buprenorphine and Cat-Diseases

Opiates have a long history of medical use as effective analgesics associated with well-described side effects, including euphoria, respiratory depression, constipation, bradycardia, and histamine release, among others. The search for opiate analogs that retain effective analgesic qualities without detrimental side effects has yielded numerous compounds, including buprenorphine. Early studies of buprenorphine demonstrated analgesic effectiveness with a favorable safety profile, leading to the approval of formulations for use in humans. Since then, advances in receptor theory and molecular cloning of opioid receptors have led to a deeper understanding of buprenorphine pharmacology. More recent studies of receptor affinity and intrinsic activity have shown that buprenorphine is a μ- and κ-opioid receptor agonist, a nociceptin orphanin peptide agonist, and a δ-opioid receptor antagonist. Buprenorphine appears to have a primary spinal analgesic mechanism with complex supraspinal actions. It is considered a full agonist for pain but a partial agonist for other clinical endpoints such as respiratory depression. In feline medicine, buprenorphine is approved as low- and high-concentration injectable solutions, in addition to the most recently introduced long-acting transdermal formulation. Several investigational and compounded formulations have also been evaluated. There are contrasting differentiable features that include pharmacokinetics, onsets- and durations-of-action, routes of administration, and formulation constituents. Available buprenorphine formulations allow clinicians to select a formulation based on the anticipated duration of pain associated with various surgical procedures, and to provide interventions as needed. In light of the newly approved transdermal buprenorphine solution in cats and progress in buprenorphine pharmacology, the objective of this review is to examine the history and pharmacology of buprenorphine relative to full opioid agonists, where appropriate, integrating these insights into advances within feline medicine.

Topics: Analgesics; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Pain; Respiratory Insufficiency

To compare the thermoregulatory and analgesic effects of high-dose buprenorphine versus morphine in cats undergoing ovariohysterectomy.. 94 client-owned cats.. Cats were randomized to receive either buprenorphine 0.24 mg/kg or morphine 0.1 mg/kg subcutaneously (SC) during recovery from ovariohysterectomy. Body temperature measurements were obtained before anesthesia, during anesthesia (averaged), at extubation, and 2, 4, and 16 to 20 hours postoperatively. Signs of pain were assessed, and demographic characteristics were compared between groups. The effects of treatment and time on body temperature, point prevalence of hyperthermia (> 39.2 °C), and pain scores were compared with linear or generalized mixed-effect models.. Cats receiving morphine (vs. buprenorphine) were older and heavier (both, P ≤ 0.005). Other group characteristics did not differ between treatments. Cats receiving buprenorphine (vs. morphine) had higher postoperative temperatures (P = 0.03). At 2, 4, and 16 to 20 hours after extubation, the point prevalence of hyperthermia was greater (P = 0.001) for cats receiving buprenorphine (55% [26/47], 44% [21/47], and 62% [27/43], respectively) versus morphine (28% [13/46], 13% [6/46], and 47% [21/44], respectively). There were no differences in pain scores between groups or over time. Five cats receiving buprenorphine and 6 receiving morphine required rescue analgesia within the 24-hour period.. Administration of buprenorphine (0.24 mg/kg SC), compared with morphine (0.1 mg/kg SC), resulted in higher body temperatures without an apparent advantage with regard to analgesia during the first 20 postoperative hours than morphine. Opioid-induced postoperative hyperthermia could confound the diagnosis of fever from different sources.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Female; Hyperthermia, Induced; Hysterectomy; Morphine; Ovariectomy; Pain, Postoperative

A prospective, double-masked, placebo-controlled, multicentered phase 2 clinical study was conducted to select the transdermal buprenorphine solution (TBS) dosage for the control of postoperative pain in cats. One-hundred fifteen (115) cats were randomized to a single topical dose of placebo solution, low-TBS dosage (1.91-2.07 mg/kg) or high-TBS dosage (4.27-4.88 mg/kg) prior to surgical reproductive sterilization in conjunction with forelimb onychectomy. The low- and high-TBS doses were applied 2-4 and 1-2 hours prior to surgery. Interactive pain assessments and physiological variables were quantified through 96 hours post-anesthetic recovery and rescue analgesia was administered any time that analgesia was considered inadequate. Cats requiring rescue analgesia were considered treatment failures. The estimated overall treatment success rates from generalized linear mixed effects model analysis were 0.10 (95% CI: [0.02-0.36]), 0.56 (95% CI: [0.25-0.83]), 0.71 (95% CI: [0.38-0.91]) in the placebo-, low-, and high-TBS dose groups, respectively. Success rates for both TBS treatment groups were superior to placebo. Adverse events were infrequent in all treatment groups although the postoperative body temperatures over the duration of the study were on average 0.31 (95% CI: [0.08-0.55]) and 0.30 (95% CI: [0.05-0.53]) °C higher in low- and high-TBS dose cats, respectively, compared to placebo. It is concluded that both the low- and high-TBS dosages were safe and effective. The high-TBS dosage resulted in a greater proportion of treatment successes over 96 h, had a more acceptable preoperative application time of 1-2 h prior to surgery, and was therefore selected for further study.

