Pseudohyperchloraemia due to bromvalerylurea abuse

Sir,

Electrolyte imbalance is one of most common causes of unexplained neuropsychological manifestations, but disturbed consciousness due to hyperchloraemia is very rare today. Medication history is generally not easy to obtain spontaneously while obtaining a patient's history; clinicians need to consider carefully the possibility of bromism due to chronic bromide intoxication as one option in an insidious toxic syndrome. We present a case of a patient who suffered from progressive ataxia, dysarthria, dysphagia, delusions, and auditory and visual hallucinations for a year. To our knowledge, this is the first case report of chronic bromvalerylurea (BVU) intoxication presenting with pseudohyperchloraemia in the English literature.

A 73-year-old man with no chronic disease history developed incoherent speech and loss of short-time memory 1 year ago, dysarthria, deteriorated cognitive function and frequent falls had also been noticed for 6 months. Ten days before hospitalization, he was found lying on the floor at home with residual consciousness, worsened dysarthria and incoherent speech. Delirium was also noted over the following days. On arrival at our Emergency Department, a neurological examination revealed incoherent speech, disorientation as to place and time, mild dysarthria, a poor gag reflex with easy choking and gait disturbance (wide-based). His muscle power was full and his bilateral deep tendon reflex, sensory system and autonomic functions were intact. The Romberg's test was negative but he failed the tandem gait test. The rapid alternative movement and finger–nose–finger tests were done clumsily. Other aspects of the physical examination were unremarkable. Initial laboratory studies revealed that haemogram, electrolyte (including sodium, potassium and calcium), liver function and renal function tests were all within the normal range, except for a marked hyperchloraemia (179 mmol/l) and a negative anion gap (the calculated anion gap was –67.1 mEq/l). The work-up for the negative anion gap, including serum lithium level (a suspicion of lithium toxicity), and electrophoresis with immunofixation (a suspicion of multiple myeloma) were all negative. It should be noted that serum chloride levels are rarely as high as that in our patient with lithium toxicity or multiple myeloma. During hospitalization, he also presented with persecutory delusion and bizarre behaviour, as well as both visual and auditory hallucinations. Brain magnetic resonance imaging (MRI) showed periventricular leukoaraiosis and possible microangiopathy. An electroencephalogram (EEG) recording revealed patterns of moderate diffuse cortical dysfunction.

A careful medication history inquiry with his family revealed the patient took ‘Ming-Tong Chih Tong Dan (MTCTD)’, a non-steroidal anti-inflammatory drug (NSAID) containing BVU that is sold over the counter. He had taken 4–5 packages of this drug daily for about 5–6 years to treat his persistent headache; this drug contains ethoxybenzamide (350 mg), caffeine anhydrous (50 mg), acetaminophen (200 mg) and BVU (200 mg) per package. Six months prior to admission, the total daily dosage had been gradually increased to 10–15 packages per day due to a worsening of the headache.

We examined the serum at ~11 days after the last dose of MTCTD and the result showed a bromide level of 101.5±1.9 mg/dl, measured by inductively coupled plasma mass spectrometry (ICP-MS). Forced diuresis with intravenous normal saline, as well as intravenous furosemide was carried out. The neurological symptoms and signs (dysarthria, delirium and cerebellar ataxia) recovered rapidly over the next 3–5 days. Repeat analysis at ~24 days after the last dose of MTCTD showed that the serum chloride and bromide levels had declined [chloride, 104 mmol/l measured by an ion-selective electrode (ISE); and bromide, 6.15±2.6 mg/dl measured by ICP-MS]. Two weeks later, his score on the Mini-Mental State Examination (MMSE) showed a significant improvement. Occasional cases of bromide intoxication have been reported previously [1–6], mainly due to the use of bromide-containing products in non-prescription preparations, such as analgesic, antitussive or anti-epileptic drugs. As with our patient, most diagnoses were aided by a negative anion gap and hyperchloraemia, because bromide is always regarded as chloride by automated analysis when measurement is by an ISE. The ISE method results in a higher apparent chloride concentration in sera when it also contains bromide or another halide [6].

The neurological manifestations seem to be dose related, but the correlation between the blood level of bromide and its toxicity is uncertain. A serum level >20 mg/dl is considered toxic [4]. Bromides have a long half-life (10–14 days) and the ion is eliminated mainly through the kidney. The half-life can be reduced from 12 days to <3 days with saline diuresis alone [7] and 1–2 h with haemodialysis therapy [3]. Although emergent haemodialysis is very effective due to the rapid clearance that occurs [5], it is unusual to use this as the first choice because most patients respond well to saline diuresis.

In conclusion, although bromism is rare today, a review of the patient's medical history for bromide-containing compounds is necessary if there is no obvious and reasonable cause for a negative anion gap and hyperchloraemia. It is then necessary to confirm the presence of another halide ion such as bromide by measuring the ion level directly in the serum.

Yu-Ting Wang1, Shao-Yu Yang2, Vin-Cent Wu1,3, Kwan-Dun Wu1 and Cheng-Chung Fang4

1 Department of Internal Medicine4 Emergency Medicine National Taiwan University Hospital3 Yun-Lin Branch National Taiwan University College of Medicine2 Departments of Internal Medicine Far Eastern Memorial Hospital Taipei Taiwan Email: conrad{at}ha.mc.ntu.edu.tw

Acknowledgments

This study was supported by The Ta-Tung Kidney Foundation.

Conflicts of interest statement. None declared.

References

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  6. Danel VC, Saviuc PF, Hardy GA, Lafond JL, Mallaret MP. Bromide intoxication and pseudohyperchloremia. Ann Pharmacother 2001; 35: 386–387[Free Full Text]
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