Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses

ObjectiveTo compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration.Study designRandomized, masked, crossover design.AnimalsA total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg.MethodsHorses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg^⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg^⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (f_R), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant.ResultsThe mean ± SD hydromorphone terminal half-life (t_1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute^⁻1 kg^⁻1 and 1125 ± 309 mL kg^⁻1. The t_1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL^⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02).Conclusions and clinical relevanceIM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration.IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.     

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.     

Thermographic imaging of superficial temperature in dogs sedated with medetomidine and butorphanol with and without MK‐467 (L‐659’066)

ObjectiveTo record, with a thermal camera, peripheral temperature changes during different sedation protocols and to relate the results to changes in the rectal temperature.Study designRandomized crossover part-blinded experimental study.AnimalsEight healthy purpose-bred neutered Beagles (two females and six males) weight 14.5 ± 1.6 kg (mean ± SD) and aged 3–4 years.MethodsEach dog was sedated four times. Treatments were medetomidine 20 μg kg^?1 and butorphanol 0.1 mg kg^?1 (MB) with or without MK-467 500 μg kg^?1 (MK). Both drug combinations were administered IV and IM as separate treatments. A thermal camera (T425, FLIR) with a resolution of 320 by 240 was used for imaging.The dogs were placed in lateral recumbency on an insulated mattress. Digital (DFT) and metatarsal footpad temperatures (MFT) were measured with thermography. Thermograms and rectal temperature (RT) were taken before and at 3, 10, 20, 30, 45 and 60 minutes after treatment.ResultsAt 60 minutes after drug administration, MFT was higher (p < 0.001) after MB+MK (34.5 ± 1.1 IV, 34.8 ± 0.5 IM) than MB (31.1 ± 2.9 IV, 30.5 ± 3.6 IM), DFT was higher (p < 0.001) after MB+MK (33.6 ± 1.4 IV, 34.0 ± 0.6 IM) than MB (26.7 ± 1.4 IV, 26.7 ± 2.5 IM), and RT was lower (p < 0.001) after MB+MK (36.7 ± 0.8 IV, 36.9 ± 0.3 IM) than MB (37.5 ± 0.3 IV, 37.4 ± 0.4 IM), with both routes. The change from baseline was greater with MB+MK than MB in all variables.ConclusionsSuperficial temperature changes can be seen and detected with thermography. MK-467 used with MB resulted in increased superficial temperatures and a decline in rectal temperature compared to MB alone.Clinical relevanceThe sedation protocol may influence core temperature loss, and may also have an effect on thermographic images.     

Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

Comparison of the pharmacokinetics and thermal antinociceptive pharmacodynamics of 20 µg kg−1 buprenorphine administered sublingually or intravenously in cats

Little is known about the analgesic action of buprenorphine (BUP) in cats. Relative to man, the cat has a more alkaline oral pH, which may make this an effective route for administering BUP in this species. This study aimed to assess and compare the pharmacokinetics and pharmacodynamics of sublingual (S‐L) and IV administration of BUP. Thermal threshold (TT) was measured and blood samples were collected following IV or S‐L administration (20 µg kg^?1) of the injectable formulation. Six cats (five spayed females, one castrated male, 4.1–6.6 kg) were used. Each cat received both treatments in a randomized cross‐over study design with 1 month between experiments. Twenty‐four hours prior to each study, the lateral thorax of each of the cats was shaved, cephalic and jugular catheters placed, and oral pH measured. On the day of the study, TT was measured using a ‘thorax‐mounted’ thermal threshold‐testing device specifically developed for cats. The cats were free to move around. Skin temperature was recorded before each test, then the heater activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. The thermal threshold cut‐off point was 55.5 °C. Three baseline thresholds were recorded before treatment with S‐L or IV (via cephalic catheter) BUP (20 µg kg^?1). Blood was withdrawn (jugular) at 1, 2, 4, 6, 10, 15, 30, 45, 60 minutes and at 2, 4, 6, 8, 12, and 24 hours post‐administration. TT was measured every 30 minutes?6 hours, 1–12 hours, and at 24 hours post‐administration. Plasma was immediately separated, stored at ?20.5 °C, and assayed within 4 months using a commercially available ¹²⁵I radioimmunoassay. Threshold data were analyzed using anova with a repeat factor of time. No adverse effects were noted. Pupils were dilated for up to 9 hours post‐BUP. Behavioral changes were calm euphoria. Measured oral pH was 9 in each cat. Pre‐treatment mean threshold (±SD) was 41.2 ± 0.9 °C in the S‐L group and 40.8 ± 0.85 °C in the IV group. There were no significant differences between the groups with respect to thresholds over time (p = 0.72). Thresholds were significantly increased from 30 to 360 minutes in both the groups (>44.615 °C). Peak plasma BUP (C_max) was lower (11 ± 6.7 ng mL^?1vs. 92.9 ± 107.9 ng mL^?1) and occurred later (T_max) (30 minutes vs. 1 minute) after S‐L compared to IV administration, respectively. BUP (20 µg kg^?1)‐administered S‐L or IV provided antinociception between 30 and 360 minutes after administration. Plasma levels did not correspond to TT.     

