Download Serum Chloride Analysis, Bromide Detection, and the Diagnosis of

Serum Chloride Analysis, Bromide Detection,
and the Diagnosis of Bromism
R O B E R T E. W E N K , M.D., J A C K A. L U S T G A R T E N , P H . D . , N. J O H N P A P P A S ,
R O B E R T I. LEVY, M.D.,
AND R O G E R J A C K S O N ,
M.D.,
M.D.
Departments of Pathology and Medicine, Sinai Hospital of Baltimore and Crownsville
Hospital Center, Baltimore, Maryland
ABSTRACT
Wenk, Robert E., Lustgarten, Jack A., Pappas, N. John, Levy, Robert I.,
and Jackson, Roger: Serum chloride analysis, bromide detection, and the
diagnosis of bromism. Am J Clin Pathol 64: 4 9 - 5 7 , 1976. Current methods
for determining serum chloride concentration vary in specificity. Laboratory
detection of bromide in serum is usually dependent on spuriously high
chloride values. In the absence of historical information, the chemical
identification of bromide in serum may be the only diagnostic sign of
bromism. Bromide may be found in as many as 1% of sera obtained
from inpatients of a general hospital. Ion-selective electrodes and some
thiocyanate methods for chloride analysis can be highly sensitive to bromide
(interference). Chloride electrodes are also sensitive to iodide. (Key words:
Chloride; Bromide; Bromism; Ion-selective electrode [ISE].)
BROMIDE THERAPY has largely been out- tion, which in turn depends on the method
moded by the use of other hypnotics and of chloride analysis, and 3) the interference
sedatives. Bromide poisoning has therefore of bromide with various methods of
become an unfamiliar disorder; a 1975 chloride analysis.
review of 100 toxicologic agents 1 that omits
bromide from the list attests to the obMethods
solescence of bromism as a suspected diagnosis. Nevertheless, occasional cases of
Effect of Inorganic Bromide on Methods
bromide intoxication (bromism) are still
of Chloride Analysis
reported. 3,10 Since some cases are first sus(1) Aqueous Br~ solutions (100 mmol.
pected as a result of apparently elevated
Br~ per 1.) were prepared by weighing
serum chloride values, diagnosis is partly
out sodium bromide salt. Dilutions yielda function of the chloride method utilized
ing solutions of concentrations ranging
by clinical laboratories. 2,9 We have evalfrom 1 to 100 mmol. per 1. were made.
uated 1) the occurrence of bromide in
These solutions, which contained no
contemporary serum samples of hospitalchloride, were subjected to chloride analyized patients, 2) the dependence of the
sis by five common procedures: ion-selecdiagnosis of bromism on bromide detective electrode (Stat/Ion, Technicon Corp.,
Received February 18, 1975; accepted for publica- Tarrytown, N.Y.), coulometry (Chlorition April 10, 1975.
dometer, American Instrument Co., Silver
Address reprint requests to Dr. Wenk: Department of Pathology, Sinai Hospital, Baltimore, Spring, Md.), and thiocyanate-colorimetry
Maryland 21215.
(Chloride Analyzer, I n s t r u m e n t a t i o n
49
50
WENK ET
AL.
AJ.C.P.—Vol.
65
were compared with the apparent measured CI - concentrations in all three kinds
of solutions. Comparisons were expressed
as a ratio of apparent (measured) chloride
minus known chloride divided by known
bromide:
[Apparent Cl~] - [known CI - ] /
[known B r - ]
20
40
60
80
100
BROMIDE CONCENTRATION - mmol / liter
FIG. 1. Effects of bromide and bromide plus
chloride to constant halide of 100 mmol. per 1.
in aqueous solution on various methods for chloride.
a, DuPont ACA plus chloride; b, DuPont ACA—
no chloride; c, Stat/Ion—no chloride; d, Stat/Ion,
lus chloride; e, Chloride Analyzer plus chloride;
/ Chloride Analyzer, no chloride; g, Chloridometer,
no chloride; h, Chloridometer plus chloride; i, Theoretical one-to-one response of bromide to chloride.
