Thermal antinociceptive pharmacodynamics of 0.1 mg kg−1 hydromorphone administered intramuscularly in cats and effect of concurrent butorphanol administration

Hydromorphone (HY) has not been objectively assessed as an analgesic in cats. It has been suggested that butorphanol (B) can have a synergistic action with pure μ‐agonists. The aim of this study was to assess the antinociceptive activity of a single dose of HY, and to examine the effect of concurrent B administration on the thermal threshold (TT). Thermal thresholds were measured following IM administration of HY, B, a combination of B and HY (HY‐B), or saline (S). Six cats (four spayed females, two castrated males, 4.75–6.8 kg) were used. Each cat received HY (0.1 mg kg^?1), B (0.4 mg kg^?1), HY (0.1 mg kg^?1), and B (0.4 mg kg^?1) (HY‐B), or S (0.05 mL kg^?1) in a randomized, blinded, cross‐over study design. Each cat received each treatment, with at least 12 days interval between the treatments. All injections were IM randomized to left or right quadriceps using a 24 SWG needle. Twenty‐four hours prior to each study, the thorax of each of the cats was shaved. On the day of the study, TT was measured using a thorax‐mounted thermal threshold‐testing device specifically developed for cats. Skin temperature was recorded before each test and then the heater was activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. Three baseline thresholds were recorded over 1 hour before IM injection of test drug. Thermal threshold cut‐off was 55.5 °C. TT was measured at 5 and 15 minutes, every 15 to 360 minutes, every 30 minutes to 8 hours, every hour to 12 hours, and at 24 hours post‐injection. Threshold data were analyzed using an anova with a repeat factor of time. Behavioral adverse effects (dysphoria) were associated with B administration, but not with HY or HY‐B administration (these produced calm euphoria). The control group was stable over time (p = 0.22) (mean threshold 40.15 °C). Overall, there was no period effect, no significant effect of administering B, but a significant effect (raised TT) of administering HY or HY‐B. If the mean value of one of the experimental groups differed from the control group (40.075 °C) by more than 2.355 °C (>42.425 °C), that mean was significantly different from control at p < 0.05 (Bonferroni's t‐tests). This occurred between 15 and 165 minutes for B, from 15 to 345 minutes for HY, and between 15 and 540 minutes for HY‐B. In this model, HY provided up to 5.75 hours of antinociception at 0.1 mg kg^?1, and concurrent administration of butorphanol (0.4 mg kg^?1) decreased the intensity of antinociception over the first 2 hours, but extended the duration of significant antinociception to about 9 hours.     

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.     

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.     

Adaptation of thermal threshold analgesiometry for NSAIDs in cats: effects of ketoprofen

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

Evaluation of the side-effects and thermal antinociceptive effects of intravenous hydromorphone in cats

Hydromorphone (H) may be an effective analgesic agent in cats, but fear of negative behavioral side‐effects associated with opioids is cited as a reason for avoiding this class of analgesics in cats. This study was designed to assess onset and duration of antinociception using an established feline thermal threshold model in cats, given an accepted clinical dose of 0.1 mg kg^?1 of H. In addition, cats were observed for changes in behavior and other side‐effects. Six adult cats from an established colony (four spayed females and two castrated males, 4.7–7.0 kg) received 0.1 mg kg^?1 H IV following establishment of baseline thermal threshold (TT) values. TT was tested at 15 minutes post‐injection, then at every 30–60 minutes for 12 hours. Side‐effects and behavior changes were recorded for 12 hours. Changes in TT over time were analyzed using a one‐way anova ; a p‐value <0.05 was considered significant. TT increased from a pre‐treatment value of (mean ± SD) 40.9 ± 1.65 °C to instrument cutout (55.5 °C) within 30 minutes for 5/6 cats. Mean TT was significantly elevated above baseline from 15 to 450 minutes after treatment. There was a significant increase in skin temperature from 15 to 300 minutes with peak increase of 1.55 °C at 135 minutes. Side‐effects included mydriasis (6/6) and nausea (4/6), characterized by licking, foaming, and gagging. Mydriasis occurred within 10–30 seconds of injection and persisted for 5–7 hours. Nausea was noted within 2 minutes of injection and persisted for 30–90 minutes; no vomiting occurred. Commonly observed behavioral changes included ventral tail curl (6/6 cats, onset 5–45 minutes, duration 4–5 hours) and euphoria (5/6 cats, onset <6 minutes for 4/6, duration 1–6 hours). 2/6 cats were profoundly sedate. Three cats showed signs of dysphoria with or without increased motor activity with variable onset and duration. Dysphoric behavior included staring, pacing, vocalizing, and sudden movements. 3/6 cats exhibited both euphoria and dysphoria at different times during the study. At no time were cats difficult to restrain or work with. Return to baseline behavior occurred 7–8.5 hours post‐injection. Mydriasis did not correlate closely with antinociception. Signs of sedation and euphoria corresponded with onset of antinociception, but not duration. Tail curl signs correlated with antinociception. In this model, H proved to be a rapid acting, potent, analgesic with a long (7.5 hours) duration of action. The most common behavioral changes noted were ventral tail curl, euphoria, and sedation. Mydriasis and nausea were noted as side‐effects.     