Hyoscine‐N‐butylbromide premedication on cardiovascular variables of horses sedated with medetomidine

ObjectiveTo evaluate the effects of intravenous (IV) or intramuscular (IM) hyoscine premedication on physiologic variables following IV administration of medetomidine in horses.Study designRandomized, crossover experimental study.AnimalsEight healthy crossbred horses weighing 330 ± 39 kg and aged 7 ± 4 years.MethodsBaseline measurements of heart rate (HR), cardiac index (CI), respiratory rate, systemic vascular resistance (SVR), percentage of patients with second degree atrioventricular (2^oAV) block, mean arterial pressure (MAP), pH, and arterial partial pressures of carbon dioxide (PaCO₂) and oxygen (PaO₂) were obtained 5 minutes before administration of IV hyoscine (0.14 mg kg^?1; group HIV), IM hyoscine (0.3 mg kg^?1; group HIM), or an equal volume of physiologic saline IV (group C). Five minutes later, medetomidine (7.5 μg kg^?1) was administered IV and measurements were recorded at various time points for 130 minutes.ResultsMedetomidine induced bradycardia, 2^oAV blocks and increased SVR immediately after administration, without significant changes in CI or MAP in C. Hyoscine administration induced tachycardia and hypertension, and decreased the percentage of 2^oAV blocks induced by medetomidine. Peak HR and MAP were higher in HIV than HIM at 88 ± 18 beats minute^?1 and 241 ± 37 mmHg versus 65 ± 16 beats minute^?1 and 192 ± 38 mmHg, respectively. CI was increased significantly in HIV (p ≤ 0.05). Respiratory rate decreased significantly in all groups during the recording period. pH, PaCO₂ and PaO₂ were not significantly changed by administration of medetomidine with or without hyoscine.Conclusion and clinical relevanceHyoscine administered IV or IM before medetomidine in horses resulted in tachycardia and hypertension under the conditions of this study. The significance of these changes, and responses to other dose rates, requires further investigation.     

RESEARCH PAPER: Sedative and cardiorespiratory effects of dexmedetomidine and buprenorphine administered to cats via oral transmucosal or intramuscular routes

ObjectiveTo determine if buprenorphine plus dexmedetomidine administered via the oral transmucosal route produces sufficient sedation in cats so that students can insert intravenous catheters.Study DesignProspective, randomized, blinded, clinical trial.AnimalsEighty‐seven shelter‐owned female cats aged 4–48 months, weighing 1.1–4.9 kg.MethodsCats were randomly allocated to two treatment groups based on route of drug administration: oral transmucosal (OTM), or intramuscular (IM). Buprenorphine (20 μg kg^?1) plus dexmedetomidine (20 μg kg^?1) were administered as pre‐medicants via one of these two routes. Prior to and 20 minutes after drug administration, heart and respiratory rates, systolic arterial pressure, and posture were measured and recorded. Twenty minutes after drug administration the same variables plus each cat’s response to clipper sound, clipping, and restraint were recorded; higher scores indicated more sedation.ResultsThere were no significant differences between the two groups prior to pre‐medication. Within each treatment group heart rate was significantly lower 20 minutes after treatment, but it did not differ significantly between the two groups. Twenty minutes after treatment, respiratory rate was significantly less in the OTM group, but did not differ significantly between the two groups. Systolic arterial pressure did not differ within or between the two groups at either time. Scores for posture increased significantly within both groups, and cats in the IM group had higher scores after treatment. Twenty minutes after treatment, cats in the IM group had higher scores for clipping and restraint than OTM cats. Ketamine (IM) was necessary to facilitate catheterization in 25% and 16% of cats in the OTM and IM groups, respectively, but this was not significantly different.Conclusions and clinical relevanceAdministration of dexmedetomidine plus buprenorphine by the OTM route is easy to perform, but produces less sedation than the IM route for IV catheterization in cats.     

