What is your diagnosis? Marked hyperchloremia in a dog

Abstract: A 5‐year‐old neutered male Cavalier King Charles Spaniel was evaluated for a 3‐week history of progressive paresis. The dog had been receiving potassium citrate capsules to acidify urine for the past 2 years because of an earlier history of urolithiasis. Results of neurologic examination, spinal cord radiography, and magnetic resonance imaging of the skull and spinal cord revealed no lesions that could have accounted for the neurologic signs. The main abnormalities on a clinical chemistry profile were marked hyperchloremia (179 mmol/L, reference interval 108–122 mmol/L) and an anion gap of ?50.4 mmol/L (reference interval 16.3–28.6 mmol/L). Because of the severe hyperchloremia, serum bromide concentration was measured (400 mg/dL; toxic concentration >150 mg/dL; some dogs may tolerate up to 300 mg/dL). Analysis of the potassium citrate capsules, which had been compounded at a local pharmacy, yielded a mean bromide concentration of 239 mg/capsule. Administration of the capsules was discontinued and there was rapid resolution of the dog's neurologic signs. This case of extreme bromide toxicity, which apparently resulted from inadvertent use of bromide instead of citrate at the pharmacy, illustrates the importance of knowing common interferents with analyte methodologies and of pursing logical additional diagnostic tests based on clinical and laboratory evidence, even when a patient's history appears to rule out a potential etiology.     

Determination of the acute oral toxicity of theophylline in conscious dogs

The purpose of this study was to define the minimum toxic concentrations and clinical signs of theophylline toxicity in healthy, conscious dogs. Five dogs were dosed orally in a five-way crossover design with sustained release theophylline (Theo-Dur tablets, Key Pharmaceuticals) at 0, 20, 40, 80, and 160 mg/kg. They were observed for a 9-h period for clinical signs of toxicity which had been previously determined in a pilot study. These signs included sinus tachycardia and central nervous stimulation (manifested as restlessness, excitement, or vomition). The Physiotel radiotransmitter telemetry system was used for the acquisition of the heart rate and ECG. Blood samples were obtained every hour for theophylline determination by high pressure liquid chromatography. The results showed that toxicity occurs at higher theophylline plasma concentrations in the dog (37-60 micrograms/ml) as compared to man (greater than 20 micrograms/ml) when dosed orally. Since current dosage regimens in dogs are designed to maintain trough-peak theophylline plasma concentrations between 10 and 20 micrograms/ml, the results indicate that the upper limit of this range appears to be safe in the dog.     

Ureterocolonic anastomosis in clinically normal dogs

Ureterocolonic anastomosis was evaluated in 13 clinically normal dogs. Urinary continence was maintained after surgery, and the procedure was completed without technique errors in all but 2 dogs. Three dogs died within 5 weeks (2 of undetermined causes and 1 of aspiration pneumonia and neurologic disease), and 1 dog was euthanatized 4 months after surgery because of neurologic signs. Two healthy dogs were euthanatized 3 months after surgery for light microscopic evaluation of their kidneys. Five dogs were euthanatized 6 months after surgery for light microscopic evaluation of their kidneys. Gastrointestinal and neurologic disturbances developed in 4 dogs at various postoperative intervals. Plasma ammonia concentration measured in 2 dogs with neurologic signs was increased. Plasma ammonia concentration measured in 5 dogs without neurologic signs was within normal limits. All 5 dogs, in which metabolic acidosis was diagnosed, had high normal or above normal serum chloride concentration. Serum urea nitrogen values were increased after surgery because of colonic absorption of urea. Serum creatinine concentration was increased in 1 dog 6 months after surgery. Individual kidney glomerular filtration rate was reduced in 38% (3/8) of the kidneys from 4 other dogs at 6 months after surgery. Of 5 dogs euthanatized at 3 to 4 months after surgery, 4 had bilateral pyelitis, and 1 had unilateral pyelonephritis. Six months after surgery, pyelonephritis was diagnosed in 40% (4/10) of the kidneys from 5 dogs. The ureterocolonic anastomosis procedure is a salvage procedure that should allow complete cystectomy. However, variable degrees of metabolic acidosis, hyperammonemia, and neurologic disease may result.     