Laboratories, Lexington, Mass.; Automatic
Clinical Analyzer, DuPont, Wilmington,
Del.; Sequential Multiple Analyzer 6/60,
Technicon Corp.).*
(2) Similar solutions were prepared in
protein-based media and were analyzed by
the same procedures.
(3) Bromide solutions of similar concentrations were also prepared in saline solution so that total halide, bromide plus
chloride, equalled a constant 100 mmol.
per 1. T h e concentrations of the two halides
together were considered more clinically
relevant since physiologically, bromide replaces chloride 12 and because these halides
occur together in laboratory samples.
These solutions were analyzed for chloride
by the procedures noted above.
(4) The known concentrations of B r * Apparent chloride test results have not been
corrected for those values exceeding the linearity
of any particular method.
Ratios were plotted graphically against the
known bromide concentrations for each
method in order to delineate bromide
interference with chloride analyses.
(5) A study of ion-selective electrodes
(ISE) was made because of the relatively
recent emergence of ion-selective electrode
technology as a routine clinical laboratory
tool. To study the effect of loss of
selectivity over time, electrode responses
using a brand-new CI - sensor electrode
and one utilized for several months in
our laboratory were compared. Study was
made of interelectrode variation, fatigue,
change in response time, and the effects
of "poisoning" by B r - , I - , and F - . T h e
sensors were exposed to pure bromide
solutions, to pure chloride solutions, or
to mixtures of B r - and CI - in solutions
of constant halide concentration.
Exposure of the chloride electrodes to
bromide (10 mmol. B r - + 90 mmol. Cl per 1.), for periods of 1.5 minutes and
for 1 hour, was followed by tests for sensor
damage, i.e., refractory or augmented
response to aqueous CI - solutions of 100
mmol. per 1. and solutions of CI - + B r (total halide = 100 mmol. per 1., Br~
= 5, 10, 20 mmol. per 1.).
The sensors were similarly exposed to
aqueous iodide solutions (1 mmol. I + 99 mmol. CI - per 1.) and fluoride solutions (1 mmol. F - + 99 mmol. CI - per 1.).
Frequency of Bromide Occurrence in
Serum Samples
(1) Random sampling was made of hospitalized patients' sera over several months.
The samples, 133 sera, were analyzed for
January 1976
51
SERUM Cl~ METHODS, BROMIDE AND BROM1SM
bromide spectrophotometrically. 13 T h e
bromide method was evaluated by calculating the percentage of bromide recovered from aqueous solutions (2-100
mmol. per 1.) in the presence of various
concentrations of chloride ( 0 - 9 8 mmol.
per 1.). Recovery was also determined from
serum pools containing similar concentrations of halides.
Precision was determined from statistical
analysis of 18 repeated B r - determinations on serum pools containing 1.8 to 3.7
mmol. per 1.
(2) It was found that routine analysis
of electrolytes by ion-selective electrodes
over six months occasionally produced
spuriously high chloride values (range
110-306 mmol. per 1.). These values were
not accompanied by cation abnormalities
and caused a decrease in the normal
anion gap ( [ N a + ] minus the [Cl~
+ H C 0 3 - ] ) . Spurious chloride elevations
occurred in about 0.75% of samples. 9
Each anomalous result initiated a search
for historical evidence that the patient
used bromide agents. The serum in question was chemically analyzed for bromide.
(3) During the course of study, three
cases of bromism were diagnosed, and are
described.
(4) An attempt was made to determine
the effect of small amounts of bromide
in serum on chloride analysis. One of the
authors intentionally ingested 900 mg
NaBr (about 14.5 mg. per kg.). Chloride
analysis by coulometry, electrode, and thiocyanate (Chloride Analyzer) methods was
carried out.
