Bromism: An overlooked and elusive toxidrome from chronic dextromethorphan abuse.

A 47 year old woman presented to the emergency department for an intentional overdose of an over the counter cough suppressant. She had been seen multiple times over the last several months with the same presentation. Her work up revealed a significantly elevated chloride level (125 mmol/L, normal 98-107) as well as an anion gap of 1. She denied any other co-ingestions, including other over the counter medications or alcohol, and was otherwise asymptomatic. She was given fluids and supportive care. Ultimately, a significantly elevated bromide level was noted on a send out lab. She was diagnosed with chronic bromide toxicity (bromism) from recurrent over the counter Robitussin HBr use, which was the source of her hyperchloremia and decreased anion gap.

Effects of three infusion fluids with different sodium chloride contents on steady-state serum concentrations of bromide in dogs.

Potassium bromide overdose (bromism) in the management of canine epilepsy has been known. However, a protocol to reduce bromide concentrations rapidly has not been previously established. The effects of three infusion fluids with different chloride contents on the steady-state serum concentrations of bromide in beagles were determined. After stabilization of the serum bromide concentrations, seven dogs were infused with saline (Na+ 154 mmol/L; Cl- 154 mmol/L), lactated Ringer's (Na+ 131 mmol/L; Cl- 110 mmol/L), or maintenance solutions (Na+ 35 mmol/L; Cl- 35 mmol/L) at a rate of 2 or 10 ml kg-1  hr-1 for 5 hr. Serum and urine were collected hourly, and the bromide concentrations were measured. When saline and lactated Ringer's solutions were infused at a rate of 10 ml kg-1  hr-1 for 5 hr, serum bromide concentrations were decreased by 14.24% and urine bromide concentrations by 17.63%, respectively. Of all compositions of infusion fluids, only sodium and chloride contents were associated with the decreased serum concentrations and the increased renal clearance of bromide. In summary, saline and lactated Ringer's solutions reduced serum bromide concentrations in a sodium chloride-dependent manner in dogs were found when infused at 10 ml kg-1  hr-1 for 5 hr.

A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy.

Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0-9·89/month) in comparison with the placebo diet (2·67/month, 0·33-22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68-43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0-7·58/month) in comparison with the placebo diet (1·69/month, 0·33-13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood ß-hydroxybutyrate concentrations in comparison with placebo diet (0·071 (sd 0·035) v. 0·053 (sd 0·028) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment.

Compounding errors in 2 dogs receiving anticonvulsants.

Two cases that involve drug compounding errors are described. One dog exhibited increased seizure activity due to a compounded, flavored phenobarbital solution that deteriorated before the expiration date provided by the compounder. The other dog developed clinical signs of hyperkalemia and bromine toxicity following a 5-fold compounding error in the concentration of potassium bromide (KBr).

Quantification of bromide ion in biological samples using headspace gas chromatography-mass spectrometry.

OBJECTIVES: In this study, we aimed to establish a method for quantifying bromide ions (Br- ) in blood and urine using gas chromatograph-mass spectrometer (GC-MS) equipped with a headspace sampler, for biological monitoring of workers exposed to methyl bromide. METHODS: Samples were mixed with dimethyl sulfate, and Br- ions were detected using GC-MS with a headspace sampler. The validity of the proposed method was evaluated based on most of the US FDA guidance. The values obtained were compared with reference values by analysis using SeronormTM Trace Elements Whole Blood L-1 RUO. RESULTS: The calibration curve showed good linearity in the Br- concentration range of 0.1-20.0 mg/L, and the coefficient of determination R2 value was >.999. Intraday and interday accuracy values were 99.3%-103.1% and 97.4%-101.8%, respectively. The measured and reference values of Seronorm were concordant. Herein, eight urine and serum samples of workers were analyzed; the samples' Br- concentrations were known. The correlation coefficients of urine and serum samples were 0.97 and 0.96, respectively, and results were consistent. CONCLUSIONS: This study established a simple and rapid method for the determination of Br- concentration in biological samples using GC-MS with a headspace sampler. Moreover, it can be used for biological monitoring of occupational exposure to methyl bromide and for the determination of Br- concentration in a wide range of biological samples.

Perchlorate and iodide in whole blood samples from infants, children, and adults in Nanchang, China.

