Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

ObjectiveTo evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses.Study designProspective, blinded, randomized cross-over study.AnimalsTen healthy adult horses weighing 527–645 kg and aged 11–21 years old.MethodsElectrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg^?1, romifidine 0.08 mg kg^?1, or xylazine, 1 mg kg^?1, was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation.ResultsThe administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively.Conclusions and clinical relevanceDetomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.     

Pharmacokinetic–pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses

ObjectiveTo evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration.Study designProspective, experimental, nonrandomized trial.AnimalsA total of 10 healthy adult warmblood horses.MethodsRomifidine (loading dose: 0.08 mg kg^–1, infusion: 0.03 mg kg^–1 hour^–1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic–pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested.ResultsA two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33).Conclusions and clinical relevanceRomifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration.     

A comparative study of xylazine-induced mechanical hypoalgesia in donkeys and horses

ObjectiveTo compare the effects of xylazine on mechanical nociceptive thresholds in donkeys and horses.Study designRandomized, controlled, crossover, Latin-square, operator-blinded design.AnimalsSix 3.1 ± 0.89 year old standard donkeys weighing 145.0 ± 30.5 kg and six 9.6 ± 4.4 year old Thoroughbred horses weighing 456.0 ± 69.0 kg.MethodsEach animal received one of four doses of xylazine (0.5, 0.7, 0.9, and 1.1 mg kg^?1), or acepromazine (0.05 mg kg^?1) or saline solution (0.9%) intravenously and mechanical nociceptive thresholds were assessed over 90 minutes. The areas under the threshold change versus time curve values for 60 minutes (AUC_0-60) post-drug administration were used to compare the effect of treatment. A 1-week interval was allowed between successive trials on each animal.ResultsAll doses of xylazine, but not acepromazine or saline, increased mechanical thresholds for up to 60 minutes. Xylazine-induced hypoalgesia was dose-dependent and corresponding AUC_0-60 values for each treatment were not significantly different between donkeys and horses (p≥ 0.0697).ConclusionThe hypoalgesic effects of xylazine at four different doses were not different between donkeys and horses.Clinical relevanceXylazine induced a similar degree of mechanical hypoalgesia in donkeys and horses suggesting that similar doses are needed for both species with regard to analgesia.     

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.     

Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses

Objective

To evaluate intravenous (IV) detomidine with methadone in horses to identify a combination which provides sedation and antinociception without adverse effects.

The anti-nociceptive and cardiopulmonary effects of extradural fentanyl–xylazine in sheep

Objective To compare the anti‐nociceptive effects of extradural xylazine, fentanyl and a xylazine–fentanyl combination in sheep, and to measure the cardiopulmonary effects of the xylazine–fentanyl combination. Study design Prospective, randomized study. Animals Twenty‐five half‐merino ewes 2–4 years of age and body mass 54.2 ± 1.1 kg. Methods Six sheep in group 1 received 0.2 mg kg^?1 xylazine by extradural injection, six in group 2 received fentanyl 1.5 µg kg^?1 and 13 in group 3 received the combination of both treatments. In all groups, drugs were mixed with saline (0.15 mL kg^?1 before injection). Pulmonary and carotid arterial catheters were placed in seven sheep of group 3 which were used to evaluate cardiopulmonary effects. Anti‐nociception was determined by the response to electrical stimulation (40 V for 1.5 milliseconds) of the left flank and by superficial and deep muscular ‘pinpricking’ stimulation of the pelvic and thoracic limbs and thoracolumbar region. Results Lack of response to electrical stimulation at the left flank was present in 10 ± 1.1 minutes (mean ± SEM) (group 1) and in 4.5 ± 0.5 minutes in group 3. The duration of lack of response to electrical stimulation at the left flank was 96 ± 6 minutes in group 1 and 315 ± 6 minutes in group 3. Responses persisted in group 3. Significant decreases (p < 0.05) in cardiac output 30, 45, 60 and 90 minutes after injection, and in cardiac work at 30 and 45 minutes were observed in the seven animals of group 3. Arterial blood pH was lowest at 90 minutes, arterial bicarbonate was lowest at 60 minutes and values for both arterial and mixed venous base excess increased significantly at 60 and 90 minutes. There was no significant change from baseline values in heart rate, mean arterial blood pressure, respiratory rate, body temperature, systemic vascular resistance, arterial and mixed venous PO₂, PCO₂, oxygen saturation, blood oxygen content, haemoglobin concentration, mixed venous blood bicarbonate and pH. Conclusions Fentanyl decreases the onset time and prolongs the duration of anti‐nociception produced by xylazine. The combination decreases cardiac output but is without significant respiratory effects. Clinical relevance Further studies are required to show that surgery is possible in sheep after extradural xylazine–fentanyl injection.     