Serum digoxin concentrations in dogs before and during concomitant administration of furosemide

Healthy dogs were treated once a day for 16 days with a liquid, oral dosage form of digoxin (0.022 mg/kg). From day 9 to 16 they were also injected intramuscularly with furosemide (4.4 mg/kg). Serum digoxin was measured by a radioimmunoassay technique. Eight hours after the eighth dose of digoxin had been administered, serum digoxin concentration was in the accepted therapeutic range. After 8 days of concomitant administration of digoxin and furosemide, serum digoxin concentration was found to be in the accepted moderate-to-severe toxic range. Clinical signs of digitalis toxicosis were consistently observed during the combined digoxin-plus-furosemide treatment period. There was no significant ( P >0.05) change in the serum concentrations of potassium, sodium, or in osmolality during digoxin treatment alone. Serum creatinine concentrations remained within the accepted normal range for dogs. Serum sodium concentration was significantly ( P <0.05) lower during combined digoxin-plus-furosemide treatment when compared to digoxin treatment only.
Results indicate that an interaction between digoxin and furosemide occurred which led to significantly ( P <0.05) higher concentrations of serum digoxin during combined digoxin and furosemide treatment.     

Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in epileptic dogs treated with anticonvulsants.

OBJECTIVE: To determine whether administration of phenobarbital, potassium bromide, or both drugs concurrently was associated with abnormalities in baseline serum total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone; TSH) concentrations in epileptic dogs. DESIGN: Prospective case series. ANIMALS: 78 dogs with seizure disorders that did not have any evidence of a thyroid disorder (55 treated with phenobarbital alone, 15 treated with phenobarbital and bromide, and 8 treated with bromide alone) and 150 clinically normal dogs that were not receiving any medication. PROCEDURE: Serum total T4, total T3, free T4, and TSH concentrations, as well as serum concentrations of anticonvulsant drugs, were measured in the 78 dogs with seizure disorders. Reference ranges for hormone concentrations were established on the basis of results from the 150 clinically normal dogs. RESULTS: Total and free T4 concentrations were significantly lower in dogs receiving phenobarbital (alone or with bromide), compared with concentrations in clinically normal dogs. Administration of bromide alone was not associated with low total or free T4 concentration. Total T3 and TSH concentrations did not differ among groups of dogs. CLINICAL IMPLICATIONS: Results indicate that serum total and free T4 concentrations may be low (i.e., in the range typical for dogs with hypothyroidism) in dogs treated with phenobarbital. Serum total T3 and TSH concentrations were not changed significantly in association with phenobarbital administration. Bromide treatment was not associated with any significant change in these serum thyroid hormone concentrations.     

Serum triglyceride concentration in dogs with epilepsy treated with phenobarbital or with phenobarbital and bromide

OBJECTIVE: To compare serum triglyceride concentrations obtained after food had been withheld (i.e., fasting concentrations) in dogs with epilepsy that had been treated long term (> or = 3 months) with phenobarbital or with phenobarbital and potassium bromide with concentrations in healthy control dogs. DESIGN: Cross-sectional study. ANIMALS: 57 epileptic dogs that had been treated with phenobarbital (n=28) or with phenobarbital and bromide (29) and 57 healthy, untreated control dogs matched on the basis of age, breed, sex, neuter status, and body condition score. PROCEDURES: Blood samples were collected after food had been withheld for at least 12 hours, and serum biochemical and lipid concentrations were determined. Oral fat tolerance tests were performed in 15 control dogs and 9 dogs with epilepsy treated with phenobarbital alone. RESULTS: 19 of the 57 (33%) epileptic dogs had fasting serum triglyceride concentrations greater than the upper reference limit. Nine (16%) dogs had a history of pancreatitis, and 5 of the 9 had high fasting serum triglyceride concentrations at the time of the study. A significant relationship was found between body condition score and fasting serum triglyceride concentration in all dogs, but serum triglyceride concentration was not significantly associated with phenobarbital dosage or serum phenobarbital concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that dogs treated long term with phenobarbital or with phenobarbital and bromide may develop hypertriglyceridemia. Fasting serum triglyceride concentration should be periodically monitored in dogs treated with phenobarbital because hypertriglyceridemia is a risk factor for pancreatitis.     

