Pharmacokinetics and tolerability of a new formulation of omeprazole in the horse

A new formulation of omeprazole in gastro‐resistant granules was tested with regard to its pharmacokinetics and tolerability. Twenty‐four horses were randomly divided into three groups (8 horses/group) and treated, according a parallel study design, as follows: Group A untreated (control group), Group B received 4 mg/kg of omeprazole, and Group C received 12 mg/kg of omeprazole, both of which were treated orally once a day for 90 days. Blood samples, taken from Group B subjects during the 1st and the 29th day of treatment at pre‐established time points, were used to determine the concentration–time curves of omeprazole. The treatments were found to be safe and well tolerated by the horses. The serum hematological and biochemical values were within reference ranges for the entire observational time. No accumulation of the drug was found after 29 days of treatment. Lower C_max and AUCs were obtained at the 29th day of treatment.     

Effects of detomidine or romifidine during maintenance and recovery from isoflurane anaesthesia in horses

ObjectiveTo evaluate the effects of detomidine or romifidine on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing isoflurane anaesthesia.Study designProspective, randomized, blinded, clinical study.AnimalsA total of 63 healthy horses undergoing elective surgery during general anaesthesia.MethodsHorses were randomly allocated to three groups of 21 animals each. In group R, horses were given romifidine intravenously (IV) for premedication (80 μg kg^–1), maintenance (40 μg kg^–1 hour^–1) and before recovery (20 μg kg^–1). In group D2.5, horses were given detomidine IV for premedication (15 μg kg^–1), maintenance (5 μg kg^–1 hour^–1) and before recovery (2.5 μg kg^–1). In group D5, horses were given the same doses of detomidine IV for premedication and maintenance but 5 μg kg^–1 prior to recovery. Premedication was combined with morphine IV (0.1 mg kg^–1) in all groups. Cardiovascular and blood gas variables, expired fraction of isoflurane (Fe′Iso), dobutamine or ketamine requirements, recovery times, recovery events scores (from sternal to standing position) and visual analogue scale (VAS) were compared between groups using either anova followed by Tukey, Kruskal-Wallis followed by Bonferroni or chi-square tests, as appropriate (p < 0.05).ResultsNo significant differences were observed between groups for Fe′Iso, dobutamine or ketamine requirements and recovery times. Cardiovascular and blood gas measurements remained within physiological ranges for all groups. Group D5 horses had significantly worse scores for balance and coordination (p = 0.002), overall impression (p = 0.021) and final score (p = 0.008) than group R horses and significantly worse mean scores for VAS than the other groups (p = 0.002).Conclusions and clinical relevanceDetomidine or romifidine constant rate infusion provided similar conditions for maintenance of anaesthesia. Higher doses of detomidine at the end of anaesthesia might decrease the recovery quality.     

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.     

Pharmacokinetics of intravenous,plain oral and enteric‐coated oral omeprazole in the horse

The objectives were to document the pharmacokinetics of intravenous, enteric‐coated oral and plain oral omeprazole in fasted horses and to investigate the impact of feeding on the bioavailability of an enteric‐coated omeprazole. Twelve horses received four treatments: intravenous omeprazole (0.5 mg/kg) in the fasted state (IV‐Fasted), enteric‐coated omeprazole (4 mg/kg) orally in the fasted state (ECO‐Fasted), enteric‐coated omeprazole (4 mg/kg) orally in the fed state (ECO‐Fed) and plain omeprazole (4 mg/kg) orally in the fasted state (PL‐Fasted). Plasma omeprazole concentrations were determined by UHPLC‐MS. Bioavailability was higher (P = 0.038) in the ECO‐Fasted group (21.5 [9.0–27.7]%) than the PL‐Fasted group (10.1 [7.7–13.3]%). Similarly, AUC_0‐∞ was higher in the ECO‐Fasted group than the PL‐Fasted group (P = 0.027). No significant differences were present between the ECO‐Fasted and ECO‐Fed groups with regards to bioavailability, C_max, T_max or AUC_0‐∞. When the half‐life data from the oral formulations was pooled, it was longer than that observed in the IV‐Fasted group (100 [73–118] min) and 35 [34‐39] min, respectively; P < 0.0001). Bioavailability of enteric‐coated omeprazole was higher than previously reported and feeding had minimal impact. Bioavailability of plain omeprazole was approximately half that of enteric‐coated omeprazole. The longer half‐life observed following oral administration was consistent with the flip‐flop effect and has not previously been described for omeprazole in the horse.     