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.     

Effects of selective α2‐adrenergic receptor agonists on electrical field‐stimulated contractions of isolated bronchi in horses

We investigated the effects of different selective α₂‐adrenergic receptor (AR ) agonists (detomidine, medetomidine, xylazine, and brimonidine) on the contractions of horse‐isolated bronchi induced by electrical field stimulation (EFS ) and by carbachol. No effects were observed on the contraction induced by carbachol, while α₂‐AR agonists reduced EFS ‐evoked contractions in a concentration‐related fashion. The rank order of potency (pD ₂) was brimonidine (7.40 ± 0.20) >medetomidine (7.09 ± 0.24) >detomidine (6.13 ± 0.55) >xylazine (4.59 ± 0.16). The maximal effects (E_max) were ?56.3% ± 6.3%, ?40.4% ± 6.9%, ?48.6% ± 9.9%, and ?72.7% ± 12.7% for brimonidine, medetomidine, detomidine, and xylazine, respectively. Adrenergic block by guanethidine enhanced the potency (8.10 ± 0.05, 7.30 ± 0.15, 6.83 ± 0.41, and 5.40 ± 0.22) and the efficacy (?95.2% ± 0.7%, ?45.2% ± 11.7%, ?58.5% ± 9.8%, and ?97.9% ± 0.6%) of brimonidine, medetomidine, detomidine, and xylazine, respectively. Selective α₂‐AR antagonist, atipamezole, competitively antagonized the inhibition of EFS ‐evoked contractions induced by all agonists except xylazine. These results suggest the existence of presynaptic α₂‐AR s on cholinergic neurons, negatively regulating the release of acetylcholine in horse bronchial muscle, and that α₂‐AR agonists may be beneficial against vagally mediated bronchoconstriction.     

Effects of Intravenous Detomidine on Schirmer Tear Test Results in Clinically Normal Horses

This study was conducted to determine the effects of intravenous detomidine on Schirmer tear test (STT) results in clinically normal horses. Eighteen adult horses were randomly divided into two groups of nine horses each. The treatment group was sedated with intravenous detomidine alone (20 μg/kg), and the control group received only intravenous saline (0.2 mL/100 kg). Schirmer tear test was performed just before intravenous administration of detomidine or saline in treatment and control groups, respectively. Schirmer tear tests were repeated 5, 20, 60, and 120 minutes later. Horses enrolled in this study consisted of nine males and nine females. Breeds were Arabian and Hanoverian, ranging from 3 to 6 years in age. In the treatment group, the pretreatment and subsequent posttreatment mean ± standard deviation values were 17.0 ± 6.9 (0 minutes), 11.8 ± 2.9 (5 minutes), 12.1 ± 2.0 (20 minutes), 12.1 ± 3.1 (60 minutes), and 15.0 ± 2.8 (120 minutes) mm wetting/min. In this group of horses, a significant reduction was observed in STT values at 5, 20, and 60 minutes after treatment with detomidine hydrochloride in comparison to the pretreatment values (analysis of variance with post hoc testing; P₅ = 0.004, P₂₀ = 0.007, P₆₀ = 0.006). There was no significant difference between baseline values and posttreatment values in the control saline group (P ≥ .08). We conclude that intravenous detomidine causes a significant reduction in STT values in clinically normal horses. In horses, practitioners should measure STT values before intravenous administration of detomidine to accurately assess the results.     

