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Case Reports |
Department of Laboratory Medicine, Box 357110, School of Medicine, University of Washington, Seattle WA, 98195.
a Author for correspondence. Fax 206-548-6189; e-mail mkenny{at}u.washington.edu
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Abstract |
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 Top Abstract IntroductionCase ReportMaterials and MethodsResultsDiscussionReferences |
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Key Words: indexing terms: blood gases • oxygen saturation • hemoglobin • toxicology
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Introduction |
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TopAbstractIntroductionCase ReportMaterials and MethodsResultsDiscussionReferences |
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We describe here a patient poisoned by paint ingestion who also had sulfhemoglobinemia. At admission, the patient was comatose, which limited the information available to clinicians. We report the clinical course of this patient and our efforts to identify and quantify SulfHb in his blood. We also describe our evaluation of a modified operating mode of the OSM3 CO-oximeter that could provide quantitative data in future episodes of sulfhemoglobinemia.
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Case Report |
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TopAbstractIntroductionCase ReportMaterials and MethodsResultsDiscussionReferences |
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The Human Subjects Review committee of the University of Washington, which subscribes to the ethical standards laid down in the Helsinki Declaration of 1975 as revised in 1983, authorized the use of patient information and specimens as described here.
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Materials and Methods |
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TopAbstractIntroductionCase ReportMaterials and MethodsResultsDiscussionReferences |
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Preparation of hemolysate.
Hemolysates of the patient's
and the control's blood were prepared by freezing the specimens at
-20 °C overnight, thawing, and removing the stroma by
centrifugation (900g for 15 min). Two drops of 10 g/L
potassium cyanide solution were added to 1 mL of hemolysate from the
patient's specimen to eliminate interference from methemoglobin
(MetHb) at wavelengths >600 nm.
Preparation of SulfHb-containing blood samples.
Most of
the sample preparation procedures for SulfHb require tonometry,
centrifugation, and elimination of other Hb derivatives except
oxyhemoglobin (3)(4)(5)(6)(7). These complex procedures produce a
nonphysiological profile for Hb fractions and cannot simulate specimens
from real patients in which only the SulfHb fraction is increased.
Therefore, for our method evaluation, we prepared blood samples with
high proportions of SulfHb that contained other Hb derivatives as well.
The preparation of SulfHb-containing samples was based on principles
described by Siggaard-Andersen et al. (5) and Zwart et al.
(6) but with the following modifications to prepare
specimens of mixed composition:
The apparatus was constructed with a 10-mL cylindrical test tube and a 50-mL three-neck flask. About 2 mL of heparinized venous blood from healthy volunteers was placed in the test tube, 2 g of sodium sulfide was placed in the flask, and 1 mL of concentrated HCl was placed in the syringe. Glass tubing was used to connect the gas-generating flask with the blood sample in the test tube. Two to three drops (~0.08-0.12 mL) of concentrated HCl was added to the sodium sulfide, which produced H2S. A couple of minutes after the addition, the color of the fresh blood started to change from red to chocolate brown. We allowed a 30-min stabilization period for completion of the reaction and evaporation of the excess H2S. SulfHb fractions of 15–25% can be produced in blood samples by this method. Measurement of blood pH before and after the sample preparation detected no substantial pH change. Specimens with various proportions of SulfHb were obtained by diluting the above concentrate with untreated aliquots of whole blood from the same source.
Analysis of SulfHb by OSM3.
The service software program
on the OSM3 provides the absorbances at all six wavelengths (535, 560,
577, 622, 636, and 670 nm) and the concentration of each Hb derivative,
obtained by solving linear equations. Summing the concentrations for
five derivatives—oxyhemoglobin, deoxyhemoglobin, SulfHb,
carboxyhemoglobin (COHb), and MetHb—yields the concentration of total
Hb, and the percentage of each individual derivative present was
obtained by dividing each concentration by the total Hb concentration.
To compare the OSM3 service program-derived results with the results of
another device, we used the Model 912 CO-oximeter from AVL Scientific
Co. (Roswell, GA).
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Results |
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TopAbstractIntroductionCase ReportMaterials and MethodsResultsDiscussionReferences |
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Evaluation of SulfHb measurement by OSM3.
In their
evaluation of the performance of the OSM3, Zijlstra et al.
(9) compared measurement of SulfHb by the OSM3 with that
by multiwavelength measurement. Although they indicated that the
fraction of SulfHb can be measured accurately, there was no detailed
statistical evaluation for the SulfHb determination.
