Compounds containing bromide ions (including potassium-, sodium-, and ammonium bromide) were once used as sedatives and anticonvulsants and were a major ingredient in over-the-counter products (eg, Bromo-Seltzer, Dr. Miles' Nervine) until 1975. Bromides are still used to treat epilepsy in dogs. Bromism (chronic bromide intoxication) was once common; 10% of patients admitted to psychiatric hospitals once had measurable bromide levels. Although now rare, bromism cases are still reported worldwide owing to bromide-based medications. Examples include: Cordial de Monell, a teething/colic medication recalled because of infant bromism (United States); pipobroman, an alkylating agent used for polycythemia vera (UK); and bromovaleryl urea (bromisoval) used as an analgesic (Taiwan); several of the aforementioned preparations are still available for purchase online or in certain countries. In 2007, table salt contamination led to the greatest recorded outbreak of bromide poisoning, with 467 officially recognized cases (Angola). Case reports indicate that bromism can result from chronic ingestion of dextromethorphan hydrobromide and some soft drinks containing brominated vegetable oil. Bromide is also found in photographic chemicals, in some well water, and in bromide-containing hydrocarbons (eg, methyl bromide, ethylene dibromide, halothane). Foods fumigated with methyl bromide may contain some residual bromide, but the amounts are too small to cause bromide toxicity.

1. Bromide ions substitute for chloride in various membrane transport systems, particularly within the nervous system. Bromide ions diffuse more readily through GABA_A receptor-mediated chloride channels, enhancing inhibitory neuronal effects. Bromide is preferentially reabsorbed over chloride by the kidney, and chloride excretion further increases when bromide ion intake exceeds elimination. Up to 45% of chloride may be replaced in the body. With high bromide levels, the membrane-depressant effect progressively impairs neuronal transmission.
2. Pharmacokinetics. The volume of distribution is 0.35-0.48 L/kg; bioavailability of bromide salts is nearly 100%. The half-life is 9-12 days, and bioaccumulation occurs with chronic exposure. Clearance is about 26 mL/kg/d; elimination is renal. Bromide is excreted in breast milk. It crosses the placenta, and neonatal bromism has been described.

The adult therapeutic dose is 3-5 g. One death was reported after ingestion of 100 g of sodium bromide. Ingestion of 0.5-1 g per day may cause bromism.

Death is rare. Acute oral overdose usually causes nausea and vomiting from gastric irritation. Chronic ingestion can result in a variety of neurologic, psychiatric, GI, and dermatologic effects.

1. Neurologic and psychiatric manifestations are protean and include restlessness, irritability, ataxia, confusion, memory impairment, hallucinations, schizophreniform psychosis, weakness, stupor, and coma.
2. Gastrointestinal effects include nausea and vomiting (acute ingestion) and anorexia and constipation (chronic use).
3. Dermatologic effects include acneiform, pustular, granulomatous, bullous, and erythematous rashes. Up to 25-30% of patients are affected.

Consider bromism in any confused or psychotic patient with a high serum chloride level and a low or negative anion gap. The serum chloride level is often falsely elevated (up to >200 mEq/L in some reports) due to interference by bromide when ion selective electrodes are used. The degree of elevation varies with the method of chloride measurement.

1. Specific levels. Assays are not readily available from most clinical laboratories, although veterinary facilities may have measurement capabilities. Endogenous serum bromide does not usually exceed 5 mg/L (0.06 mEq/L). The threshold for detection by usual methods is 50 mg/L. Therapeutic levels are 50-100 mg/L (0.6-1.2 mEq/L); levels above 3,000 mg/L (40 mEq/L) may be fatal.
2. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, and abdominal radiography (bromide is radiopaque).

1. Emergency and supportive measures
   1. Protect the airway and assist ventilation if needed.
   2. Treat coma if it occurs.
2. Specific drugs and antidotes. There is no specific antidote. However, administering chloride will promote bromide excretion (see below).
3. Decontamination. After a recent large ingestion, gastric lavage may decrease further absorption. Activated charcoal does not adsorb inorganic bromide ions, but it may adsorb organic bromides (eg, methyl bromide).
4. Enhanced elimination. Bromide is eliminated entirely by the kidney. The serum half-life can be reduced dramatically with fluids and chloride loading, although levels may rebound due to redistribution from intracellular compartments. The goal of treatment is resolution of symptoms.
   1. Administer sodium chloride IV as normal saline (0.9% sodium chloride) at a rate sufficient to obtain a urine output of 2-4 mL/kg/h. Furosemide, 1 mg/kg, may assist urinary excretion.
   2. Hemodialysis is effective and may be indicated in patients with renal insufficiency or severe toxicity; case reports indicate that hemodialysis may speed resolution of symptoms.