Pharmacokinetics of low-dose methotrexate in horses

This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concentrations were measured using LC-MS/MS. The absolute bioavailability of MTX was 73% following subcutaneous administration but less than 1% following oral administration. The plasma clearance was 1.54 ml min⁻¹ kg⁻¹ (extraction ratio = 2%). After 24 hr, plasma concentrations were below the LOQ. No adverse effects were noted except for a moderate reversible elevation in liver enzymes (GLDH). With regards to the main metabolites of MTX, very low concentrations of 7-hydroxy-MTX were found, whereas polyglutamated forms (mainly short chains) were found in red blood cells. A subcutaneous dose of 0.2 mg kg⁻¹ week⁻¹ may be safe and relevant in horses, although this has yet to be clinically confirmed.     

Behavioral and Antinociceptive Effects of Alfentanil,Butorphanol, and Flunixin in Horses

To determine the behavioral and antinociceptive effects of narcotic and non-narcotic analgesics administered by intravenous injection in horses, 10 thoroughbred mares weighing between 450 and 550 kg and ranging in age from 8 to 13 years old were analyzed. The effects of alfentanil, butorphanol, flunixin, and saline solution on the general activity of the horses were investigated by measuring spontaneous locomotor activity (SLA) and head height (HH) in two behavior stalls. The antinociceptive effects of alfentanil (0.02 mg kg⁻¹), butorphanol (0.1 mg kg⁻¹), flunixin meglumine (0.5 mg kg⁻¹), and saline were determined by measuring skin twitch reflex latency (STRL) after thermal cutaneous nociceptive stimulation. A paired Student t-test was used to compare SLA and HH between the groups of horses receiving different doses of the same drug at various time points. The Tukey test was used to compare the antinociceptive effect of the treatments. Differences were considered significant when P value was <.05. Horses treated with opioid analgesics demonstrated excitation, as shown by a significant increase in SLA at all doses tested and by neighing and demonstrating attentive attitudes with movement of the ears, stereotypical walking, and ataxia in most of the animals. HH was elevated only in animals treated with alfentanil. Antinociception was observed at 5 and 30 minutes after administration of alfentanil and butorphanol, respectively. Increased SLA was observed at 30 and 90 minutes after administration of alfentanil and butorphanol, respectively. We observed no effect on antinociception in horses given flunixin. In conclusion, this study suggests that alfentanil has a faster onset and a shorter duration than butorphanol; however, both drugs are able to stimulate the central nervous system.     

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

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

Comparison of single-breath continuous positive airway pressure manoeuvre with inhaled salbutamol to improve oxygenation in horses anaesthetized for laparotomy

