mg kg^?1 butorphanol + acepromazine if their VAS (pain) score was >50. Parametric variables were analyzed using Student's t‐test or repeated measures anova as appropriate. Non‐parametric variables were analyzed by χ²‐test. Results There were no significant differences in age, weight, incision length, surgery time, anesthesia time, or total thiopental dose among groups. Peak post‐surgical pain scores for all groups occurred at 0.5 hours and returned to baseline by 18 hours. Dogs in the BUP group had significantly lower VAS‐pain scores overall than dogs in the SAL group. Seven out of 10 dogs in the SAL group, 4/10 in the LID group and 2/10 in the BUP group were treated with supplemental acepromazine and butorphanol. No differences between groups were detected with the CPS. No adverse side‐effects were observed. Conclusions and clinical relevance Our findings support the use of IP and SC bupivacaine for post‐operative analgesia following OHE in the dog.     

An effective buprenorphine analgesic protocol increases post-operative adhesions in rats after laparotomy

The use of analgesics in post‐operative adhesion (POA) research is problematic due to POA‐inhibiting effects of anti‐inflammatory agents and bowel motility‐inhibiting effects of opioids, which may increase adhesion formation. This study was conducted to assess a buprenorphine (BUP) protocol for analgesic efficacy and its effects on POA formation in a rat cecal abrasion model. The protocol was approved by the University of Florida's Institutional Animal Care and Use Committee (IACUC). Forty‐one female Sprague‐Dawley rats were randomized into two groups (n = 20 or 21 group). Body weight, food and water intake were recorded daily from 2 days before until 7 days after surgery. Treatment rats received 0.05 mg kg^–1 BUP SQ at anesthesia induction and 0.3 mg kg^–1 BUP orally in flavored gelatin 6 hours after surgery. Control rats received saline placebo injection and plain gelatin. All rats underwent laparotomy and controlled cecal abrasion. At 3, 6 and 24 hours post‐operatively rats were individually observed in 10‐minutes periods for pain related behavior incidence: ‘twitch’ (contraction of muscles along dorsum and/or head), ‘back arch’ (cat‐like position with front legs extended and pushing backward), ‘writhe’ (flank contraction), and ‘stagger/fall’ (momentary loss of balance while grooming or ambulating), using the method of Roughan and Flecknell (Pain 2001,90, 65–74). On post‐op day seven rats were euthanized by CO₂ inhalation and POA evaluated (0 to 4 scale; ³Grade 2 = clinically significant.) BUP treated rats had lower mean pain scores than control rats at 3 hours (1.6 ± 1.7 versus 20.3 ± 13.5 (mean ± SD); p < 0.001) and 6 hours (2.1 ± 2.7 versus 23.7 ± 12.9; p < 0.001) but not 24 hours (1.5 ± 1.3 versus 4.9 ± 6.6; p = 0.35) post‐operatively. Predominant pain behavior was ‘writhe’ (flank contraction) in contrast to ‘twitch,’‘back arch,’ and ‘stagger/fall’ reported as most common pain indicators in other rat strains. BUP rats had greater mean adhesion incidence (2.4 ± 1.7 versus 1.4 ± 1.8; p < 0.03) and severity (90%³Gr.2 versus 65% of controls; p < 0.05). The BUP protocol appeared to provide effective analgesia for at least 24 hours post‐operatively. Strain of rat may affect pain related behavior. BUP should be used with caution after abdominal surgical procedures having high risk of POA formation.     

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

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

Comparison of postoperative effects between lidocaine infusion,meloxicam, and their combination in dogs undergoing ovariohysterectomy

ObjectiveTo compare the postoperative analgesic effects of intravenous (IV) lidocaine, meloxicam, and their combination in dogs undergoing ovariohysterectomy.Study designProspective, randomized, double‐blind, controlled clinical trial.AnimalsTwenty‐seven dogs aged (mean ± SD) 16.1 ± 7.5 months and weighing 22.4 ± 17.9 kg scheduled for ovariohysterectomy.MethodsAnaesthesia was induced with propofol and maintained with isoflurane. Dogs (n = 9 in each group) were allocated to receive just prior to and during surgery one of the following regimens: M group, 0.2 mg kg^?1 IV meloxicam then a continuous rate infusion (CRI) of lactated Ringer's at 10 mL kg^?1 hour^?1; L group, a bolus of lidocaine (1 mg kg^?1 IV) then a CRI of lidocaine at 0.025 mg kg^?1 minute^?1; and M + L group, both the above meloxicam and lidocaine treatments. Pain and sedation were scored, and venous samples taken for serum cortisol and glucose measurement before and at intervals for 12 hours after anaesthesia. Pain scores were assessed using a multi‐parameter subjective scoring scale (cumulative scale 0–21) by three observers. The protocol stated that dogs with a total score exceeding 9 or a sub‐score above 3 in any one category would receive rescue analgesia. Sedation was scored on a scale of 0–4.ResultsThere were no significant differences in subjective pain scores, serum cortisol, and glucose concentrations between the three groups. The highest pain score at any time was 5, and no dog required rescue analgesia. None of the three regimens caused any observable side effects during or after anaesthesia. At 1 and 2 hours after extubation dogs in group L were significantly more sedated than in the other two groups.Conclusions and Clinical relevanceThis study suggests that, with the scoring system used, IV lidocaine and meloxicam provide similar and adequate post‐operative analgesia in healthy dogs undergoing ovariohysterectomy.     

