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1.
A delayed‐release formulation of liposome‐encapsulated oxymorphone (LEO) was produced using a novel dehydration–rehydration technique. Preparations were standardized spectrophotometrically against a known concentration of the drug. The purpose of this study was to test the analgesic properties of LEO in a rat model of neuropathic pain. Sprague–Dawley rats were divided into control (non‐neuropathic) and test (neuropathic) groups. Control and test groups were administered one SC injection of (i) vehicle liposomes (negative control treatment); (ii) liposome‐encapsulated morphine, 2.8 mg kg?1 (positive control treatment); or (iii) LEO, 1.2 mg kg?1. All treatments were administered after baseline thermal withdrawal latencies (TWL) were determined (9.2 ± 0.39 seconds (mean ± SEM)). Test groups then underwent sciatic ligation to induce neuropathic pain. TWL were determined in all six groups (n = 8) daily for 1 week. In a separate group of age‐matched rats, blood (0.3 mL from the jugular vein) and urine (1–2 mL via metabolism cages) were collected daily for 7 days after administration of LEO (1.2 mg kg?1). TWL did not change in the control rats given liposome‐encapsulated sucrose or morphine. There was a small increase (p = 0.04) in TWL in control rats given LEO, likely as a result of the relatively higher dose of oxymorphone compared with morphine based on receptor affinity. TWL in test rats given blank liposomes decreased significantly (p < 0.001) by day 4 (7.1 ± 0.5 seconds), with a maximal decrease by day 7 (5.1 ± 0.36 seconds), indicating development of full hyperalgesia. In contrast, rats given liposome‐encapsulated morphine or oxymorphone had no change in TWL at day 4, indicating that these preparations prevented hyperalgesia after a single injection. This treatment effect persisted through day 7. Serum concentrations of oxymorphone after a single injection of LEO peaked at 4 hours (6.8 ± 0.82 ng mL?1) and were detectable through day 4 (0.98 ± 0.003 ng mL?1), while urine concentrations of drug were detectable through day 7. This result suggests that oxymorphone metabolites might have been responsible for the protracted analgesic response. The encapsulation efficiency of oxymorphone using this novel technique was approximately 96%. In conclusion, liposome encapsulation of oxymorphone proved to be an efficient mechanism to provide a delayed‐release formulation of this opioid. This single dose of subcutaneously administered liposome‐encapsulated oxymorphone was effective in preventing hyperalgesia for 7 days in this animal model of neuropathic pain.  相似文献   

2.
ObjectiveTo evaluate the pharmacokinetics, in dogs, of liposome–encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG).AnimalsFour healthy purpose–bred Beagles aged 9.5 ± 3.2 months and weighing 13.4 ± 2.3 kg.Study designRandomized cross–over design.MethodsEach dog was given either 4.0 mg kg?1 of ASG–oxymorphone or 8.0 mg kg?1 of ASG–hydromorphone SC on separate occasions with a 3–month washout period. Blood was collected at baseline and at serial time points up to 1032 hours (43 days) after injection for determination of serum opioid concentrations. Serum opioid concentrations were measured with HPLC–MS and pharmacokinetic parameters were calculated using commercial software and non–compartmental methods.ResultsSerum concentrations of oxymorphone remained above the limit of quantification for 21 days, while those for hydromorphone remained above the limit of quantification for 29 days. Cmax for ASG–oxymorphone was 7.5 ng mL?1; Cmax for ASG–hydromorphone was 5.7 ng mL?1.Conclusions and clinical relevanceOxymorphone and hydromorphone, when encapsulated into liposomes using the ammonium sulfate gradient loading technique, result in measureable serum concentrations for between 3 to 4 weeks. This formulation may have promise in the convenient use of opioids for clinical treatment of chronically painful conditions in dogs.  相似文献   