Perchlorate, ClO(4)(-), interferes with iodide (I(-)) uptake by the sodium-iodide symporter (NIS) and thereby affects thyroid hormone production in the body. Studies have reported human exposures to perchlorate based on measurements in urine, but little is known about the levels in blood. In this study, we determined concentrations of perchlorate, iodide, and other anions (e.g., chlorate [ClO(3)(-)], bromate [BrO(3)(-)], bromide [Br(-)]) in 131 whole blood samples collected from Chinese donors aged 0.4 to 90 yr, in Nanchang, China. Perchlorate, iodide, and bromide were detected in all of the samples analyzed, whereas chlorate was found in only 27% of the samples and bromate was found in only 2%. The mean (range) concentrations of perchlorate, iodide, and bromide were 2.68 (0.51-10.5), 42.6 (1.58-812), and 2120 (1050-4850) ng/mL, respectively. Perchlorate levels in blood from Nanchang adults were 10-fold greater than levels that have been previously reported for U.S. adults. The iodide/perchlorate molar ratio ranged from 3.05 to 15.3 for all age groups, and the ratio increased with age (r = 0.732, p < 0.01). Perchlorate and bromide concentrations decreased significantly with age, whereas iodide concentrations increased with age. No significant gender-related differences in blood perchlorate, iodide, or bromide levels were found. A significant negative correlation was found between the concentrations of perchlorate and iodide in blood. Exposure doses of perchlorate were estimated for infants, toddlers, children, adolescents, and adults based on the measured concentrations in blood, using a simple pharmacokinetic model. The mean exposure doses of perchlorate for our age groups ranged from 1.12 (adults) to 2.22 µg/kg bw/day (infants), values higher than the United States Environmental Protection Agency's (USEPA) reference dose (RfD: 0.7 µg/kg bw/day). This is the first study on perchlorate and iodide levels in whole blood from infants, toddlers, children, adolescents, and adults from a city in China with known high perchlorate levels.

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Population pharmacokinetic methods were used to characterize the pharmacokinetics of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) when administered as a fixed-dose combination via a single closed inhaler. METHODS: Plasma concentration data from three studies were analyzed using non-linear mixed-effects modeling in NONMEM®. RESULTS: The pooled dataset consisted of 2948, 2589, and 3331 FF, UMEC, and VI observations from 714, 622, and 817 patients with COPD, respectively. There were 41%, 13%, and 21% of observations below the quantification limit for FF, UMEC, and VI, respectively. The pharmacokinetics of FF, UMEC, and VI were all adequately described by a two-compartment model with first-order absorption. The following covariates were statistically significant, but none were considered to be clinically relevant. For FF, Japanese heritage and FF/VI treatment on apparent inhaled clearance (CL/F) with FF CL/F 35% lower in patients of Japanese heritage across all treatments and FF CL/F 42% higher in patients with COPD following FF/VI administration. This is in line with the product label. For UMEC, weight, age, and smoking status on CL/F and weight on apparent volume of distribution (V2/F) with every 10% increase in age from 60 years of age leading to approximately a 6% decrease in UMEC CL/F and every 10% increase in weight from 70 kg leading to approximately a 6% increase in UMEC CL/F and approximately an 8% increase in UMEC V2/F. For a subject with COPD who smoked, UMEC CL/F was 28% higher. For VI, weight on CL/F and smoking status on V2/F with an approximately 4% increase in VI CL/F for every 10% increase in weight from 70 kg, and for a subject with COPD who smoked, VI V2/F was 46% higher. The majority of these covariates have been previously identified in historical analyses. None of these effects were clinically relevant in terms of systemic exposures and do not warrant dose adjustment. CONCLUSIONS: All FF, UMEC, and VI plasma concentrations were well interspersed with historical data and were all adequately described by a two-compartment model with first-order absorption. There were no clinically relevant differences in FF, UMEC, or VI systemic exposures when administered as FF/UMEC/VI, FF/VI + UMEC, or the dual combinations FF/VI and/or UMEC/VI.

What is your diagnosis? Marked hyperchloremia in a dog.

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.

Environmental exposure of humans to bromide in the Dead Sea area: Measurement of genotoxicy and apoptosis biomarkers.