Evaluation of intramuscular anesthetic protocols in healthy domestic horses

ObjectiveTo assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses.Study designRandomized, blinded, three-way crossover prospective design.AnimalsA total of eight healthy adult horses weighing 470–575 kg.MethodsHorses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine–zolazepam (1.2 mg kg⁻¹), ketamine (1 mg kg⁻¹) and detomidine (0.04 mg kg⁻¹) (treatment TKD); ketamine (3 mg kg⁻¹) and detomidine (0.04 mg kg⁻¹) (treatment KD); and tiletamine–zolazepam (2.4 mg kg⁻¹) and detomidine (0.04 mg kg⁻¹) (treatment TD). Parametric data were analyzed using mixed model linear regression. Nonparametric data were compared using Skillings–Mack test. A p value <0.05 was considered statistically significant.ResultsAll horses in treatment TD became recumbent. In treatments KD and TKD, one horse remained standing. PaO₂ 15 minutes after recumbency was significantly lower in treatments TD (p < 0.0005) and TKD (p = 0.001) than in treatment KD. Times to first movement (25 ± 15 minutes) and sternal recumbency (55 ± 11 minutes) in treatment KD were faster than in treatments TD (57 ± 17 and 76 ± 19 minutes; p < 0.0005, p = 0.001) and TKD (45 ± 18 and 73 ± 31 minutes; p = 0.005, p = 0.021). There were no differences in induction quality, muscle relaxation score, number of attempts to stand or recovery quality.Conclusions and clinical relevanceIn domestic horses, IM injections of tiletamine–zolazepam–detomidine resulted in more reliable recumbency with a longer duration when compared with ketamine–detomidine and tiletamine–zolazepam–ketamine–detomidine. Recoveries were comparable among protocols.     

The comparative hypoxaemic effect of four α2 adrenoceptor agonists (xylazine, romifidine, detomidine and medetomidine) in sheep

In the present study, the hypoxaemic potential of four α₂ agonists possessing different selectivity for α₂ adrenoceptors and of a saline placebo was studied in five clinically healthy sheep using a randomized Latin square design and equipotent sedative doses. Baseline values for heart rate (HR), mean arterial pressure (MAP), arterial oxygen (PaO₂) and carbon dioxide (PaCO₂) tensions, respiration rate and maximum change in pleural pressure (ΔPpl) were obtained, followed by the intravenous administration of either: xylazine (150 μg/kg); romifidine (50 μg/kg); detomidine (30 μg/kg); medetomidine (10 μg/kg) or placebo. Subsequent recordings were made up to 60 min after drug administration. No significant (P 0.05) alterations in any variable occurred with placebo. All the α₂ agonists significantly (P 0.05) decreased PaO₂ levels without a significant (P 0.05) change in PaCO₂. The lowest PaO₂ values were 29–42 mm Hg (3.9–5.5 kPa) with no significant difference between drugs. Respiratory rate and ΔPpl increased significantly within 2 min of drug administration; the duration of this effect varied with the α₂ agonist, lasting longest with romifidine. As compared to the saline treated group, a significant increase in MAP was observed up to 10 min after administration of romifidine and detomidine, however, a significant decrease was seen at 10 and 45 min after xylazine and medetomidine, respectively. The α₂ agonists studied induced a similar change in PaO₂ at peak effect, despite their reported variable selectivity for α₂ vs. α₁ adrenoceptors.     

Antinociceptive and Behavioral Effects of Methadone Alone or in Combination with Detomidine in Conscious Horses

The antinociceptive and behavioral effects of methadone (MET) alone or combined with detomidine (DET) were studied in horses. Intravenous treatments were randomly administered in a two-phase crossover study. In phase 1, six horses were treated with saline (control) or 0.2 or 0.5 mg/kg methadone (MET_0.2; MET_0.5, respectively). In phase 2, six horses were treated with 0.01 mg/kg DET alone or with DET combined with 0.2 mg/kg MET (DET/MET_0.2). Thermal nociceptive threshold (TNT) and electrical nociceptive thresholds (ENT) were recorded by using a heat projection lamp and electrodes placed in the coronary band of the thoracic limbs, respectively. Spontaneous locomotor activity (SLA) was studied by movement sensors in the stall (phase 1). Chin-to-floor distance was assessed in phase 2. In phase 1, the TNT increased significantly for 30 minute after MET_0.5 but not after saline or MET_0.2. Hyperesthesia and ataxia were observed in 2 of 6 and 6 of 6 horses after MET_0.2 and MET_0.5, respectively. SLA increased significantly for 120 minutes after MET in a dose-dependent way, but not after placebo. In phase 2, DET and DET/MET_0.2 significantly increased the TNT and ENT above baseline for 15 and 30 minutes, respectively; thresholds were significantly higher with DET/MET_0.2 than with DET at the same times. Chin-to-floor distance decreased significantly from baseline for 30 minutes, and no excitatory behavior was observed in both treatments. Although the higher dose of MET induced short-acting antinociception, the associated adverse effects may contraindicate its clinical use. The lower dose of MET potentiated DET-induced antinociception without adverse effects, which might be useful under clinical circumstances.     

