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.     

Effects of Intravenous Detomidine on Intraocular Pressure Readings Obtained by Applanation Tonometry in Clinically Normal Horses

This study was conducted to determine effects of intravenous detomidine on intraocular pressure (IOP) readings obtained by applanation tonometry in clinically normal horses. Twenty horses were randomly divided into two groups of 10 each (treatment and control). All horses in the treatment group received intravenous detomidine alone (20 μg/kg). The horses in the control group received only intravenous saline (0.2 mL/100 kg). The IOP values were measured before the treatment (T₀) and then at 5 (T₅), 20 (T₂₀), 60 (T₆₀), and 120 (T₁₂₀) minutes after drug administration in both groups. A significant decrease in IOP values was observed in both right and left eyes of the horses in the treatment group at T₅, T₂₀, and T₆₀ in comparison with the baseline values (P < .001). The observed decrease was only statistically significant in the right eyes of the treatment group horses at T₁₂₀ (P = .044). Mean IOP was not significantly altered at any time point during the treatment period compared with the baseline evaluations in both eyes of the horses in the control group. This study demonstrates that the use of intravenous detomidine lowers IOP quickly.     

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.     

Sedation and Pain Management with Intravenous Romifidine−Butorphanol in Standing Horses

The objective of this study was to determine the sedation, analgesia, and clinical reactions induced by an intravenous combination of romifidine and butorphanol in horses. The study was conducted on six saddle horses weighing 382 to 513 kg (mean ± SD; 449 ± 54 kg) and aged 6 to 14 years. The horses each underwent three treatments: intravenous romifidine 0.1 mg/kg body weight (RM; mean dose, 4.5 mL); intravenous butorphanol 0.05 mg/kg body weight (BT; mean dose, 2.4 mL); and intravenous romifidine 0.1 mg/kg body weight plus butorphanol 0.05 mg/kg body weight (RMBT; mean dose, 7.0 mL). The order of treatments was randomized. Heart rate, arterial pressure, respiratory rate, rectal temperature, sedation, and analgesia were measured at two times before treatments, 15 minutes apart (times –15 and 0) and at 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, and 180 minutes after drug administration. The onset of sedation was approximately 5 minutes after intravenous injection of RM and RMBT, whereas BT did not present this effect. The duration of complete sedation was approximately 60 minutes for RMBT and approximately 35 minutes for RM. The RMBT treatment provided 30 minutes and the RM treatment 20 minutes of complete analgesia. Heart rate decreased significantly (P < .05) from basal values in the RM and RMBT treatments. Only RM caused significant decreases (P < .05) in the respiratory rate. Arterial pressure did not change significantly (P > .05) in any treatment. Intravenous administration of a romifidine−butorphanol combination to horses resulted in longer duration of sedation and analgesia than administration of romifidine or butorphanol alone. These effects probably resulted from a synergistic effect of the two drugs.     

Evaluation of Echocardiographic Parameters During Increasing Infusion Rates of Dobutamine in Isoflurane-Anesthetized Horses

The purpose of this study was to evaluate changes in echocardiographic parameters during increasing infusion rates of dobutamine in isoflurane-anesthetized horses and to compare our results with those of previous studies. Six Standardbred female healthy horses were included in this study. All animals were anesthetized and infused with dobutamine at different rates. mean arterial pressure (MAP), heart rate (HR), and some echocardiographic measurements were recorded. Statistical analysis was applied. Under basal conditions (time 0 [T0]), HR ranged between 32 and 42 beats per minute (bpm), and MAP was between 39 and 63 mm Hg. MAP increased significantly from T0 compared with values at T2, T2, and T3 in a dose-dependent manner, while HR increased significantly only at T3 if compared to the other measuring times. Left ventricular internal diameter during diastole (LVDs) decreased significantly in a dose-dependent manner, with increasing of the infusion rate of dobutamine. Interventricular septal dimension during diastole (IVSs) increased significantly, and end-systole left ventricular volumes (LVVols) decreased significantly at T2 and T3 compared to T1. Ejection fraction (%) increased significantly between T0 and T1, T2, and T3. Cardiac output increased significantly only at the higher dosage (T3 vs. others) of dobutamine, but cardiac power output was enhanced significantly at T2 versus that at T0 and T1 and at T3 versus all the previous measurements. Arrhythmias were diagnosed in 5 of 6 (83.3%). In this study, the increase of MAP was found to be dose-dependent, according with literature. The HR and MAP values registered at T0 were comparable to previous results obtained both in anesthetized and conscious horses, while at T1, T2, and T3, HR and MAP values were similar only too those reported in anesthetized horses. IVSs increased and LVDs decreased significantly with the increment of dobutamine infusion rate. These findings suggest that dobutamine, even at low infusion rates, induces an enhancement in cardiac systolic function. The dose-dependent increase of IVSs and decrease of LVDs measurements are in line with those reported for dobutamine administered in conscious horses but with lower values. The LVVols dose-dependent reduction obtained in this study is in line with that in other reports, but both LVold and LVVols values after dobutamine infusion at different dosages are lower if compared to previous studies. The low LVol values and the wide standard deviation have influenced consequently the derived indices values (stroke volume [SV], EF, cardiac output [CO]). In the present study, SV did not significantly increase during dobutamine infusion. These results disagree with those reported by others. The increment of CO might be due mainly to the enhanced HR rather than to the weak changes of SV. Cardiac power output increased significantly from the 5 mcg/kg/min dosage in a dose-dependent manner, as reported by others.     

