H. Kinoshita 1; N. Yoshioka 2; A. Kuse 3; M. Nishiguchi 4; N. Tanaka 1; M. Jamal 1; M. Kumihashi 1; Y. Nagasaki 5; Y. Ueno 3; K. Ameno 1
Department of Forensic Medicine, Faculty of Medicine, Kagawa University, Japan
1; Public Health Science Research Center, Hyogo Prefectural Institute of Public Health and Consumer Sciences, Japan
2; Division of Legal Medicine, Department of Environmental Health and Safety, Kobe University Graduate School of Medicine, Japan
3; Department of Legal Medicine, Hyogo College of Medicine, Japan
4; Hyogo Medical Examiners Office, Japan
Soud Lék., 56, 2011, No. 3, p. 43-44
A fatal case due to severe methemoglobinemia is presented. A male in his forties was found unconscious in his house and, despite intensive care, death was confirmed approximately 11 hours later. Toxicological analysis using ion chromatography revealed the presence of chlorate in the stomach contents. However, chlorate was not detected in the blood, and no other drugs or ethanol were detected in the blood either. We concluded that the cause of death was presumably due to chlorate poisoning, based on the results of the autopsy and the toxicological examination.
Keywords: methemoglobinemia – poisoning – chlorate – ion chromatography
Methemoglobin is an oxidized form
of hemoglobin (8). The most cause of methemoglobin is ingestion or
exposure to an oxidizing agent (10). It oxidizes ferrous iron (Fe2+)
to ferric iron (Fe3+)
within a hemoglobin molecule, and causes that impairment of O2
transport leading to tissue or cellular hypoxia (10). Here we report
on a case of death by severe methemoglobinemia which was
presumably due to the ingestion of chlorate.
A male in his forties
(height 173 cm, weight 67 kg) was found unconscious in the bathroom
of his house. The deceased had a history of liver dysfunction.
Severe methemoglobinemia was diagnosed following admission to the
hospital. Despite intensive care, including blood transfusion and
methylene blue administration, his death was confirmed approximately
11 hours later.
No external evidence of violence
was found. The heart weighed 325 g and contained 460 ml of
chocolate brown colored blood without coagulum, and the brain weighed
1374 g, neither having any abnormal findings. The left and right
lungs weighed 463 and 542 g, respectively, and were severely
congested. Histological examination revealed marked congestion and
edema of the lungs. The kidneys showed congestion with degradation of
the tubules. The stomach contained approximately 300 ml of
blueish brown fluid, without food residue. Femoral blood and stomach
contents were collected for subsequent toxicological examination and
kept at -70 °C until analysis.
A drug screening test using
(Biosite Diagnostic Inc, San Diego, USA) panel was negative.
Quantitation of ethanol was performed using head-space
gas-chromatography. The presence of methemoglobin was determined by
spectrophotometry, according to the Evelyn and Malloy method (2).
Toxicological screening was performed using a high performance
liquid chromatography drug analysis system (Class-VP system,
Shimadzu, Kyoto, Japan) (4). The operation of this system was in
accordance with the manufacturer’s specifications.
The ion chromatography is
equipped for the screening of anions, since the high concentration of
methemoglobin was detected. The ion chromatography system, consisted
of a pump LC-10AD and column oven CTO-10A, equipped with
a conductivity detector CDD-6A (Shimadzu, Kyoto, Japan) was
used. Analysis was carried out using a Shin-Pak IC-A3 column
(4.6mm i.d. X 150 mm, Shimadzu, Kyoto, Japan), at 40 °C. The flow
rate of the mobile phase (8 mM p-Hydroxybenzoic acid /3.2 mM
Bis(2-hydroxyethyl) iminotris(hydroxymethyl)methane /50 mM Boric
acid) was 1.2 ml/min. The blood and the stomach contents were
subjected to toxicological analysis. Sample preparation was as
follows; Samples (0.1 ml) were diluted with distilled water (1:19).
Following centrifugation, liquid-solid extraction using SepPak light
(Waters, Milford, USA) was performed. The 10 μl
of the eluent was injected into the ion chromatography.
The concentrations of
methemoglobin in postmortem blood was 60.1 %. No ethanol or other
drugs were detected in blood. As the normal methemoglobin level is
less than 1 % in healthy subjects, this levels of methemoglobinemia
cause severe cyanosis and symptoms such as dyspnea, headache, seizure
and coma (8,10). As the most common cause of acquired
methemoglobinemia is exposure to an oxidizing agent, such as
nitrates, nitrites or chlorate (3,7,8,10), we performed an additional
examination using ion chromatography.
Figure 1 (a) shows the
chromatogram of stomach contents by ion chromatography. Chlorate ion
was detected in the stomach contents, but not in the blood sample. It
would be difficult to detect in blood sample, as described previously
(8,9). Although the metabolism of chlorate is not well understood, it
is probably reduced to chlorite and then to chloride (3). In the
present case, we were able to detect the presence of chlorate in the
stomach contents, which provided supportive diagnostic evidence of
chlorate intake (1,3). This also emphasizes the importance of
chemical analysis of stomach contents (5,6), especially in case of
ingestion of unstable substances such as chlorate or hypochlorite
(3,5). From the results of the toxicological examination and autopsy
finding, we conclude that the cause of death was severe
methemoglobinemia presumably due to chlorate poisoning.
H. Kinoshita Department
of Forensic Medicine Faculty
of Medicine, Kagawa University, 1750-1,
Miki, Kita, Kagawa, 761-0793, Japan tel.:
+81-87-891-2140 begin_of_the_skype_highlighting+81-87-891-2140end_of_the_skype_highlighting fax: +81-87-891-2141 e-mail:
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