Effect of low dose rate ketamine infusions on thermal and mechanical thresholds in conscious cats

ObjectiveTo determine the thermal and mechanical antinociceptive effects of two different subanesthetic constant rate infusions of racemic ketamine in cats.Study designProspective, randomized, blinded, experimental study.AnimalsEight healthy adult domestic shorthair cats (two intact females and six neutered males).MethodsThe thorax and the lower thoracic limbs of each cat were shaved for thermal (TT) and mechanical threshold (MT) testing and a cephalic catheter was placed. Three intravenous treatments of equivalent volume were given as loading dose (LD) followed by an infusion for 2 hours: (K5) 0.5 mg kg^?1 ketamine followed by 5 μg kg^?1 minute^?1 ketamine infusion, (K23) 0.5 mg kg^?1 ketamine followed by 23 μg kg^?1 minute^?1 ketamine infusion or (S) 0.9% saline solution. Effects on behavior, sedation scores, MT and TT were obtained prior to drug treatment and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.25, 2.5 2.75, 3 hours then every 0.5 hours for 7 hours and 10, 12, 14 and 26 hours after loading dose administration.ResultsKetamine induced mild sedation for the period of the infusion, no adverse behavioral effects were observed. Thermal threshold was significantly higher than baseline (K5: 44.5 ± 0.7 °C; K23: 44.5 ± 0.5 °C) at 15 minutes in the K5 group (46.8 ± 3.5 °C) and at 45 minutes in the K23 group (47.1 ± 4.1 °C). In the K23 group TT was significantly increased compared to S and K5 at 45 minutes. In K5 at 15 minutes MT (9.6 ± 4.0 N) was different to baseline (6.1 ± 0.8 N) and to the S group (5.9 ± 2.3 N).Conclusion and clinical relevanceLow dose rate ketamine infusions minimally affect thermal and mechanical antinociception in cats. Further studies with different nociceptive testing methods are necessary to assess whether ketamine could be a useful analgesic in cats.     

Use of thermal threshold response to evaluate the antinociceptive effects of butorphanol in cats

OBJECTIVE: To characterize the antinociceptive actions of several doses of butorphanol by use of a thermal threshold testing device specifically designed for cats. ANIMALS: 6 domestic shorthair cats. PROCEDURE: The study was a masked, randomized, crossover design. Thermal thresholds were measured by use of a thermal threshold-testing device specifically developed for cats. A small probe containing a heater element and temperature sensor was held with consistent contact against a shaved area of the cat's skin with an elasticized band. Skin temperature was recorded before each test, prior to activation of the heater. On detection of a response (eg, the cat flinched, turned, or jumped), the stimulus was terminated and the threshold temperature recorded. Three baseline measurements were recorded before IV injection of 0.1, 0.2, 0.4, or 0.8 mg of butorphanol/kg. Each cat received all doses in a randomized order at least 1 week apart. The investigator was unaware of the treatment received. Thermal thresholds were measured every 15 minutes for 6 hours. RESULTS: Mean+/-SD pretreatment threshold temperature for all cats was 40.8+/-2.2 degrees C. There were no dose-related differences among treatments. There was a significant increase in threshold values for all treatments from 15 to 90 minutes after injection. Mydriasis was detected in all cats after treatment with butorphanol and dysphoric behavior was frequently exhibited. CONCLUSIONS AND CLINICAL RELEVANCE: Results obtained by use of a thermal stimulus indicated that the duration of antinociceptive action of butorphanol was 90 minutes and there was no dose-response relationship in cats.     