Hyperthermia and Delayed-Onset Myopathy after Recovery from Anesthesia in a Horse

A 13-year old Thoroughbred cross gelding (528 kg) underwent lameness investigation. Because of his temperament, general anesthesia was required to facilitate ultrasound of the left fore fetlock and intra-articular medication of three joints. Anesthesia was induced with ketamine/diazepam after acepromazine/detomidine premedication. Anesthesia was maintained for 40 minutes with a guaifenesin/detomidine/ketamine intravenous infusion. Recovery from anesthesia was initially uneventful, although of a moderate duration (70 minutes). Once standing, the horse proceeded to box walk in an agitated state and became recumbent on two occasions. The horse was manually restrained, at which time its rectal temperature was 41.8°C. Cooling measures were employed (fans, ice-water enemas, wet rugs, intravenous fluid therapy (IVFT), and topical application of surgical spirit) until rectal temperature reached 38.7°C. IVFT was continued for a further 16 hours. Four days after recovery from anesthesia, bilateral triceps, deltoideus, trapezius, and rhomboideus muscle swelling was observed. Blood creatinine kinase was elevated (24,898 IU/L). Treatment for postanesthetic myopathy was initiated (hot packing of the muscle groups, topical dimethylsulfoxide [DMSO] cream application, and oral phenylbutazone). Myoglobinuria was not observed at any time. Muscle swelling decreased over the following 3 days. The horse was discharged on day 11 and has since returned to work.     

Effect of Recovery Periods during Conditioning of Horses on Fitness Parameters

The effect of recovery from training has not been studied in horses. Therefore, the effect of recovery was examined with exercise of known effect within a conditioning period (CP). A standardized exercise test was performed at the beginning of CP to determine v₄, v₁₀, and v₁₈₀ (horse’s speed, which produced a blood lactate concentration of 4 and 10 mmol/L and a heart rate of 180 beats/min). Six horses were conditioned for three periods of 2 weeks, 5 times per fortnight at their individual v₁₀ for two bouts of 5 minutes on a treadmill. Every 2 weeks of conditioning was followed by 1 week with reduced workload. Standardized exercise test was repeated after each 2 weeks of conditioning and 2 weeks after finishing CP. Exercise speed was individually adapted to the new v₁₀ for every 2 weeks of conditioning. In addition, peak oxygen consumption before, after 3 weeks of conditioning, and at the end of the CP was measured. The mean v₄ increased steadily during CP. v₁₈₀ did not change, whereas peak oxygen consumption increased between the beginning and after 3 weeks of conditioning and leveled off thereafter. In conclusion, reducing the workload for 1 week after 2 weeks of conditioning 5 times per fortnight at v₁₀ for two bouts of 5 minutes allowed for a continuous increase of v₄, but the extent of the increase was smaller than in another study with a similar conditioning program but for the recovery week. The effect of recovery from training needs further studies.     