Brachial plexus block using electrolocation for pancarpal arthrodesis in a dog

Conduction blockade was achieved at the brachial plexus of a dog undergoing surgery for pancarpal arthrodesis. The lidocaine/bupivacaine mixture used was the sole analgesic treatment applied during surgery and for 3 hours post-operatively. Location of the plexus brachialis was facilitated using a nerve stimulator. A low volume of lidocaine and bupivacaine (0.26 mL kg(-1)) resulted in successful blockade, which was evident from stable cardiorespiratory variables at low end-tidal (1.3-1.4%) isoflurane concentrations. Pain scoring and examination of motor and sensory function indicated adequate pain relief for 7 hours. While localization of the plexus brachialis can be performed 'blindly', electrolocation improves the success rate for less experienced anaesthetists.     

Comparison of perioperative analgesic protocols for dogs undergoing tibial plateau leveling osteotomy

OBJECTIVE: To compare effects of 3 commonly used perioperative analgesic protocols (epidural injection, intra-articular injection, and intravenous [IV] injection) for management of postoperative pain in dogs after tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: Fifty-six healthy dogs with naturally occurring cranial cruciate ligament rupture. METHODS: Dogs were premedicated with IV hydromorphone and acepromazine and were randomly assigned to receive either E (preoperative epidural injection with morphine and bupivacaine), IA (pre- and postoperative intra-articular injections of bupivacaine), or C (neither epidural morphine and bupivacaine, nor intra-articular bupivacaine). All dogs were administered hydromorphone (0.05 mg/kg IV) at extubation and as needed to maintain comfort postoperatively. Patients were observed and monitored continuously for 24 hours and discomfort was assessed using visual analog pain scores (VASs), multifactorial pain scores (MPSs), and response to a pressure nociceptive threshold (PNT) measuring device. Time to 1st dose and the total doses of hydromorphone required to achieve adequate comfort for each dog were recorded. RESULTS: No differences in measured indices of postoperative pain were observed between dogs of each treatment group; VAS (P=.190), MPS (P=.371), and PNT (P=.160). Time to 1st analgesic intervention was longer for Group E compared with Group C (P=.005) and longer for Group IA compared with Group C (P=.032). Although time to 1st intervention between Groups E and IA were longer for Group E, differences were not significant. To provide an adequate level of comfort, more analgesic interventions were administered to dogs in Group C compared with dogs in group E (P=.015). On average, more hydromorphone was administered to Group C compared with Group IA (P=.072) and to Group IA compared with Group E (P=.168), but statistical significance was not reached for these data. CONCLUSIONS: In this study population, significant differences were seen in time to 1st hydromorphone dose between Groups E and IA compared with Group C. As well, more supplemental analgesia was administered to Group C compared with Group E to maintain the same level of postoperative comfort. Although differences between Groups E and IA tended to favor the epidural group, differences were minimal and not statistically significant. CLINICAL RELEVANCE: Our results suggest that regardless of analgesic protocol, measured indices of pain in dogs after TPLO can be minimized if dogs are continuously observed and appropriately supplemented with parenteral opioids. However, the frequency of postoperative opioid dosing can be minimized and may be a factor when contemplating supplementary use of epidural or intra-articular injections as part of a balanced analgesic approach.     

