Archives of
Arch. Toxicol. 36, 147-149 (1976)
TOXICOLOGY 9 by Springer-Verlag 1976
A Universally Applicable Rapid Bromine Test* W. Butte** and R. Wronski Department of Internal Medicine in the Center of Conservative Medicine I of the Christian Albrechts University Kiel, Sclaittenhelmstr. 12, D-2300 Kiel, Federal Republic of Germany
Abstract. A rapid and simple screening test for bromine, that can be used for Bromureide intoxication as well as for cases of bromism, is described. Key words: Bromine test -- Bromism -- Acute bromureide intoxication.
Zusammenfassung. Ein Brom-Schnell-Test, der sowohl bei akuten BromureidIntoxikationen als auch bei chronischem Schlafmittelabusus - Bromismus anwendbar ist, wird vorgestellt.
Screening tests have become indispensable for the diagnosis of acute intoxication. They allow quick orientation by simple means. Therefore they should be specific for one group of chemical substances and they must not need much time or personnel. If intoxication has been detected by a screening test, detoxification can already be started, followed by quantitative evaluation, which often requires time and complicated apparatus. Statistical data from information centers and hospitals - specializing in the treatment of poisoning - show that 3 0 - 5 0 % of all intoxications by hypnotic drugs in Germany are caused by bromureides. This figure is still rising (Schuster and Sch6nborn, 1976). The clinical progress of bromureide intoxication often is aggravated by complications. Death is caused, in almost equal frequency, by acute insufficiency of the heart and cardiovascular system, renal insufficiency, respiratory failure resistant to therapy, and disseminated intravascular coagulopathies (Spfith, 1975). Unfortunately there are no detailed reports on the chronic abuse of bromureides leading to bromism. Medical publications only indicate that chronic bromine intoxication is more widespread than commonly assumed and that the clinical pictures are polymorphous, complicating the differential diagnosis vs. psychiatric diseases (Weispfennig, 1974; Meyer, 1974). * The authors will be pleased to deliver test paper and test liquid upon request ** To whom offprint requests should be sent
148
w. Butte and R. Wronski
To date there has been no universally applicable test for quick detection of bromine in urine, saliva, blood, tissue, etc. Those bromine tests available are only suitable for the investigation of saliva (Gaff et al., 1969) or for high concentrations of bromide ions as occurs only with chronic abuse of bromureides or bromides (Poser et al., 1974a). Using the test suggested by Poser et al. on a patient who had arrived in the hospital with acute carbromal intoxication led to negative results, although the bromine concentration in his serum had been as high as 150 mg/1. To provide a screening test for quick and simple detection of bromine, applicable for acute intoxications (with high concentrations of organic bromine compounds 1) as well as for chronic abuse of hypnotic drugs (with high concentrations of free bromide ions [Poser et al., 1974b]), a test was developed that avoids the limitations mentioned above. To accomplish this, the wet analysis of bromine (Kisser, 1967) was transferred to a test paper procedure. Material and Methods
Preparation of Test Paper and Test Liquid. Filter paper (Schleicher and Sch/ill No. 2668) is impregnated with a solution of 30 mg Phenolrot (Merck) in 500 ml acetate buffer (34 mg sodium acetate x 2 H~O and 15 ml glacial acetic acid ad 500 ml water). It is dried immediately with a fan or in an oven at 50 ~ C. After drying the test paper should be yellow (not reddish or pale pink). The test liquid is an aqueous solution (0.02% w/v) of Chloramin T (Merck). Both reagents are stable for at least 6 months if stored in a refrigerator.
Performance of the Test. One drop (50 ~1) of the material to be analyzed (urine, saliva, blood, serum, gastric juice, etc.) is incinerated in a small test tube (refractory glass), until there is only a grey residue left. When the test tube has cooled (ca. 2 min), 10 drops (500 ~1) of test liquid are added and the probe is well agitated. Then 1 drop (50 ~1) of the resulting suspension is applied to the test paper. A deep blue color will appear immediately if the bromine concentration of the analyzed material exceeds 100 mg/1 (0.6 mmol/1, 10 mg/100 ml). The test can be made more sensitive by adding only 5 drops (250 ~.1) of the test liquid to the residue. Then 50 mg/1 (0.3 mmol/1, 5 mg/100 ml) can still be detected. Thus the approximate concentration of bromine can be estimated by a series of dilutions. The test has to be considered negative if the test paper lightens in the wetted area. Misinterpretations will rarely happen, due to the obvious blue-yellow contrast. In case of doubt, however, it is advisable to submit a solution containing 100 mg/1 bromide (from potassiumbromide) to the procedure described above. Normal concentrations of bromine in urine are 3.0-8.6 mg/l, in blood 2.3-5.3 mg/1; 0.7-13.3 mg/1 in serum and 0.2-1.7 mg/1 in saliva (Documenta Geigy). Discussion
The bromine screening test was applied to the urine of 200 patients chosen arbitrarily from the intensive care unit of our hospital. Beside the expected negative results, Carbromal and Bromisoval and their decomposition products containing bromine
A Universally Applicable Rapid Bromine Test
149
two positive results showed up. The patients concerned could thus be shown to be abusers o f hypnotic drugs, which they had not declared in their histories. In four cases o f bromureide intoxication, which were delivered to our hospital during the period of this investigation, the first hints could be found of the kind of intoxication and the approximate bromine concentration by using the bromine screening test. Hence the performance of intensive treatment could be immediately adjusted to the degree o f poisoning. Blood and urine specimens were investigated in 10 patients who received iodine-containing contrast medium for X - r a y investigations. N o n e of these cases gave positive results. Since not even the contrast medium itself reacted with our test, it can be assumed that iodine will not interfere. Neither will chlorides, because they are not oxidized by the test liquid. Acknowledgement. The authors wish to thank Miss M. Asmussen and Miss J. Weidhfiner for their excellent technical assistance.