Results
Method Studies
(1) Aqueous bromide solutions, analyzed for chloride by several methods,
registered variable apparent chloride concentrations (Fig. 1). All methods showed
positive interference—the higher the
bromide concentration, the higher the ap-
5.0
A (no chloride)
4.0
3.0
-
o
ex
CO
~
2.0
01
1.0
-
id
*e
t=*=
3.0
2.0
1.0
20
40
60
80
100
BROMIDE CONCFNTRATION - mmol / liter
FlG. 2. Effects of bromide (A) and bromide plus
chloride (B) to constant halide of 100 mmol. per
1. aqueous solution on: a, DuPont ACA; b, Stat/
Ion; c, SMA 6/60; d, IL Chloride Analyzer; e,
Chloridometer.
parent chloride concentration (Figs. 2A
and 4). T h e ISE results followed a sigmoidal response curve, while the curves
with other methods were linear or curvilinear in response to increasing bromide
concentrations.
(2) Solutions of bromide in the presence
of chloride, with final halide totalling 100
mmol. per 1., when analyzed for chloride,
showed similar responses (Figs. 1 and 2B).
The electrode response was diminished in
magnitude and appeared curvilinear
rather than sigmoidal. Other methods
showed response curves that were either
parallel to, or identical to, the curves
derived from pure bromide solutions
(coulometry, Chloride Analyzer thiocyanate, ACA thiocyanate).
(3) Results of chloride analysis of pooled
52
WENK ET
BROMIDE CONCENTRATION - mmol / liter
FlG. 3. Analysis of pooled sera containing various
bromide concentrations with constant chloride, by
various chloride methods, a, DuPont ACA; b, Stat/
Ion; c, 1L Chloride Analyzer; d, Chloridometer.
serum in the presence of constant chloride
of 97 mmol. per 1. containing bromide
over the range of 1-20 mmol. per 1.
are shown in Figure 3. The ISE method
yielded, at low bromide concentrations,
an a p p a r e n t ratio (chloride/bromide)
greater than 4, which decreased to approximately 3 over the Br~ range of 10-20
mmol. per 1. For the DuPont ACA, this
ratio was also high at low bromide concentrations; however, the ratio decreased
to about half that for the ISE method
at high B r - concentrations. Other methods also showed initially high ratios, which,
however, were approximately 1 or slightly
less over the same bromide concentration
range.
(4) The magnitude of inappropriate
response of each chloride measurement
to bromide interference is expressed more
fully in Figures 2 and 3. In the absence
of chloride (Fig. 2A) the Cl~ electrode
method is less selective at low concentrations of bromide and more selective at
high concentrations. The reverse is true
for the ACA thiocyanate procedure. (Some
of the curves are foreshortened at low
levels since the methods are known not
to be linear at these extreme, non-
AL.
A.J.C.P.—Vol.
65
physiologic concentrations. Manufacturer's recommendations were followed
when possible.) Least interference among
the methods was noted for the IL thiocyanate procedure, SMA 6/60 method, and
coulometry. The coulometric method
showed slightly more interference at the
lowest bromide levels. Chloride analysis
of solutions containing chloride as well
as bromide showed similar, but less augmented, interference. Again, the electrode
and ACA procedures showed greater responses to bromide than to chloride on a
mole-for-mole basis. Other methods signalled one mmol of chloride per liter for
each mmol of bromide present.
(5) Used and new chloride electrodes
did not differ greatly in their responses
to pure bromide and bromide plus chloride
with constant halide concentrations (Table
1). The greatest difference was found at
low concentration of bromide in the absence of chloride.
Exposure of electrodes to bromide for
short intervals (minutes) caused a refractory or slow response in the one sample
cup that followed the bromide-containing
solution (Fig. 5). Repeated exposure of an
electrode to bromide at intervals of about
ten minutes (every six samples on the turntable) appeared to decrease the magnitude
of erroneous response to subsequent
bromide solutions; however, no predictable
magnitude of response was apparent. Exposures of electrodes to bromide, iodide,
or fluoride solutions for an hour did not
appear to affect subsequent chloride
analysis-response further. However, iodide (1 mmol. per 1.) showed interference:
a three- to tenfold response as apparent
chloride (mmol. per 1.) was signalled for
the one mmol of iodide present per liter.
