Characterization of the pharmacokinetics,behavioral effects and effects on thermal nociception of morphine 6-glucuronide and morphine 3-glucuronide in horses

ObjectiveTo describe the pharmacokinetics, behavioral and physiologic effects and effects on thermal thresholds of morphine, morphine 6-glucuronide (M6G) and morphine 3-glucuronide (M3G) following administration to horses.Study designRandomized balanced crossover study.AnimalsA total of seven University-owned horses, five mares and two geldings, aged 3–6 years.MethodsHorses were treated with a single intravenous dosage of saline, morphine (0.2 mg kg^–1), M6G (0.01 mg kg^–1) and M3G (0.03 mg kg^–1). Blood was collected prior to (baseline) and at several times post administration. Drug and metabolite concentrations were determined by liquid chromatography–mass spectrometry, and plasma pharmacokinetics were calculated. Behavioral observations and physiologic variables (heart rate, step counts, packed cell volume, total plasma protein and gastrointestinal sounds) were determined at baseline and for up to 6 hours. The effects on thermal nociception were determined and thermal excursion was calculated.ResultsThe volumes of distribution were 4.75–10.5, 0.244–0.295 and 0.215–0.356 L kg^–1 for morphine, M6G and M3G, respectively. Systemic clearances were 26.8–39.6, 3.16–3.88 and 1.46–2.13 mL minute^?1 kg^?1 for morphine, M6G and M3G, respectively. Morphine administration resulted in signs of excitation as evidenced by an increase in step counts and subjective behavioral observations, whereas M6G and M3G, based on the same criteria, appeared to cause sedative-like effects. Significant effects on thermal nociception were observed until 4 hours post morphine administration, 1 hour post M6G administration and at various times post M3G administration.Conclusions and clinical relevanceResults of this study provide additional information regarding the use of morphine in horses. Less locomotor excitation and gastrointestinal adverse effects, compared with morphine, coupled with favorable effects on thermal nociception are encouraging for further study of the pharmacodynamics of both M6G and M3G in horses.     

ULTRASONOGRAPHIC DIAGNOSIS OF A DEEP MUSCLE ABSCESS IN A HORSE

A deep muscle abscess was diagnosed in a horse with a clinical history of a painful swelling in the left gluteal region. The thick walled hypoechoic structure seen on presentation and the multiloculated hyperechoic mass seen on reevaluation are common Ultrasonographic appearances of abscesses. Ultrasonographic evaluation allowed characterization of a chronic mass with subsequent successful surgery and treatment.     

Rethinking equine gastric ulcer syndrome: Part 1 – Terminology,clinical signs and diagnosis

Equine gastric ulcer syndrome (EGUS) is a common condition in the horse. A series of recent articles highlighting differences in healing of squamous and glandular ulceration have reinvigorated interest in the condition. The purpose of this series of articles is to review the current thinking on EGUS with particular emphasis on the differences between diseases of the squamous and glandular mucosae. This article, the first will review the terminology, clinical signs and diagnosis of EGUS in the horse.     

Validation of a transendoscopic glandular and nonglandular gastric biopsy technique in horses

Reasons for performing study: In order to study the evolution of histopathological and immunohistochemical changes in the gastric mucosa of horses with EGUS (equine gastric ulcer syndrome), a feasible, useful, valid and safe in vivo gastric biopsy technique is required. Objectives: To determine the average gastric mucosal healing time following endoscopic gastric biopsy sampling, and evaluate the feasibility, safety and usefulness of samples obtained by this method for histopathological analysis. Methods: Six mature mares from the Faculté de Médecine Vétérinaire research herd were used. Transendoscopic gastric biopsy was performed on Days 0 and 9 using a flexible forceps with oval and fenestrated jaws to obtain gastric mucosal samples from 4 different sites: cardia (C), fundus (F), margo plicatus (MP) and glandular mucosa (GL). A maximum of 4 samples per site was taken and processed routinely for histopathology, evaluated by a pathologist. On Days 1–4 and 9–11 the lesions created by the biopsies were evaluated by gastroscopy. Lesions were evaluated over time based on a score from 0–4, where 4 was the most severe. Results: Biopsy samples could be obtained from all targeted sites except C. No abnormal clinical signs were observed up to 7 days post biopsy. The average biopsy lesion scores decreased significantly with time for all sites. The average lesion score was significantly higher for the MP compared to the other sites at Days 1 and 2. Samples taken from the nonglandular portion of the stomach were considered inadequate for histopathology, while those taken from the glandular mucosa were adequate. Conclusion: The transendoscopic gastric biopsy technique described here is a feasible, safe and useful technique for obtaining samples from the equine gastric glandular mucosa. Although biopsy samples could be obtained from several areas in the nonglandular mucosa, these were very small, took longer to heal and were not considered adequate for histopathological evaluation, and another technique should therefore be validated.     