References Documenta Geigy, Wissenschaftliche Tabellen. Basel: J. R. Geigy A.G. 1969 Gaff, G., Rand, M. J., Diamond, J.: A rapid screening test for Bromism. Meal. J. Aust. 1969 I, 967-969 Kisser, W.: Uber den Nachweis und die quantitative Bestimmung bromierter Harnstoffderivate in der Toxikologie. Arch. Toxikol. 22, 404--409 (1967) Meyer, G.: Klinische Untersuchungen bei chronischen Bromintoxikationen. Schweiz. Arch. Neurol. Neurochir. Psychiat. 114, 169-194 (1974) Poser~ W., Poser, S., Echternkamp, M.: Mil3brauch Brom-haltiger Schlaf- und Beruhigungsmittel. Dtsch. med. Wschr. 99, 2489--2497 (1974b) Poser, W., Poser, S., Mfiller-Oerlinghausen, B., Joost, H. G.: Teststreifen zum Nachweis erh6hter Bromid-Konzentrationen in K6rperfliJssigkeiten. Nervenarzt 45, 211--212 (1974a) Schuster, H. P., Sch6nborn, H." H/iufigkeit, Erkennung und Behandlung von Vergiftungen. Pharm. Ztg. (Frankfurt) 121, 655--661 (1976) Sp/ith, G.: Bromcarbamid-Vergiftungen. Diagnostik 8, 606-609 (1975) Weispfennig, H.-G.: Verwaschene neurologische Symptome bei Bromabusus. Dtsch. med. Wschr. 99, 1500-1502 (1974) Received June 3, 1976
Arch. Toxicol. 36, 147-149 (1976)
TOXICOLOGY 9 by Springer-Verlag 1976
A Universally Applicable Rapid Bromine Test* W. Butte** and R. Wronski Department of Internal Medicine in the Center of Conservative Medicine I of the Christian Albrechts University Kiel, Sclaittenhelmstr. 12, D-2300 Kiel, Federal Republic of Germany
Abstract. A rapid and simple screening test for bromine, that can be used for Bromureide intoxication as well as for cases of bromism, is described. Key words: Bromine test -- Bromism -- Acute bromureide intoxication.
Zusammenfassung. Ein Brom-Schnell-Test, der sowohl bei akuten BromureidIntoxikationen als auch bei chronischem Schlafmittelabusus - Bromismus anwendbar ist, wird vorgestellt.
Screening tests have become indispensable for the diagnosis of acute intoxication. They allow quick orientation by simple means. Therefore they should be specific for one group of chemical substances and they must not need much time or personnel. If intoxication has been detected by a screening test, detoxification can already be started, followed by quantitative evaluation, which often requires time and complicated apparatus. Statistical data from information centers and hospitals - specializing in the treatment of poisoning - show that 3 0 - 5 0 % of all intoxications by hypnotic drugs in Germany are caused by bromureides. This figure is still rising (Schuster and Sch6nborn, 1976). The clinical progress of bromureide intoxication often is aggravated by complications. Death is caused, in almost equal frequency, by acute insufficiency of the heart and cardiovascular system, renal insufficiency, respiratory failure resistant to therapy, and disseminated intravascular coagulopathies (Spfith, 1975). Unfortunately there are no detailed reports on the chronic abuse of bromureides leading to bromism. Medical publications only indicate that chronic bromine intoxication is more widespread than commonly assumed and that the clinical pictures are polymorphous, complicating the differential diagnosis vs. psychiatric diseases (Weispfennig, 1974; Meyer, 1974). * The authors will be pleased to deliver test paper and test liquid upon request ** To whom offprint requests should be sent
148
w. Butte and R. Wronski
To date there has been no universally applicable test for quick detection of bromine in urine, saliva, blood, tissue, etc. Those bromine tests available are only suitable for the investigation of saliva (Gaff et al., 1969) or for high concentrations of bromide ions as occurs only with chronic abuse of bromureides or bromides (Poser et al., 1974a). Using the test suggested by Poser et al. on a patient who had arrived in the hospital with acute carbromal intoxication led to negative results, although the bromine concentration in his serum had been as high as 150 mg/1. To provide a screening test for quick and simple detection of bromine, applicable for acute intoxications (with high concentrations of organic bromine compounds 1) as well as for chronic abuse of hypnotic drugs (with high concentrations of free bromide ions [Poser et al., 1974b]), a test was developed that avoids the limitations mentioned above. To accomplish this, the wet analysis of bromine (Kisser, 1967) was transferred to a test paper procedure. Material and Methods
Preparation of Test Paper and Test Liquid. Filter paper (Schleicher and Sch/ill No. 2668) is impregnated with a solution of 30 mg Phenolrot (Merck) in 500 ml acetate buffer (34 mg sodium acetate x 2 H~O and 15 ml glacial acetic acid ad 500 ml water). It is dried immediately with a fan or in an oven at 50 ~ C. After drying the test paper should be yellow (not reddish or pale pink). The test liquid is an aqueous solution (0.02% w/v) of Chloramin T (Merck). Both reagents are stable for at least 6 months if stored in a refrigerator.