ObjectiveTo compare the efficacy of single-breath continuous positive airway pressure manoeuvre (CPAP-M) with inhaled salbutamol, and a combination of both.Study designRandomized, clinical study.AnimalsA total of 62 client-owned horses (American Society of Anesthesiologists status III–V) anaesthetized for laparotomy.MethodsHorses were premedicated with intravenous (IV) xylazine (0.4–0.6 mg kg^–1), anaesthesia was induced with midazolam (0.06 mg kg^–1 IV) and ketamine (2.2 mg kg^–1 IV) and maintained with isoflurane in oxygen using volume-controlled ventilation without positive end-expiratory pressure. If PaO₂ was < 100 mmHg (13.3 kPa), either a CPAP-M (50 cmH₂O for 45 seconds) or salbutamol (0.002 mg kg^–1) was administered. The intervention was considered successful if PaO₂ reached 100 mmHg (13.3 kPa). If PaO₂ remained < 100 mmHg (13.3 kPa), treatments were switched. PaO₂/FiO₂ ratio and estimated shunt fraction (F-shunt) were derived from data obtained from arterial blood gas measurements. Dynamic compliance (C_dyn) was calculated from variables recorded at the moment of arterial blood analysis. Fisher’s exact tests compared success rates between treatments, and linear models were performed to test whether the treatment modified the values of the measurements; p < 0.05.ResultsSalbutamol was the first intervention in 28 horses and was effective in 22 horses. CPAP-M was the first intervention in 34 horses and was effective in 26 horses. CPAP-M after salbutamol was performed in six horses, with four responders, and salbutamol after CPAP-M was administered to eight horses, with one responder. Salbutamol, but not CPAP-M, significantly decreased F-shunt. Both salbutamol and CPAP-M significantly increased C_dyn.Conclusions and clinical relevanceSalbutamol and CPAP-M were comparably effective in improving oxygenation and C_dyn in anaesthetized horses with PaO₂ < 100 mmHg (13.3 kPa). Whether combining both treatments might be beneficial needs to be confirmed on a larger number of horses.     

Efficacy of omeprazole paste for prevention of recurrence of gastric ulcers in horses in race training

OBJECTIVE: To determine whether omeprazole oral paste administered at a dosage of 0.5 or 1 mg/kg (0.23 or 0.45 mg/lb), PO, every 24 hours would effectively prevent the recurrence of gastric ulcers in horses in race training. DESIGN: Prospective study. ANIMALS: 135 horses. PROCEDURES: Horses with gastric ulcers were treated with omeprazole at a dosage of 4 mg/kg (1.8 mg/lb), PO, every 24 hours for 28 days. Horses in the dose selection portion of the study were sham dose treated or received 0.5 or 1 mg of omeprazole/kg, PO, every 24 hours for an additional 28 days. Horses in the dose confirmation portion of the study were sham dose treated or received 1 mg of omeprazole/kg, PO, every 24 hours for an additional 28 days. Gastric ulcers were scored before and after the preventive phase of the study (day 28 to day 56) via gastroscopy, and ulcer scores were compared. RESULTS: Sham-dose-treated horses and horses receiving 0.5 mg of omeprazole/kg had significantly higher ulcer scores than did horses receiving 1 mg of omeprazole/kg. There was a significant difference between the proportion of horses receiving 1 mg of omeprazole/kg (38/48 179%]) that remained ulcer free and the proportion of sham-dose-treated horses (7/44 [16%]) that remained ulcer free. CONCLUSIONS AND CLINICAL RELEVANCE: Omeprazole oral paste administered at a dosage of 1 mg/kg, PO, every 24 hours for 28 days was effective for prevention of recurrence of gastric ulcers in horses in race training.     

Epidural administration of tiletamine/zolazepam in horses

Objectives To evaluate the analgesic, physiologic, and behavioral effects of the epidural administration of tiletamine/zolazepam in horses. Study design Prospective, double‐blind, randomized experimental study. Animals Five adult, healthy horses aged 10–16 years and weighing (mean ± SD) 400 ± 98 kg. Methods The horses were sedated with 1.0 mg kg^?1 intravenous (IV) xylazine, and an epidural catheter was placed into the first intercoccygeal intervertebral space. After a 48‐hour resting period, epidural tiletamine/zolazepam, 0.5 mg kg^?1 (treatment I) or 1.0 mg kg^?1 (treatment II), diluted up to 5 mL in sterile water, was administered with a 1‐week interval between the treatments. Heart rate, respiratory rate, arterial blood pressure, and sedation were evaluated. In order to evaluate the respiratory effects, blood from the carotid artery was withdrawn at time 0 (baseline), and then after 60 and 240 minutes. Analgesia was evaluated by applying a noxious stimulus with blunt‐tipped forceps on the perineal region, and graded as complete, moderate, or absent. Data were collected before tiletamine/zolazepam administration and at 15‐minute intervals for 120 minutes, and 4 hours after tiletamine/zolazepam administration. Data were analyzed with anova and Bonferroni's test with p < 0.05. Results The results showed no significant difference between treatments in cardiovascular and respiratory measurements. Sedation was observed with both doses, and it was significantly different from baseline at 60, 75, and 90 minutes in treatment II. Moderate analgesia and locomotor ataxia were observed with both the treatments. Conclusions and clinical relevance The results suggest that caudal epidural 0.5 and 1.0 mg kg^?1 tiletamine/zolazepam increases the threshold to pressure stimulation in the perineal region in horses. The use of epidural tiletamine/zolazepam could be indicated for short‐term moderate epidural analgesia. There are no studies examining spinal toxicity of Telazol, and further studies are necessary before recommending clinical use of this technique.     