Topics: Administration, Cutaneous; Analgesia; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Delayed-Action Preparations; Pain, Postoperative; Prospective Studies

A prospective, double masked, placebo-controlled, multicentered phase 3 clinical study was conducted to evaluate the safety and effectiveness of transdermal buprenorphine solution (TBS) for the control of post-operative pain in cats. A total of 228 cats from 12 US investigational sites met the enrollment criteria of which 107 placebo- and 112 TBS-treated cats were included into the per protocol efficacy analysis. The dose of TBS was 8 mg (0.4 ml) to cats 1.2 to 3 kilograms and 20 mg (1 ml) to cats >3 to 7.5 kilograms applied topically to the dorsal unclipped cervical skin 1-2 h prior to the undergoing elective surgical reproductive sterilization in conjunction with forelimb onychectomy. Interactive pain assessments and physiological variables were quantified through 96 h following recovery from anesthesia, and rescue analgesia was administered any time that pain control was scored inadequate. Cats requiring rescue analgesia or experiencing an adverse event suspected to be treatment related were considered treatment failures. Sixty-five and 23 cats were considered treatment failures in the placebo and TBS groups, respectively, with most occurring on the day of surgery. The treatment success rates were 0.40 (95% confidence interval [CI]: [0.28-0.53]) and 0.81 (95% CI: [0.70-0.89]) in the placebo and TBS groups, respectively, and the difference was significant (p < .05). Adverse events occurred at a similar frequency and were not clinically meaningful in either treatment group. The post-operative body temperatures over the duration of the study were on average 0.35 (95% CI: [0.20-0.50]) °C higher than baseline in TBS-treated cats and were not clinically meaningful, an observation typical of opioids in cats. These results serve as substantial evidence that TBS is safe and effective for the control of orthopedic and soft tissue post-operative pain in cats when a single topical dose is applied 1-2 h prior to surgery.

Topics: Administration, Cutaneous; Analgesia; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Delayed-Action Preparations; Pain, Postoperative; Prospective Studies

Transdermal buprenorphine solution (TBS) is approved for the control of postoperative pain in cats where a single preoperative dose provides 4 days of analgesia. It is administered as a unit dose of 8 mg to cats weighing 1.2-3 kg and 20 mg to cats weighing to >3-7.5 kg, which is equivalent to a dosage on a bodyweight basis of 2.7-6.7 mg/kg. In this safety study, the 1X dose was defined as 6.7 mg/kg. Thirty-two cats (16 males and 16 females) were randomly allocated to placebo, 1, 2, and 3X TBS administered topically to the dorsal cervical skin every 4 days for 3 doses. Clinical observations, behavioral scores, mydriasis score (yes/no), and physiological variables were assessed or measured prior to each dose administration (0 h) and at 1, 2, 4, 8, 12, 24, 36, 48, and 72 h following each treatment and prior to euthanasia on Day 12 or 13. Blood samples for clinical pathology were collected on Days - 1, 4, 8, and prior to euthanasia. There was little evidence of respiratory, cardiovascular, or gastrointestinal effects. Respiratory rates were above the reference range in all groups and lower by 10 breaths/min in the 3X group during the third dosing interval compared to placebo. There were no differences in heart rates. Constipation was transiently observed in approximately equal numbers in placebo- and TBS-treated cats. Behavioral scores showed sedation or euphoria was transient in the first dosing interval but became more prolonged with each dosing interval. Mydriasis was prolonged in the first dosing interval and diminished by the third dosing interval consistent with accommodation. Mean body temperatures in TBS-treated cats were up to 0.6°C (1.8°F) greater than placebo-treated cats. There were no clinically relevant changes to serum chemistry, hematology, or urinalysis outcomes nor gross or microscopic observations attributable to TBS. These data demonstrate that TBS is safe and well-tolerated when administered to 16-week-old cats at multiples of the approved dose and duration and supports clinical safety in the event of delayed buprenorphine metabolism, medication errors, or alterations in the dosing regimen.

Topics: Analgesia; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Female; Male; Mydriasis; Pain, Postoperative

To determine whether physiological, haematological, biochemical or electrolyte variables can predict severe haemorrhage in cats.. Randomized crossover study whereby each cat underwent mild and severe haemorrhage, with a 2 month period between events.. A group of six domestic cats aged 21 ± 1 months and weighing 4.9 ± 1.2 kg, mean ± standard deviation.. Cats were anaesthetized (buprenorphine, alfaxalone, isoflurane in oxygen at a fixed end-tidal concentration of 1.7%) before the haemorrhage event. In total, 34 variables were measured twice (prehaemorrhage and posthaemorrhage). The difference and percent change for each variable were compared between haemorrhage events (paired t test). Significant variables were placed into 13 different ratios (posthaemorrhage value of one variable divided by a posthaemorrhage value of a second variable) and compared (paired t test), and Cohen's d (d) was calculated. Receiver operating characteristic curves were plotted and cut-off values for weak, moderate and strong indicators of severe haemorrhage were obtained.. The blood loss was 4.5 ± 1.1 mL kg. and clinical relevance Cats subjected to mild and severe haemorrhage demonstrated statistically and clinically relevant changes whereby four ratios could be created to make up the CABSS. The ratios detected and quantified the presence of severe haemorrhage in anaesthetized cats.

