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Bromide Toxicity from Consumption of Dead Sea Salt

      To the Editor:
      Bromide salt is an effective antiepileptic and sedative in small doses and was once a common ingredient of many medicines and patent tonics such as Dr. Miles' Nervine and Bromo-Seltzer.
      • Bowers Jr, G.N.
      • Onoroski M.
      Hyperchloremia and the incidence of bromism in 1990.
      Unfortunately, the long 10-12 day half-life of bromide results in an intolerably narrow therapeutic window. Bromide toxicity or “bromism” accounted for over 2% of admissions to psychiatric hospitals before the removal of bromide salts from most US medications in 1975.
      • Bowers Jr, G.N.
      • Onoroski M.
      Hyperchloremia and the incidence of bromism in 1990.
      With the advent of Internet commerce, patients now have greater access to relatively unregulated medications and products.
      • Bessell T.L.
      • Silagy C.A.
      • Anderson J.N.
      • et al.
      Quality of global e-pharmacies: can we safeguard consumers?.
      We report a case of bromide toxicity after the consumption of Dead Sea salt obtained over the Internet.
      A 57-year-old man with Asperger syndrome presented complaining of diffuse pain and generalized malaise. Mentally, he was impaired, with disjointed thoughts, labile mood, and disorganized, slurred speech. He denied taking any over-the-counter or herbal medications, and his history was otherwise uninformative. A screening basic metabolic panel returned with a chloride level of “>175 mEq/L” (normal 95-110), yielding an anion gap of −55 mEq/L. To rule out laboratory error, a repeat basic metabolic panel was performed and confirmed the initial value. Such marked hyperchloremia prompted a measurement of the patient's serum bromide, which was found to be 2540 mg/L (32 mEq/L).
      Upon further questioning, the patient reported consuming 3-4 tablespoons of Dead Sea salt daily for several months. He stated that he purchased the Dead Sea salt due to websites' claims of its holistic, calming effects and health benefits. The Dead Sea has the highest bromide concentration of any large body of water in the world, with a bromide concentration of approximately 5 g/L.
      • Grinbaum B.
      • Freiberg M.
      Bromine.
      Bromide intoxication is reported at serum levels as low as 400 mg/L (5 mEq/L), with 1500 mg/L (19 mEq/L) considered toxic.
      • Bowers Jr, G.N.
      • Onoroski M.
      Hyperchloremia and the incidence of bromism in 1990.
      Our patient's bromide level was impressive by these criteria.
      The most common manifestations of bromism are psychiatric and dermatologic. Patients present with weakness, slurred speech, emotional instability, agitation, hallucinations, seizures, and coma.
      • Trump D.L.
      • Hochberg M.C.
      Bromide intoxication.
      Bromoderma occurs in approximately 35% of cases and is characterized by acneiform eruptions or, less commonly, granulomatous plaques, ulcers, or bullae, usually on the face and trunk.
      • Trump D.L.
      • Hochberg M.C.
      Bromide intoxication.
      The finding of hyperchloremia was instrumental in establishing the diagnosis. On many laboratory assays, bromide causes a false hyperchloremia sufficient to yield a negative anion gap. Assays register an additional 3-4 mEq of Cl per mEq of Br due to the greater affinity of bromide for the silver or mercury species used in measuring chloride levels.
      • Bowers Jr, G.N.
      • Onoroski M.
      Hyperchloremia and the incidence of bromism in 1990.
      • Trump D.L.
      • Hochberg M.C.
      Bromide intoxication.
      Other etiologies of a negative anion gap include hyperlipidemia and, rarely, iodide intoxication or paraproteinemia in multiple myeloma.
      • Bowers Jr, G.N.
      • Onoroski M.
      Hyperchloremia and the incidence of bromism in 1990.
      • Kraut J.A.
      • Madias N.E.
      Serum anion gap: its uses and limitations in clinical medicine.
      Bromism should be considered whenever new-onset psychiatric symptoms accompany an elevated chloride level, especially in the setting of a negative anion gap.
      • Bowers Jr, G.N.
      • Onoroski M.
      Hyperchloremia and the incidence of bromism in 1990.
      A case of bromism can be missed if hyperchloremia is dismissed as laboratory error.
      Awareness of this diagnosis is important because the symptoms of bromism are usually completely reversible with cessation of bromide ingestion. Bromide is renally excreted, and its 10-12 day half-life can be shortened to <1 day with saline loading and diuresis.
      • Trump D.L.
      • Hochberg M.C.
      Bromide intoxication.
      Dialysis should be considered in patients with severe symptoms or renal impairment.
      • Trump D.L.
      • Hochberg M.C.
      Bromide intoxication.
      Our patient was successfully treated with saline and furosemide over 5 days and discharged with improved mental status and the recommendation to avoid consuming Dead Sea salt. (Figure).
      Figure thumbnail gr1
      FigureElectrolyte concentrations over time. Patient's admission electrolytes on day 1 were: Na+ 144, K+ 3.6, Cl 175, HCO3 25, Ca2+ 8.3 (reported in mEq/L). The patient was seen several months earlier in outpatient appointment and as reflected in day −195, had normal chloride levels. Saline diuresis was initiated on day 2. Bromide and chloride levels over the next 5 days show a decrease in both values over time. Normal range of chloride and sodium levels are denoted by dashed blue (95-110 mEq) and red (135-145 mEq) lines, respectively. Toxic bromide levels are denoted by dashed black line (5 mEq).

      References

        • Bowers Jr, G.N.
        • Onoroski M.
        Hyperchloremia and the incidence of bromism in 1990.
        Clin Chem. 1990; 36: 1399-1403
        • Bessell T.L.
        • Silagy C.A.
        • Anderson J.N.
        • et al.
        Quality of global e-pharmacies: can we safeguard consumers?.
        Eur J Clin Pharmacol. 2002; 58: 567-572
        • Grinbaum B.
        • Freiberg M.
        Bromine.
        Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc., Hoboken, NJ2001
        • Trump D.L.
        • Hochberg M.C.
        Bromide intoxication.
        Johns Hopkins Med J. 1976; 138: 119-123
        • Kraut J.A.
        • Madias N.E.
        Serum anion gap: its uses and limitations in clinical medicine.
        Clin J Am Soc Nephrol. 2007; 2: 162-174