Autogenous osteochondral grafting for treatment of stifle osteochondrosis in dogs

Objective— To develop and assess clinical outcomes for osteochondral autografting for treatment of stifle osteochondrosis (OC) in dogs. Study Design— Retrospective case series. Animals— Dogs with stifle OC (n=10). Methods— Osteochondral autografting was developed and optimized in canine cadavers and purpose‐bred research dogs using the Osteochondral Autograft Transfer System (OATS). Dogs with stifle OC (n=10 dogs, 12 stifles) were then treated using the OATS system. Outcomes were assessed by radiography (n=12), magnetic resonance imaging (1), second‐look arthroscopy (9), lameness scoring (12), and telephone survey of owners (10 clients, 12 stifles) 6–15 months after surgery. Results— Complications were documented in 4 of the 12 stifles treated and included peri‐incisional seromas (3) and marked stifle effusion (1). Subjective assessment of follow‐up radiographs revealed evidence of integration of the grafts with maintenance of subchondral bone surface architecture. Subjective assessment of follow‐up MRI in 1 stifle revealed evidence for incorporation of grafts with restoration of articular surface contour. Second‐look arthroscopy 6–30 weeks after surgery revealed maintenance of articular cartilage at the graft site. Dogs were significantly (P<.001) less lame at follow‐up compared with preoperative scores. Based on follow‐up owner surveys, only 2 dogs had no pain or lameness; the other dogs were judged to have mild pain and/or lameness. All owners noticed improvement in the dogs' quality of life after surgery. Conclusion— Osteochondral autografting deserves consideration and further evaluation as a primary treatment option for stifle OC in dogs. Clinical Relevance— Osteochondral autografting for treatment of lateral femoral condylar OC lesions in dogs using OATS instrumentation is safe and results in improved function and quality of life based on owners' perception 6–15 months after treatment.     

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

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

Experiences With Morphine Injected Into the Subarachnoid Space in Sheep

The effects of morphine (M), 0.1 mg/kg, administered into the lumbosacral subarachnoid space of sheep used for experimental stifle surgery, were investigated. In a pilot study, preservative-free morphine was administered to three sheep, morphine containing preservatives to two sheep, and saline (S) to one sheep. After recovery from anesthesia, all five sheep administered M displayed rear limb weakness. One sheep, which had received morphine containing preservatives, also licked and chewed incessantly at its flank and hindquarters during recovery. A group of 24 sheep was used to study the effects of morphine containing preservatives, injected intrathecally, on recovery from general anesthesia and hindlimb orthopedic surgery. Eight sheep received M, eight sheep received S, and eight sheep had a needle placed in the subarachnoid space without any injection (N). Times from end of anesthesia to standing varied greatly and did not differ significantly among groups (P=.73), with M sheep averaging 119 minutes; S sheep, 87 minutes; and N sheep, 83 minutes. One sheep administered M licked and chewed at its hindquarters during recovery. Another group of 24 sheep was used to study the effects of morphine containing preservatives, injected intrathecally, on postoperative lameness. Treatments were as described previously. Sheep were videotaped intermittently for 36 hours after surgery, and each sheep was scored as follows; 0 = not lame; 1 = slightly lame; and 2 = very lame. The average lameness scores, which did not differ significantly among groups (P=.21), were: M sheep, 1.07; S sheep, 0.81; and N sheep, 0.68. One sheep administered M displayed extensor spasms of the hindlimbs, and could not stand until several hours after surgery. We conclude that subarachnoid morphine at the dosage used produces no apparent benefit in sheep which have had stifle surgery, and in fact may cause detrimental side effects, such as hindlimb weakness, and pruritis or irritation of the hindquarters.     

The pre-emptive effect of epidural ketamine on wound sensitivity in horses tested by using von Frey filaments

Objective To evaluate the pre‐emptive analgesic effect of pre‐incisional epidural ketamine. Study Design A blinded, randomized experimental study. Animals Sixteen mixed breed mares, 7.6 ± 2.8 years old, weighing 352 ± 32 kg. Methods In a pilot study, an incision was made on one lateral thigh using a lidocaine block and no further analgesics, and it was verified that the nociceptive threshold was lower on the incised side than nonincised side (p ≤ 0.05), and that von Frey filaments evoked a pain response. The 16 animals were divided into group A (ketamine, n = 9) and B (saline, n = 7). An epidural catheter was inserted 24 hours before the trials. The thigh was shaved bilaterally, and the right side was blocked (incised side) using lidocaine. Twenty‐five minutes later, ketamine (A) or saline (B) was administered epidurally. Five minutes later, a 10‐cm skin incision was made on the right side, and then sutured. Nociceptive threshold was determined with von Frey filaments at 1, 3, and 5 cm around the incision at 15‐minute intervals for 2 hours, then at 4, 6, and 8 hours. Behavioral alterations, heart and respiratory rates were recorded. Nociceptive thresholds from these points were averaged to obtain mean values at each time, converted to a logarithmic scale, and submitted to a nonparametric analysis (Mann–Whitney and one‐way repeated measures anova test, p ≤ 0.05). Results After 8 hours, the global range score revealed reduced hyperalgesia (p < 0.01) around the incision in 92% (4.65–4.27) of evaluated intervals in group A (ketamine). There were no significant changes in behavior, heart and respiratory rates. Conclusions It was concluded that pre‐emptive epidural ketamine reduced post‐incisional pain in the horse, and that von Frey filaments were able to quantify cutaneous sensitivity after tissue damage. Clinical relevance Epidural ketamine injection can reduce post‐incisional sensitivity in the horse.     