Bromide (Br-) is a bromine atom with a negative charge which is released mainly in the production of pesticides and flame retardants. It is also found naturally in seawater. Br¯ has been associated with many detrimental effects such as respiratory problems, gastric hemorrhages, and dermal burns. The aim of the study was to monitor serum bromide in humans and to correlate its level with genotoxicity and apoptosis in human. The study utilized comet assay, to measure DNA damage in peripheral leukocytes (i.e. T%DNA), enzyme-linked immunosorbent assay were used to determine fortilin level as an apoptosis marker, and spectrophotometry to measure serum Br¯ in two populations at the Dead Sea area, which are located close to and far from a local bromine factory: Ghor As-safi and Deir Alla, respectively. The biomarkers were compared with the correlating serum Br¯. A total of 397 individuals were involved in the study. The serum Br- and the genotoxicity biomarker were significantly higher (p < 0.001) in Ghor As-safi than in Deir Alla. In contrast, serum fortilin did not differ significantly between the two regions (p > 0.05). T%DNA was significantly correlated (r = 0.867, p < 0.01) to serum Br¯. In conclusion, residing near a bromide source site is increasing the bromide body burden, and enhancing genotoxicity with no detectible apoptosis. Furthermore, the selected biomarkers could serve as tools to assess the toxicity of bromide as a consequence of environmental exposure.

Determination of bromide in canine plasma using ion chromatography.

A new ion chromatographic procedure has been developed and validated for the determination of bromide in canine plasma. Following a simple dilution, samples were separated on a Metrosep A Supp 5 column. The mobile phase was an isocratic mixture of 2.2 mM Na(2)CO(3), 1.0 mM NaHCO(3), and 1% acetonitrile, with a flow-rate of 0.7 ml/min. The procedure produced a linear curve over the concentration range of 50-2500 microg/ml. The development of the assay permitted the determination of therapeutic levels after oral administration of potassium bromide to dogs being treated for epilepsy.

Pharmacokinetics of potassium bromide in adult horses.

OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after a single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned into two treatment groups. In Part 1 of the study, horses were given a single oral dose of 120 mg/kg KBr. 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 bromide were determined by colorimetric spectrophotometry following drug administration to permit determination of concentration versus time curves from which pharmacokinetic parameters could be calculated. 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 bromide concentration following a single dose of KBr (120 mg/kg) was 284 +/- 15 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 days) gave a maximum serum bromide concentration of 1098 +/- 105 microg/mL. The administration of lower, maintenance doses of KBr (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 700 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: A loading dose of 120 mg/kg daily over 5 days and maintenance doses of approximately 90-100 mg/kg of KBr administered once daily are predicted to result 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.

Development of a rat dosimetry model for bromate.

Bromate is a known animal carcinogen that is found in drinking water supplies treated with ozone. Bromate targets the kidney for toxicity and cancer, the peritoneum for cancer (mesotheliomas derived from testes), testes for lowered sperm count and the thyroid for follicular cell cancer. Kidney tumors as well as other toxicities may be caused by the metabolism of bromate to reactive intermediates. There is evidence that bromate and its stable metabolite bromide are actively transported by the sodium iodide transporter (NIS) protein found in the thyroid, kidney and testes. This association strongly suggests that characterizing the preferential distribution of bromate into the NIS-rich tissues and its subsequent metabolism to reactive metabolites is important for interpreting the dose-response characteristics of bromate in rodents. In this paper the current evidence for NIS dependent dosimetry for bromate is developed and studies are proposed to develop a physiologically based pharmacokinetic (PBPK) model for bromate. The recent PBPK models describing NIS protein transport of perchlorate and radiolabeled iodide offer a template for the development of the bromate model in rodents and humans. The proposed research is expected to be instrumental in quantifying the human health risks associated with ingestion of low levels of bromate in drinking water.

Analysis of bromate and bromide in blood.

Bromate is a regulated disinfection byproduct primarily associated with the ozonation of water containing bromide, but also is a byproduct of hypochlorite used to disinfect water. To study the pharmacokinetics of bromate, it is necessary to develop a robust and sensitive analytical method for the identification and quantitation of bromate in blood. A critical issue is the extent to which bromate is degraded presystemically and in blood at low (environmentally relevant) doses of ingested bromate as it is delivered to target tissue. A simple isolation procedure was developed using blood plasma spiked with various levels of bromate and bromide. Blood proteins and lipids were precipitated from plasma using acetonitrile. The resulting extracts were analyzed by ion-chromatography with inductively-coupled plasma mass spectrometry (IC-ICP/MS), with a method reporting limit of 5 ng/mL plasma for both bromate and bromide. Plasma samples purchased commercially were spiked with bromate and stored up to 7 days. Over the 7 day storage period, bromate decay remained under 20% for two spike doses. Decay studies in plasma samples from spiked blood drawn from live rats showed significant bromate decay within short periods of time preceding sample freezing, although samples which were spiked, centrifuged and frozen immediately after drawing yielded excellent analytical recoveries.