The precision of SulfHb measurements made with the service operating mode was evaluated with the SulfHb-positive aqueous dye control provided by Radiometer America (cat. no. S2160). The within-run precision study, performed by analyzing the control material 22 times, gave a CV of 0.2% for a mean SulfHb content of 8.42%. Day-to-day precision, evaluated by analyzing the control material in duplicates on 22 shifts over a 7-day period, indicated a CV of 0.4% for a mean SulfHb content of 8.43%. To evaluate the precision of the method for patients' specimens, we analyzed in duplicate 26 specimens with SulfHb contents ranging from 0.02% to 23.4%. The mean difference between pairs was 0.013% SulfHb and the overall mean was 5.25% ± 0.05%, for a CV of 0.97%.
Finally, we compared SulfHb measurement by the OSM3 service program
with measurement by AVL 912 CO-oximeter, which uses 17 wavelengths to
measure the Hb derivatives and quantifies SulfHb in its routine
operating mode. Twenty-seven parallel measurements were performed with
both instruments. The test range was limited to 0–3.4% SulfHb because
the Model 912 does not provide analysis for SulfHb proportions >3.5%.
The correlation of results was good, with a slope of 1.025 and an
intercept of 0.004 (r = 0.998). Fig. 1
shows a Bland–Altman plot (10) of the difference
between the measurements from the two instruments vs their average. The
mean bias (Radiometer OSM3 - AVL 912) was 0.05% SulfHb (SD
0.06%). From these results, we conclude that measurement of SulfHb by
the OSM3 service program is reproducible and agrees well with
measurement by the AVL 912 at lower SulfHb values; however, the
agreement deteriorates somewhat at higher SulfHb contents.
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Difference in oxyhemoglobin fraction.
Measurement of 61
samples with various proportions of SulfHb (0–23.4%) demonstrated a
deviation between the oxyhemoglobin fractions calculated from
concentrations obtained with the OSM3 service program and those
originally reported by the routine analysis mode. This difference in
values for the oxyhemoglobin fraction originates from the fact that
SulfHb is omitted as a component of total Hb as calculated in the
routine operational mode. This deviation, calculated as the difference
between routine mode output and service mode output, is linearly
related to percentage of SulfHb in the samples. The correlation
equation is: difference = -0.215% + 1.11 SulfHb
(r = 0.997).
Retrospective study of the patient's specimens.
After
the OSM3 service program was evaluated, we carried out a retrospective
study with the patient's specimens from day 1. Table 1
displays the results. Because the specimen had been frozen for
2 months, no negative MetHb was present. For each analysis, the results
for the operating mode were compared with the calculated values based
on the service program. According to the manufacturer's users'
handbook, a SulfHb presence of ~10% decreases the MetHb measurement
by ~3.5% and increases the COHb by ~2.5%. This would explain the
negative result for MetHb and the possibly increased COHb values
obtained on day 1. Lack of quantitative monitoring techniques on day 1
meant that we could not determine the initial SulfHb composition.
However, our retrospective data showed that a high amount of SulfHb was
clearly present, in concentrations sufficient to cause the central
cyanosis observed on admission.
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Discussion |
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TopAbstractIntroductionCase ReportMaterials and MethodsResultsDiscussionReferences |
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The ingestion of paint has not previously been described as a cause of sulfhemoglobinemia. Drug overdose is the most widely reported cause. Of 62 cases reviewed at the Mayo Clinic (11), all were associated with just four drugs, taken alone or in combination with other drugs: Bromo-Seltzer, acetanilide, sulfonamide, and phenacetin. Although constipation, which could lead to drug metabolism or modification by gut flora, was present in some of the 62 cases, its absence in others suggests that intestinal conversion of the drugs does not account for SulfHb formation in all cases. Three reports have described sulfhemoglobinemia associated with phenazopyridine ingestion [12–14], and several others report dapsone ("DDS") as a cause (2)(15)(16)(17)(18). The synthesis of phenazopyridine from diazotized aniline suggests that aniline, a documented chemical cause of SulfHb, may be a contaminant in the phenazopyridine preparations and cause illness. Metoclopramide can produce both methemoglobinemia and sulfhemoglobinemia (19). Occupational exposure to H2S gas is also reportedly a cause of sulfhemoglobinemia but this is controversial (20)(21)(22). Sulfhemoglobinemia was described in four fatal cases of acute exposure to H2S gas associated with industrial waste effluents or sewage (23); the greenish skin color of massive SulfHb occurred in only one of these cases. A high incidence of sulfhemoglobinemia reported among the population of a city with excessive environmental pollution from volatile sulfur-containing compounds (24) may have been caused by either acute or chronic exposure to the volatiles. In our setting, SulfHb measurement is requested or a case of sulfhemoglobinemia is observed every 3–4 months.
