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Methemoglobinemia is a disorder of the red blood cell. Exposure to various xenobiotics can adversely affect the red cell membrane, intracellular metabolism, and, as is the case with methemoglobinemia, interfere with hemoglobin function. Methemoglobin occurs when the iron atom in hemoglobin loses one electron to an oxidant, and the ferrous (Fe2+) or oxidized state of iron is transformed into the ferric (Fe3+) state. Although methemoglobin is always present at low concentrations in the body, methemoglobinemia is defined herein as an abnormal elevation of the methemoglobin level above 1%. The ubiquity of oxidants, both in the environment and in the hospital, has increased the number of cases of reported methemoglobinemia.

Methemoglobin was first described by Felix Hoppe-Seyler in 1864.35 Subsequently, in 1891, a case of transient drug induced methemoglobinemia was described.73 In the late 1930s, methemoglobinemia was recognized as a predictable adverse effect of sulfanilamide use, and methylene blue was recommended for treatment of the ensuing cyanosis.46,108 Some authors even recommended concurrent use of methylene blue when sulfanilamides were used.108 Methylene blue was used prophylactically during general surgery to treat an individual with congenital methemoglobinemia.7 In 1948, an enzyme identified as coenzyme 1 was reported in six patients in two families who had idiopathic methemoglobinemia. The defect in coenzyme 1(NADH methemoglobin reductase) caused cyanosis in the absence of cardiopulmonary disease and responded to ascorbic acid.37

Methemoglobinemia may be hereditary or acquired. The hereditary types are rare, with only several hundred cases reported.47,103 Although the frequency with which xenobiotic-induced methemoglobinemia occurs is unknown, the American Association of Poison Control Centers’ annual data over the past 5 years has shown approximately 100 yearly uses of methylene blue as an antidote. These data substantially underestimate the incidence of this poisoning because poison centers are not notified in most cases (Chap. 136).

Methemoglobinemia is relatively common and generally produces no clinical findings. Cooximetry data collected at two teaching hospitals noted a significant number of elevated methemoglobin levels.4 Of a total of 5248 cooximetry tests over 28 months on 1267 patients, 660 tests revealed methemoglobin levels above 1.5% in 414 patients (some patients had more than one test). Thus, 12.5% of all tests and 19.1% of all patients who had cooximetry performed had an abnormal methemoglobin level. A total of 138 patients with peak methemoglobin levels greater than 2% were identified. The mean peak methemoglobin level was 8.4% (range, 2.1%–60.1%), and the ages of the patients ranged from 4 days to 86 years.4

Benzocaine spray accounted for the most seriously poisoned patients (n = 5), with a mean peak methemoglobin level of 43.8% (range, 19.1%–60.1%).4 Dapsone accounted for the largest number of cases (n = 58), with a mean peak of 7.6% (range, 2.1%–34.1%). Of those patients who had ­elevated methemoglobin levels, 8% ...

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