TRANSRECTAL ULTRASONOGRAPHY OF THE LEFT ADRENAL GLAND IN HEALTHY HORSES

Little information is available on medical imaging of the adrenal glands in horses. We investigated the feasibility of transrectal ultrasonography to characterize the normal equine adrenal gland. Transrectal ultrasonography was performed in 25 healthy horses using a 7.5 MHz linear array probe at a displayed depth of 8 cm. Transrectal ultrasonography of the right adrenal gland was not feasible. For the left adrenal gland, the left kidney, the abdominal aorta, the left renal artery, the left renal vein, and the cranial mesenteric artery were used as landmarks. The size of the left adrenal gland was variable, but it generally appeared as a long, flat structure with a hyperechoic medulla surrounded by a hypoechoic cortex. The most cranial part of the gland could not be delineated appropriately in 11 horses (44%). The mean (±SD) thickness of the gland and medulla was 0.66±0.15 cm (n=25) and 0.28±0.09 cm (n=25) near the caudal pole, 0.87±0.25 cm (n=14) and 0.40±0.18 cm (n=12) near the cranial pole, and 0.89±0.18 cm (n=25) and 0.36±0.13 cm (n=25) in the middle of the gland, respectively. The mean (±SD) length of the entire adrenal gland and of the medulla was 6.22±0.77 cm (n=14) and 5.45±0.71 cm (n=6), respectively. Transrectal ultrasonography allowed adequate visualization of the left adrenal gland in horses.     

Morphine-associated pruritus after single extradural administration in a horse

Pruritus following a single administration of 100 microg kg(-1) of preservative-free morphine sulphate given via an extradural catheter was seen in a 580 kg horse. The catheter was placed in the first intercoccygeal space. Focal irritation, represented by both local alopecia over the left gluteal muscles and serum exudation, occurred 4-8 hours after injection. This was attributed to the extradural morphine administration.     

Presumed generalised seizure following caudal epidural administration of morphine and detomidine in a pony

A 9-year-old show pony mare became acutely lame following removal of a bone sequestrum of the distal phalanx of the right thoracic limb. The mare also suffered from ongoing right dorsal colitis secondary to previous long-term nonsteroidal anti-inflammatory drug (NSAID) use. To avoid further NSAID use, a protocol for caudal epidural administration of morphine and detomidine in an increased volume was used to provide analgesia to the thoracic limbs. A total volume of 50 mL (0.2 mL/kg bwt) was administered over approximately 90 s. Immediately following the injection, the pony collapsed into lateral recumbency and experienced an apparent generalised seizure characterised by loss of consciousness and frantic paddling of all four limbs. The pony recovered rapidly without intervention, and no residual neurological deficits were noted. The epidural analgesia resulted in a marked improvement in comfort levels. The speed of injection is thought to have caused a change in epidural and intracranial pressures resulting in a generalised seizure and highlights the importance of administering large volumes slowly.     

Clinical pathology and ultrasonographic findings from a Warmblood gelding with primary,severe, acute pancreatitis

A 24-year-old Warmblood gelding presented with a 6-hour history of recurrent colic signs of increasing severity. Upon presentation, he was mildly painful, tachycardic and tachypnoeic and had decreased borborygmi. Nasogastric intubation resulted in no net reflux and rectal palpation revealed an ascending colon impaction. Percutaneous abdominal ultrasonography revealed dilated, thickened and hypomotile loops of small intestine. Complete blood count revealed leucopenia with neutropenia and an increased packed cell volume. Serum biochemistry revealed hyperproteinaemia, hyperglycaemia, hypocalcaemia, hyperbilirubinaemia, hypercholesterolaemia and elevated liver enzymes. Despite sedation and fluid resuscitation, the gelding became severely colicky. A repeat ultrasound was performed, revealing a moderate amount of free fluid and a mass effect between the liver and right dorsal colon. Abdominocentesis yielded a yellow, turbid fluid containing free-floating white debris with an increased total protein and lactate concentration. Cytology of the fluid revealed necrotic mesothelial cells. The gelding was humanely euthanised due to poor prognosis. Necropsy revealed acute, severe pancreatitis and duodenitis. The mass effect on ultrasonography was retrospectively identified as the pancreas exhibiting a similar architecture to that seen in cases of acute pancreatitis in small animals.     