Medetomidine/midazolam/ketamine anaesthesia in ferrets: effects on cardiorespiratory parameters and evaluation of plasma drug concentrations

ObjectiveTo evaluate the cardiorespiratory effects and plasma concentrations of medetomidine-midazolam-ketamine (MMK) combinations administered by intramuscular (IM) or subcutaneous (SC) injection in sable ferrets (Mustela putorius furo).Study designProspective randomized experimental study.AnimalsEighteen adult ferrets: weight median 1.19 (range 0.81–1.60) kg.MethodsAnimals were allocated to one of three groups: group IM07 received 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 7 mg kg^?1 ketamine IM; group IM10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine IM; and group SC10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine SC. Following instrumentation, cardiorespiratory parameters and plasma drug concentrations were measured every 5 minutes (T5–T30) for 30 minutes Ferrets were then euthanased. Data were analysed using anova for repeated measures. p < 0.05 was considered significant.ResultsResults are mean ± SD. Induction of anaesthesia (minutes) in IM07 and IM10 [2 (1)] was significantly faster than in SC10 [5 (2)]. All groups demonstrated the following: results given as groups IM07, IM10 and SC10 respectively. Mean arterial blood pressures (mmHg) were initially high [186 (13); 174 (33) and 174 (9) at T5] but decreased steadily. Pulse rates were initially 202 (20), 213 (17) and 207 (33) beats minute^?1, decreasing with time. PaO₂ (mmHg) was low [54.0 (8), 47.7 (10) and 38.5 (1)] at T5, although in groups IM07 and IM10 it increased over time. Plasma concentrations of all drugs were highest at T5 (36, 794 and 8264 nmol L^?1 for medetomidine, midazolam and ketamine, respectively) and decreased thereafter: for both midazolam and ketamine, concentrations in IM07 and IM10 were higher than SC10.Conclusions and clinical relevanceMMK combinations containing either 7 or 10 mg kg^?1 ketamine and given IM are suitable combinations for anaesthetising ferrets, although the observed degree of hypoxaemia indicates that oxygen administration is vital.     

Pharmacokinetics and selected behavioral responses to butorphanol and its metabolites in goats following intravenous and intramuscular administration