Effects of meperidine or saline on thermal, mechanical and electrical nociceptive thresholds in cats

ObjectiveTo measure cutaneous electrical nociceptive thresholds in relation to known thermal and mechanical stimulation for nociceptive threshold detection in cats.Study designProspective, blinded, randomized cross-over study with 1-week washout interval.AnimalsEight adult cats [bodyweight 5.1 ± 1.8 kg (mean + SD)].MethodsMechanical nociceptive thresholds were tested using a step-wise manual inflation of a modified blood pressure bladder attached to the cat’s thoracic limb. Thermal nociceptive thresholds were measured by increasing the temperature of a probe placed on the thorax. The electrical nociceptive threshold was tested using an escalating current from a constant current generator passed between electrodes placed on the thoracic region. A positive response (threshold) was recorded when cats displayed any or all of the following behaviors: leg shake, head turn, avoidance, or vocalization. Four baseline readings were performed before intramuscular injection of meperidine (5 mg kg⁻¹) or an equal volume of saline. Threshold recordings with each modality were made at 15, 30, 45, 60, 90, and 120 minutes post-injection. Data were analyzed using anova and paired t-tests (significance at p < 0.05).ResultsThere were no significant changes in thermal, mechanical, or electrical thresholds after saline. Thermal thresholds increased at 15–60 minutes (p < 0.01) and mechanical threshold increased at 30 and 45 minutes after meperidine (p < 0.05). Maximum thermal threshold was +4.1 ± 0.3 °C above baseline at 15 minutes while maximum mechanical threshold was 296 ± 265 mmHg above baseline at 30 minutes after meperidine. Electrical thresholds following meperidine were not significantly different than baseline (p > 0.05). Thermal and electrical thresholds after meperidine were significantly higher than saline at 30 and 45 minutes (p < 0.05), and at 120 minutes (p < 0.05), respectively. Mechanical thresholds were significantly higher than saline treatment at 30 minutes (p ≤ 0.05).Conclusion and clinical relevanceElectrical stimulation did not detect meperidine analgesia whereas both thermal and mechanical thresholds changed after meperidine administration in cats.     

Effects of opioids and anesthetic drugs on body temperature in cats

ObjectiveTo determine which class of opioid alone or in conjunction with other anesthetic drugs causes post-anesthetic hyperthermia in cats.Study designProspective, randomized, crossover study.AnimalsEight adult, healthy, cats (four spayed females and four castrated males weighing 3.8 ± 0.6 kg).MethodsEach cat was instrumented with a wireless thermistor in the abdominal cavity. Temperature in all phases was recorded every 5 minutes for 5 hours. Population body temperature (PBT) was recorded for ～8 days. Baseline body temperature is the final 24 hours of the PBT. All injectable drugs were given intramuscularly. The cats were administered drugs in four phases: 1) hydromorphone (H) 0.05, 0.1, or 0.2 mg kg^?1; 2) morphine (M) (0.5 mg kg^?1), buprenorphine (BUP) (0.02 mg kg^?1), or butorphanol (BUT) (0.2 mg kg^?1); 3) ketamine (K) (5 mg kg^?1) or ketamine (5 mg kg^?1) plus hydromorphone (0.1 mg kg^?1) (KH); 4) isoflurane in oxygen for 1 hour. Fifteen minutes prior to inhalant anesthetic, cats received either no premed (I), hydromorphone (0.1 mg kg^?1) (IH), or hydromorphone (0.1 mg kg^?1) plus ketamine (5 mg kg^?1) (IHK).ResultsMean PBT for all unmedicated cats was 38.9 ± 0.6 °C (102.0 ± 1 °F). The temperature of cats administered all doses of hydromorphone increased from baseline (p < 0.03) All four opioids (H, M, BUP and BUT) studied increased body temperature compared with baseline (p < 0.005). A significant difference was observed between baseline temperature values and those in treatment KH (p < 0.03). Following recovery from anesthesia, temperature in treatments IH and IHK was different from baseline (p < 0.002).Conclusions and clinical relevanceAll of the opioids tested, alone or in combination with ketamine or isoflurane, caused an increase in body temperature. The increase seen was mild to moderate (<40.1 °C (104.2 °F) and self limiting.     