Efficacy of omeprazole paste for prevention of gastric ulcers in horses in race training

OBJECTIVE: To determine the minimal effective dosage of omeprazole oral paste for the prevention of naturally occurring ulcers in horses starting race training. DESIGN: Prospective study. ANIMALS: 175 horses. PROCEDURE: Horses in the dose selection portion of the study were sham dose treated or received 1 mg (0.45 mg/lb) or 2 mg (0.9 mg/lb) of omeprazole/kg, PO, every 24 hours for 28 days or 4 mg of omeprazole/kg (1.8 mg/lb; loading dose), PO, every 24 hours for 4 days, then 1 or 2 mg of omeprazole/kg, PO, every 24 hours for 24 days. Horses in the dose confirmation portion of the study were sham dose treated or received 1 mg of omeprazole/kg, PO, every 24 hours for 28 days. Gastric ulcer scores at the beginning and end of the study were compared. RESULTS: Sham-dose-treated horses had significantly higher ulcer scores than did horses treated with any of the omeprazole dosages evaluated. Among horses treated with omeprazole, there was no significant interaction of dose (1 or 2 mg/kg) and loading dose; therefore, the lowest effective dose (1 mg/kg) was evaluated in the dose confirmation portion of the study. In the dose confirmation study, 4 of 39 (10%) sham-dose-treated horses remained ulcer free, which was significantly different from the proportion of horses (31/38 [82%]) receiving 1 mg of omeprazole/kg that remained ulcer free. CONCLUSIONS AND CLINICAL RELEVANCE; Results indicated that omeprazole administered at a dosage of 1 mg/kg, PO, every 24 hours for 28 days was effective for prevention of gastric ulcers in horses starting race training.     

Effects of dietary amino acid supplementation on measures of whole‐body and muscle protein metabolism in aged horses

The objective of this study was to examine markers of whole‐body and muscle protein metabolism in aged horses fed a diet typical for North American aged horses, supplemented with amino acids. In a replicated Latin square design, six aged horses (20 ± 1.1 years) were studied while receiving each of three isocaloric, isonitrogenous diets, a control treatment concentrate (CON; 100 mg/kg^?1 BW day^?1 lysine, 84 mg kg^?1 day^?1 threonine, 51 mg kg^?1 day^?1 methionine), LYS/THR (134 mg kg^?1 BW day^?1 lysine, 110 mg kg^?1 BW day^?1 threonine, 52 mg kg^?1 BW day^?1 methionine) and LYS/THR/MET (132 mg kg^?1 BW day^?1 lysine, 112 mg kg^?1 BW day^?1 threonine, 62 mg kg^?1 BW day^?1 methionine). In each 15‐days period, urine and faeces were collected for assessment of nitrogen balance. Blood samples were collected before and after feeding for analysis of plasma urea nitrogen (PUN), glucose, insulin and plasma amino acid concentrations. Skeletal muscle samples were collected for measurement of proteins associated with muscle protein synthesis and degradation, and horses underwent stable isotope infusion procedures for comparison of differences in whole‐body rates of protein synthesis and degradation. There was no effect of treatment on relative abundance of proteins involved in protein synthesis, nitrogen retention or phenylalanine kinetics. PUN concentrations tended to be higher for LYS/THR (p = 0.054) and were higher for LYS/THR/MET (p = 0.0056) than for CON. Atrogin‐1 abundance tended to be higher in the post‐absorptive state for the CON treatment (p = 0.07), indicating that amino acid supplementation resulted in less muscle protein degradation when horses were in the post‐absorptive state. However, lack of differences in nitrogen retention and phenylalanine kinetics indicated that whole‐body protein metabolism was not improved, and higher PUN concentrations in the supplemented diets suggest that the supplemented amino acids may have been catabolized. Amino acid availability was not limiting protein synthesis in the sedentary aged horses in this study when fed the CON diet.     