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.     

Estimated plasma bupivacaine concentration after single dose and eight-hour continuous intra-articular infusion of bupivacaine in normal dogs

Objective— To estimate maximum plasma concentration (C_max) and time to maximum plasma (t_max) bupivacaine concentration after intra‐articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Study Design— Cross‐over design with a 2‐week washout period. Animals— Healthy Coon Hound dogs (n=8). Methods— Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration–time curves and estimate C_max, T_max and other pharmacokinetic variables for comparison of SI and CI. Results— Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (C_max, 1.33±0.954 μg/mL) occurred at 11.37±4.546 minutes. For CI, mean C_max (1.13±0.509 μg/mL) occurred at 10.37±4.109 minutes. The area under the concentration–time curve was smaller for SI (143.59±118.390 μg/mL × min) than for CI (626.502±423.653 μg/mL × min, P=.02) and half‐life was shorter for SI (61.33±77.706 minutes) than for CI (245.363±104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 μg/mL for SI and 2.3 μg/mL for CI. Conclusion— Intra‐articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean C_max below that considered toxic and no systemic drug accumulation. Clinical Relevance— Intra‐articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra‐articular injection.     

Comparison of the cytotoxic effects of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes

Objective To compare the chondrotoxicity of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes in vitro. Study design Prospective, experimental study. Study material Equine articular chondrocytes. Methods Primary cultured equine chondrocytes were exposed to 0.5% bupivacaine, 2% lidocaine, or 2% mepivacaine for 30 or 60 minutes. After treatment, cell viability was evaluated by trypan blue exclusion and the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) colorimetric assay in a dose dependent manner. Apoptosis and necrosis of chondrocytes were analyzed with the double staining of Hoechst 33258 and propidium iodide using fluorescence microscopy, and the results were confirmed using flow cytometry. Results After 30‐minute exposure, trypan blue exclusion assay revealed that cell viability of 0.5% bupivacaine group was 28.73 ± 8.44%, and those of 2% lidocaine and 2% mepivacaine were 66.85 ± 6.03% and 86.27 ± 2.00%, respectively. The viability of chondrocytes after saline treatment was 95.95 ± 2.75%. The results of MTT assay and fluorescence microscopy had similar tendency with trypan blue assay. Each result showed that bupivacaine was the most toxic of the three local anaesthetics. Mepivacaine was less toxic than lidocaine. The results of the viability test suggest that bupivacaine and lidocaine exhibit a marked chondrotoxicity, and that this is mainly due to necrosis rather than apoptosis. Conclusions and clinical relevance Bupivacaine may induce detrimental chondrotoxicity when administered intra‐articularly, especially in patients with joint disease, and we suggest that it should be used cautiously in equine practice. Mepivacaine may be an alternative to both bupivacaine and lidocaine.     

Analgesic efficacy of intra‐articular morphine in experimentally induced radiocarpal synovitis in horses

ObjectiveTo compare the analgesic effect of intra-articular (IA) and intravenous (IV) morphine in horses with experimentally induced synovitis.AnimalsEight adult horses.Study designRandomized, observer blinded, double dummy trial with sequential crossover design.MethodsRadiocarpal synovitis was induced by IA injection of lipopolysaccharide on two occasions separated by a 3-week washout period. In one study period horses received treatment IA; morphine IA (0.05 mg kg^?1) plus saline IV and in the other study period they received treatment IV; saline IA plus morphine IV (0.05 mg kg^?1). Lameness and pain were evaluated repeatedly by two observers throughout each of the two 168-hour study periods. Pain was evaluated by use of a visual analogue scale of pain intensity (VAS) and a composite measure pain scale (CMPS). Comparison of treatments was performed by analysis of variance with repeated measurements. Significance level was set to p ≤ 0.05. Inter-observer agreement and agreement between the VAS and CMPS was assessed by use of the Bland–Altman method.ResultsIntra-articular injection of LPS elicited a marked synovitis resulting in lameness and pain. IA morphine resulted in significantly less lameness than IV morphine (p = 0.03). CMPS (p = 0.09) and VAS (p = 0.10) pain scores did not differ significantly between treatments. Inter-observer agreement of the CMPS was classified as good, but only fair for the VAS. Agreement between the two pain scales was considered fair.Conclusions and clinical relevanceAn analgesic effect of IA morphine was demonstrated by significantly reduced lameness scores. The results support the common practice of including IA morphine in a multimodal analgesic protocol after arthroscopic surgery, although further studies in clinical cases are needed. The employed CMPS had good reproducibility, and was easy to use, but may have limited sensitivity at mild intensity pain.     