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.     

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.     

Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.     

Intramuscular administration of alfaxalone in red‐eared sliders (Trachemys scripta elegans) – effects of dose and body temperature

ObjectiveTo characterise the effects of alfaxalone by intramuscular (IM) injection in red-eared slider turtles and the influence of body temperature on anaesthetic duration and depth.Study designProspective, randomised part-blinded experimental trial.AnimalsTen healthy adult female red-eared sliders.MethodsEach turtle was anaesthetized four times with 10 and 20 mg kg^?1 alfaxalone at 20 and 35 °C respectively. Time to maximal effect and plateau and recovery periods were recorded. Skeletal muscle tone, presence of various reflexes, response to noxious stimuli, and heart rate were assessed.ResultsResults are given for protocols 10 mg kg^?1 20 °C; 20 mg kg^?1 20 °C; 10 mg kg^?1 35 °C and 20 mg kg^?1 35 °C, respectively: mean time (±SD) to maximal effect was 16 ± 8, 19 ± 6, 5 ± 2 and 7 ± 5 minutes; duration of the plateau phase was 13 ± 12, 28 ± 13, 8 ± 5 and 8 ± 5 minutes and recovery time was 76 ± 20, 126 ± 17, 28 ± 9 and 41 ± 20 minutes. Endotracheal intubation was successful in 80%, 100%, 0% and 30% of turtles, respectively. At 35 °C, all animals retained nociceptive sensation in the front limbs, hind limbs and vent, whereas at 20 °C a few turtles lost peripheral nociceptive sensation. Corneal and tap reflexes were retained in all trials. Mean heart rates were 30 ± 2 and 66 ± 4 beats minute^?1 at 20 and 35 °C, respectively.Conclusions and clinical relevanceAlfaxalone administered IM in red-eared sliders provided smooth, rapid induction and uneventful recovery. At 35 °C either dosage provided only short (5–10 minutes) and light sedation. At 20 °C, 10 mg kg^?1 provided sedation suitable for short non-invasive procedures. About 20 mg kg^?1 provided anaesthesia of approximately 20 minutes duration, appropriate for induction of inhalational anaesthesia or for brief surgical procedures with supplemental analgesia.     

Thermal antinociception following oral administration of tapentadol in conscious cats

Objective

To evaluate the onset, magnitude and duration of thermal antinociception after oral administration of two doses of tapentadol in cats.