Topics: Anesthesia; Anesthetics; Animals; Blood Pressure; Buprenorphine; Cat Diseases; Cats; Cross-Over Studies; Hemorrhage; Isoflurane; Pregnanediones; Severity of Illness Index

Objectives The objective of this study was to compare the sedative effect of butorphanol-dexmedetomidine with buprenorphine-dexmedetomidine following intramuscular (IM) administration in cats. Methods Using a prospective, randomised, blinded design, 40 client-owned adult cats were assigned to receive IM dexmedetomidine (10 µg/kg) combined with either butorphanol (0.4 mg/kg) ('BUT' group) or buprenorphine (20 µg/kg) ('BUP' group). Sedation was scored using a previously published multidimensional composite scale before administration (T0) and 5, 10, 15 and 20 mins afterwards (T5, T10, T15 and T20, respectively). Alfaxalone (1.5 mg/kg) was administered IM at T20 if the cat was not deemed adequately sedated to place an intravenous catheter. Adverse events were recorded. Friedman two-way ANOVA analysed sedation scores within groups. Mann-Whitney Rank Sum test compared sedation scores between groups; Fisher's exact test analysed the frequency of alfaxalone administration and adverse events. P <0.05 was considered statistically significant. Results Sedation scores between groups were similar at baseline, but at T5, T10, T15 and T20 scores were higher in the BUT group ( P <0.01). Within both groups, sedation scores changed over time and the highest sedation scores were reached at T10. Requirement for additional sedation was similar between groups: two cats in the BUT group and five cats in the BUP group. One cat and 11 cats vomited ( P = 0.002) in the BUT and BUP groups, respectively. No other adverse events were recorded. Conclusions and relevance At these doses, IM buprenorphine-dexmedetomidine provides inferior sedation and a higher incidence of vomiting than butorphanol-dexmedetomidine in cats. Butorphanol-dexmedetomidine may be preferred for feline sedation, especially where vomiting is contraindicated.

Topics: Anesthesia; Animals; Blood Pressure; Buprenorphine; Butorphanol; Cat Diseases; Cats; Dexmedetomidine; Drug Therapy, Combination; Female; Hypnotics and Sedatives; Injections, Intramuscular; Male; Pain Measurement; Prospective Studies; Random Allocation

Objectives The objective of this study was to evaluate the analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease. Methods Six adult client-owned cats with chronic gingivostomatitis (weighing 5.1 ± 1.1 kg) were recruited for a randomised, prospective, blinded, saline-controlled, crossover study. Pain scores, dental examination, stomatitis score and buccal pH measurement were conducted on day 1 under sedation in all cats. On day 2, animals were randomised into two groups and administered one of the two treatments buccally (group A received buprenorphine 0.02 mg/kg and group B received 0.9% saline) and vice versa on day 3. Pain scores and food consumption were measured at 30, 90 and 360 mins after the administration of buprenorphine. Blood samples were taken at the same time and plasma buprenorphine concentration was measured by liquid chromatography-mass spectrometry. Data were statistically analysed as non-parametric and the level of significance was set as P <0.05. Results There were no major side effects after buprenorphine administration. Buccal pH values ranged between 8.5 and 9.1 and the stomatitis disease activity index between 10 and 22 (17.8 ± 4.5), with the scale ranging from 0-30. The maximum buprenorphine plasma concentration (14.8 ng/ml) was observed 30 mins after administration and there was low inter-individual variability. There was a significant difference between baseline pain scores compared with pain scores after buprenorphine ( P <0.05), and between the saline and buprenorphine group at 30 mins ( P = 0.04) and 90 mins ( P = 0.04). There was also a significant effect of the stomatitis index on the pain score. Regarding the pharmacokinetic parameters, cats with stomatitis showed lower bioavailability and shorter absorption half-life after buccal administration of buprenorphine compared with normal cats in previous studies. Conclusions and relevance Buccal administration of buprenorphine in cats with gingivostomatitis produces an analgesic effect and low inter-individual variability in plasma concentration, and it can be incorporated in their multimodal analgesia plan.

Topics: Administration, Buccal; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Female; Male; Mouth Diseases; Pain; Pain Measurement; Random Allocation

Objectives The aim of the study was to evaluate the analgesic efficacy of gabapentin-buprenorphine in comparison with meloxicam-buprenorphine or buprenorphine alone, and the correlation between two pain-scoring systems in cats. Methods Fifty-two adult cats were included in a randomized, controlled, blinded study. Anesthetic protocol included acepromazine-buprenorphine-propofol-isoflurane. The gabapentin-buprenorphine group (GBG, n = 19) received gabapentin capsules (50 mg PO) and buprenorphine (0.02 mg/kg IM). The meloxicam-buprenorphine group (MBG, n = 15) received meloxicam (0.2 mg/kg SC), buprenorphine and placebo capsules (PO). The buprenorphine group (BG, n = 18) received buprenorphine and placebo capsules (PO). Gabapentin (GBG) and placebo (MBG and BG) capsules were administered 12 h and 1 h before surgery. Postoperative pain was evaluated up to 8 h after ovariohysterectomy using a multidimensional composite pain scale (MCPS) and the Glasgow pain scale (rCMPS-F). A dynamic interactive visual analog scale (DIVAS) was used to evaluate sedation. Rescue analgesia included buprenorphine and/or meloxicam if the MCPS ⩾6. A repeated measures linear model was used for statistical analysis ( P <0.05). Spearman's rank correlation between the MCPS and rCMPS-F was evaluated. Results The prevalence of rescue analgesia with a MCPS was not different ( P = 0.08; GBG, n = 5 [26%]; MBG, n = 2 [13%]; BG, n = 9 [50%]), but it would have been significantly higher in the BG (n = 14 [78%]) than GBG ( P = 0.003; n = 5 [26%]) and MBG ( P = 0.005; n = 4 [27%]) if intervention was based on the rCMPS-F. DIVAS and MCPS/rCMPS-F scores were not different among treatments. A strong correlation was observed between scoring systems ( P <0.0001). Conclusions and relevance Analgesia was not significantly different among treatments using an MCPS. Despite a strong correlation between scoring systems, GBG/MBG would have been superior to the BG with the rCMPS-F demonstrating a potential type II error with an MCPS due to small sample size.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Gabapentin; Hysterectomy; Ovariectomy; Pain Management; Pain Measurement; Pain, Postoperative; Random Allocation