Exposure of an electrode to I - for one
hour slightly increased the electrode response to bromide, but had no longterm effect. Response to subsequent
chloride solutions was appropriate. Fluoride caused no interference either with
short or long exposures.
January 1976
53
SERUM CI" METHODS, BROMIDE AND BROMISM
Patient Studies
(1) Of the 133 patients' sera, selected
at random over several weeks, two showed
the presence of bromide (both approximately 1 mmol. per 1.) by the gold chloride
method. This method is considered relatively specific for serum bromide determination. 13 O u r data on constant total
halide solutions with bromide in concentrations ranging from 2 to 100 mmol.
per 1. showed average recoveries of 100.3%,
range 93.8 to 105.0%. Precision and recovery data on serum pools are shown
in Table 2.
(2) Patients who had spurious chloride
elevations in their sera are tabulated below
along with historical information and
serum B r - concentrations (Table 3). Some
of these patients were receiving bromide
by prescription; others had taken it in
proprietary preparations; still others had
no evidence of bromide administration.
T h e bromide compounds determined by
investigation are listed.
(3) The three cases of bromism found
in six months of study are summarized
as follows:
Case 1. R.B., a 78-year-old white woman,
was admitted to Sinai Hospital with
lethargy, disorientation to time, place, and
person; and dehydration. Electrolyte studies using selective ion electrodes revealed
, 160
-
5.0 >
APPARENT
.
CHLORIDE / BROMIDE
X
3.0 5
140
TO
2.0
1
•
120
SZ
^F
°
CD
1.0 o
100
' APPARENT
CHLORIDE
< 20
0
20
40
60
80
100
INDIVIDUAL HALIDE CONCENTRATION - mmol / liter
FIG. 4. Electrode responses to aqueous solutions
containing increasing chloride and bromide concentrations.
an initial chloride value of 216 mmol.
per 1. Chloride analysis was repeated
colorimetrically (IL Chloride Analyzer)
and coulometrically (Aminco Chloridometer), yielding values of 106 and 108
Table 1. Responses of Old and New CI Electrodes to Bromide Solutions and to Bromide
plus Chloride Solutions (at Constant Halide of 100 mmol. per 1.)
New Electrode
Br" Concentration
Apparent
Cl-/Br-
Apparent Cl"/Br
(in Presence
of CI")
10
20
30
40
50
60
70
80
90
100
5.6
5.0
3.7
2.9
2.4
2.1
1.9
1.7
1.6
1.6
2.9
2.5
2.2
2.0
1.9
1.7
1.6
1.5
1.5
1.4
Old Electrode
_
CrVBr-
Apparent C I ' / B r (in Presence
of CI")
4.0
4.1
3.5
3.1
2.5
2.1
1.9
1.7
1.7
1.6
3.0
2.5
2.2
2.0
1.9
1.8
1.6
1.6
1.5
1.5
Apparent
54
WENK ET AL.
20Br
UJ
oo
t—
ELE
o
210
200
UJ
>
•—
190
ELE
(J
180
o
170
mol / litei
(/z>
160
150
E
(J
z
o
o
UJ
o
en
140
130
120
9X
(_> 110
H-
z
UJ
<
Q_
<
100
Q_
90
5
10
15
20
25
30
35
40
SAMPLE NO. AND SEQUENCE
FlG. 5. Effect of increasing concentration of
bromide on the subsequent ion-selective electrode
response to halide. Test solutions contained increasing concentrations of bromide (mmol. per 1.—
perpendicular lines) with chloride to a total halide
concentration of 100 mmol. per 1. Wash solution
contained chloride, 100 mmol. per 1. Numbers in
parentheses represent apparent chloride/bromide.
mmol. per 1., respectively. The patient's
family was asked to bring all of the patient's medications to the hospital. Search
revealed that the patient had chronically
ingested a locally-prescribed sedative compound that contained both bromodiethylacetylurea and alpha-bromoisovalerylurea.