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

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

Effect of pre-medication on gastroduodenoscopy in isoflurane-anesthetized cats

The pre‐medicant chosen may influence the ease with which gastroduodenoscopy (GD) is performed. The purpose of this study was to evaluate the relative ease of GD in cats under ketamine and isoflurane anesthesia after IM injection of hydromorphone (H, 0.1 mg kg^?1), hydromorphone plus glycopyrrolate (HG, 0.1 mg kg^?1 (H), 0.01 mg kg^?1 (G)), medetomidine (M, 0.03 mg kg^?1), or butorphanol (B, 0.4 mg kg^?1). Eight cats were assigned randomly to receive each treatment in a cross‐over design with at least 7 days between treatments. Twenty minutes after pre‐medication, medetomidine produced greater (p = 0.001) sedation than the other treatments when assessed, using a subjective ordinal scale. The cats were injected with ketamine (10 mg kg^?1 IM), orotracheally intubated, connected to a pediatric circle breathing system, and allowed to spontaneously breathe isoflurane in oxygen. Once end‐tidal isoflurane concentration was stable at 1.4% for 15 minutes, endoscopy was started. A single endoscopist (REG), who was unaware of the treatment used, performed all endoscopies. The endoscopist scored the difficulty of endoscopy subjectively (0–3). The significance of differences between treatments was evaluated using Friedman's test. Time for entering the stomach was 9.4 (4.7–15.9) (median (minimum–maximum)), 6.6 (5.2–11.7), 8.4 (6.3–16.5), and 7.7 (5.1–14.7) seconds and for entering the duodenum from the stomach was 20.5 (13.8–40.9), 18.2 (10.3–39.8), 20.2 (16.2–119.5), and 22.2 (11.8–83.8) seconds for H, HG, M, and B treatments, respectively. There were no significant differences in the time for, or difficulty of, endoscopy. We conclude that any of these drugs can be used satisfactorily at the doses and combinations tested to pre‐medicate cats prior to general anesthesia for GD.     

A randomized, blinded, controlled trial of the antiemetic effect of ondansetron on dexmedetomidine-induced emesis in cats

ObjectiveTo determine the effect of ondansetron on the incidence of vomiting in cats pre-medicated with dexmedetomidine and buprenorphine.Study designRandomized, blinded, controlled trial.AnimalsEighty-nine female domestic shorthair cats, aged 3–60 months (median, 12 months) and weighing 1.2–5.1 kg.MethodsEach 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.ResultsThere 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.Conclusions and clinical relevanceIn 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.     

Effects of two fentanyl constant rate infusions on thermal thresholds and plasma fentanyl concentrations in awake cats

Objective

To determine the pharmacokinetics and effects on thermal thresholds (TT) of two fentanyl constant rate infusions in awake cats.

Use of naltrexone to antagonize high doses of remifentanil in cats: a dose-finding study

ObjectiveTo determine the dose of naltrexone necessary to fully antagonize a high dose of remifentanil in cats.Study designProspective experimental study.AnimalsSix healthy adult cats weighing 4.9 ± 0.7 kg.MethodsIn a first phase, remifentanil (200 μg kg^?1 followed by 60 μg kg^?1 minute^?1) was administered intravenously to two cats, causing an increase in locomotor activity. Naltrexone (100 μg kg^?1) was then administered intravenously every minute until the increase in locomotor activity had been reversed. In a second phase, six cats were used. Baseline thermal threshold was determined, naltrexone (600 μg kg^?1) was administered intravenously and 30 minutes later thermal threshold determination repeated. Remifentanil (200 μg kg^?1 followed by 60 μg kg^?1 minute^?1) was administered intravenously and thermal threshold determination repeated at 60, 120, 180, and/or 240 minutes after naltrexone administration. Thermal threshold determinations were started shortly after the start of the continuous rate infusion (CRI) of remifentanil and this CRI was discontinued immediately after thermal threshold determination. If an increase in thermal threshold was found, naltrexone administration was repeated at decreasing intervals in the next experiment (all cats were not used for all dosing intervals). Experiments were repeated until a naltrexone dosing interval was found that prevented increases in thermal threshold for 4 hours in all six cats.ResultsIn the first phase, both cats became severely dysphoric following remifentanil administration. A cumulative naltrexone dose of 300 μg kg^?1 was necessary to restore normal behavior in both cats. In the second phase, hourly administration of naltrexone (600 μg kg^?1) prevented increases in thermal threshold associated with hourly administration of remifentanil for 4 hours. Less frequent administration did not prevent increases in thermal threshold consistently.ConclusionsHourly administration of naltrexone (600 μg kg^?1) antagonizes the behavioral and antinociceptive effects of a high dose of remifentanil in cats.Clinical relevanceNaltrexone may be useful for the treatment of opioid overdose in cats.