The aim of this study was to evaluate the analgesic effects of maxillary and/or inferior alveolar nerve blocks with lidocaine and bupivacaine in cats undergoing dental extractions. Twenty-nine cats were enrolled. Using an adapted composite pain scale, cats were pain scored before the dental procedure and 30 mins, and 1, 2 and 4 h after isoflurane disconnection. Cats were sedated with buprenorphine (20 µg/kg), medetomidine (10 µg/kg) and acepromazine (20 µg/kg) intramuscularly. Anaesthesia was induced using alfaxalone (1-2 mg/kg) intravenously and maintained with isoflurane in oxygen. Each cat was randomly assigned to receive maxillary and/or inferior alveolar nerve blocks or no nerve blocks prior to dental extractions. Each nerve block was performed using lidocaine (0.25 mg/kg) and bupivacaine (0.25 mg/kg). Heart rate, systolic arterial blood pressure, respiratory rate, end tidal carbon dioxide and isoflurane vaporiser settings were recorded 5 mins before and after the dental extractions, and the difference calculated. Group mean differences (mean ± SD) for heart rate (-9.7 ± 10.6 vs 7.6 ± 9.5 beats/min [nerve block vs control group, respectively], P <0.0001), systolic arterial blood pressure (-10.33 ± 18.44 vs 5.21 ± 15.23 mmHg, P = 0.02) and vaporiser settings (-0.2 ± 0.2 vs 0.1 ± 0.4, P = 0.023) were significantly different between groups. The control group had higher postoperative pain scores (median [interquartile range]) at 2 h (3 [1.75-4.00] vs 1 [0-2], P = 0.008) and 4 h (4 [2-6] vs 2 [1-2], P = 0.006) after the dental extractions. Maxillary and inferior alveolar nerve blocks with lidocaine and bupivacaine administered prior to dental extractions resulted in a reduction in heart rate and blood pressure while allowing for a reduction in isoflurane. Cats receiving nerve blocks had lower postoperative pain scores than the group without nerve blocks.

Topics: Anesthesia, Dental; Animals; Bupivacaine; Buprenorphine; Cat Diseases; Cats; Isoflurane; Lidocaine; Medetomidine; Nerve Block; Pain, Postoperative; Preanesthetic Medication; Pregnanediones; Tooth Extraction

The aim of this study was to evaluate the potential thermal antinociceptive effects of oral administration of a single dose of codeine in cats compared with positive (buprenorphine) and negative (saline 0.9%) controls.. Six adult healthy cats weighing 5.14 ± 0.6 kg were used. Skin temperature and thermal thresholds (TTs) were evaluated using a wireless device (Topcat Metrology) at baseline, 0.5, 1, 3, 6 and 10 h after treatment. In period 1, TTs were evaluated after subcutaneous administration of saline 0.9%. In period 2, cats were administered either oral codeine (10 mg total, 2.0 ± 0.2 mg/kg) or buccal buprenorphine (0.04 mg/kg) in a cross-over, blinded study design. Half of the volume of buprenorphine was administered into each cheek pouch. Δ TT (difference between TTs after and before treatment) was used for data comparison. Mean ± SD data were analyzed using one-way ANOVA followed by Dunnett's or Tukey's test when appropriate (P <0.05).. Adverse effects did not occur in any group. Skin temperature was not different between groups nor over time. Temporal changes in TTs were not observed after saline or codeine. Buprenorphine increased Δ TT at 3 h (2.7 ± 3.3°C) when compared with baseline or saline (P <0.05). For buprenorphine, TTs were not >47.6°C at any time point in four cats. The mean highest temperature recorded in the two other cats in that group was 54.5 and 52.8°C at 3 h.. At the dose administered, codeine did not produce thermal antinociception. Mild increases in TT after buccal buprenorphine might be related to the first-pass effect after drug swallowing, drug spillage during administration and/or individual variability. These factors should be taken in to consideration when administering buprenorphine by this route in the clinical setting.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Codeine; Cross-Over Studies; Drug Therapy, Combination; Hot Temperature; Injections, Subcutaneous; Nociceptors; Pain Measurement; Skin Temperature

To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats.. Randomized, 'blinded' crossover study, with 1 month washout between treatments.. Six healthy neutered female cats, weighing 5.3-7.5 kg.. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range.. There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing.. In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats.