Electrocardiographic and cardiopulmonary effects of intramuscular administration of glycopyrrolate and romifidine in conscious beagle dogs

Objective To determine the electrocardiographic and cardiopulmonary effects of IM administration of romifidine with and without prior administration of glycopyrrolate in conscious dogs. Study design Prospective randomized study. Animals Twelve healthy, adult beagles. Materials and methods Dogs were assigned at random to each of three treatments with glycopyrrolate (six dogs), and to each of three treatments without glycopyrrolate (six dogs). Baseline data were recorded, and saline solution or glycopyrrolate (10 µg kg^–1) was given IM. After 15 minutes, saline solution (control) or romifidine (20 or 40 µg kg^–1) was given IM. An ECG, heart rate (HR), systemic blood pressures, and respiratory rate (RR) were recorded before and 2.5, 5, 10, 15, 30, 45, 60, 75, 90, 105 and 120 minutes after romifidine administration. Rectal temperature (RT), pH, PaCO₂, PaO₂, hematocrit and plasma protein were determined before and 15, 30, 60 and 120 minutes after romifidine administration. Data were analyzed using analysis of variance for repeated measures and Tukey multiple comparison tests. Results Without glycopyrrolate, HR (beats minute^–1) decreased to minimum values (mean ± SD) of 52 ± 7 and 49 ± 12 (control 89 ± 20) 45 minutes after administration of romifidine at doses of 20 and 40 µg kg^–1, respectively. Sinus bradycardia (HR < 60 beats minute^–1), which persisted for up to 120 minutes, was observed in five of six and six of six dogs given romifidine at doses of 20 and 40 µg kg^–1, respectively. With glycopyrrolate, decreases in HR were prevented and mean arterial pressure (mm Hg) increased to maximum values of 139 ± 25 and 173 ± 17 (control 113 ± 11) 30 minutes after administration of romifidine at doses of 20 and 40 µg kg^–1, respectively. With and without glycopyrrolate, RR did not change appreciably, RT decreased, and pH, PaCO₂, PaO₂, hematocrit and plasma protein did not change after administration of romifidine. Conclusions and clinical relevance In healthy conscious beagles, IM administration of romifidine at doses of 20 and 40 µg kg^–1 causes sinus bradycardia which persists for up to 120 minutes. Administration of glycopyrrolate 15 minutes before administration of romifidine, prevents sinus bradycardia and induces moderate increases in arterial pressure.     

Antinociceptive,physiologic and biochemical effects of electroacupuncture combined with xylazine in hybrid goats

ObjectiveTo elucidate the antinociceptive, physiologic and biochemical effects of electroacupuncture (EA) and xylazine in hybrid goats.Study designProspective experimental study.AnimalsA total of 30 female hybrid goats aged 1–2 years and weighing 25 ± 2.9 kg (mean ± standard deviation).MethodsThe goats were divided into five groups and administered xylazine (0.1 mg kg⁻¹; group XYL.1), xylazine (0.3 mg kg⁻¹; group XYL.3), EA (group EA), EA + xylazine (0.1 mg kg⁻¹; group XYL.1-EA) and 0.9% saline (0.3 mL; control group CON). Nociceptive threshold and serum glucose concentration were measured at time 0 and at 15, 30, 45, 60 minutes and 24 hours after treatment. Nociceptive threshold was measured by passing potassium ions through the skin using potassium iontophoresis. Mean arterial pressure (MAP), heart rate (HR), respiratory frequency (f_R) and rectal temperature (RT) were recorded at times 0 and at 5, 10, 15, 20, 30, 45, 60 minutes and 24 hours. Repeated-measures analyses were performed for each response variable; p < 0.05 was considered significant for all analyses.ResultsAntinociceptive effects in groups XYL.1 and XYL.3 were increased significantly at 15–60 minutes compared with group CON. Antinociceptive effect was higher in group XYL.1-EA than groups XYL.1 or EA at 15–60 minutes (p < 0.05). No significant difference in the nociceptive threshold was recorded in groups XYL.1-EA and XYL.3, except at 30 minutes. HR, MAP, f_R, RT values were higher in group XYL.1-EA than in groups XYL.1 or XYL.3. Serum glucose concentration was higher in group XYL.3 at 15–60 minutes than in CON.Conclusions and clinical relevanceThe XYL.1 and EA combination was effective for antinociception with minimum physiologic alteration, suggesting that the combination may be a new and effective strategy for pain relief during clinical procedures in goats.     