3.
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.  相似文献   

4.
The purpose of the study was to assess the pharmacokinetics of liposome‐encapsulated (DPPC‐C) hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs. A total of eight healthy Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg were used. Dogs randomly received liposome encapsulated hydromorphone, 0.5 mg/kg IV (n = 6), 1.0 mg/kg (n = 6), 2.0 mg/kg (n = 6), or 3.0 mg/kg (n = 7) SC with a 14–28 day washout between trials. Blood was sampled at serial intervals after drug administration. Serum hydromorphone concentrations were measured using liquid chromatography with mass spectrometry. Serum concentrations of hydromorphone decreased rapidly after IV administration of the DPPC‐C formulation (half‐life = 0.52 h, volume of distribution = 12.47 L/kg, serum clearance = 128.97 mL/min/kg). The half‐life of hydromorphone after SC administration of DPPC‐C formulation at 1.0, 2.0, and 3.0 mg/kg was 5.22, 31.48, and 24.05 h, respectively. The maximum serum concentration normalized for dose (CMAX/D) ranged between 19.41–24.96 ng/mL occurring at 0.18–0.27 h. Serum hydromorphone concentrations fluctuated around 4.0 ng/mL from 6–72 h after 2.0 mg/kg and mean concentrations remained above 4 ng/mL for 96 h after 3.0 mg/kg DPPC‐C hydromorphone. Liposome‐encapsulated hydromorphone (DPPC‐C) administered SC to healthy dogs provided a sustained duration of serum hydromorphone concentrations.  相似文献   

5.
A prospective, double‐blinded, positive‐controlled, multicenter, noninferiority study was conducted to evaluate the safety and effectiveness of transdermal fentanyl solution (TFS) compared with oxymorphone for the control of postoperative pain in dogs. Five hundred and two (502) client‐owned dogs were assigned to a single dose of TFS (2.7 mg/kg) applied 2–4 h prior to surgery or oxymorphone hydrochloride (0.22 mg/kg) administered subcutaneously 2–4 h prior to surgery and q6h through 90 h. Pain was evaluated over 4 days by blinded observers using a modified Glasgow composite pain scale, and the a priori criteria for treatment failure was a pain score ≥8 or adverse event necessitating withdrawal. Four TFS‐ and eight oxymorphone‐treated dogs were withdrawn due to lack of pain control. Eighteen oxymorphone‐treated, but no TFS‐treated dogs were withdrawn due to severe adverse events. The one‐sided upper 95% confidence interval of the difference between TFS and oxymorphone treatment failure rates was −5.3%. Adverse events associated with oxymorphone were greater in number and severity compared with TFS. It was concluded that a single administration of TFS was safe and noninferior to repeated injections of oxymorphone for the control of postoperative pain over 4 days at the dose rates of both formulations used in this study.  相似文献   

6.
Objective To evaluate the effect of intra‐articular (IA) lidocaine plus bupivacaine on post‐operative pain in sheep undergoing stifle arthrotomy. Study design Randomized controlled experimental trial. Animals Sixteen adult Rambouillet‐cross ewes. Methods Sheep were randomly assigned to one of two treatment groups. The lidocaine/bupivacaine group (L/B, n = 8) received IA lidocaine (40 mg (2 mL)) prior to incision and IA bupivacaine (10 mg (2 mL)) post‐closure, while the control group (n = 8) received no IA injections. IA local anesthetics were an addition to the standard analgesic protocol of phenylbutazone (1 g orally, every 24 hours for 5 days) and transdermal fentanyl (equivalent to 15 mg), initiated 24 hours prior to surgery. A stifle arthrotomy was performed with the purpose of creating a full‐thickness articular cartilage defect. Two observers blinded to treatment assessed sheep for total pain score using a numeric ranking scale that included: comfort, movement, and flock behavior. The first observation (T = 0) was obtained the evening of surgery (3–7 hours post‐operatively); subsequent observations occurred every 12 hours for 72 hours. Nonparametric statistical tests were used to evaluate differences between groups for total pain score. Results L/B sheep had significantly lower total pain scores at T = 0 than control sheep (p < 0.05). No significant differences between treatments were noted at any subsequent time periods. There were no differences attributable to the use of different observers. Conclusions and clinical relevance IA lidocaine plus bupivacaine provided analgesia at 3–7 hours post‐operatively. Use of IA lidocaine and bupivacaine is a simple, effective, yet inexpensive perioperative analgesic protocol for joint surgery in sheep.  相似文献   