Topics: Administration, Mucosal; Analgesics; Animals; Buprenorphine; Cat Diseases; Cats; Dexmedetomidine; Drug Therapy, Combination; Female; Hypnotics and Sedatives; Injections, Intramuscular; Pain

To compare the analgesic effects of buprenorphine and butorphanol in domestic cats.. 2-phase positive-controlled randomized masked clinical trial.. 39 healthy female cats (10 in phase 1 and 29 in phase 2).. Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively.. Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time.. Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Butorphanol; Cat Diseases; Cats; Female; Hysterectomy; Ovariectomy; Pain, Postoperative; Perioperative Period

The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n=10; GB), robenacoxib (2mg/kg, n=10; GR) or their combination at the same dosages (n=10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ≥ 3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone.

Topics: Analgesics; Animals; Buprenorphine; Cat Diseases; Cats; Diphenylamine; Drug Therapy, Combination; Hysterectomy; Ovariectomy; Pain, Postoperative; Phenylacetates

This randomised, blinded, cross-over study investigated the ease of oral transmucosal administration of two formulations of buprenorphine using glucose as a control in 12 cats. The cats received three treatments: buprenorphine multi-dose, buprenorphine and the equivalent volume of glucose 5%. Ease of treatment administration, observation of swallowing, changes in pupil size, sedation, salivation, vomiting, behaviour and food intake were assessed. The data were analysed using MLwiN and multi-level modelling. Ease of administration of buprenorphine multi-dose was statistically different from glucose (P <0.001), and the administration of all treatments became easier over the study periods. Swallowing was not statistically different between groups (P >0.05). Mydriasis was evident after the administration of both formulations of buprenorphine. Sedation, salivation, vomiting, behavioural changes or in-appetence were not observed after any treatment. Cats tolerated oral transmucosal administration of glucose better than buprenorphine multi-dose, while buprenorphine administration was tolerated as well as glucose.

Topics: Administration, Buccal; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Chemistry, Pharmaceutical; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glucose; Hemodynamics; Intestinal Absorption

One hundred female cats undergoing routine ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia were included in a blinded, randomised, prospective clinical study to compare postoperative analgesia produced by four analgesic drug combinations given preoperatively (n = 25 per group). A secondary aim was to assess the effects in kittens and pregnant animals. Buprenorphine 180 µg/m(2) or butorphanol 6 mg/m(2) were given with either carprofen 4 mg/kg (groups BUPC and BUTC, respectively) or meloxicam 0.3 mg/kg (groups BUPM or BUTM, respectively). Medetomidine was not antagonised. A simple, descriptive scale (SDS; 0-4), a dynamic and interactive visual analogue scale (DIVAS; 0-100 mm) and mechanical nociceptive thresholds (MT; 2.5-mm diameter probe) were used to evaluate postoperative pain. All pain scores were low (DIVAS <10 mm, SDS <2 and MT >10 N) and there were no significant differences between the groups. It was concluded that all protocols provided adequate analgesia and when used with midazolam-medetomidine-ketamine are effective for routine feline ovariohysterectomy.

Topics: Analgesics, Opioid; Anesthesia, Obstetrical; Anesthetics, Combined; Animals; Behavior, Animal; Buprenorphine; Carbazoles; Cat Diseases; Cats; Double-Blind Method; Female; Humans; Hysterectomy; Meloxicam; Ovariectomy; Pain, Postoperative; Postoperative Care; Pregnancy; Premedication; Prenatal Exposure Delayed Effects; Prospective Studies; Thiazines; Thiazoles; Time Factors; Treatment Outcome

To determine the effect of ondansetron on the incidence of vomiting in cats pre-medicated with dexmedetomidine and buprenorphine.. Randomized, blinded, controlled trial.. Eighty-nine female domestic shorthair cats, aged 3-60 months (median, 12 months) and weighing 1.2-5.1 kg.. Each cat received dexmedetomidine (40 μg kg(-1)) plus buprenorphine (20 μg kg(-1)), intramuscularly as pre-anesthetic medication. Cats were assigned to three treatment groups: ondansetron (0.22 mg kg(-1), intramuscular [IM]), either 30 minutes before the pre-anesthetic medication (ONDA group, n = 31) or with the pre-anesthetic medication (OPM group, n = 30) mixed with the pre-anesthetic medications in the same syringe, or not to receive the antiemetic (control group, n = 28). Emesis was recorded as an all-or-none response. The number of episodes of emesis and the time until onset of the first emetic episode were recorded for each cat. Clinical signs of nausea were recorded whenever they occurred, and a numerical rating scale was used to quantify these signs. Data were analyzed using Kruskal-Wallis and Chi-square test; a Bonferroni correction was made for six comparisons; thus, the two-sided p for significance was 0.05/6 = 0.008.. There was a significant reduction in the number of cats vomiting, in the episodes of vomiting/cat, the time elapsed between the premedication and the first vomiting and the severity of nausea in the OPM group compared to the ONDA and control groups.. In cats, the administration of ondansetron (0.22 mg kg(-1)) ameliorates and reduced the severity of dexmedetomidine-induced nausea and vomiting only when it was administered in association with this drug.