Antioxidant and haematological biomarkers in different groups of horses supplemented with polyunsaturated oil and vitamin E

Oxidative stress has been correlated with pathologies that impair the performance of athlete horses. The aim of this study was to assess the effects of supplementation with a mixture of polyunsaturated oil and vitamin E on the antioxidant and haematological biomarkers of horses. Horses under maintenance care (n = 6) and horses in training (n = 10) received 100 and 300 ml of the oil mixture respectively. Supplementation was provided for a period of 8 weeks, together with isocaloric inclusion. Blood samples were collected at three time periods (pretest, after 4 weeks and after 8 weeks) to analyse the following: the red blood cell count (RBCc); haemoglobin (Hb); haematocrit (HT); leucocytes; lymphocytes; platelets; the mean corpuscular volume (MCV); the mean corpuscular haemoglobin concentration (MCHC); the standard deviation of the red blood cell distribution width (RDW‐SD); the coefficient of variation of the red blood cell distribution width (RDW‐CV); glutathione peroxidase (GPx); superoxide dismutase (SOD); uric acid (UrAc); total plasma proteins (TPP); and creatine kinase (CK). After the 8 weeks of supplementation, animals under maintenance care exhibited significant increases in SOD, UrAc, the white blood cell count (WBCc), the RDW‐SD and the RDW‐CV (p < 0.05). The animals in training exhibited increases in GPx, SOD and UrAc (p < 0.05). In conclusion, supplementation with polyunsaturated oil and vitamin E increases blood antioxidants among animals under maintenance and in training, with different trends, while contributing to the fight against oxidative stress in each group analysed.     

Comparison of hydromorphone and butorphanol for management of pain in equine patients undergoing elective arthroscopy: a randomized clinical trial

ObjectiveTo compare the effects of hydromorphone and butorphanol in horses undergoing arthroscopy and describe the pharmacokinetics of hydromorphone in anesthetized horses.Study designRandomized controlled clinical trial.AnimalsA total of 40 adult horses admitted for elective arthroscopy.MethodsHorses were randomly assigned to be administered intravenous hydromorphone (0.04 mg kg^–1; group TxH; n = 19) or butorphanol (0.02 mg kg^–1; group TxB; n = 21) prior to surgery as part of a standardized anesthetic protocol. Pain was scored by two observers unaware of group assignment using the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) and a composite pain scale (CPS) prior to surgery (baseline), 2 hours (P2) and 4 hours (P4) following recovery from anesthesia. Blood samples were collected at various time points for determination of plasma hydromorphone concentration using liquid chromatography–tandem mass spectrometry. Data were analyzed with a mixed-effect model.ResultsMedian (range) baseline EQUUS-FAP was 1.2 (0.0–4.0) with no effect of group, time points or interaction. Baseline CPS was similar between groups. Group TxH baseline CPS was 2.5 (0.0–10.0), increased at P2 [4.5 (0–10.0); p = 0.046] and returned to baseline values at P4 [3.0 (0.0–11.0)]. Group TxB baseline CPS was 2.0 (0.0–8.0), increased at P2 [3.5 (0.0–11.0); p = 0.009] and P4 [5.0 (0.0–11.0); p < 0.001]. Pharmacokinetic terminal half-life was 774 ± 82.3 minutes, area under the curve was 1362 ± 314 ng minutes mL^–1, clearance was 30.7 ± 7.23 mL minute^–1 kg^–1 and volume of distribution at steady state was 884 ± 740 mL kg^–1.ConclusionsHydromorphone, but not butorphanol, decreased CPS back to baseline at P4 after recovery.Clinical relevanceHydromorphone may provide superior postoperative analgesia compared with butorphanol in horses undergoing arthroscopy.     