Severe hypophosphatemia associated with diabetes mellitus in six dogs and one cat

Severe hypophosphatemia was found in 6 diabetic dogs and in one diabetic cat. The cat suffered from hemolysis, and one dog had seizures, both apparently as a result of the severe hypophosphatemia. Clinical signs were not determined solely by the serum concentration of phosphorus, as seen in 5 other patients that did not have signs of disease despite similar serum phosphorus concentrations.     

Pharmacokinetics and toxicity of bromide following high-dose oral potassium bromide administration in healthy Beagles

The pharmacokinetics of a multidose regimen of potassium bromide (KBr) administration in normal dogs was examined. KBr was administered at 30 mg/kg p.o. q 12 h for a period of 115 days. Serum, urine, and cerebrospinal fluid (CSF) bromide (BR) concentrations were measured at the onset of dosing, during the accumulation phase, at steady-state, and after a subsequent dose adjustment. Median elimination half-life and steady-state serum concentration were 15.2 days and 245 mg/dL, respectively. Apparent total body clearance was 16.4 mL/day/kg and volume of distribution was 0.40 L/kg. The CSF:serum BR ratio at steady-state was 0.77. Dogs showed no neurologic deficits during maintenance dosing but significant latency shifts in waves I and V of the brainstem auditory evoked response were evident. Following a subsequent dose adjustment, serum BR concentrations of approximately 400 mg/dL were associated with caudal paresis in two dogs. Estimated half-life during the accumulation phase was shorter than elimination half-lives reported in other studies and was likely related to dietary chloride content. The range of steady-state concentrations achieved suggests individual differences in clearance and bioavailability between dogs. The described protocol reliably produced serum BR concentrations that are required by many epileptic patients for satisfactory seizure control.     

Disposition and clinical use of bromide in cats

OBJECTIVE: To establish a dosing regimen for potassium bromide and evaluate use of bromide to treat spontaneous seizures in cats. DESIGN: Prospective and retrospective studies. ANIMALS: 7 healthy adult male cats and records of 17 cats with seizures. PROCEDURE: Seven healthy cats were administered potassium bromide (15 mg/kg [6.8 mg/lb], p.o., q 12 h) until steady-state concentrations were reached. Serum samples for pharmacokinetic analysis were obtained weekly until bromide concentrations were not detectable. Clinical data were obtained from records of 17 treated cats. RESULTS: In the prospective study, maximum serum bromide concentration was 1.1 +/- 0.2 mg/mL at 8 weeks. Mean disappearance half-life was 1.6 +/- 0.2 weeks. Steady state was achieved at a mean of 5.3 +/-1.1 weeks. No adverse effects were detected and bromide was well tolerated. In the retrospective study, administration of bromide (n = 4) or bromide and phenobarbital (3) was associated with eradication of seizures in 7 of 15 cats (serum bromide concentration range, 1.0 to 1.6 mg/mL); however, bromide administration was associated with adverse effects in 8 of 16 cats. Coughing developed in 6 of these cats, leading to euthanasia in 1 cat and discontinuation of bromide administration in 2 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Therapeutic concentrations of bromide are attained within 2 weeks in cats that receive 30 mg/kg/d (13.6 mg/lb/d) orally. Although somewhat effective in seizure control, the incidence of adverse effects may not warrant routine use of bromide for control of seizures in cats.     

Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989).