Topics: Analgesics, Opioid; Animals; Antiemetics; Buprenorphine; Cat Diseases; Cats; Dexmedetomidine; Drug Administration Schedule; Female; Hypnotics and Sedatives; Injections, Intramuscular; Ondansetron; Prospective Studies; Single-Blind Method; Vomiting

To determine efficacy of a protocol for managing urethral obstruction (UO) in male cats without urethral catheterization.. Clinical trial.. 15 male cats with UO in which conventional treatment had been declined.. Laboratory testing and abdominal radiography were performed, and cats with severe metabolic derangements or urinary calculi were excluded. Treatment included administration of acepromazine (0.25 mg, IM, or 2.5 mg, PO, q 8 h), buprenorphine (0.075 mg, PO, q 8 h), and medetomidine (0.1 mg, IM, q 24 h) and decompressive cystocentesis and SC administration of fluids as needed. Cats were placed in a quiet, dark environment to minimize stress. Treatment success was defined as spontaneous urination within 72 hours and subsequent discharge from the hospital.. Treatment was successful in 11 of the 15 cats. In the remaining 4 cats, treatment was considered to have failed because of development of uroabdomen (n=3) or hemoabdomen (1). Cats in which treatment failed had significantly higher serum creatinine concentrations than did cats in which treatment was successful. Necropsy was performed on 3 cats in which treatment had failed. All 3 had severe inflammatory disease of the urinary bladder, but none had evidence of bladder rupture.. Results suggested that in male cats, a combination of pharmacological treatment, decompressive cystocentesis, and a low-stress environment may allow for resolution of UO without the need for urethral catheterization. This low-cost protocol could serve as an alternative to euthanasia when financial constraints prevent more extensive treatment.

Topics: Acepromazine; Analgesics; Animals; Buprenorphine; Cat Diseases; Cats; Hypnotics and Sedatives; Male; Stress, Physiological; Treatment Outcome; Urethral Obstruction; Urinary Catheterization

A model of nociceptive threshold determination was developed for evaluation of NSAID analgesia in cats. In a crossover study, eight cats received carprofen (4 mg/kg), buprenorphine (0.01 mg/kg) or saline (0.3 ml) subcutaneously before intradermal kaolin injection on the antebrachium to induce mild inflammation. Pressure thresholds were measured at the injected site using blunt-ended pins advanced by manual inflation of a bladder within a bracelet. Bladder pressure was recorded as threshold (PT) at the behavioural end point. Baseline PT were recorded before kaolin injection (time 0). PT was measured at 2-10 h intervals for 52 h. PT below the lower 95% confidence interval (CI) of baseline values indicated hyperalgesia. After saline, hyperalgesia was detected from 2-6 h, 22-26 h, and at 30 and 36 h. After carprofen, PT remained within the 95% CI. After buprenorphine, PT remained within the 95% CI except at 2h. Carprofen and to some extent buprenorphine, prevented inflammatory hyperalgesia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Carbazoles; Cat Diseases; Cats; Cross-Over Studies; Female; Hyperalgesia; Inflammation; Male; Pain

Six domestic shorthair cats, aged three to four years and weighing 5.1 to 7.4 kg, were used to assess the thermal antinociceptive effect of a transdermal buprenorphine patch, designed to supply 35 mug buprenorphine/hour, which was applied to the shaved thorax. The cats' thermal thresholds were tested before the patch was applied and two, four, six, eight, 10, 12, 14 and 16 hours after it had been applied, and then every six hours until it was removed after 72 hours, and for a further 24 hours afterwards. Blood was collected at each time to measure the plasma concentration of buprenorphine. The patches did not produce a significant change in the thermal thresholds of the cats throughout the testing period. The mean (sd) peak plasma buprenorphine concentration was 10 (0.81) ng/ml.

Topics: Administration, Cutaneous; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Female; Male; Pain; Time Factors

Sixty cats which underwent an ovariohysterectomy were randomly allocated into four treatment groups. One group (controls) received no analgesics postoperatively, and the others received either a single dose of buprenorphine (0.006 mg/kg) intramuscularly, or pethidine (5 mg/kg) intramuscularly, or ketoprofen (2 mg/kg) subcutaneously. The analgesia obtained after each treatment was assessed by three measures. There were significant differences between the groups both for the requirement for intervention analgesia (P = 0.0008) and for the overall clinical assessment (P = 0.0003) with ketoprofen requiring least intervention analgesia and having the best overall clinical assessment, followed by buprenorphine then pethidine. The control group required the most intervention analgesia and had the worst overall clinical assessment. Visual analogue scale scoring for pain produced significant differences between the groups from one hour after the operation, with the cats which were given ketoprofen tending to have lower pain scores than the other groups.

Topics: Analgesia; Animals; Buprenorphine; Cat Diseases; Cats; Female; Hysterectomy; Ketoprofen; Meperidine; Ovariectomy; Pain, Postoperative; Postoperative Care

Topics: Analgesia; Animals; Buprenorphine; Cat Diseases; Cats; Female; Humans; Hysterectomy; Methadone; Ovariectomy