Direct analysis of bromide in human serum by capillary electrophoresis.

The purpose of the present work was the development and validation of a simple, rapid and reliable method for direct bromide quantification in serum based on capillary electrophoresis (CE). The analysis was carried out with an automated capillary electropherograph. Analytical conditions were as follows. Capillary: uncoated fused silica, effective length 50 cm, internal diameter 50 microm; voltage: 20 kV in reverse polarity mode; temperature: 25 degrees C; running buffer: 90 mmol/L sodium tetraborate decahydrate and 10 mmol/L NaCl, pH 9.24; detection: direct UV absorption at 200 nm; sample treatment: dilution of serum 1:10 with the internal standard solution (2 mmol/L thiocyanate). Under the described conditions, bromide ions and internal standard were baseline separated in 7 min. No interferences from other serum components were observed. The analytical sensitivity was characterized by a LOD: 0.05 mmol/L and a LOQ of 0.1 mmol/L. Excellent linearity was verified in the range from 2.5 to 60 mmol/L [y = 0.0746x - 0.0372; R2 = 0.9995 (x = bromide concentration; y = bromide peak area/internal standard (I.S.) peak area)]. Quantitative imprecision in intra-day (n = 7) and day-to-day (n = 7) experiments was always within R.S.D. values <2%. Recovery was quantitative throughout the range of linearity of the method. Clinical cases of infants undergoing potassium bromide therapy for refractory epilepsy were analyzed with results in agreement with literature data. On the basis of these considerations, capillary electrophoresis can be proposed as the method of choice for bromide analysis in serum samples, especially for therapeutic drug monitoring purposes.

Assessment of the use of plasma and serum chloride concentrations as indirect predictors of serum bromide concentrations in dogs with idiopathic epilepsy.

BACKGROUND: Bromide (BR) administration causes pseudohyperchloremia when plasma or serum chloride (Cl-) concentrations are determined with commonly available automated analytical assays. In humans receiving BR, it has been previously demonstrated that the plasma Cl- concentration is a useful indirect estimator of the measured BR concentration. OBJECTIVE: The objective of this study was to determine if the magnitude of pseudohyperchloremia seen in epileptic dogs treated with BR could be used as a predictor of the measured serum BR concentration. METHODS: Plasma and serum Cl- concentrations, analyzed by ion-specific electrode (ISE) and colorimetric techniques, and serum BR concentrations, determined using the gold-trichloride assay, were simultaneously determined in 88 blood samples from dogs with idiopathic epilepsy that were treated with BR. RESULTS: For all methods used to quantify Cl- concentrations, there were significant (P < .0001) linear relationships between BR and Cl- concentrations. Linear relationships between BR and Cl- concentrations were significantly different (P < .0001) between blood samples from dogs obtained during routine therapeutic monitoring and those obtained during emergency hospital admissions. Calculated 95% prediction intervals for future values of BR using measured Cl- concentrations contained considerable error. Plasma Cl- values determined with ISE generally provided the best prediction of serum BR concentrations. Agreement between the measured BR and Cl- using all Cl- assay techniques was moderate, but was statistically significant only when Cl- was assayed in plasma using one ISE method. CONCLUSIONS: The pseudohyperchloremia observed in epileptic dogs receiving BR is an inadequate indirect estimator for the measured BR concentration, although in certain clinical situations identified through construction of a clinical decision tree, the measured Cl- value can be used to guide general therapeutic decisions regarding alterations in BR therapy. Optimal tailoring of BR therapy in dogs with idiopathic epilepsy should be based on results of therapeutic monitoring of BR concentrations.

Bromoderma mimicking pyoderma gangrenosum caused by commercial sedatives.