Efficacy of orally administered gabapentin in horses with chronic thoracic limb lameness

ObjectiveTo evaluate the analgesic effects of orally administered gabapentin on horses with chronic thoracic limb lameness.Study designRandomized, crossover design.AnimalsA total of 14 adult horses with chronic thoracic limb lameness.MethodsFollowing baseline measurement of lameness, horses were administered each of four treatments orally in grain: treatment G, gabapentin (20 mg kg^–1) twice daily for 13 doses; treatment F, firocoxib (171 mg once, then 57 mg once daily for six doses); treatment GF, gabapentin and firocoxib at previously stated doses and frequencies; or treatment C, grain only as a control. Treatments were administered in a randomized, crossover design, separated by 2 weeks. Subjective lameness score (SLS), inertial sensor vector sum (VS) calculations, peak vertical ground reaction force (PVGRF) measurements and vertical impulse (VI) calculations were determined immediately prior to each initial treatment dose and 2–4 hours after the final treatment dose for each treatment. Mean change in SLS, VS, PVGRF and VI for each treatment were compared among treatments.ResultsThe rank change in SLS of treatment GF was significantly greater than that of treatments C (p = 0.01) and G (p = 0.01) but not of treatment F (p = 0.08). No differences in VS (p = 0.4), PVGRF (p = 0.4) or VI (p = 0.1) were observed among treatments.Conclusions and clinical relevanceGabapentin, as administered here, did not improve subjective or objective measures of lameness in horses with chronic thoracic limb musculoskeletal pain. Although subjective evaluation identified an improvement in lameness with treatment GF, it was not different from that observed with treatment F. Higher oral dosing and longer treatment regimens of gabapentin may be indicated for the treatment of chronic musculoskeletal pain in horses.     

Effects of epidural morphine on gastrointestinal transit in unmedicated horses

ObjectiveTo evaluate the effect of epidural morphine on gastrointestinal (GI) motility in horses.Study designRandomly ordered crossover design.AnimalsSix healthy adult horses weighing 585 ± 48 kg (mean ± SD).MethodsHorses were randomly assigned to receive either 0.2 mg kg^?1 morphine or an equal volume (0.04 mL kg^?1) of saline epidurally (the first inter coccygeal space) with 2 weeks between treatments. The horses were stabled, fed a standardized diet and allowed water ad libitum throughout the duration of the study. Radiopaque spheres were administered by stomach tube. Xylazine 0.2 mg kg^?1 intravenously was administered prior to epidural injection. Heart rate, respiratory rate, GI sounds score and behavior score were recorded before drug administration and after epidural injection at 4, 8, 12, 18, 24 hours and every 12 hours thereafter for 6 days. Feces were weighed, radiographed and the number of spheres counted. Data were analyzed using a mixed effect model.ResultsAt no time did horses exhibit signs of colic or show significant differences between treatments regarding heart rate, respiratory rate, GI sounds score, behavior score, or cumulative number of spheres. The concentration of spheres per kg of feces was significantly lower (p < 0.05) for the morphine group at 18 and 24 hours. Using the centroid of the curves (spheres kg^?1 plotted versus time) the average transit time after saline epidural was 38 hours and after morphine it was 43 hours. The weight of feces hour^?1 was significantly lower (p < 0.05) at only 4 and 8 hours after morphine.Conclusions and clinical relevanceEpidural morphine, at a dose of 0.2 mg kg^?1, temporarily reduced GI motility but did not cause ileus or colic in this small group of healthy unfasted horses. Care should be taken when extrapolating these data to situations in which other factors may also affect GI motility.     