To evaluate the potential benefits of high-dose buprenorphine formulations for analgesia in cats, serial and crossover studies were undertaken to investigate their pharmacokinetics and thermal antinociceptive effects.. Twelve healthy adult domestic shorthair cats (6.0 ± 1.1 kg body weight) were studied. Aqueous solutions of buprenorphine hydrochloride at 0, 0.02, 0.06, 0.12 and 0.24 mg/kg body weight and formulations containing 0, 0.3, 0.6 and 1.2 mg/ml with and without preservatives were given subcutaneously. Blood samples were taken and thermal threshold (TT) measured prior to and at regular time points up to 72 h after dosing. Descriptive statistics and analyses of variance were applied as appropriate.. Baseline TT was 47.6 ± 4.1°C, which increased in all groups treated with all buprenorphine dosages and formulations. After doses of 0.12 mg/kg and above, TT was significantly higher than baseline at most time points from 1-30 h post-treatment. The time to maximum effect (Tmax) ranged between 0.25 and 2.00 h; and plasma concentrations associated with maximum antinociceptive effect (Cmax) were 1.01-1.72 ng/ml after the 0.02 mg/kg dose, 1.4-4.9 ng/ml after the 0.06 mg/kg dose, 4.6-51.4 ng/ml after the 0.12 mg/kg dose and 5.3-22.3 ng/ml after the 0.24 mg/kg dose. The range of estimates for the buprenorphine elimination half-life were as follows: 0.02 mg/kg = 1.35-5.33 h; 0.06 mg/kg = 16.1-31.2 h; 0.12 mg/kg = 10.1-34.0 h; and 0.24 = mg/kg 16.1-31.6 h. The mean 'plasma concentration for the offset of analgesia' was 2.3 ± 2.0 ng/ml. No adverse effects were seen. The addition of preservatives to a high-concentration buprenorphine formulation had no impact on antinociception nor any side effects.. Aqueous high-concentration buprenorphine formulations administered at 0.12 or 0.24 mg/kg have potential for clinical use in cats, providing prolonged antinociception in a single subcutaneous injection of minimal dose volume.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Injections, Subcutaneous; Pain; Pain Measurement

A 6-year-old, neutered male, domestic shorthair cat was presented with shifting leg lameness and palpable effusion of the carpal and tarsal joints. Blood work, arthrocentesis, and radiographs identified an immune-mediated erosive polyarthritis. The cat was positive for feline syncytia-forming virus, and with his signalment, was diagnosed with feline chronic progressive polyarthritis.

Topics: Amines; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Buprenorphine; Cat Diseases; Cats; Chronic Disease; Cyclohexanecarboxylic Acids; Cyclosporine; Gabapentin; gamma-Aminobutyric Acid; Immunosuppressive Agents; Male; Pain; Prednisolone; Retroviridae Infections; Spumavirus

Topics: Amoxicillin-Potassium Clavulanate Combination; Analgesics, Opioid; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Cat Diseases; Cats; Diphenylamine; Male; Phenylacetates; Spondylitis

Topics: Acepromazine; Animals; Buprenorphine; Cat Diseases; Cats; Hypnotics and Sedatives; Male; Stress, Physiological; Urethral Obstruction; Urinary Catheterization

Topics: Amines; Analgesia; Analgesics; Animals; Buprenorphine; Cat Diseases; Cats; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Gabapentin; gamma-Aminobutyric Acid; Injections, Intravenous; Male; Methadone; Multiple Trauma; Pain; Pain Measurement

To compare the postoperative analgesic effects of intravenous (IV), intramuscular (IM), subcutaneous (SC) or oral transmucosal (OTM) buprenorphine administered to cats undergoing ovariohysterectomy.. Randomized, prospective and blinded clinical trial.. 100 female cats.. Cats were assigned to receive 0.01 mg kg(-1) of buprenorphine administered by the IV, IM, SC or OTM route (n = 25/group). Buprenorphine was made up to 0.3 mL with 0.9% saline. DIVAS (0-100 mm) and simple descriptive scale (SDS) (from 0 to 4) pain and sedation scores were assigned to each cat before and 1, 2, 3, 4, 6, 8, 12 and 24 hours after ovariohysterectomy. Buprenorphine and carprofen were administered for rescue analgesia. Data were analyzed using anova and Fisher's exact test (p < 0.05).. There were no significant differences between groups for breed, body weight, anesthetic time or surgery time (p > 0.05). There were no significant differences between groups for sedation scores at any time. SDS pain scores did not detect any differences between groups (p > 0.05). DIVAS pain scores after OTM administration were significantly higher than IV and IM administration at 1 hour and at 3, 4, 6, 8 and 12 hours, respectively (p < 0.05). DIVAS pain scores after SC administration were significantly higher than IV and IM administration at 2 hours and at 2, 3, 4, 8, 12 and 24 hours (p < 0.05), respectively. Six, four, 13 and 17 cats that received IV, IM, SC and OTM buprenorphine required rescue analgesia, respectively. There was a significantly higher incidence of treatment failure in cats that received SC and OTM buprenorphine compared with cats that received IV and IM buprenorphine (p < 0.05).. IV and IM administration of buprenorphine provided better postoperative analgesia than SC or OTM administration of the drug and these routes of administration should be preferred when buprenorphine is administered to cats.