Evaluation of topical nalbuphine or oral tramadol as analgesics for corneal pain in dogs: a pilot study

Objective To evaluate the effectiveness of topical nalbuphine or oral tramadol in the treatment of corneal pain in dogs. Animals studied Fourteen male Beagle dogs. Procedures Dogs were divided into three treatment groups and sedated with dexmedetomidine (5 μ/kg IV). A 4 mm corneal epithelial wound was created in the right eye (OD) of all dogs. Sedation was reversed with atipamazole IM. All dogs received pre/post ophthalmic examinations. Post operatively, Group NB (n = 5) received topical 1% preservative‐free nalbuphine OD q8 h and an oral placebo PO q8 h. Group TR (n = 5) received tramadol (4 mg/kg) PO q8 h and topical sterile saline OD q8 h. Group CNTRL (n = 4) received topical sterile saline OD q8 h and an oral placebo q8 h. All dogs received topical 0.3% gentamicin OD TID until healed. Dogs were pain scored using a pain scoring system modified from the University of Melbourne pain scale at 0, 1, 2, 4, and 6 h, then every 6 h by observers masked to treatment, until corneal wounds were healed. Treatment failure was recorded if cumulative pain scores were above a minimum threshold of acceptable pain and rescue analgesia of morphine (1.0 mg/kg IM) was administered subsequently. Result Four dogs in Group NB, one dog in Group TR, and two dogs in Group CNTRL required rescue analgesia. There was no significant difference in the incidence of treatment failure between groups (P = 0.184). Mean time to rescue was 9.16 h. All corneal wounds were healed by 84 h. Conclusions The results of this study suggest tramadol rather than nalbuphine should be further investigated for the treatment of corneal pain.     

Liposome-encapsulated oxymorphone provides prolonged relief of post-surgical visceral pain in rats

A delayed‐release formulation of liposome‐encapsulated oxymorphone was produced using a novel dehydration–rehydration technique. The purpose of this study was to (i) compare the analgesic properties of this preparation with those of repeated injections of standard oxymorphone in rats with post‐operative visceral pain and (ii) determine whether liposome‐encapsulated oxymorphone differed from standard oxymorphone in duration of the effect. Visceral pain was elicited in approximately 300 g Sprague–Dawley rats by intestinal resection performed under isoflurane anesthesia. Rats were monitored with pulse oximetry; mean anesthesia time (35 ± 10 minutes) did not differ between the groups. Rats were randomly divided into two groups: Group 1 received 1.2 mg kg^?1 liposome‐encapsulated oxymorphone SC once at skin closure and 0.2 mL of saline SC every 4 hours; Group 2 received 0.2 mL liposome‐encapsulated sucrose SC once at skin closure and 0.3 mg kg^?1 standard oxymorphone SC every 4 hours. In both groups, a behavioral ethogram for pain score (grooming, porphyrin staining, body position) was recorded every 4 hours for 48 hours after surgery. Observers were blinded to the treatment. Body weight, food consumption, and urine output were recorded daily for 7 days after anesthetic recovery. Data were analyzed using anova , with significance at p < 0.05. Based on the behavioral pain score, a single injection of liposome‐encapsulated oxymorphone was as effective for relief of post‐surgical visceral pain in rats as multiple (every 4 hours) injections of standard oxymorphone administered over a 48 hour period (p = 0.18). In rats, given one dose of liposome‐encapsulated oxymorphone, the mean body weight change from day 0 to day 7 was +9.4 g, whereas rats given multiple injections of standard oxymorphone had a mean body weight change of ?3.6 g over this time (p < 0.01). Mean daily food consumption was significantly less in rats given multiple injections of standard oxymorphone (p < 0.05). There was no difference between groups in urine production. In conclusion, a single dose of liposome‐encapsulated oxymorphone was effective in treating visceral pain in rats. Rats treated with liposome‐encapsulated oxymorphone had improved recovery, based on body weight changes and food consumption, compared with rats treated with multiple doses of standard oxymorphone. Liposome‐encapsulated oxymorphone offered advantages including provision of effective analgesia, prolonged dosing intervals, and minimal handling stress.