Performance of the Test. One drop (50 ~1) of the material to be analyzed (urine, saliva, blood, serum, gastric juice, etc.) is incinerated in a small test tube (refractory glass), until there is only a grey residue left. When the test tube has cooled (ca. 2 min), 10 drops (500 ~1) of test liquid are added and the probe is well agitated. Then 1 drop (50 ~1) of the resulting suspension is applied to the test paper. A deep blue color will appear immediately if the bromine concentration of the analyzed material exceeds 100 mg/1 (0.6 mmol/1, 10 mg/100 ml). The test can be made more sensitive by adding only 5 drops (250 ~.1) of the test liquid to the residue. Then 50 mg/1 (0.3 mmol/1, 5 mg/100 ml) can still be detected. Thus the approximate concentration of bromine can be estimated by a series of dilutions. The test has to be considered negative if the test paper lightens in the wetted area. Misinterpretations will rarely happen, due to the obvious blue-yellow contrast. In case of doubt, however, it is advisable to submit a solution containing 100 mg/1 bromide (from potassiumbromide) to the procedure described above. Normal concentrations of bromine in urine are 3.0-8.6 mg/l, in blood 2.3-5.3 mg/1; 0.7-13.3 mg/1 in serum and 0.2-1.7 mg/1 in saliva (Documenta Geigy). Discussion
The bromine screening test was applied to the urine of 200 patients chosen arbitrarily from the intensive care unit of our hospital. Beside the expected negative results, Carbromal and Bromisoval and their decomposition products containing bromine
A Universally Applicable Rapid Bromine Test
149
two positive results showed up. The patients concerned could thus be shown to be abusers o f hypnotic drugs, which they had not declared in their histories. In four cases o f bromureide intoxication, which were delivered to our hospital during the period of this investigation, the first hints could be found of the kind of intoxication and the approximate bromine concentration by using the bromine screening test. Hence the performance of intensive treatment could be immediately adjusted to the degree o f poisoning. Blood and urine specimens were investigated in 10 patients who received iodine-containing contrast medium for X - r a y investigations. N o n e of these cases gave positive results. Since not even the contrast medium itself reacted with our test, it can be assumed that iodine will not interfere. Neither will chlorides, because they are not oxidized by the test liquid. Acknowledgement. The authors wish to thank Miss M. Asmussen and Miss J. Weidhfiner for their excellent technical assistance.
References Documenta Geigy, Wissenschaftliche Tabellen. Basel: J. R. Geigy A.G. 1969 Gaff, G., Rand, M. J., Diamond, J.: A rapid screening test for Bromism. Meal. J. Aust. 1969 I, 967-969 Kisser, W.: Uber den Nachweis und die quantitative Bestimmung bromierter Harnstoffderivate in der Toxikologie. Arch. Toxikol. 22, 404--409 (1967) Meyer, G.: Klinische Untersuchungen bei chronischen Bromintoxikationen. Schweiz. Arch. Neurol. Neurochir. Psychiat. 114, 169-194 (1974) Poser~ W., Poser, S., Echternkamp, M.: Mil3brauch Brom-haltiger Schlaf- und Beruhigungsmittel. Dtsch. med. Wschr. 99, 2489--2497 (1974b) Poser, W., Poser, S., Mfiller-Oerlinghausen, B., Joost, H. G.: Teststreifen zum Nachweis erh6hter Bromid-Konzentrationen in K6rperfliJssigkeiten. Nervenarzt 45, 211--212 (1974a) Schuster, H. P., Sch6nborn, H." H/iufigkeit, Erkennung und Behandlung von Vergiftungen. Pharm. Ztg. (Frankfurt) 121, 655--661 (1976) Sp/ith, G.: Bromcarbamid-Vergiftungen. Diagnostik 8, 606-609 (1975) Weispfennig, H.-G.: Verwaschene neurologische Symptome bei Bromabusus. Dtsch. med. Wschr. 99, 1500-1502 (1974) Received June 3, 1976