Objective To evaluate disposition of a single dose of butorphanol in goats after intravenous (IV) and intramuscular (IM) administration and to relate behavioral changes after butorphanol administration with plasma concentrations. Design Randomized experimental study. Animals Six healthy 3‐year‐old neutered goats (one male and five female) weighing 46.5 ± 10.5 kg (mean ± D). Methods Goats were given IV and IM butorphanol (0.1 mg kg^?1) using a randomized cross‐over design with a 1‐week interval between treatments. Heparinized blood samples were collected at fixed intervals for subsequent determination of plasma butorphanol concentrations using an enzyme linked immunosorbent assay (ELISA). Pharmacokinetic values (volume of distribution at steady state [Vd_SS], systemic clearance [Cl_TB], extrapolated peak plasma concentration [C₀] or estimated peak plasma concentration [C_MAX], time to estimated peak plasma concentration [T_MAX], distribution and elimination half‐lives [t_1/2], and bioavailability) were calculated. Behavior was subjectively scored. A two‐tailed paired t‐test was used to compare the elimination half‐lives after IV and IM administration. Behavioral scores are reported as median (range). A Friedman Rank Sums test adjusted for ties was used to analyze the behavioral scores. A logit model was used to determine the effect of time and concentration on behavior. A value of p < 0.05 was considered significant. Results Volume of distribution at steady state after IV administration of butorphanol was 1.27 ± 0.73 L kg^?1, and Cl_TB was 0.0096 ± 0.0024 L kg^?1 minute^?1. Extrapolated C₀ of butorphanol after IV administration was 146.5 ± 49.8 ng mL^?1. Estimated C_MAX after IM administration of butorphanol was 54.98 ± 14.60 ng mL^?1, and T_MAX was 16.2 ± 5.2 minutes; bioavailability was 82 ± 41%. Elimination half‐life of butorphanol was 1.87 ± 1.49 and 2.75 ± 1.93 hours for IV and IM administration, respectively. Goats became hyperactive after butorphanol administration within the first 5 minutes after administration. Behavioral scores for goats were significantly different from baseline at 15 minutes after IV administration and at 15 and 30 minutes after IM administration. Both time and plasma butorphanol concentration were predictors of behavior. Behavioral scores of all goats had returned to baseline by 120 minutes after IV administration and by 240 minutes after IM administration. Conclusions and Clinical Relevance The dose of butorphanol (0.1 mg kg^?1, IV or IM) being used clinically to treat postoperative pain in goats has an elimination half‐life of 1.87 and 2.75 hours, respectively. Nonpainful goats become transiently excited after IV and IM administration of butorphanol. Clinical trials to validate the efficacy of butorphanol as an analgesic in goats are needed.     

Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain‐free female cats

ObjectiveTo assess the potential of a thermal carbon dioxide (CO₂) laser to explore antinociception in pain-free cats.Study designExperimental, prospective, blinded, randomized study.AnimalsSixty healthy adult female cats with a (mean ± standard deviation) weight of 3.3 ± 0.6 kg.MethodsCats were systematically allocated to one of six treatments: saline 0.2 mL per cat; morphine 0.5 mg kg⁻¹; buprenorphine 20 μg kg⁻¹; medetomidine 2 μg kg⁻¹; tramadol 2 mg kg⁻¹, and ketoprofen 2 mg kg⁻¹. Latency to respond to thermal stimulation was assessed at baseline and at intervals of 15–30, 30–45, 45–60, 60–75, 90–105 and 120–135 minutes. Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO₂ laser. Within-treatment differences in response latency were assessed using Friedman’s test. Differences amongst treatments were assessed using independent Kruskal–Wallis tests. Where significant effects were identified, pairwise comparisons were conducted to elucidate the direction of the effect.ResultsCats treated with morphine (X² = 12.90, df = 6, p = 0.045) and tramadol (X² = 20.28, df = 6, p = 0.002) showed significant increases in latency to respond. However, subsequent pairwise comparisons indicated that differences in latencies at specific time-points were significant (p < 0.05) only for tramadol at 60–75 and 90–105 minutes after administration (21.9 and 43.6 seconds, respectively) in comparison with baseline (11.0 seconds). No significant pairwise comparisons were found within the morphine treatment. Injections of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond.Conclusions and clinical relevanceThe CO₂ laser technique may have utility in the assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and may provide a simpler alternative to existing systems. Further exploration is required to examine its sensitivity and comparative utility.     

Cardiopulmonary and isoflurane‐sparing effects of epidural or intravenous infusion of dexmedetomidine in cats undergoing surgery with epidural lidocaine

