The thermal antinociceptive effects of a high-concentration formulation of buprenorphine alone or followed by hydromorphone in conscious cats

ObjectiveTo evaluate the thermal antinociceptive effects of a high-concentration formulation of buprenorphine alone or followed by hydromorphone in conscious cats.Study designRandomized, blinded, placebo-controlled crossover study design.AnimalsA total of six purpose-bred, adult female ovariohysterectomized Domestic Short Hair cats.MethodsCats were allocated into three treatments each consisting of two injections, subcutaneous then intravenous (IV) administration, 2 hours apart: treatment SS, two injections of 0.9% saline; treatment BS, buprenorphine (0.24 mg kg^–1, 1.8 mg mL^–1) and saline; and treatment BH, buprenorphine (0.24 mg kg^–1) and hydromorphone (0.1 mg kg^–1). Skin temperature (ST) and thermal threshold (TT) were recorded before (baseline) and for 24 hours following first injection. TT data were analyzed using mixed linear models and a Benjamini–Hochberg sequential adjustment procedure (p < 0.05).ResultsThere were no significant differences among treatments for baseline ST and TT values, treatment SS over time and between treatments BS and BH. Compared with baseline, TT was significantly increased at all time points in treatments BH and BS except at 2 hours in treatment BS. TT was significantly higher than SS at 3–18 hours and 4–12 hours for treatments BS and BH, respectively. Maximal increases in TT were 47.5 °C at 2 hours, 53.9 °C at 3 hours and 52.4 °C at 6 hours in treatments SS, BS and BH, respectively.Conclusions and clinical relevanceAdministration of IV hydromorphone following high-concentration buprenorphine provided no additional antinociception and decreased the duration of effect when compared with high-concentration buprenorphine alone. Alternative analgesics should be considered if additional analgesia is required after administration of high-concentration buprenorphine.     

Opioid requirements after locoregional anaesthesia in dogs undergoing tibial plateau levelling osteotomy: a pilot study

ObjectiveTo determine the intraoperative and early postoperative opioid requirement after ultrasound-guided sciatic and/or femoral nerve block or epidural anaesthesia in dogs undergoing tibial plateau levelling osteotomy (TPLO).Study designProspective, masked, pilot, randomized, clinical trial.AnimalsA total of 40 client-owned dogs undergoing TPLO.MethodsEach dog was randomly assigned to group SF (combined sciatic and femoral nerve block), group S (sciatic nerve block), group F (femoral nerve block) or group E (epidural anaesthesia). A total of 0.3 mL kg^–1 of ropivacaine 0.5% was administered to each nerve or in the epidural space. Intraoperatively, fentanyl (2 μg kg^–1) was administered intravenously when heart rate, mean arterial pressure or respiratory rate increased by >30% compared with baseline values. Postoperatively, a visual analogue scale (VAS) and a modified German version of the French pain scale (4AVet) were used to assess pain every 30 minutes for 150 minutes and again once the morning after surgery. Methadone (0.1 mg kg^–1) was administered intravenously if the VAS was ≥ 4 cm [maximal value 10 cm; median (interquartile range)] or the composite pain score was ≥5 [maximal value 15; median (interquartile range)]. Significance was defined as p ≤ 0.05.ResultsGroups SF and E required less total intraoperative and early postoperative opioid doses compared with groups S and F (p = 0.031). No dogs in group SF had a block failure or required postoperative methadone. A reduced methadone requirement was found in group SF compared with all the other groups up to 150 minutes after recovery (p = 0.041).Conclusions and clinical relevanceCombined sciatic and femoral nerve block and epidural anaesthesia lead to less cumulative consumption of perioperative opioids than single nerve blockade. Sciatic or femoral nerve block alone might be insufficient to control nociception and early postoperative pain in dogs undergoing TPLO.     

Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats

ObjectiveTo compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats.Study designRandomized, ‘blinded’ crossover study, with 1 month washout between treatments.AnimalsSix healthy neutered female cats, weighing 5.3–7.5 kg.MethodsA 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.ResultsThere 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.Conclusions and clinical relevanceIn 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.     

Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site

ObjectiveTo describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.Study designRandomized crossover experiment; prospective study.AnimalsEleven healthy adult horses between 6 and 20 years of age and weighing 487–592 kg.MethodsIn the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg^?1) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg^?1 SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.ResultsFollowing IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg^?1 minute^?1 and volume of distribution at steady-state was 3.16 ± 0.65 L kg^?1. Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.Conclusions and clinical relevanceBuprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.     

A study to evaluate buprenorphine at 40 μg kg(-1) compared to 20 μg kg(-1) as a post-operative analgesic in the dog

ObjectiveComparison of the analgesic effect of buprenorphine at 20 or 40 μg kg^?1.Study designAn investigator ‘blinded’, randomised study.AnimalsTwenty six dogs presented for ovariohysterectomy.MethodsDogs were premedicated intramuscularly with acepromazine 0.03 mg kg^?1 and buprenorphine at either 20 (B20, n = 12) or 40 μg kg^?1 (B40, n= 14) followed by anaesthetic induction with propofol and maintenance with isoflurane. During anaesthesia non invasive blood pressure, heart rate, respiratory rate, blood oxygen saturation, inspired and expired volatile agent, end-tidal carbon dioxide and ECG were recorded. Pain and sedation were assessed using interactive VAS scores; mechanical nociceptive thresholds were measured at the wound and hindlimb - all were assessed before and up to 22 hours after administration. Carprofen was used for rescue analgesia.ResultsThere were no significant differences between the two groups for any of the parameters examined. Rescue analgesia was required around 5 hours after administration of buprenorphine in a significant number of animals. Sedation was good preoperatively and scores decreased over time postoperatively. Hock thresholds did not change over time; wound thresholds decreased significantly compared to the baseline value from 3 hours onwards.ConclusionsAdministration of buprenorphine at either 20 or 40 μg kg^?1 IM with acepromazine provided good pre-operative sedation. Cardiovascular and respiratory values remained within clinically acceptable limits during anaesthesia. There was no evidence that increasing dose increased adverse events that may be associated with opioid administration (e.g. bradycardia and respiratory depression).Clinical relevanceIncreasing the dose of buprenorphine from 20 to 40 μg kg^?1 did not provide any benefits with respect to analgesia after ovariohysterectomy as assessed using the VAS scoring system.     

Postanesthetic hyperthermia in cats: a retrospective comparison between hydromorphone and buprenorphine

OBJECTIVE: To determine the prevalence of postanesthetic hyperthermia [rectal temperature >40 degrees C (104 degrees F)] in a clinical population of cats. STUDY DESIGN: Retrospective study. ANIMAL POPULATION: One hundred and twenty-five cats with an age range of 2 months to 16.1 years, and weighing 3.9 +/- 1.5 kg. MATERIALS AND METHODS: 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. STATISTICAL ANALYSES: 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. RESULTS: 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. CONCLUSIONS: This study indicates an association between hyperthermia and perioperative administration of hydromorphone in cats. CLINICAL RELEVANCE: When hydromorphone is used in cats their body temperature should be closely monitored.