Hindlimb lameness associated with proximal suspensory desmopathy and injury of the accessory ligament of the suspensory ligament in five horses

The accessory ligament of the hindlimb suspensory ligament arises from the plantar aspect of the calcaneus and fourth tarsal bones and blends with the suspensory ligament in the proximal aspect of the metatarsus. The accessory ligament of the suspensory ligament of both hindlimbs of 12 mature horses, with no history of hindlimb lameness, was assessed ultrasonographically. The ligament comprised linear parallel echoes which were consistently shorter than those of the lateral digital flexor tendon; the dorsal and plantar borders were parallel. Lameness associated with injury of the accessory ligament of the suspensory ligament was identified in 6 of 8 lame hindlimbs of 5 horses, unilaterally in 4 horses and bilaterally in one horse. In all horses there was concurrent proximal suspensory desmopathy. There was localised oedematous swelling on the distal medial aspect of the chestnut extending distally in 2 horses. Lameness was best identified when the horses were ridden. Perineural analgesia of the deep branch of the lateral plantar nerve abolished lameness in 3 horses but perineural analgesia of the tibial nerve was required to abolish lameness in the hindlimb with injury of the accessory ligament of the suspensory ligament in 2 horses. Injury of the accessory ligament of the suspensory ligament was characterised by marked decrease in echogenicity of the ligament and loss of parallel alignment of the linear echoes, which were shorter than normal in longitudinal images.     

Use of ultrasonography to detect pulmonary lesions in Thoroughbred foals in Argentina

Rhodococcus equi is an important cause of pulmonary disease in foals often related to economic losses and death. A study was performed on a Thoroughbred farm (Buenos Aires Province, Argentina) where this disease was enzootic causing 1–2% of foal deaths every year. One hundred foals were monitored by thoracic ultrasonography at ages 1–5 months to detect pulmonary lesions in order to initiate an early treatment. This strategy allowed reducing the number of foal deaths almost totally. In our experience, thoracic ultrasonography was proved to be very efficient in detection of early cases of pneumonia on a farm with high density of horses and intensive management.     

Rethinking equine gastric ulcer syndrome: Part 2 – Equine squamous gastric ulcer syndrome (ESGUS)

It has recently been highlighted that significant differences in prevalence, risk factors and the response to treatment exist between ulceration of the squamous gastric mucosa and ulceration of the glandular gastric mucosa in the horse. In the first article in the series, the term equine squamous gastric ulcer syndrome (ESGUS) was used to describe disease of the squamous gastric mucosa with clinical signs and diagnosis discussed. The purpose of this article is to review the pathophysiology, risk factors, prevalence, treatment and prevention of ESGUS.     

A comparison of the prevalence of gastric ulceration in feral and domesticated horses in the UK

Equine gastric ulcer syndrome is common in domesticated horses, especially those performing in athletic endeavours. However, the prevalence of equine gastric ulcer syndrome in feral populations of horses is not documented. This study investigated the prevalence and severity of squamous and glandular gastric ulceration in an abattoir population of horses in the UK. Both squamous and glandular ulceration were more prevalent in domesticated horses when compared to the feral horses studied.     

Effect of romifidine on gastrointestinal motility, assessed by transrectal ultrasonography.

A technique of transrectal ultrasonography was developed to investigate the effects of romifidine 80 and 120 microg/kg bwt on intestinal motility in the horse. Motility of the small intestine, caecum and left ventral colon were assessed following injection of romifidine and a saline control, using a blinded, cross-over study design in 6 horses. Measurements were taken at 15, 30, 60, 120, 180 and 240 min after drug administration. There was a slight nonsignificant decrease in motility in the control group over the 4 h study period. Both doses of romifidine produced a marked decrease in gastrointestinal motility and were associated with the presence of reduced (nonpropulsive) contractions. Transrectal ultrasonography proved suitable for monitoring changes in the type and frequency of intestinal motility in the horse.