7.
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.  相似文献   

8.
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.  相似文献   

9.
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.  相似文献   

10.
Our lab has developed a slow‐release liposomal formulation of oxymorphone (LEOx). The purpose of this study was to compare serum concentrations of oxymorphone after administration of LEOx and standard oxymorphone (STDOx) to healthy female rhesus macaques. At baseline, 1 mL of blood was drawn from the femoral vein with the animal in a restraint cage. Primates were divided into two groups: (i) LEOx 1.0 mg kg–1(n = 4); 2) STDOx 0.1 mg kg–1(n = 4). Unloaded liposomal vehicle (0.5 mL) was used as a control (n = 2). All treatments were given subcutaneously in a shaved area proximal to the right ileal wing. Femoral venous blood was drawn and serum concentrations of drug were measured at 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours. Serum concentrations were measured with ELISA. Serum concentrations were compared between groups and within groups across time with anova . Drug was not detected at any time point in the control group. While sedation was not objectively measured, no animal appeared overly sedate after either treatment. All animals willingly accepted treats and did not appear nauseated or somnolent. Serum concentrations of drug were not significantly different between the two treatment groups from 0 to 2 hours. From 4 hours through 72 hours, however, serum concentrations were significantly higher (p < 0.05) in the animals that received LEOx. By 12 hours, serum concentrations of drug fell below the limit of detection (1.5 ng mL–1) in animals that received STOx. In animals that received LEOx, serum concentrations at 72 hours were comparable to those measured at 4 hours in animals that received STOx. These results suggest that subcutaneous administration of liposomal oxymorphone yields extended serum levels of drug. These results also suggest that liposomal oxymorphone may provide therapeutic (i.e. analgesic) serum concentrations of drug for 2–3 days after a single subcutaneous administration. Further studies are warranted to assess analgesic efficacy and pharmacokinetics of lipsomal oxymorphone in primates.  相似文献   

11.
Our lab has developed a slow‐release liposomal formulation of oxymorphone (LEOx). The purpose of this study was to compare sedative effects and serum concentrations of oxymorphone after administration of LEOx and standard oxymorphone (STDOx) to dogs. At baseline, 1 mL of blood was drawn from the cephalic vein and sedation score was recorded. Dogs were divided into four groups (n = 6): (i) LEOx 1.0 mg kg–1; (ii) LEOx 0.5 mg kg–1; (iii) STDOx 0.1 mg kg–1; (iv) STDOx 0.05 mg kg–1. Unloaded liposomal vehicle (0.5 mL) was used as a control (n = 2). All treatments were given subcutaneously between the scapulae. Sedation score and serum concentration of drug were recorded at 0.5, 1, 2, 4, 8, 12, 16, 24 hours and daily for 5 days. Serum concentrations were measured with ELISA. At all time points, drug was not detected and sedation score was 0 in the control group. Sedation score for group 1 was significantly higher (p < 0.05) at 1 hour than for groups 2,3, and 4. There was no difference in sedation score between treatment groups at any other time. Serum concentrations of drug were significantly higher (p < 0.05) for group 1 at all time points measured after baseline. In groups 2, 3, and 4, serum concentrations of drug fell below the limit of detection (1.5 ng mL–1) by 24 hours. Serum concentrations after 0.1 mg kg–1of STDOx were 11.1 ± 3.6 ng mL–1at 4 hours, which is the recommended time for redosing and presumably reflects the lower end of a therapeutic serum concentration. Serum concentrations were comparable after 1.0 mg kg–1 of LEOx (10.5 ± 2.4 ng mL–1) 48 hours after administration. These results suggest that liposomal oxymorphone may provide therapeutic serum concentrations of drug for 2 days after a single subcutaneous administration without undue sedation or other deleterious effects in healthy dogs. Further studies are warranted to assess analgesic efficacy and pharmacokinetics of lipsomal oxymorphone in dogs.  相似文献   