Serum Concentrations of Lidocaine and Its Metabolites MEGX and GX During and After Prolonged Intravenous Infusion of Lidocaine in Horses after Colic Surgery

Lidocaine is the most commonly used prokinetic after gastrointestinal surgery in horses. Cardiovascular status, hepatic function, and duration of therapy are the primary determinants of lidocaine metabolism, and these factors could affect equine patients after colic surgery. This study examined the systemic concentrations of lidocaine and its active metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in horses that had undergone colic surgery and subsequently received prolonged postoperative lidocaine infusions. The mean lidocaine concentration increased over the course of treatment but did not exceed the therapeutic range. Concentrations of MEGX and GX increased progressively, and concentrations exceeding 1,000 ng/ml were observed frequently after 72 hours of infusion. None of the horses in the study developed severe signs of toxicity; however, the progressively increasing concentrations of lidocaine, MEGX, and GX are cause for concern in clinically ill patients receiving prolonged lidocaine therapy. The potential contribution of MEGX and GX should be considered when evaluating adverse reactions to prolonged lidocaine infusions.     

Recovery From Sevoflurane Anesthesia in Horses: Comparison to Isoflurane and Effect of Postmedication With Xylazine

Objective—To compare recovery from sevoflurane or isoflurane anesthesia in horses. Study Design—Prospective, randomized cross-over design. Animals—Nine Arabian horses (3 mares, 3 geldings, and 3 stallions) weighing 318 to 409 kg, 4 to 20 years old. Methods—Horses were anesthetized on three occasions with xylazine (1.1 mg/kg), Diazepam (0.03 mg/kg intravenously [IV]), and ketamine (2.2 mg/kg IV). After intubation, they were maintained with isoflurane or sevoflurane for 90 minutes. On a third occasion, horses were maintained with sevoflurane and given xylazine (0.1 mg/kg IV) when the vaporizer was turned off. Horses were not assisted in recovery and all recoveries were videotaped. Time to extubation, first movement, sternal, and standing were recorded as was the number of attempts required to stand. Recoveries were scored on a 1 to 6 scoring system (1 = best, 6 = worst) by the investigators, and by three evaluators who were blinded to the treatments the horses received. These blinded evaluators assessed the degree of ataxia present at 10 minutes after each horse stood, and recorded the time at which they judged the horse to be ready to leave the recovery stall. Results—Mean times (± SD) to extubation, first movement, sternal, and standing were 4.1 (1.7), 6.7 (1.9), 12.6 (4.6), and 17.4 (7.2) minutes with isoflurane; 3.4 (0.8), 6.6 (3.1), 10.3 (3.1), and 13.9 (3.0) minutes with sevoflurane; and 4.0 (1.2), 9.1 (3.3), 13.8 (6.5), and 18.0 (7.1) with sevoflurane followed by xylazine. Horses required a mean number of 4 (2.3), 2 (0.9), and 2 (1.6) attempts to stand with isoflurane, sevoflurane, and sevoflurane followed by xylazine respectively. The mean recovery score (SD) for isoflurane was 2.9 (1.2) from investigators and 2.4 (1.1) from blinded evaluators. For sevoflurane, the mean recovery score was 1.7 (0.9) from investigators and 1.9 (1.1) from evaluators, whereas the recoveries from sevoflurane with xylazine treatment were scored as 1.7 (1.2) from investigators and 1.7 (1.0) from blinded evaluators. Conclusions—Recoveries appeared to vary widely from horse to horse, but were significantly shorter with sevoflurane than isoflurane, although sevoflurane followed by xylazine was no different from isoflurane. Under the conditions of the study, recoveries from sevoflurane and sevoflurane followed by xylazine were of better quality than those from isoflurane. Clinical Relevance—Sevoflurane anesthesia in horses may contribute to a shorter, safer recovery from anesthesia.     

Analysis of Behaviors Observed During Mechanical Nociceptive Threshold Testing in Donkeys and Horses

The aims of the study were to analyze and compare behaviors in horses and donkeys observed during nociceptive threshold tests with a mechanical stimulus applied to the limb. The purpose was to identify end point behaviors suggesting the animals had perceived the stimulus to be noxious. Six male castrated horses (aged 3–4 years, weighing 415–503 kg) and eight castrated male donkeys (aged 4–9 years, weighing 152.5–170.5 kg) were studied. Video data recorded during mechanical nociceptive threshold test were analyzed by a single observer. Behaviors were classified into short-duration event behaviors and longer duration activity/state behaviors. Frequency of behaviors within a test (event behaviors) and percentage time spent during the test (activity/state behaviors) were calculated. Data were compared between horses and donkeys using Mann–Whitney tests (nonparametric data) or t-test (parametric data). Significance was taken as P < .05. Behaviors during the tests were observed which could indicate the animals perceived the stimulus as noxious. These included flattening ears back against the head, and turning the head (horses) and chewing (donkeys) although these were not consistent across both species. Foot lifts were often preceded by other behaviors which suggests that the foot lift was not purely a reflex withdrawal response. A shift in weight toward the contralateral limb was a consistent prodromal sign for an end point foot lift.     