Antinociceptive effect of intrathecally applied alpha2 agonists (xylazine and detomidine) in sheep and the response to atipamezole

This study evaluated the antinociceptive and physiologic effects of xylazine (X) and detomidine (D) administered intrathecally (IT) at the lumbosacral space, before and after the injection of atipamezole (A) IV. The study was approved by the National Animal Protection Authorities. Five adult healthy female sheep were anaesthetized with propofol on four occasions to inject the following treatments IT: groups 1 and 2, 0.05 mg kg^?1 X (2 mg mL^?1 saline) IT; groups 3 and 4, 0.01 mg kg^?1 D (0.5 mg mL^?1 saline) IT ( Waterman et al. 1988 ). Nociceptive threshold (TH) was tested by applying pulsed and stepwise enhanced direct current ( Ludbrook et al. 1995 ) at one hind leg pastern and noting the current at the moment of foot lift. Maximum current applied was 40 mA. Baseline TH was measured twice before anaesthesia and every 10 minutes when the sheep regained consciousness. Atipamezole was given IV immediately after reaching maximum analgesic action of X and D as defined by two equal or decreasing TH values and measurements were continued for 90 minutes. The dose of A for groups 1 and 3 was 0.005 mg kg^?1 (0.25 mg mL^?1 saline) IV, and for groups 2 and 4 was 0.0025 mg kg^?1 A (0.25 mg mL^?1 saline) IV. Heart rate (HR), mean direct arterial pressure (MAP), PaO₂ and PaCO₂ were measured. The differences between measurements recorded before and after treatment were analysed using a paired t‐test for the drug effects and a nonparametric Wilcoxon's rank sum test for the comparison between groups. A p‐value < 0.05 was considered significant. All sheep were able to stand before A IV. Threshold baseline value was 4.5 ± 1.7 (mean ± SD) mA for all animals. Xylazine caused a significantly higher TH rise (35.2 ± 1.8 mA), faster onset (21.1 ± 16.0 minutes) and longer duration of the TH enhancement (104.1 ± 8.6 minutes) than D (TH: 16.3 ± 7.8 mA, onset: 49.5 ± 28.4 minutes, duration: 59.3 ± 27.3 minutes). A significant increase in PaCO₂ was observed in the X and D treated animals, 0.39 ± 0.21 kPa (2.9 ± 1.6 mm Hg) and 0.39 ± 0.29 kPa (2.9 ± 2.2 mm Hg), respectively. Heart rate was significantly decreased by ?21 ± 17 beats minute^?1 for X animals and ?13 ± 13 beats minute^?1 for D. Mean arterial pressure (?9 ± 13 mm Hg for X and ?1 ± 11 mm Hg for D animals) and PaO₂ 0.65 ± 1.32 kPa (4.9 ± 9.9 mm Hg) for X and 1.45 ± 4.19 kPa (10.9 ± 31.4 mm Hg) for D animals) did not change significantly. The nociceptive threshold was not affected by A in any group. Threshold values of all X treated animals before A was 39.3 ± 1.4 mA and after was 37.2 ± 6.3 (group 1) and 40 ± 0 (group 2). Threshold values of all D treated animals before A was 21.0 ± 8.3 and after was 19.4 ± 7.3 (group 3) and 24.8 ± 8.0 (group 4). At the dosages administered intrathecally in this study, X and to a lower degree D induce antinociception without major physiologic changes. Atipamezole up to 0.005 mg kg^?1 IV does not affect the resulting antinociception as assessed by electrical stimulation.     