Serum bromide initially was 10 mmol.
per 1. (80 mg. per dl.). Treatment was
carried out with intravenous administration of saline solution, diuretics, and withdrawal of bromides. Serum Br" decreased
over three weeks' time. The patient was
discharged in an alert state of mind.
Br~ and CI - in serum were monitored.
Values are summarized in Table 4.
Case 2. C.S., a 54-year-old black man
with a long history of alcoholism, was
admitted to Crownsville Hospital Center
in an obtunded state. He was weak, drowsy,
A.J.C.P.—Vol.
65
confused, and showed marked ptyalism.
No history was obtained on admission.
Vital signs were normal. Serologic tests
for syphilis (RPR, VDRL, and FTA) were
positive. A tentative diagnosis of alcohol
intoxication was made despite a nurse's
note that there was absence of alcoholic
breath odor. On the fourth day, the patient
was still confused, was unable to swallow,
was incontinent of urine and feces, and required restraint. On the fifth day, the
pupils were very contracted, plantar reflexes had decreased, and there was a tendency for the head and eyes to turn
right. Possible subdural hematoma was
considered. At this time, marked elevation of serum chloride was noted (more
than 130 mmol. per 1. by Technicon
AutoAnalyzer, thiocyanate method). Bromism was suspected; serum bromide analysis revealed a concentration of 62.6 mmol.
per 1. (500 mg./dl.). Chloride measurement of the serum, by selective ion
electrode, was 209 mmol. per 1.; by
Chloride Analyzer, 117 mmol per 1. Treatment with fluids, diuretics, and magnesium
sulfate lowered serum bromide to 30.8
mmol. per 1. in two days, and to 17.8
mmol. per 1. in another four days. Serum
chloride continued to be greater than 130
mmol. per 1. (AutoAnalyzer thiocyanate).
By the eighteenth hospital day, the patient
was alert. He admitted taking daily one
large bottle of tablets containing triple
bromide (NaBr, KBr, NH 4 Br) for two to
three weeks before his hospitalization. Bromide concentration decreased to 9 mmol.
per 1. by day 23 and to 6.3 mmol. per
1. by day 29. Chloride levels returned to
normal.
Case 3. H.C., a 94-year-old black woman,
was admitted to Sinai Hospital with a
five-day history of confusion and disorientation following a fall. The patient was
poorly responsive except to loud verbal
commands and painful stimuli. Examination showed slight dehydration, decreased
breath sounds, and fever (temperature
38 C ) . The pulse rate was 140 per min.
Initial laboratory findings included normal
January
1976
55
SERUM CI" METHODS, BROMIDE AND BROM1SM
plasma glucose and urea concentrations,
hemoglobin 13 Gm. per dl., leukocytosis
(13,000 per cu. mm.), and positive RPR
and FTA tests. Electrolytes were: Na +
= 145, K = 4.7, C\~ = 114 (mmol. per 1.
by 1SE) and H C 0 3 _ = 27 mmol. per 1.
The clinical staff suggested diagnoses
that included pneumonia, dehydration,
and possible subdural hematoma. The
patient was given penicillin and cephalothin when sputum showed Klebsiella on
culture, but Gram-positive diplococci on
smear. The respiratory symptoms cleared
along with the dehydration and fever,
but the patient remained confused. Skull
series and echoencephalograms disclosed
no abnormality.
Laboratory follow-up of the initial elevated chloride showed the following data
for serum obtained two days later (mmol.
per 1.): Chloridometer, 108; ISE,, 183;
ISE 2 , 186; ACA, 128; IL, 108. Bromide
was 338 mg. per dl. (42 mmol. per 1.).
T h e repeat CI" on the initial specimen
was again 114 mmol. per 1. The reason
for the initially lower CI" serum value
is obscure. Cl~ in another serum specimen
one week later was as follows (mmol.
per 1.): Chloridometer, 98; ISE 1; 131;
ISE 2 , 148; ACA, 112; IL, —. Bromide
was 23 mmol. per 1. Renewed efforts to
obtain a history of Br" ingestion were
rewarding. The patient was taking un-
Table 2. Measurement of Bromide by
Au + + + Method (Summary)
Within run
Precision
(mmol. per 1.)