The medical records of 18 dogs that had hepatic disease and received phenobarbital as an anticonvulsant for 5 to 82 months were reviewed. Clinical signs included sedation and ataxia in all dogs, 5 dogs were also anorectic, 2 had coagulopathy, 3 were icteric, and 5 had ascites. Serum biochemical analysis revealed serum albumin concentration less than or equal to 2.2. g/dl in 12 dogs, serum alkaline phosphatase activity greater than or equal to 169 U/L in 18 dogs, serum alanine transaminase activity greater than or equal to 57 U/L in 15 dogs, and total bilirubin concentration greater than or equal to 1 mg/dl (in the absence of lipemia) in 7 dogs. Serum phenobarbital concentration was greater than or equal to 40 micrograms/ml in 12 of 17 dogs. Sulfobromophthalein excretion was prolonged in 8 of 10 dogs. Preprandial serum bile acid concentrations were high in 8 of 10 dogs, and 2-hour postprandial serum bile acid concentrations were high in 9 of 10 dogs. Two of 4 dogs tested had resting plasma ammonia concentrations greater than 200 mg/dl. An ammonia tolerance test was performed on 2 other dogs; both had ammonia concentration greater than or equal to 200 mg/dl in the plasma 30 minutes after receiving 100 mg of ammonium chloride/kg of body weight, PO. Nine dogs died, 1 was euthanatized, and necropsies were performed on these 10 dogs. Biopsies and necropsies of 6 dogs revealed chronic hepatic fibrosis with nodular regeneration (cirrhosis). One dog had hepatocellular carcinoma and mild cirrhosis. In 1 dog, after phenobarbital had been withheld, necropsy revealed complete recovery of the previously observed lesions.     

Kinetic study of serum gentamicin concentrations in baboons after single-dose administration

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.     

Bromide Therapy in Refractory Canine Idiopathic Epilepsy

On a retrospective basis, the response to adding chronic oral bromide (BR) to phenobarbital (PB) administration in 23 refractory canine idiopathic epileptics between 1986 and 1991 was studied. The mean age for an observed first seizure was 24 months (range 7 to 72) for all dogs. Thirteen (57%) dogs were males with no breed predisposition observed. All dogs were diagnosed as having idiopathic epilepsy based on normal metabolic and neurologic diagnostic evaluations. Dogs were evaluated before BR therapy for a mean time of 22 months (range 5 to 75 months). Seventeen dogs (74%) received multiple antiepileptic drugs (AEDs) before BR therapy. All animals were maintained on PB at least 4 months before the onset of BR therapy, with a mean trough serum concentration of 37.8 mcg/mL and no improvement in seizure severity or recurrence. Twelve dogs presented with generalized isolated seizures and 11 with generalized cluster seizures (two or more seizures within 24 hours) as their first seizure. The effects of BR therapy were evaluated for a mean time of 15 months (range 4 to 33), with 17 dogs (74%) followed for 12 or more months. The mean BR serum concentration for the 0 to 4 months time period was 117 mg/dL compared with 161 mg/dL for the greater than 4 months period. Overall, response to BR therapy was associated with a reduction in the total number of seizures in 83% of the dogs when compared with their respective pre-BR period. For those followed for 1 year after BR, there was a 53% reduction in the number of seizures compared with the previous 12 months. Furthermore, owners reported a decrease in seizure intensity (65% of dogs) and change to a less severe seizure type (22% of dogs) in those dogs that continued to have seizures. Seizure-free status was obtained in 26% of the dogs with protection continuing up to 31 months in one dog. No correlations could be determined between response to BR and either age of onset of the first seizure or interval from the first AED therapy to BR therapy. Adverse effects of concomitant BR and PB therapy were polydipsia (56% of dogs), polyphagia (30% of dogs), excessive sedation (30% of dogs), and generalized ataxia (17% of dogs). As a result of BR treatment, the PB dosage was reduced in eight dogs (35%). In conclusion, concomitant BR and PB was well tolerated in dogs of this study and was effective in treating refractory canine idiopathic epilepsy, regardless of prior interval of seizure activity or previous treatment. (Journal of Veterinary Internal Medicine 1993; 7:318–327. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Serum salicylate concentrations and endoscopic evaluation of the gastric mucosa in dogs after oral administration of aspirin-containing products