ObjectiveTo compare the cardiorespiratory, anesthetic-sparing effects and quality of anesthetic recovery after epidural and constant rate intravenous (IV) infusion of dexmedetomidine (DEX) in cats given a low dose of epidural lidocaine under propofol-isoflurane anesthesia and submitted to elective ovariohysterectomy.Study designRandomized, blinded clinical trial.AnimalsTwenty-one adult female cats (mean body weight: 3.1 ± 0.4 kg).MethodsCats received DEX (4 μg kg^?1, IM). Fifteen minutes later, anesthesia was induced with propofol and maintained with isoflurane. Cats were divided into three groups. In GI cats received epidural lidocaine (1 mg kg^?1, n = 7), in GII cats were given epidural lidocaine (1 mg kg^?1) + DEX (4 μg kg^?1, n = 7), and in GIII cats were given epidural lidocaine (1 mg kg^?1) + IV constant rate infusion (CRI) of DEX (0.25 μg kg^?1 minute^?1, n = 7). Variables evaluated included heart rate (HR), respiratory rate (f_R), systemic arterial pressures, rectal temperature (RT), end-tidal CO₂, end-tidal isoflurane concentration (e′ISO), arterial blood gases, and muscle tone. Anesthetic recovery was compared among groups by evaluation of times to recovery, HR, f_R, RT, and degree of analgesia. A paired t-test was used to evaluate pre-medication variables and blood gases within groups. anova was used to compare parametric data, whereas Friedman test was used to compare muscle relaxation.ResultsEpidural and CRI of DEX reduced HR during anesthesia maintenance. Mean ± SD e′ISO ranged from 0.86 ± 0.28% to 1.91 ± 0.63% in GI, from 0.70 ± 0.12% to 0.97 ± 0.20% in GII, and from 0.69 ± 0.12% to 1.17 ± 0.25% in GIII. Cats in GII and GIII had longer recovery periods than in GI.Conclusions and clinical relevanceEpidural and CRI of DEX significantly decreased isoflurane consumption and resulted in recovery of better quality and longer duration, despite bradycardia, without changes in systemic blood pressure.     

Comparison of two injectable anesthetic regimes in feral cats at a large-volume spay clinic

Same‐day mass sterilization of feral cats requires rapid onset, short‐duration anesthesia. The purpose of this study was to compare our current anesthetic protocol, Telazol–ketamine–xylazine (TKX) with medetomidine–ketamine–buprenorphine (MKB). Feral female cats received either IM TKX (n = 68; 0.25 mL cat^?1; tiletamine 12.5 mg, zolazepam 12.5 mg, K 20 mg, and X 5 mg per 0.25 mL) or MKB (n = 17; M 40 µg kg^?1, K 15 mg kg^?1, and B 10 µg kg^?1). Intervals measured included time from injection to recumbency, time to surgery, duration of surgery, and time from reversal of anesthesia (TKX: yohimbine 0.50 mg cat^?1 IV; MKB: atipamezole 0.50 mg cat^?1 IM) to sternal recumbency. Following instrumentation (Vet/Ox 4403 and Vet/BP Plus 6500), physiological measurements were recorded at 5‐minute intervals, and included rectal temperature, heart rate (HR), respiratory rate (RR), SpO₂ (lingual or rectal probes), and indirect mean arterial blood pressure (MAP) (oscillometric method). Nonparametric means were compared using Mann–Whitney U‐tests. Parametric means were compared using a two‐factorial anova with Bonferroni's t‐tests. The alpha‐priori significance level was p < 0.05. Values were mean ± SD. Body weight (TKX: 2.9 ± 0.5 kg, MKB: 2.7 ± 0.7 kg), time to recumbency (TKX: 4 ± 1 minutes, MKB: 3 ± 1 minutes), time to surgery (TKX: 28 ± 7 minutes, MKB: 28 ± 5 minutes), and duration of surgery (TKX: 11 ± 7 minutes, MKB: 8 ± 5 minutes) did not differ between groups. In contrast, MKB cats required less time from reversal to sternal recumbency (TKX: 68 ± 41 minutes, MKB: 7 ± 2 minutes) and were recumbent for shorter duration (TKX: 114 ± 39 minutes, MKB: 53 ± 6 minutes). Temperature decreased during the study in both groups, but overall temperature was higher in MKB cats (38.0 ± 0.95 °C) than in TKX cats (37.5 ± 0.95 °C). RR, HR, and SpO₂ did not change during the study in either group. However, overall HR and RR were higher in TKX cats (RR: 18 ± 8 breaths minute^?1, HR: 153 ± 30 beats minute^?1) compared to MKB cats (RR: 15 ± 7 breaths minute^?1, HR: 128 ± 19 beats minute^?1). In contrast, overall SpO₂ was lower in the TKX group (90 ± 6%) compared to the MKB group (94 ± 4%). MAP was also lower in the TKX group (112 ± 29 mm Hg) compared to that in the MKB group (122 ± 20 mm Hg). However, MAP increased in the TKX group during surgery compared to pre‐surgical values, but did not change in the MKB group. The results of this study suggested that MKB might be more suitable as an anesthetic for the purpose of mass sterilization of feral female cats.     