Pharmacokinetics and Effects of Alkalization During Oral and Intravenous Administration of Naproxen in Horses

The use of suitable therapeutic protocols is particularly important when extra-label drugs are used or when physiological parameters are modified, as in the case of the administration of alkaline substances to racehorses. The pharmacokinetics of naproxen (NAP), after both intravenous (iv) and oral administration of 10 mg/kg body weight (BW), was investigated in horses under normal metabolic conditions and in horses whose conditions were modified by the iv administration of 250 mg/kg BW of sodium bicarbonate (NaHCO₃). The hypothesis that blood and consequent urinary alkalization could modify NAP pharmacokinetics was evaluated. Drug quantification was performed on serum and urine using High Performance Liquid Chromatography (HPLC) with ultraviolet-visible detection. Results were also integrated with cycloxygenase (COX)-inhibition published data to suggest an appropriate schedule for NAP dosage in horses. After iv administration, NAP was rapidly distributed (t_1/2α: 0.71 ± 0.43 iv NaHCO₃ and 0.55 ± 0.62 hours No NaHCO₃), whereas its elimination was quite slow (t_1/2β: 6.74 ± 0.41 hours), particularly in iv NaHCO₃ animals (t_1/2β: 8.95 ± 1.37 hours). After oral treatments, NAP was more rapidly absorbed and elimination was slower in iv NaHCO₃ animals (t_1/2λ_z: 17.50 ± 6.66 vs. 7.17 ± 0.91 hours). The oral bioavailability of NAP was approximately 87% and 77% in No NaHCO₃ and iv NaHCO₃, respectively. Urinary excretion of the drug as a parent compound was low. The alkalization procedure did not anticipate the elimination of the acidic drug as expected, but it also influenced the absorption of the drug that was administered orally. The dosage scheme of 10 mg/kg BW iv or orally seems to be appropriate to produce an anti-inflammatory effect for 12 to 24 hours.     

Inflammatory Cytokine Gene Expression in Blood During the Development of Oligofructose-Induced Laminitis in Horses

Systemic inflammation is a risk factor for laminitis in horses and precedes the onset of lameness in experimental models. We therefore hypothesized that whole-blood inflammatory cytokine expression would increase during the development of laminitis in a carbohydrate overload model. Blood samples were obtained from 14 horses undergoing laminitis induction with 10 g/kg oligofructose as part of another study. Samples were collected at 0, 8, 12, 16, 20, and 24 hours, and lameness evaluations were performed every 4 hours. Expression levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor-α were measured in whole blood by using real-time PCR. IL-1β, IL-8, and IL-10 expression increased above baseline from 8 to 24 hours (P < .001), and IL-6 expression increased at 16 and 20 hours (P = .005). Expression of tumor necrosis factor-α did not change over time. All horses developed clinical laminitis between 12 and 24 hours. Increased mean IL-1β, IL-8, and IL-10 expression detected at 8 hours therefore preceded the onset of lameness. We conclude that peripheral leukocyte cytokine expression increases as systemic inflammation develops in an alimentary carbohydrate overload model of laminitis, and this precedes detection of lameness. Results support current recommendations to control the systemic inflammatory response in order to lower the risk of laminitis in horses.     