The serum salicylate concentration produced by oral administration of plain aspirin and several aspirin-containing products given at 8-hour intervals for 7 treatments was measured in 36 laboratory-conditioned adult dogs. The dogs were randomly allotted to 6 groups of 6 dogs each: group 1 was given plain aspirin at a dosage of 25 mg/kg of body weight: group 2 was given plain aspirin at a dosage of 10 mg/kg; group 3 was given buffered aspirin at a dosage of 25 mg/kg; group 4 was given enteric-coated aspirin at a dosage of 25 mg/kg; group 5 was given buffered aspirin at a dosage of 25 mg/kg; and, group 6 was given a placebo. Serum salicylate concentration was measured at 2-hour intervals for the first 8 hours, and then at 8-hour intervals for the next 40 hours. Following the last dosing, serum salicylate concentration was measured at 2-hour intervals until 56 hours; the final 2 samples were measured at 64 and 72 hours. The effect of aspirin on the gastric mucosa was studied in 12 dogs, 3 each randomly selected from groups 1, 3, 4, and 5. The gastric mucosa of each dog was examined with a fiberoptic gastroscope 3 days before the beginning of treatment; lesions were not seen. The drugs were administered as described and the gastric mucosa of each dog was reexamined at 72 hours. Administration of the aspirin-containing products at 8-hour intervals resulted in sustained therapeutic serum salicylate concentrations (greater than 5 mg/dl) in all dogs, except those of group 2. The greatest fluctuation in serum salicylate concentration was found in dogs of group 4. Gastric lesions were seen only in the 3 dogs of group 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of potassium bromide in adult horses

OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned to two treatment groups. Group 1 horses were given a single oral dose of 120 mg/kg potassium bromide. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of KBr were measured to construct concentration versus time curves and to calculate pharmacokinetic parameters. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. RESULTS: Maximum mean serum concentration following a single dose of KBr (120 mg/kg) was 423 +/- 22 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 d) gave a maximum serum concentration 1639 +/- 156 microg/mL. The administration of lower, maintenance doses (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 1000 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. CONCLUSIONS: and clinical relevance Loading doses of 120 mg/kg daily over 5 d and maintenance doses of approximately 90 mg/kg of KBr administered once daily resulted in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.     

Transient neuromyopathy after bromide intoxication in a dog with idiopathic epilepsy

A seven-year old Australian Shepherd, suffering from idiopathic epilepsy under treatment with phenobarbitone and potassium bromide, was presented with generalised lower motor neuron signs. Electrophysiology and muscle-nerve biopsies revealed a neuromyopathy.The serum bromide concentration was increased more than two-fold above the upper reference value.Clinical signs disappeared after applying diuretics and reducing the potassium bromide dose rate. This is the first case report describing electrophysiological and histopathological findings associated with bromide induced lower motor neuron dysfunction in a dog.     

Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy

Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally with gabapentin for a minimum of three months at an initial dose of 10 mg/kg every eight hours. They were all experiencing episodes of generalised tonic-clonic seizures and had been treated chronically with a combination of phenobarbital and potassium bromide at doses sufficient to reach acceptable therapeutic serum levels without causing significant side effects. In each dog, the number of seizures per week, the average duration of the seizures and the number of days on which seizures occurred were compared for the three months before and after they were treated with gabapentin. A minimum 50 per cent reduction in the number of seizures per week was interpreted as a positive response to gabapentin, and six of the dogs showed a positive response. After the addition of gabapentin, both the number of seizures per week (P= 0.005) and the number of days with any seizures in a one-week period (P=0.03) were significantly reduced. Mild side effects of ataxia and sedation were observed in five of the dogs, but they were not severe enough to warrant the treatment being discontinued during the trial.     