Cardiovascular,respiratory, electrolyte and acid–base balance during continuous dexmedetomidine infusion in anesthetized dogs

ObjectiveTo evaluate the cardiovascular, respiratory, electrolyte and acid–base effects of a continuous infusion of dexmedetomidine during propofol–isoflurane anesthesia following premedication with dexmedetomidine.Study designProspective experimental study.AnimalsFive adult male Walker Hound dogs 1–2 years of age averaging 25.4 ± 3.6 kg.MethodsDogs were sedated with dexmedetomidine 10 μg kg^?1 IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg^?1) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg^?1 IV was administered over 5 minutes followed by an infusion of 0.5 μg kg^?1 hour^?1. Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid–base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD.ResultsNo statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute^?1, 78 ± 18 beats minute^?1 and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute^?1, 78 ± 14 beats minute^?1 and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO₂, PaCO₂, pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion.Conclusions and clinical relevanceDexmedetomidine infusion using a loading dose of 0.5 μg kg^?1 IV followed by a constant rate infusion of 0.5 μg kg^?1 hour^?1 does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg^?1, in propofol–isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters.     

Effects of intramuscular and intranasal administration of midazolam–dexmedetomidine on sedation and some cardiopulmonary variables in New Zealand White rabbits

ObjectiveTo compare the sedative and cardiopulmonary effects of intranasal (IN) and intramuscular (IM) administration of dexmedetomidine and midazolam combination in New Zealand White rabbits.Study designA randomized, crossover experimental study.AnimalsA total of eight healthy New Zealand White rabbits, aged 6–12 months, weighing 3.1 ± 0.3 kg (mean ± standard deviation).MethodsThe animals were randomly assigned to administration of dexmedetomidine (0.1 mg kg^–1) with midazolam (2 mg kg^–1) by either IN or IM route separated by 2 weeks. The electrocardiogram, pulse rate (PR), peripheral haemoglobin oxygen saturation (SpO₂), mean noninvasive arterial pressure (MAP), respiratory frequency (f_R) and rectal temperature were measured before drug administration (baseline), T₀ (onset of sedation) and at 5 minute intervals until recovery. The onset of sedation, duration of sedation and sedation score (SS) were also recorded.ResultsThe PR was significantly lower in treatment IM than in treatment IN over time (p = 0.027). MAP < 60 mmHg developed in two and four rabbits in treatments IN and IM, respectively. SpO₂ progressively decreased over time in both treatments. f_R was lower than baseline at several time points in both treatments. Onset of sedation was shorter in treatment IN (90 ± 21 seconds) than in treatment IM (300 ± 68 seconds) (p = 0.036). Duration of sedation was longer in treatment IM (55.2 ± 8.7 minutes) than in treatment IN (39.6 ± 2.1 minutes) (p = 0.047). No significant difference in SS was observed between treatments (p > 0.05).Conclusions and clinical relevanceCombination of dexmedetomidine (0.1 mg kg^–1) and midazolam (2 mg kg^–1) decreased f_R, PR and SpO₂ regardless of the administration route in New Zealand White rabbits. A more rapid action and shorter duration of sedation were observed after treatment IN than after treatment IM administration.     

The cardiopulmonary effects of a peripheral alpha‐2‐adrenoceptor antagonist,MK‐467, in dogs sedated with a combination of medetomidine and butorphanol

ObjectiveTo compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467.Study designProspective, randomized experimental cross-over.AnimalsEight purpose–bred beagles (two females, six males), 3–4 years old and weighing 14.5 ±1.6 kg (mean ± SD).MethodsAll dogs received four different treatments as follows: medetomidine 20 μg kg^?1 and butorphanol tartrate 0.1 mg kg^?1 IV and IM (MB), and MB combined with MK-467,500 μg kg^?1 (MBMK) IV and IM. Heart rate (HR), arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac output, respiratory rate (f_R), rectal temperature (RT) were measured and arterial blood samples were obtained for gas analysis at baseline and at 3, 10, 20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI), systemic vascular resistance index (SVRI) and oxygen delivery index (DO₂I) were calculated. After the follow-up period atipamezole 50 μg kg^?1 IM was given to reverse sedation.ResultsHR, CI and DO₂I were significantly higher with MBMK after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT were significantly lower after MBMK than with MB. There were no differences in f_R between treatments, but arterial partial pressure of oxygen decreased transiently after all treatments. Recoveries were uneventful following atipamezole administration after all treatments.Conclusions and clinical relevanceMK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration.     