Number/run
Mean
S.D.
Range
18
0.85
0.075
0.70-1.0
Recovery (%)
Level of 1.8-3.7
mmol. per 1. Serum
95
93-97
known quantities of a triple-bromide
preparation (Nervine, Miles Laboratories),
which she had taken for years for insomnia. Diuretics, oral fluids, and withdrawal of medication allowed the sensorium to clear. At discharge B r - was
20 mmol. per 1.
(4) Results of one of the authors' ingesting 9 mmol. bromide on several methods are outlined in Table 5.
Discussion
Bromide is an interfering anion in all
of the chloride methods evaluated. The
coulometric procedure produced only a
relatively small error: 1:1 on a molar
basis or 100% interference. Unknown to
previous investigators, the colorimetric
methods which use thiocyanate reagent
vary in their specificity for chloride. Some
are relatively specific, yielding 1:1 bromide:
chloride interference, while others yielded
Table 3. Br in Nontoxic Patient Sera Detected by Chloride Electrode*
Apparent ci- Concentration
(mmol . per 1.)
(mmol. per 1.)
Patient
Patient
Patient
Patient
Patient
Patient
Patient
Patient
Patient
Patient
1
2
3
4
5
6
7
8
9
10
12.8
5.5
21.0
9.0
4.0
2.3
1.5
2.0
1.7
13.3
BrMedication
Multiple Br~t
Multiple Br~t
Triple Br"$
Triple Br~J
Bromisovalum
Triple Br"t
Electrode
ACA
IL
211
138
306
117
134
134
113
126
116
130
130
126
138
—
—
—
—
—
—
—
118
* Found in routine serum electrolyte studies ol'genera) hospital patients as a result of spuriously high CI". Incidence = 0.75£
t NaBr 1,800 mg., KBr 1,800 mg., NH.Br 1,800 mg., ZnBr 2 36 mg.
X NaBr 290 mg., KBr 290 mg., NH,Br 30 mg.
—
—
109
127
122
106
116
107
106
56
WENK ET
A.J.C.P.—Vol.
AL.
65
Table 4. Patient R.B., Serum Br and CI during Hospitalization
Serum Chloride (mmol. per 1.)
Hospital
Day
Serum Bromide
(mmol. per 1.)
1
8
9
10
14
22
10.1
Coulometry
HgTh locyanate
Ion -selective
Electrode
—
108
113
106
111
216
162
7.5
6.4
5.9
4.8
—
—
—
103
103
107
101
104
105
140
138
129
much higher bromidexhloride responses.
The extent of error may vary directly
with the concentration of halides present
in solution, and is now known to depend
on Hg + + concentration. 8
The ISE also produced falsely elevated
chloride values in the presence of bromide.
Clinically, bromide in concentrations of as
little as 1 mmol. per 1. may elevate chloride
values enough to raise suspicion of interference. One cannot predict the actual concentrations of bromide because the curves of
the response of the chloride electrode
to bromide concentrations in the presence of various concentrations of chloride are complex. A specific bromide
electrode method would be useful for
confirming suspiciously high chloride values in clinical specimens which the selective (but not specific) chloride sensor
detects. 5,11 A specific spot test for bromide
is available,4 and quantitation is easily carried out. 6 ' 13
Older and brand-new chloride electrodes respond in similar ways. T h e
chloride electrode (as a chloride sensor)
appears to be little affected by shortor long-term exposure to bromide, iodide,
or fluoride. T h e only exception to this
generalization was that the one or two
samples following the Br~-contaminated
sample showed falsely decreased chloride
concentrations (by 4 - 1 0 mmol. per 1.).
Samples should be rerun when there is
suspicion of Br~ interference in antecedent
specimens.