12.
We prospectively studied 26 dogs that presented for intercostal thoracotomy. Dogs were pre-medicated with oxymorphone, induced with diazepam and etomidate, and anesthesia was maintained with isoflurane in oxygen. Preoperatively, animal patients were randomly assigned to one of two groups. Group 1 (n = 13) received buprenorphine (10 μg/kg intravenously [IV]) every 6 hours for 24 hours starting 10 minutes before tracheal extubation. Group 2 (n = 13) received 0.5% bupivacaine (1.5 mg/kg) administered interpleural (IP) by slow injection through a pediatric feeding tube fixed to the most dorsal aspect of the thoracotomy incision. Interpleural injections were administered with each dog placed in lateral recumbency with the incision positioned ventrally; IP injections were administered every 4 hours for 24 hours starting 10 minutes before tracheal extubation. All cases were monitored in the intensive care unit for 24 hours postoper-atively. The analgesic efficacy of each regimen was evaluated using a pain scoring system that included a subjective pain score, heart rate, and respiratory rate. Arterial blood pressure, arterial blood gases, oxygen saturation, body temperature, and changes in the electrocardiogram or neurological status were also noted. Significant increases in mean heart rate, respiratory rate, and total pain score occurred after surgery in dogs in the buprenorphine group. In contrast, dogs in the bupivacaine group had no significant changes when compared with their preoperative values. Dogs in the bupivacaine group had significantly decreased total pain scores and better PaO2 and oxygen saturation values when compared with the dogs receiving buprenorphine. Hypoventilation did not occur in either group.  相似文献   

13.
Pharmacokinetic properties and tissue concentrations of enrofloxacin and ciprofloxacin were compared after intramuscular (i.m.) administrations of free and liposome‐encapsulated enrofloxacin at the dose of 5 mg/kg body weight (bw). Twelve healthy adult New Zealand white rabbits were used in the experiment. Blood samples were obtained at 10, 20, 40, 60 and 90 min and 2, 4, 6, 8 and 12 h and tissue samples were collected 24 h after injection. Concentrations of drugs in serum were determined by high‐performance liquid chromatography. Pharmacokinetics were best described by a two‐compartment open model. Results indicated that absorption rate was slow, peak concentration was higher (P < 0.05), and the time to peak concentration (tmax ? 1.5 h) was significantly longer (P < 0.05) for liposome‐encapsulated enrofloxacin (LEE) when compared with free enrofloxacin. Values of elimination half‐life (t1/2β = 12.9 h) and mean residence time (MRT = 17.6 h) of liposome‐encapsulated enrofloxacin were longer (P < 0.05) and total clearance (Cl = 0.43 l/h/kg) was lower than those of free form. Moreover, the distribution volume at steady‐state (Vd(ss) = 14.4 l/kg) of enrofloxacin administered encapsulated into liposomes was significantly higher (P < 0.05) than that of free enrofloxacin (FE). The tissue levels of enrofloxacin and ciprofloxacin after LEE injection were not different (P > 0.05) from FE. In conclusion, the result of present study suggest that LEE may be a beneficial and valuable formulation in the treatment of infectious diseases caused by sensitive pathogens in animals, providing sustained drug release from injection side and prolonged therapeutic serum concentrations after i.m. administration.  相似文献   

14.
Hydromorphone is an agonist opioid with potency approximately five times that of morphine and half that of oxymorphone. The purpose of this study was to compare hydromorphone with oxymorphone, with or without acepromazine, for sedation in dogs, and to measure plasma histamine before and after drug administration. Ten dogs received IM hydromorphone (H; 0.2 mg kg?1), oxymorphone (O; 0.1 mg kg?1), hydromorphone with acepromazine (H; 0.2 mg kg?1, A; 0.05 mg kg?1) or oxymorphone with acepromazine (O; 0.1 mg kg?1, A; 0.05 mg kg?1) in a randomized Latin‐square design. Sedation score, heart rate, respiratory rate, blood pressure, and SpO2 were recorded at baseline and every 5 minutes after drug administration up to 25 minutes. Plasma histamine was measured at baseline and at 25 minutes post‐drug administration. Data were analyzed with repeated measures anova . Mean ± SD body weight was 21.62 ± 1.54 kg. Mean ± SD age was 1.07 ± 0.19 years. Sedation score was significantly greater for OA after 5 minutes than O alone (4.1 ± 3.5 versus 1.9 ± 1.5) and for HA after 15 minutes than H alone (8.6 ± 2.9 versus 5.9 ± 2.5). There was no significant difference in sedation between H and O at any time point. There was no significant difference between groups at any time with respect to heart rate, respiratory rate, blood pressure or SpO2. Mean ± SD plasma histamine (nM ml?1) for all groups was 1.72 ± 2.69 at baseline and 1.13 ± 1.18 at 25 minutes. There was no significant change in plasma histamine concentration in any group. Hydromorphone is effective for sedation in dogs and does not cause measurable increase in histamine. Sedation with hydromorphone is enhanced by acepromazine.  相似文献   