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

The role of ketamine (K) in pain management is controversial. It is reported to provide visceral analgesia in cats. This study aimed to assess its somatic actions using a thermal threshold (TT) model. Six cats (four spayed females, two castrated males, 4.3–7.2 kg) participated in the study. The day before each study, the thorax of each of the cats was shaved and a cephalic catheter was placed. TT was measured using a device specifically developed for cats. A heater element and temperature sensor housed in a small probe were held against the thorax of the cats with an elastic band and pressure bladder to assure consistent contact. The skin temperature was recorded before each test, then the heater was activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. Treatments were 2 mg kg^?1 of K (10 mg mL^?1), or 0.2 mL kg^?1 of saline (S) IV, given in a randomized cross‐over design with at least 1 week between treatments. The investigator was blinded to the treatment. TT was measured thrice before treatment (baseline threshold) at 15 minutes, then every 30 minutes for 8 hours and once at 24 hours after injection. Data were analyzed using a four‐factor anova . Cats were sedated for 45 minutes following K treatment. There was no difference in baseline TT between treatments (K = 41.9 ± 1.7 °C, S = 41.0 ± 1.45 °C), and no change in TT at any time in the S group. TT increased significantly at 15 and 30 minutes after K, then decreased below baseline values between 210 and 390 minutes, with a nadir of 38.8 ± ± 1.05 °C at 390 minutes. During this time period, cats exhibited normal activity, but responses to thermal stimuli were exaggerated. This study suggested that K caused a delayed onset hyperalgesia in cats.     

Antinociceptive effects of levomethadone in standing horses sedated with romifidine

ObjectiveTo evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI).Study designProspective, randomized, masked, crossover experimental study.AnimalsA group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)].MethodsLevomethadone 0.1 mg kg^–1 or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%–75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05.ResultsHorses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration.Conclusions and Clinical RelevanceA single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α₂-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked.     

Anaesthesia with a combination of ketamine and medetomidine in the rabbit: effect of premedication with buprenorphine

ObjectiveTo assess the effects of premedication with buprenorphine on the characteristics of anaesthesia induced with ketamine/medetomidine.Study designProspective crossover laboratory study.AnimalsSix female New Zealand White rabbits.MethodsRabbits received, on occasions separated by 7 days, either buprenorphine (0.03 mg kg^?1) or saline subcutaneously (SC) as premedication, followed 1 hour later by SC ketamine (15 mg kg^?1) and medetomidine (0.25 mg kg^?1) (K/M). At pre-determined time points reflex responses and cardiopulmonary parameters were recorded and arterial blood samples taken for analysis. Total sleep time was the duration of loss of the righting reflex. Duration of surgical anaesthesia was the time of suppression of the ear pinch and pedal withdrawal reflexes. Wilcoxon signed-ranks tests were used to compare data before (T₀) and 10 minutes after (T₁₀) injection with K/M.ResultsAll animals lost all three reflex responses within 10 minutes of injection of K/M. The duration of loss of these reflexes significantly increased in animals that received buprenorphine. At induction, animals that had received buprenorphine tended to have a lower respiration rate but there were no significant differences in arterial PCO₂, PO₂ or pH between treatments. Hypoxaemia [median PaO₂ < 6.0 kPa (45 mmHg)] developed in both treatments at T₁₀ but there was no significant difference between treatments. Mean arterial pressure (MAP) was lower at T₁₀ in animals that had received buprenorphine.Conclusion and clinical relevancePremedication with buprenorphine significantly increased the duration of anaesthesia induced by K/M, with no significant depression of respiration further to the control treatment within the first 10 minutes of anaesthesia. The MAP decreased but this was not reflected in a difference in other physiological parameters. These data show that premedication with buprenorphine, before K/M anaesthesia in the rabbit, has few negative effects and may provide beneficial analgesia.     

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.