There is definite direct interference by
iodide in a concentration of 1 mmol.
per 1. Clinically, this unphysiologic concentration may be reached on occasion when
patients have been given iodide preparations orally or topically. Therefore, Cl~
values will be in error when the serum
also contains bromide and/or iodide.
There is a small but important proportion of general hospital inpatients whose
sera contain bromide.t About a third of
these have recorded histories of bromide
use for sedative, hypnotic or anticonvulsant purposes. The remainder have no
t T h e frequency among psychiatric hospital patients has been much higher in the past, and it
may still be so.10,14 Our own preliminary data show
that 13% of patients admitted to Crownsville Hospital have serum Br~ concentrations of more than
2 mg. per dl.
Table 5. Results of Ingestion of 9 mmol. Bromide
Apparent CI (mmol. per 1.)
Baseline ingestion
One day after ingestion
Coulometry
ACA
IL
Stat/Ion
True Bromide
(mmol. per 1.)
102
103
103
112
101
103
104
112
0
1
January 1976
SERUM CI" METHODS, BROMIDE AND BROMISM
initial historical evidence of bromide ingestion. Their identification depends on
the chemical detection of bromide in
serum. It was in the latter group that
we discovered three cases of bromide intoxication in a 12-month interval. Two
cases involved elderly women, one of whom
had a serum bromide concentration barely
in the so-called "toxic" range of more than 9
mmol. per 1. Nevertheless, clinical toxicity
was marked: older patients with some
organic nervous-system disease, renovascular disease, and ingesting other medications are more sensitive to bromide. 7
The second case demonstrates that extremely high levels that may be lethal
in some persons are only toxic (or even
nontoxic) in others. Furthermore, a patient
may manifest a misleading past history
or neurologic signs that may avert suspicion of bromism and may prompt inappropriate therapy such as craniotomy for
suspected neoplasm or hematoma (Cases
2 and 3). 7 Elevated serum chloride may
be the first or only clue leading to the
diagnosis. (The definitive diagnosis, in
fact, may be rendered in the laboratory as well.) Therefore, there is some
justification for utilizing laboratory chloride methods that are sensitive to bromide
interference. T r u e chloride concentration
may be obtained from quantitating the Br~
concentration (e.g., colorimetrically) and
subtracting the bromide (mmol. per 1.)
from the total halide value by one of the
several methods that yield a 1:1 response
of bromidexhloride. Some physicians still
prescribe bromide, and a number of commercial agents (by our count, at least 35
in the United States) in current use still
contain bromide, despite the removal of
bromide salts from some common antacid-analgesics. (Of interest, Bromo Seltzerf manufactured in the United States
contains no Br~, but that manufactured
t Warner-Lambert Co.
57
in Canada does.) One may therefore expect continued bromide interference in
chloride methods and the appearance of
occasional cases of bromism.
Acknowledgment. Charles Byrd, B.S., and Barbara
Hall, B.S., provided technical assistance.
References
1. Baselt RC, Wright J A, Cravey RH: Therapeutic and toxic concentrations of more than
100 toxicologically significant drugs in blood,
plasma, or serum: A tabulation. Clin Chem
21:44-62, 1975
2. Blume RS, MacLowry JD, Wolfe SM: Limitations of chloride determination in the diagnosis of bromism. N Engl J Med 279:593595, 1968
3. Carney MWP: Five cases of bromism. Lancet
2:523-24, 1971
4. Claiborne TS: Bromide intoxication. N Engl J
Med 212:1214-1216, 1935
5. Degenhart HJ, Abelu G, Bevarrt B, et al:
Estimation of Br" in plasma with a Br~selective electrode. Clin Chim Acta 38:217220, 1972
6. Goodwin IF: Colorimetric measurement of serum
bromide with a bromate-rosaniline method.
Clin Chem 17:544-547, 1971
7. Hanes FM, Yates A: An analysis of four hundred
instances of chronic bromide intoxication,
South M e d J 31:667-671, 1938
8. Levinson SS, Rieder SV: T h e effect of free
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