15.
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.  相似文献   

16.
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.  相似文献   

17.
Gaining a detailed knowledge on the impact of a feedstuff on pig growth and physiological responses is critical for its effective utilization. Thus, the purpose of this study was to investigate the effect of distillers dried grains with solubles derived from co‐fermentation of wheat and corn (wcDDGS) on performance, carcass and visceral organ weights, whole‐body O2 consumption and heat production (HP) in growing barrows. The experimental diets were as follows: corn–soybean meal diet (Control), Control + 15% wcDDGS and Control + 30% wcDDGS. In Exp. 1, 48 pair‐housed pigs of average BW 18.6 ± 1.5 kg (mean ± SD) were allotted to the 3 diets (n = 8). Pigs had free access to water and feed for a 28‐day period during which ADG and ADFI were calculated weekly. Thereafter, 1 pig/pen was killed to measure carcass and visceral organ weights. Overall, wcDDGS linearly decreased (p < 0.05) ADFI and ADG but had no effect on G:F (p > 0.10). The ADFI was 1.55, 1.45 and 1.36 kg/day for diets containing 0, 15 and 30% wcDDGS respectively; corresponding values for ADG were 0.79, 0.75 and 0.67 kg/day respectively. A linear decline (p = 0.01) in eviscerated hot carcass weight was observed as dietary wcDDGS increased. In Exp. 2, 18 pigs of average BW 20.4 ± 2.4 kg (mean ± SD) were individually housed in metabolism crates and fed the 3 diets (n = 6) at 550 kcal ME kg BW?0.60day for a 16‐day period followed by measurement of O2 consumption using an indirect calorimeter. Diet had no effect (p > 0.10) on whole‐body O2 consumption and HP. In conclusion, increasing wcDDGS content in growing pig diets linearly reduced ADFI, ADG and eviscerated hot carcass weight but had no effect on G:F, visceral organ weights or HP.  相似文献   

18.
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are widely used to provide analgesia in clinical veterinary medicine, but there are few objective data evaluating this effect under controlled conditions in cats. Analgesia is more difficult to detect with acute analgesiometry after NSAIDs than after opioids. This investigation aimed to adapt the feline thermal analgesiometry method previously employed with opioids ( Dixon et al. 2002 ) for use with NSAIDs. Ketoprofen, a COX1 inhibitor licensed for cats was chosen. Six cats (2 neutered, four entire females, weighing 2.2–5.4 kg) were studied in two blinded randomized crossover trials each at least 2 weeks apart. Thermal thresholds (TT) were measured using the thermal threshold‐testing device previously developed for cats. A heater element and temperature sensor in a small probe were held at constant pressure against the cats' shaved thorax with an elasticized band. Skin temperature was recorded before each test, then the heater activated. When the cat responded by flinching, turning or jumping the heater was turned off and the temperature recorded. In the first study TT were measured following subcutaneous (SC) injection of ketoprofen (2 mg kg?1) or a similar volume of saline. In the second study, prior to TT, and under isoflurane restraint, a mild inflammatory focus was produced at the probe site by five SC injections of 5 mg kaolin in 0.1 mL saline at each corner and in the center of a 1.5‐cm square. Saline or ketoprofen as in the first study were injected at the same time. Three baseline temperatures were recorded before any injections were given. Thermal thresholds were measured at 1 and 2 hours and then two‐hourly for 24 hours. Data were analysed using anova . Baseline skin temperature increased (37.3 ± 0.5–38.1 ± 0.8 °C) 24 hours after saline injection in study 2 (p < 0.05) but did not change after any other treatment. Thermal thresholds decreased (40.0 ± 1.3 to 39.1 ± 0.4 °C) 16 hours after ketoprofen in study 1 (p < 0.05) and increased (41.6 ± 1.5–44.8 ± 6.1 °C) 16–24 hours after ketoprofen in study 2 (p < 0.05), with no significant changes after saline. No obvious increase in sensitivity to thermal stimulation after kaolin injection was detected although obvious inflammation was present for up to 36 hours and the cats responded to digital pressure at the treated site. The method detected some effects of a COX1 selective NSAID and may be suitable for future NSAID studies in cats. However, a pressure stimulus ( Dixon et al. 2000) may prove better than thermal, and it requires investigation.  相似文献   