Visual assessment of cyanosis is relatively unreliable. Tissue discoloration caused by SulfHb may be mistaken for that caused by reduced (deoxy-) Hb (25). In a complex case of unknown etiology, flagging SulfHb alerts the clinician to the cause of the discoloration and the remote potential for tissue hypoxia. The clinical emergency presented by our patient is similar to many descriptions of poisonings with sulfhemoglobinemia, in that the patient was found comatose and unable to describe what had been ingested. The fact that four sets of CO-oximeter assays were ordered in 2 h probably reflects the refractoriness of the cyanosis and the clinician's uncertainty about its origin, given that hypoxemia was not present. Central cyanosis was evident and as such required some differential evaluation in the face of toxic ingestion. Carpenter, in a recent review of cyanosis, classified sulfhemoglobinemia in the category of causes of "central cyanosis"—the blue to slate-like discoloration of the sublingual region and tongue—which "alone indicates a probable medical emergency" (26). Shapiro et al. similarly taught that cyanosis most often is indicative of tissue hypoxia caused by the presence of reduced Hb, so that cyanosis "demands a careful and thorough clinical evaluation" (27). A SulfHb concentration of <5 g/L can produce a skin discoloration equivalent to that produced by reduced Hb at 50 g/L, i.e., discernible cyanosis. Alternately, had the cyanosis been associated with MetHb, the more frequent type of poisoning that causes central cyanosis, administration of methylene blue might have been indicated. For our patient, oxygen administration was a first level of support after attempting to neutralize the effects of the toxic ingestion. The dysfunctional Hb decreases the fraction of Hb available to carry oxygen. Volume expansion for the management of hypotension, blood replacement, and other clinical choices could be influenced by rapid identification of a SulfHb burden in a multiply compromised patient. Finally, data from monitoring transcutaneous oxygen saturation, commonly used to survey for changes and provide alarms, are misleading in the presence of sulfhemoglobinemia.
In this case, the patient was hemorrhaging and received replacement blood daily for 5 days. This explains why SulfHb fell below the OSM3 alarm limits before the theoretical 120 days. Lim and Lower suggest exchange transfusion as a means of managing extreme sulfhemoglobinemia (13); this would be rare, however, because in many cases the patient can tolerate high amounts of SulfHb. Reports of SulfHb tolerance display little consistency. Some describe proportions of 20% to 60% as benign for some patients (1)(12), but these lack evaluation of tissue oxygen status or of its influence on the course of patient outcome in the face of cardiac and pulmonary involvement. At least one textbook states that no treatment is needed for sulfhemoglobinemia except to remove the toxic substance that produces it (28).
In conclusion, we present a case of sulfhemoglobinemia possibly caused by paint ingestion, an association that has not been reported before. The case was sufficiently complex during the first 24 h to elicit four measurements of Hb fractions in 2 h. We also describe a method for quantifying SulfHb with an OSM3 if alternative technology is unavailable (the manufacturer makes no claims for this application). Our evaluation of SulfHb measurement by the OSM3 service program demonstrated its reproducibility and good agreement with results obtained with an AVL 912 at SulfHb fractions <3.5%. Finally, we observed a deviation in measurements of fractional oxyhemoglobin in the routine operation mode when high proportions of SulfHb are present. Rapid quantification of SulfHb in the emergency department is rarely needed in an urban trauma hospital, but we believe this case illustrates that real-time analysis is possible and may be useful when such an occasion arises.
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Acknowledgments |
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Footnotes |
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References |
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TopAbstractIntroductionCase ReportMaterials and MethodsResultsDiscussionReferences |
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The following articles in journals at HighWire Press have cited this article:
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  E. V. Sokurenko, V. Tchesnokova, A. T. Yeung, C. A. Oleykowski, E. Trintchina, K. T. Hughes, R. A. Rashid, J. M. Brint, S. L. Moseley, and S. Lory Detection of simple mutations and polymorphisms in large genomic regions Nucleic Acids Res., November 15, 2001; 29(22): e111 - e111. [Abstract] [Full Text] [PDF]
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 H. C. Lu, R. D. Shih, S. Marcus, B. Ruck, and T. Jennis Pseudomethemoglobinemia: A Case Report and Review of Sulfhemoglobinemia Arch Pediatr Adolesc Med, August 1, 1998; 152(8): 803 - 805. [Abstract] [Full Text] [PDF]
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