Effect of a pelleted supplement fed during and after omeprazole treatment on nonglandular gastric ulcer scores and gastric juice pH in horses

Gastric ulcers are common in horses. The purpose of this study was to test the effect of a commercially available supplement, SmartGut^® Ultra pellets (SmGU) on gastric ulcer scores and gastric juice pH after omeprazole treatment in stall‐confined horses. Eight Thoroughbred horses were studied in a 2‐period, 2‐treatment crossover design, where the SmGU (40 g, twice daily) was mixed in grain feed. Horses were stall‐confined and treated with the supplement or control for 6 weeks, consisting of 2 weeks (Days 1–14) omeprazole treatment, 2 weeks (Days 14–28) following discontinuation of omeprazole treatment, one week (Days 28–35) alternating feed deprivation to induce or worsen existing ulcers and a one week (Days 35–42) recovery period. Gastroscopy was performed and gastric juice pH measured on Days 0, 14, 28, 35 and 42. Gastric ulcer lesion number (NGN) and severity (NGS) scores were assigned to each horse by an investigator (F.M.A.) masked to treatment. On Day 0 before treatment, mean NGN and NGS scores and gastric juice pH were not different (P>0.05) between treatment groups. By Day 14, mean NGN and NGS scores decreased (P<0.05) in both treatment groups. By Days 28 and 35, mean NGN score significantly increased in the untreated control horses but not the SmGU‐treated horses. By Day 42, mean NGN and NGS scores were not different in either group and were significantly lower than Day 0. Mean gastric juice pH was higher in both groups on Day 14 as a result of omeprazole treatment when compared with other days. SmartGut^® Ultra supplement added to the feed prevented the worsening of gastric ulcer number 2 weeks after omeprazole treatment, without altering the gastric juice pH. Supplementation with SmGU might aid in protection of the nonglandular stomach from recurrence of ulcers after omeprazole treatment in stall‐confined horses undergoing intermittent feeding.     

Enteral Fluid Therapy in Horses: Effects of Maintenance Hypotonic Electrolyte Solutions Containing Maltodextrin,Sucrose, or Dextrose Administered in Continuous Flow

To evaluate the effects of maintenance hypotonic electrolyte solutions containing carbohydrates administered by nasoesophageal tube in continuous flow in horses during 12 hours on body weight, waist circumference, water intake, aspect and moisture content of the stool, frequency of defecation, urine density and urinary glucose, sodium, potassium, chloride, urea and creatinine, and urinary volume in horses. We used six mares randomly divided into three treatments in two Latin squares 6 × 3, concurrent, in mixed model. All solutions had the same composition (5 g of NaCl, 0.5 g of KCl, 200 mg of magnesium pidolate, and 1 g of calcium gluconate, diluted in 1,000 mL of water), only differing in power source and osmolarity, ESMaltodextrin—electrolyte solution plus 15 g of maltodextrin (measured osmolarity of 203 mmol L⁻¹); ESSucrose—electrolyte solution plus 15 g of sucrose (measured osmolarity of 234 mmol L⁻¹); and ESDextrose—electrolyte solution plus 15 g of dextrose (measured osmolarity of 264 mmol L⁻¹). The electrolyte solutions were administered at a dose of 15 mL kg⁻¹ h⁻¹ for 12 hours in continuous flow. Maintenance hypotonic electrolyte solutions containing maltodextrin, dextrose, and sucrose were effective in promoting diuresis and decreasing urinary density, without presenting adverse effects. ESSucr was more effective in softening the stool.     

Preliminary investigation of concurrent administration of phenylbutazone and romifidine in healthy horses

ObjectiveTo characterize the cardiorespiratory and electrocardiographic effects of the combined administration of phenylbutazone and romifidine.Study designProspective four-period, four-treatment, blinded, randomized, crossover trial.AnimalsFive, healthy, mixed breed horses.MethodsPrior to treatment administration, a catheter was introduced into the intra-thoracic cranial vena cava via the jugular vein and a subcutaneously located carotid artery was catheterised. All treatments were administered intravenously (IV) and consisted of saline placebo (PLC), phenylbutazone (PBZ, 4.4 mg kg^?1) romifidine (ROM, 80 μg kg^?1) and a combination of phenylbutazone (4.4 mg kg^?1) and romifidine (80 μg kg^?1). There was at least a 1 week washout period between treatments. Heart rate (HR), respiratory rate (f_R), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures and central venous pressure (CVP) were recorded for baseline (prior to drug administration) and at 5 minute intervals thereafter for 30 minutes. Electrocardiographic abnormalities were recorded. Data were analyzed by anova.ResultsFor the cardiovascular variables there were no statistically significant (p > 0.05) differences between horses treated with ROM and PBZ_ROM. Statistically significant (p < 0.05) differences only occurred between treatments with romifidine (ROM and PBZ_ROM) and without romifidine (PLC and PBZ). Within treatments, for ROM, changes over time were statistically significant (p < 0.05) for HR, SAP, DAP, MAP and CVP. For PBZ_ROM, changes over time were statistically significant (p < 0.05) for CVP. Sino-atrial and atrio-ventricular blocks occurred in horses treated with ROM and PBZ_ROM.Conclusions and clinical relevanceThe combined IV administration of phenylbutazone and romifidine had no statistically significant effect on cardiorespiratory variables. These limited data suggest no evidence why both agents should not be included in a preoperative medication protocol for healthy horses but do not exclude the possibility of interactions occurring in a larger population.     