Hypoglycemia in Four Dogs With Smooth Muscle Tumors

Tumor-associated hypoglycemia has been reported in dogs with pancreatic β-cell tumors, hepatic tumors, and, rarely, with other neoplasms. This article describes 4 dogs with marked hypoglycemia associated with smooth muscle tumors (jejunal leiomyoma, gastric leiomyoma and leiomyosarcoma, and splenic leiomyosarcoma). Presenting clinical signs included grand mal seizures, lethargy, weakness, ataxia, and, in 1 dog, polyuria/polydipsia. The serum insulin concentration was low in 1 dog and normal in the other dog evaluated. Immunohistochemical staining for insulin was negative in the 4 tumors; the 3 tumors arising from the stomach and jejunum stained diffusely positive for glucagon. Blood glucose concentrations rapidly returned to normal after complete surgical resection of the tumors, and clinical signs associated with hypoglycemia resolved. Long-term follow-up available in 3 of the 4 dogs found no recurrence of clinical signs related to hypoglycemia at 15, 31, and 38 months after surgery, respectively.     

Cisplatin Therapy in 41 Dogs With Malignant Tumors

Forty-one dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin (cis-diamminedichloroplatinum, Platinol, Bristol Laboratories, Syracuse, NY 13221-4755) as a single agent at a dosage of 60 mg/m2 given intravenously at 3-week intervals. In an attempt to avoid renal toxicity of cisplatin, saline diuresis was induced and maintained for 4 hours before and 2 hours following cisplatin administration. The dogs received one to ten doses of cisplatin. To determine response to therapy and to monitor toxicity of the drug, the dogs were evaluated with physical examinations including tumor measurements, radiography, complete blood counts, platelet counts, urinalyses, serum urea nitrogen concentrations, and serum creatinine concentrations. An overall response rate of 19% was observed. Complete remission occurred in one of 11 dogs with squamous cell carcinomas and one of one dog with a mediastinal undifferentiated carcinoma. Partial remissions were documented in one of 11 dogs with squamous cell carcinomas, two of three dogs with metastatic osteosarcomas, one of three dogs with nasal adenocarcinomas, and one of one dog with a thyroid adenocarcinoma. Toxic side effects were primarily gastrointestinal in nature, with vomiting occurring 1-6 hours after cisplatin administration in 27 of 41 dogs. Severe anorexia occurred in three dogs, and hemorrhagic diarrhea was observed in one dog. One dog developed grand mal seizures and died 3 hours following therapy. Granulocytopenia was documented in six dogs, and thrombocytopenia was observed in four dogs. One dog showed an increase in serum urea nitrogen and creatinine concentrations, but this patient had known pre-existing renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent

OBJECTIVE: To assess whether there is a change in seizure activity in dogs with refractory epilepsy that are receiving appropriate doses of phenobarbitone and/or potassium bromide, when gabapentin is added to the therapeutic regimen. DESIGN: A prospective study of 17 dogs with a refractory seizure disorder, 16 of which have idiopathic epilepsy. PROCEDURE: Patients were stabilised using phenobarbitone and/or potassium bromide to produce tolerable therapeutic serum concentrations and dosed additionally with gabapentin at 35 to 50 mg/kg/d (divided twice or three times daily) for 4 months. Owners recorded seizure activity and side effects during this period in a standardised diary. Patients underwent monthly physical examinations and venepuncture to assess selected serum biochemical analytes, as well as phenobarbitone and bromide concentrations. Patients were further monitored for long-term response to adjunctive gabapentin therapy. RESULTS: There was no significant decrease in the number of seizures over the study period for the entire cohort, however three dogs stopped seizuring completely. There was a significant increase in the number of patients who showed an increase in the interictal period (P > 0.001). Serum alkaline phosphatase activity and triglyceride concentrations were elevated at baseline. There were no significant changes in biochemical analytes during the course of the study period. Side effects observed initially on addition of gabapentin included sedation and hind limb ataxia. The former resolved spontaneously after a few days; the latter after a slight reduction in bromide dose. Long-term, a further two patients became seizure free and ten patients remained on gabapentin indefinitely. No long-term side effects have become apparent. CONCLUSION: Addition of gabapentin to phenobarbitone and/or potassium bromide increased the interictal period and shortened the post-seizure recovery in some canine epileptics. In some dogs, seizures were prevented completely, while in others there was an increase in interictal period. The short-half life of gabapentin has advantages for seizure control, however its present high cost may prohibit therapy in large dogs.