A comparison of two intramuscular doses of xylazine–ketamine combination and tolazoline reversal in llamas

The anesthetic and cardiorespiratory effects of a low dose (LD, 0.4 mg kg^?1 xylazine and 4 mg kg^?1 ketamine) and a high dose (HD, 0.8 mg kg^?1 xylazine and 8 mg kg^?1 ketamine) of IM xylazine–ketamine combination were compared in a randomized cross‐over study using six castrated male llamas. Three llamas in each dosage group (LDT, HDT) were assigned to receive IM tolazoline (2 mg kg^?1) after 30 minutes of recumbency. All IM injections were given in the semitendinosus or semimembranosus muscles. Pulse, respiratory rate, and indirect arterial blood pressure were recorded every 10 minutes, and hemoglobin oxygen saturation was recorded every 5 minutes during lateral recumbency. Samples for arterial blood gas analysis were collected 5 minutes following recumbency and every 30 minutes thereafter. Base‐to‐apex ECG was monitored continuously. Analgesia was evaluated every 5 minutes by both a 30 minutes skin pinch and a needle prick of the toe. Most llamas breathed room air throughout anesthesia. Two llamas that developed severe hypoxemia (SpO₂ < 75%) received 5 minutes of nasal oxygen insufflation, but were maintained on room air for the rest of the anesthetic period. anova for repeated measures and Tukey's test were used to analyze cardiorespiratory data. Fischer's exact test was used to compare the ability of each to provide >30 minutes of lateral recumbency and analgesia. A p‐value < 0.05 was considered significant. Both dosages provided reasonably rapid induction following injection (LD: 10.8 ± 6.3 minutes; HD: 5.0 ± 1.1 minutes; p = 0.07). Duration of lateral recumbency and analgesia were 34.7 ± 6.7 and 27.3 ± 4.6 minutes, respectively, in the LDT llamas. None of the three remaining LD llamas remained in lateral recumbency for longer than 12 minutes. Duration of lateral recumbency and analgesia were 87.3 ± 18.5 and 67.7 ± 16.0 minutes, respectively, for the HD llamas that did not receive tolazoline. The HDT llamas were recumbent for a significantly shorter time (43.3 ± 0.6 minutes; p = 0.05). The ability to provide >30 minutes of recumbency and analgesia was better in the HD group (6/6) than in the LD group (2/6) (p = 0.03). No differences between dosages were seen in pulse rate, respiratory rate, or arterial pressures. No ECG abnormalities were seen. Transient hypoxemia was seen in the first 10 minutes of lateral recumbency in the HD group by both hemoglobin oxygen saturation (84 ± 9.5%) and by blood gas PaO₂ (44.5 ± 5.8 mm Hg). It was concluded that the HD provided more consistent results than the LD, but induced transient hypoxemia. Tolazoline shortened the recovery time in llamas receiving the HD.     

Effect of detomidine or romifidine constant rate infusion on plasma lactate concentration and inhalant requirements during isoflurane anaesthesia in horses

Objective

Influence of detomidine or romifidine constant rate infusion (CRI) on plasma lactate concentration and isoflurane requirements in horses undergoing elective surgery.

Evaluation of different doses of propofol in xylazine pre-medicated horses

Objective To characterize responses to different doses of propofol in horses pre‐medicated with xylazine. Animals Six adult horses (five females and one male). Methods Each horse was anaesthetized four times with either ketamine or propofol in random order at 1‐week intervals. Horses were pre‐medicated with xylazine (1.1 mg kg^?1 IV over a minute), and 5 minutes later anaesthesia was induced with either ketamine (2.2 mg kg^?1 IV) or propofol (1, 2 and 4 mg kg^?1 IV; low, medium and high doses, respectively). Data were collected continuously (electrocardiogram) or after xylazine administration and at 5, 10 and 15 minutes after anaesthetic induction (arterial pressure, respiratory rate, pH, PaO₂, PaCO₂ and O₂ saturation). Anaesthetic induction and recovery were qualitatively and quantitatively assessed. Results Differences in the quality of anaesthesia were observed; the low dose of propofol resulted in a poorer anaesthetic induction that was insufficient to allow intubation, whereas the high dose produced an excellent quality of induction, free of excitement. Recorded anaesthesia times were similar between propofol at 2 mg kg^?1 and ketamine with prolonged and shorter recovery times after the high and low dose of propofol, respectively (p < 0.05; ketamine, 38 ± 7 minutes; propofol 1 mg kg^?1, 29 ± 4 minutes; propofol 2 mg kg^?1, 37 ± 5 minutes; propofol 4 mg kg^?1, 50 ± 7 minutes). Times to regain sternal and standing position were longest with the highest dose of propofol (32 ± 5 and 39 ± 7 minutes, respectively). Both ketamine and propofol reversed bradycardia, sinoatrial, and atrioventricular blocks produced by xylazine. There were no significant alterations in blood pressure but respiratory rate, and PaO₂ and O₂ saturation were significantly decreased in all groups (p < 0.05). Conclusion The anaesthetic quality produced by the three propofol doses varied; the most desirable effects, which were comparable to those of ketamine, were produced by 2 mg kg^?1 propofol.     