19.
ObjectiveTo compare the duration of nociceptive and proprioceptive blockade from an experimental encapsulated lidocaine preparation with that of conventional lidocaine.Study designProspective, blinded, randomly assigned, crossover study.AnimalsA total of six adult Dorset ewes, American Society of Anesthesiologists physical status I or II, weighing 60.4 ± 18.0 kg (mean ± standard deviation).MethodsUnder general anesthesia and guided by electrolocation, the common peroneal nerve was blocked unilaterally with encapsulated lidocaine (0.1 mL kg–1, 200 mg mL–1) or conventional lidocaine hydrochloride (0.1 mL kg–1, 20 mg mL–1). Each sheep was administered both treatments with an interval of 2 weeks between treatments. Nociception and proprioception were scored (scales of 0–3) before anesthesia, at 0.5, 1, 2, 4, 8, 12, 16, 20 and 24 hours after completion of local anesthetic injection, and every 12 hours thereafter for 9 days. Nociceptive and proprioceptive blockade ended the first time each score reached ‘0’; maximum blockade duration was considered and recorded to be the time point immediately prior to this end point. Significance of differences between treatments for duration of blockade was tested with the Wilcoxon rank-sum test. Effects of time and treatment on nociceptive and proprioceptive blockade were evaluated with mixed-effect models. Significance was set at p < 0.05.ResultsCompared with conventional lidocaine, nociceptive blockade lasted 88 hours longer with encapsulated lidocaine (p = 0.008), and proprioceptive blockade lasted 6 hours longer (p = 0.03). Significant effects of time (p < 0.0001), treatment (p = 0.0435) and treatment1time (p < 0.0001) were observed for nociception. Significant effects of time (p < 0.0001) and treatment1time (p = 0.0058) were observed for proprioception.ConclusionEncapsulated lidocaine produced nociceptive blockade with a duration substantially longer than conventional lidocaine.Clinical relevanceSustained-release encapsulated lidocaine alleviates pain and may minimize systemic analgesic use.  相似文献   

20.
Objective To determine the presence and duration of analgesia after oxymorphone, acepromazine maleate, acepromazine‐oxymorphone combination and medetomidine administration in dogs. Study design Blinded, controlled study. Animals Six adult beagle dogs. Methods Each dog participated in five trials receiving acepromazine maleate (0.2 mg kg?1 IM), oxymorphone (0.2 mg kg?1 IM), acepromazine‐oxymorphone drug combination (0.2 mg kg?1 each IM), medetomidine (20 µg kg?1 IM) and sterile saline (control). Two specially designed instruments were used for analgesia determination: a heat device (HD) utilized a linear ramped intensity incandescent bulb and a pressure device (PD) consisted of a pneumatic cylinder that protruded a 2.5‐cm bolt. The minimum pressure and heat necessary to produce an avoidance response were determined. Analgesia testing was performed prior to and at 30‐minute intervals for six hours after drug administration. Results Oxymorphone, acepromazine‐oxymorphone and medetomidine significantly elevated both pressure and heat response thresholds compared to controls and acepromazine. Both medetomidine and acepromazine‐oxymorphone provided a significantly longer duration of analgesia than oxymorphone. No adverse effects were observed at any of the thermal or pressure application sites. Conclusions Oxymorphone, medetomidine and acepromazine‐oxymorphone produced significant analgesia with medetomidine and acepromazine‐oxymorphone providing the longest duration of analgesia.  相似文献   

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