1Departments of Anaesthetics and 2Clinical Chemistry, Altnagelvin Hospital, Glenshane Road, Londonderry BT47 1SB, UK*Corresponding author: Department of Anaesthetics, Queen Elizabeth Hospital, Metchley Park Road, Edgbaston, Birmingham B15 2TH, UK
Accepted for publication: August 19, 2000
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Abstract |
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Br J Anaesth 2001; 86: 27880
Keywords: pharmacology, dapsone; complications, methaemoglobinaemia
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Introduction |
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Case report |
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In view of the high PaO2 and the dark colour of the arterial blood, methaemoglobinaemia was suspected. Co-oximetry revealed MetHb levels to be 47%. Fifty milligrams of 1% methylene blue was given i.v. with 1 g of oral vitamin C. The MetHb levels ranged from 13.8 to 31% over the next 72 h and the patient required five additional doses of methylene blue 50 mg. In retrospect, there was no history of ingestion of fava beans or contact with aniline dyes. Red cell glucose-6-phosphate dehydrogenase levels were normal. A urinary screen for opiates, amphetamines, benzodiazepines, cocaine metabolites, barbiturates, cannabinoids and lysergic acid diethylamide was negative. Blood MetHb reductase activity was within the healthy population reference range. The patient was discharged to the ward on day 4 when the MetHb levels fell below 15% and she made an uneventful recovery. A basic extract of the urinary sample taken on day 3 was analysed by gas chromatography/mass spectrometry (Hewlett Packard 6890 series Gas Chromatograph and 5973 Mass Selective Detector). A peak with a retention time of 15.04 min under our operating conditions, gave a 97% match with the Pfleger MS Drug Spectral Library for dapsone. A smaller peak with a retention time of 10.81 min gave a 90% match with the Pfleger library for benzylbutylpthalate. This result suggested prior ingestion of dapsone although the patient denied that possibility. There was no history suggestive of either the patient or her immediate relatives taking dapsone for therapeutic reasons. There was no evidence of haemolysis or anaemia.
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Discussion |
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Clinical features of methaemoglobinaemia depend on the MetHb levels in blood. The discolouration of blood and appearance of cyanosis manifests when the MetHb levels reach 1520%. Levels between 2045% are associated with dyspnoea, lethargy, dizziness and headaches. MetHb levels above 45% are usually associated with impaired consciousness and levels above 55% can cause seizures, coma and cardiac arrhythmias. Although the lethal concentration for adults is considered to be >70%, survival has been reported with levels as high as 83%.1
Methaemoglobinaemia can be caused either by a genetic defect in red cell metabolism or haemoglobin structure, or acquired by a variety of drugs and toxins. About forty substances have been implicated in causing this condition, the most prominent being dapsone, nitrates, prilocaine, antimalarials, sulphonamides and dyes. Domestic causes of acquired methaemoglobinaemia include ingestion of food and water high in nitrites and nitrates,2 inhalation of room odourizers containing butyl nitrite, exposure to aniline dyes in dyed blankets, laundry markings, freshly dyed shoes, red wax crayons3 and cleaning solution.4 Most contain some form of nitrates. Methylene blue when given in doses of over 15 mg kg1 can itself cause methaemoglobinaemia and haemolysis but the MetHb levels rarely exceed 8%.5 One important differential diagnosis for methaemoglobinaemia is sulphaemoglobinaemia. Sulphaemoglobin can be detected by most standard co-oximeters. Once the diagnosis is established, all the possible causes of methaemoglobinaemia should be considered. Information from the patients relatives may prove beneficial. Apart from the potential-offending agents, a search should be made for other substances of abuse, which can be co-ingested. Where appropriate, methaemoglobin reductase activity should be measured.
There have been a number of reports of methaemoglobinaemia because of dapsone.58 In all the cases, there was a history of ingestion of the drug. Dapsone is almost completely absorbed from the gastrointestinal tract and undergoes entero-hepatic circulation.6 The plasma elimination half-life of dapsone is reported to vary from 10 to 80 h and is dose dependent. Renal excretion of unchanged dapsone is limited to approximately 20% of the administered dose. Dapsone is used in the treatment of leprosy and certain skin conditions. This patient did not have any skin lesions. The urine sample results taken on day 3 and the long duration of the methaemoglobinaemia in spite of treatment with methylene blue favoured dapsone as the offending agent. As for the source of dapsone, it is possible that the patient was given dapsone under the guise of ecstasy tablets along with the alcohol. Benzyl butylphthalate is one of the plasticizers present widely in various household substances. Although there is a risk of chronic toxicity, acute toxicity is not known in humans.
This report describes a case of severe methaemoglobaemia without any positive history. The aetiology was traced to the possible ingestion of dapsone, which was detected in the urine by gas chromatography/mass spectrometry.
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Acknowledgements |
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References |
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