Topics: Administration, Buccal; Analgesia; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Female; Hysterectomy; Injections, Intramuscular; Injections, Intravenous; Injections, Subcutaneous; Ovariectomy; Pain Measurement; Pain, Postoperative

To evaluate a prototype pressure stimulus device for use in the cat and to compare with a known thermal threshold device.. Eight healthy adult cats weighing between 3.0 and 4.9 kg.. Pressure stimulation was given via a plastic bracelet taped around the forearm. Three 2.4 mm diameter ball bearings, in a 10-mm triangle, were advanced against the craniolateral surface of the antebrachium by manual inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was also tested. Stimuli were stopped if they reached 55 degrees C or 450 mmHg without response. After four pressure and thermal threshold baselines, each cat received SC buprenorphine 0.01 mg kg(-1), carprofen 4 mg kg(-1) or saline 0.3 mL in a three period cross-over study with a 1-week interval. The investigator was blinded to the treatment. Measurements were made at 0.25. 0.5, 0.75, 1, 2, 3, 4, 6, 8, and 24 hours after injection. Data were analyzed by using ANOVA.. There were no significant changes in thermal or pressure threshold after administration of saline or carprofen, but thermal threshold increased from 60 minutes until 8 hours after administration of buprenorphine (p < 0.05). The maximum increase in threshold from baseline (DeltaT(max)) was 3.5 +/- 3.1 degrees C at 2 hours. Pressure threshold increased 2 hours after administration of buprenorphine (p < 0.05) when the increase in threshold above baseline (DeltaP(max)) was 162 +/- 189 mmHg.. This pressure device resulted in thresholds that were affected by analgesic treatment in a similar manner but to a lesser degree than the thermal method. Pressure stimulation may be a useful additional method for analgesic studies in cats.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Carbazoles; Cat Diseases; Cats; Cross-Over Studies; Double-Blind Method; Female; Hot Temperature; Injections, Subcutaneous; Male; Pain; Pain Measurement; Pressure; Sodium Chloride

To determine the prevalence of postanesthetic hyperthermia [rectal temperature >40 degrees C (104 degrees F)] in a clinical population of cats.. Retrospective study.. One hundred and twenty-five cats with an age range of 2 months to 16.1 years, and weighing 3.9 +/- 1.5 kg.. Data were obtained from the medical records of 125 cats that underwent general anesthesia. Information on perioperative rectal temperatures, breed, sex, weight, surgical procedure, anesthetic time, surgery time, anesthetic and analgesic drugs were retrieved.. Five groups of cats were compared; group 1 (n = 15) received acepromazine and no opioids; group 2 (n = 17) received acepromazine and buprenorphine; group 3 (n = 19) received acepromazine, buprenorphine and ketoprofen; group 4 (n = 45) received acepromazine and hydromorphone and group 5 (n = 29) received acepromazine, hydromorphone and ketoprofen. Data conformed to a split-plot repeated measures analysis of variance and was analyzed using SAS PROC MIXED. Post hoc tests were by means of Bonferroni t-test; < or = 0.05 was considered significant.. Rectal temperature was significantly decreased in all groups at the end of anesthesia. Rectal temperature was significantly elevated at 1, 1.5, 2, 3, 4 and 5 hours after the end of anesthesia in group 4, and at 2, 3 and 4 hours in group 5. Sixty-four percent of cats in group 4 and 69% in group 5 had rectal temperatures >40 degrees C (104 degrees F) at one or more times in the postanesthetic period. The highest temperature recorded was 42.5 degrees C (108.5 degrees F) in one cat in group 4. Mean rectal temperature did not exceed the preoperative temperature at any time during the postanesthetic period in group 1, 2 and 3 animals.. This study indicates an association between hyperthermia and perioperative administration of hydromorphone in cats.. When hydromorphone is used in cats their body temperature should be closely monitored.

Topics: Analgesics, Opioid; Anesthesia Recovery Period; Animals; Body Temperature; Buprenorphine; Cat Diseases; Cats; Female; Fever; Florida; Hydromorphone; Intraoperative Care; Male; Postoperative Care; Prevalence; Records; Retrospective Studies

Portosystemic shunts were ligated over a gauged stainless steel rod in 160 dogs and 15 cats, using a midline celiotomy. The diameter of the rod varied with the size of the shunt and the diameter of the portal vein cranial to the shunt. Shunts were narrowed to the smallest diameter that did not cause signs of portal hypertension such as cyanosis of the stomach, pancreas, and small intestine. A slight discoloration was accepted only if the heart rate, end-expiratory CO2%, or arterial blood pressure (if available) did not deviate more than 15% from the values that were recorded at the beginning of the surgical procedure. The perioperative mortality (0-30 days) was 29%. The most common cause of death was euthanasia because of hypoplasia of the portal vein cranial to the shunt. Animals with intrahepatic shunts had a significantly lower probability of survival than animals with extrahepatic portocaval or portoazygos shunts. In dogs, large breed and a high body weight were also significant risk factors for non-survival. Age had a significant effect on risk of non-survival, with an increased risk for older dogs, irrespective of the breed of the dog (large breed vs. small breed). The probability of survival without recurrence of hepatoencephalopathy (HE) after 1 and 4 years was 61.3% and 55.7%, respectively. The only variable that was significantly associated with non-recurrence of HE was the breed of the dog, there being a lower probability for large breeds. Among the animals that survived surgery for more than 30 days, there was a significant higher probability of recurrence of HE in cats than in dogs.

Topics: Abdomen; Alanine Transaminase; Ammonia; Analgesics, Opioid; Animals; Bile Acids and Salts; Buprenorphine; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Follow-Up Studies; Hepatic Encephalopathy; Hypotension; Ligation; Male; Narcotic Antagonists; Portal System; Portal Vein; Prognosis; Proportional Hazards Models; Sufentanil; Surveys and Questionnaires; Ultrasonography