Pharmacopuncture Versus Acepromazine in Stress Responses of Horses During Road Transport

Acupuncture has been shown to have the beneficial effect of reducing stress responses in animals and humans. Pharmacopuncture is the injection of subclinical doses of drugs into acupoints to give therapeutic results without side effects. This study compared the effects of injecting the usual dose of acepromazine (ACP; 0.1 mg/kg, intramuscularly [I.M.]) with those of pharmacopuncture (1/10 ACP dose at the governing vessel 1 [GV 1] acupoint) on the stress responses of healthy horses undergoing road transport for 2.5 hours. Four different treatments were applied immediately before loading, with 8 animals/treatment: injection of saline or ACP (0.1 mg/kg, I.M.) at the base of the neck; and injection of saline or 1/10 ACP (0.01 mg/kg) at the GV 1 acupoint. The road transport increased heart rate (HR), respiratory rate, body temperature, and serum cortisol of the untreated horses (injected with saline at the base of the neck). Pharmacopuncture at GV 1 reduced the average HR and transport-induced increase in HR at unloading, without changing the other variables. On the other hand, ACP (0.1 mg/kg) produced significant sedation and reduced the transport-induced increase in respiratory rate but without preventing the stress-induced increase of cortisol. Other acupuncture points and drugs should be tested to verify the beneficial effect of this therapy to reduce stress in horses during road transport.     

Changes of Circulating Total and Free Iodothyronine in Horses After Competitive Show Jumping With Different Fence Height

The effect of exercise on circulating T₃, T_4, free (f) T₃, and fT₄ concentrations were studied before and after competitive show jumping in 24 trained jumper horses with an age range of 11–13 years and having the same level of show experience. All horses, randomly divided into three groups paired by gender, participated in three competition levels with the same circuit design over 10 fences, with five upright and five cross-pole fences .The three fence height groups were group I (n = 8), 1.10 m; group II (n = 8), 1.20 m; and group III (n = 8), 1.30 m. Repeated measures analysis of variance showed a statistically significant effect of competitive exercise on fT₃ changes in all groups, whereas the effect of competitive exercise on T₃ changes was exclusively seen in group III. Two-way repeated measures analysis of variance showed that the effect of fence height (P = .0002) and performance results were significant (P = .0486) only for T₃ changes. Performance also affected fT₃ changes (P = .0152). No significant correlation was found between total and free iodothyronines. These results suggest a dependence of T₃ and fT₃ changes on exercise-related variables and performance results and that the thyroid response is different with respect to the different exercise-related variables, such as the varying level of difficulty and performance results.     

Effect of Yeast Culture Supplementation on Digestibility of Varying Forage Quality in Mature Horses

Supplementation of yeast culture to equine diets has improved digestion of nutrients in some studies but not others. Improving the digestibility of lower-quality forages could be advantageous both for the producer and for the horse's health. The objective of this study was to evaluate the effect of yeast culture on digestibility of high- and low-quality forage in mature horses. Sixteen geldings (483.6 ± 25.5 kg and 6.8 ± 3.2 years), of Quarter Horse (n = 14) and Thoroughbred (n = 2) breeding, were used in a 4 × 4 Latin square design with 28-day treatment periods. Russell Bermuda grass hay of either high (13.1% crude protein (CP), 73.1% neutral detergent fiber (NDF), 35.3% acid detergent fiber (ADF), and 6.0% ash) or low (8.1% CP, 75.3% NDF, 37.6% ADF, and 4.3% ash) quality was offered at 1.35% of body weight (BW, dry matter [DM] basis). Diets consisted of high-quality forage with the addition of yeast culture (HY), high-quality forage without yeast culture (HC), low-quality forage with the addition of yeast culture (LY), and low-quality forage without yeast culture (LC). All horses were fed a commercial grain mix (12.6% CP, 25.4% NDF, 12.1% ADF, and 4.0% ash) offered at 0.45% of BW (DM basis) daily. Yeast culture was added to the grain mix during the morning feeding at a rate of 56 g per horse. Body weight was measured weekly and feed intake was adjusted accordingly. Fecal samples were obtained every 6 hours on the last 3 days of each treatment period. Horses receiving low-quality hay (LY and LC) had greater (P < .01) intake expressed as a percentage of BW compared with horses receiving high-quality hay (HY and HC). No influence of yeast culture supplementation was seen on intake of grain or forage (P < .23 and P < .62, respectively). Digestibility of DM, organic matter (OM), CP, and NDF were greater (P < .01, P < .01, P < .01, and P < .01, respectively) for the diets with high-quality forage compared with the diets with low-quality forage. Dry matter, CP, and NDF digestibilities were greater (P < .09, P < .03, and P < .05, respectively) for horses receiving LY compared with LC. Supplementation of yeast culture to mature horses improved digestibility of lower-quality Bermuda grass hay.