Does the induction agent affect the course of halothane anaesthesia in horses?

Four hundred and ninety horses were anaesthetised with halothane for clinical surgical or diagnostic procedures following induction with either detomidine/keta-mine, detomidine/thiopentone, xylazine/ketamine or guaiphenesin/thiopentone. Routine clinical monitoring was performed during anaesthesia. All horses developed hypotension (mean arterial pressures below 80 mm Hg) and respiratory depression (significant fall in respiratory rate and arterial carbon dioxide tension above 7 kPa (53 mm Hg)) consistent with the recognised effects of halothane. All anaesthetic procedures incorporating xylazine or detomidine resulted in lower pulse rates (28–35 per min) than after guaiphenesin/thiopentone (36–44 per min) and there was greater respiratory depression after techniques employing thiopentone rather than keta-mine. Development of hypotension was delayed after techniques using the α₂ adrenoceptor agonist agents (xylazine and detomidine), particularly detomidine. Prernedication with acepromazine did not affect any of the physiological variables measured after techniques employing detomidine. Recovery to standing was fastest after xylazine/ketamine (31±1 min) and slowest after detomidine/thiopentone (53±2 min). Recovery quality was best after detomidine/thiopentone and all techniques employing an α₂ adrenoceptor agonist agent resulted in smoother recovery than after guaiphenesin/thiopentone. This study demonstrates that most of the physiological effects of individual induction agents are overridden by the cardiovascular and respiratory depressant effects of halothane. The study also shows that detomidine is an acceptable sedative for use before general anaesthesia with halothane in horses.     

The effects of a loading dose followed by constant rate infusion of xylazine compared with romifidine on sedation,ataxia and response to stimuli in horses

ObjectiveTo compare xylazine and romifidine constant rate infusion (CRI) protocols regarding degree of sedation, and effects on postural instability (PI), ataxia during motion (A) and reaction to different stimuli.Study designBlinded randomized experimental cross-over study.AnimalsTen adult horses.MethodsDegree of sedation was assessed by head height above ground (HHAG). Effects on PI, A and reaction to visual, tactile and acoustic stimulation were assessed by numerical rating scale (NRS) and by visual analogue scale (VAS). After baseline measurements, horses were sedated by intravenous loading doses of xylazine (1 mg kg^?1) or romifidine (80 μg kg^?1) administered over 3 minutes, immediately followed by a CRI of xylazine (0.69 mg kg^?1 hour^?1) or romifidine (30 μg kg^?1 hour^?1) which was administered for 120 minutes. Degree of sedation, PI, A and reaction to the different stimuli were measured at different time points before, during and for one hour after discontinuing drug administration. Data were analysed using two-way repeated measures anova, a Generalized Linear Model and a Wilcoxon Signed Rank Test (p < 0.05).ResultsSignificant changes over time were seen for all variables. With xylazine HHAG was significantly lower 10 minutes after the loading dose, and higher at 150 and 180 minutes (i.e. after CRI cessation) compared to romifidine. Reaction to acoustic stimulation was significantly more pronounced with xylazine. Reaction to visual stimulation was greater with xylazine at 145 and 175 minutes. PI was consistently but not significantly greater with xylazine during the first 30 minutes. Reaction to touch and A did not differ between treatments. Compared to romifidine, horses were more responsive to metallic noise with xylazine.ConclusionsTime to maximal sedation and to recovery were longer with romifidine than with xylazine.Clinical relevanceWith romifidine sufficient time should be allowed for complete sedation before manipulation.