The effects of pre-anesthetic administration of xylazine on the cardiovascular responses to dobutamine in halothane anaesthetized horses

Studies evaluating the effects of dobutamine in horses do not consistently report increases in cardiac output despite increases in arterial blood pressure. The concurrent administration of the α₂ agonist clonidine, in people, inhibited the chronotropic effects of dobutamine and increased left ventricular stroke work ( Zimpfer et al. 1982 ). Our study was performed to determine if pre‐medication with an α₂ agonist affects the response to dobutamine in anaesthetized horses. Eleven horses were anaesthetized on four separate occasions for one of four randomly assigned treatments; (I) no xylazine, no dobutamine (II) xylazine, no dobutamine (III) no xylazine, dobutamine, and (IV) xylazine, dobutamine. Horses received 0.02 mg kg^?1 of butorphanol IV 10 minutes prior to anesthetic induction. Two minutes prior to induction, groups II and IV received 0.5 mg kg^?1 of IV xylazine. Anaesthesia was induced with 6–7 mg kg^?1 of thiopental and maintained with halothane. End‐tidal halothane concentrations were maintained between 1.1 and 1.2% in groups I and III, and 0.9–1.0% for groups II and IV. Heart rate, cardiac output, right atrial pressure, and systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure were recorded 30 minutes after beginning halothane anaesthesia (T10). Cardiac output was estimated using Lithium dilution ( Linton et al. 2000 ). Baseline measurements were repeated twice, at 5‐minute intervals (T5 and T0). At time 0 (T0), an IV infusion of either saline (100 mL hour^?1) or dobutamine (0.001 mg kg^?1 minute^?1) was started and data recorded at 5‐minute intervals for 30 minutes (T5 – T30). Stroke volume and systemic vascular resistance (SVR) were calculated. Data were analysed using repeated measures anova (p < 0.01 significant) and Newman–Keuls for multiple comparisons. Cardiac output and stroke volume increased over time in groups III and IV. Cardiac index was higher in groups III and IV than in groups I and II from T10 until completion of the study. Estimates of cardiac index at T30 for groups I–IV were 45 ± 9, 46 ± 11, 71 ± 11, and 78 ± 19 mL kg^?1 minute^?1, respectively (mean ± SD). Stroke index was higher in groups III and IV than in groups I and II from T15 to T30. Values for stroke index at T30 for groups I–IV were 0.98 ± 0.19, 1.11 ± 0.18, 1.46 ± 0.21, 1.74 ± 0.33 mL kg^?1. Heart rate decreased from T10–T30 in groups I and II. Heart rate was greater in groups I and III than in groups II and IV at T5 and T0. Values for heart rate at T0 for groups I–IV were 48 ± 5, 42 ± 5, 50 ± 4, 43 ± 4 beats minute^?1. Systolic arterial pressure, DAP and MAP were higher in groups III and IV than in groups I and II from T5 to T30. There were no differences in SVR between groups. Dobutamine at 0.001 mg kg^?1 minute^?1 increased cardiac output, blood pressure, and stroke volume. Premedication with xylazine at 0.5 mg kg^?1 did not appear to affect the response to dobutamine.