Unusual apparent hyperchloremia induced by long-term abuse of bromide-containing drugs

Recently, we have observed 8 cases showing unusually high serum chloride (Cl-) levels of 282, 279, 257, 251, 213, 169, 123 and 120 mEq/l respectively, as measured by the ion selective electrical method (ISE). All of these cases showed almost normal Cl- levels by the coulometric method. Five of the patients had been taking Bromide (Br-)-containing drugs for a long period, and were found to have high serum levels of Br- ranging from 0.6 to 11.0 mEq/l (normal level: 0.1 mEq/l greater than). The cause of this abnormal elevation in serum Cl- as measured by ISE was investigated as follows. First, normal human pooled serum was mixed with NaBr solution to give increasing concentrations of Br- ions, which was then analyzed using the ISE method. Results showed that the selective response ratio of Br- against Cl- had values as high as 15.03 with ISE in contrast to values of 1.0 obtained by coulometry. Secondly, 7 healthy volunteers were given 4 commercially obtained Br(-)-containing tablets (Sedes A; Shionogi & Co., Ltd.) every day for 8 days. Their mean serum Cl- values measured by ISE gradually increased from 108 to 112 mEq/l, paralleling increments of mean Br- value from 0.1 to 0.6 mEq/l over 9 days. From these observations, it is concluded that serum chloride values obtained by ISE are easily interfered with by Br-. Paradoxically, however, this fact is often a good indicator of Br- intoxication. The authors therefore recommend clinicians to pay more attention to the Br- intoxication that often occurs from overdosage of Br(-)-containing drugs, some of which are commercially available without prescription.