Bromoderma is a rare skin disorder caused by bromide intake. It presents as single or multiple papillomatous nodules or plaques, and ulcers studded with small pustules on the face or limbs. The clinical features of bromoderma are similar to those of pyoderma gangrenosum. A 41-year-old Japanese woman was diagnosed with pyoderma gangrenosum 11 years prior to presentation. Pyoderma had repeatedly appeared over her entire body despite treatment. She also frequently complained of syncopal episodes. She was admitted to our hospital after loss of consciousness and an episode of generalized convulsion. Laboratory tests revealed a negative serum anion gap and hyperchloremia. Her serum bromide level was significantly elevated, suggesting bromide intoxication. The patient had a 10-year history of high serum bromide levels. After the intake of bromide-containing sedatives was stopped, there was no recurrence of pyoderma in the absence of treatment. In conclusion, this case was diagnosed as bromoderma with commercial sedative-induced bromide intoxication. Although the US Food and Drug Administration have banned the use of bromides, over-the-counter (OTC) treatments containing bromides are still used in Japan and other countries. Long-term use of OTC medicines containing bromvalerylurea may result in the development of bromoderma. If unclarified neurological or psychiatric symptoms are associated with pyoderma, we propose measurement of the patient's serum chloride concentration. Determination of hyperchloremia is helpful for the diagnosis of chronic intoxication with bromides.

Temperature dependence of anion transport in the human red blood cell.

Arrhenius plots of chloride and bromide transport yield two regions with different activation energies (Ea). Below 15 or 25 degrees C (for Cl- and Br-, respectively), Ea is about 32.5 kcal/mol; above these temperatures, about 22.5 kcal/mol (Brahm, J. (1977) J. Gen. Physiol. 70, 283-306). For the temperature dependence of SO4(2-) transport up to 37 degrees C, no such break could be observed. We were able to show that the temperature coefficient for the rate of SO4(2-) transport is higher than that for the rate of denaturation of the band 3 protein (as measured by NMR) or the destruction of the permeability barrier in the red cell membrane. It was possible, therefore, to extend the range of flux measurements up to 60 degrees C and to show that, even for the slowly permeating SO4(2-) in the Arrhenius plot, there appears a break, which is located somewhere between 30 and 37 degrees C and where Ea changes from 32.5 to 24.1 kcal/mol. At the break, the turnover number is approx. 6.9 ions/band 3 per s. Using 35Cl- -NMR (Falke, Pace and Chan (1984) J. Biol. Chem. 259, 6472-6480), we also determined the temperature dependence of Cl- -binding. We found no significant change over the entire range from 0 to 57 degrees C, regardless of whether the measurements were performed in the absence or presence of competing SO4(2-). We conclude that the enthalpy changes associated with Cl- - or SO4(2-)-binding are negligible as compared to the Ea values observed. It was possible, therefore, to calculate the thermodynamic parameters defined by transition-state theory for the transition of the anion-loaded transport protein to the activated state for Cl-, Br- and SO4(2-) below and above the temperatures at which the breaks in the Arrhenius plots are seen. We found in both regions a high positive activation entropy, resulting in a low free enthalpy of activation. Thus the internal energy required for carrying the complex between anion and transport protein over the rate-limiting energy barrier is largely compensated for by an increase of randomness in the protein and/or its aqueous environment.

Determination of bromide in whole blood and urine from humans using gas chromatography-mass spectrometry.

We devised a sensitive and simple method for determination of bromide in whole blood and urine from humans using gas chromatography-mass spectrometry. Bromide was alkylated with pentafluorobenzyl p-toluenesulphonate in the mixture of acetone and phosphate buffer (pH 6.8). The derivative obtained was analyzed using gas chromatography-mass spectrometry with the positive-ion EI mode. The lower limit of detection for the compound was 1 mg/l. The calibration curve for bromide was linear over the concentration range from 2 to 100 mg/l. With use of this method, levels of bromide in whole blood and urine were determined in cases of poisoning by inhaled brominated hydrocarbons.

Prolonged bromide intoxication resulting from a gastric bezoar.

Bromide intoxication is now a relatively uncommon disease. We describe a critically ill patient who had an elevated chloride level and neurologic abnormalities. Bromide levels were also elevated, and remained so for several days. After more than 12 days of abnormally high serum bromide and chloride levels, endoscopy was performed. This procedure disclosed a gastric bezoar containing identifiable pill fragments. The gastric washings from these fragments contained high levels of bromide. We believe that the prolonged course of bromide intoxication secondary to a gastric bezoar makes this case unique.

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.