METHAEMOGLOBINAEMIA DEFINITION Clinical condition arising from the excessive conversion of haemoglobin to methaemoglobin, which is incapable of binding and carrying oxygen. Methaemoglobin is formed when iron in the haem molecule is oxidized from the ferrous (Fe2+) to the ferric state (Fe3+). TOXIC CAUSES Methaemoglobin occurs when haemoglobin is oxidized at a rate exceeding the normal enzymatic capacity for haemoglobin reduction. Certain individuals with impaired enzymatic capacity for haemoglobin reduction may be susceptible to milder oxidative stresses. Numerous agents may be responsible for this oxidation. The most frequently encountered are: Aniline Benzocaine Chlorates Chloroquine Dapsone Ground or surface water contaminated with nitrates Nitrates Nitrites Nitrophenol Phenazopyridine Primaquine Sodium nitroprusside 4-dimethylaminophenol NON-TOXIC CAUSES Congenital enzyme deficiencies CLINICAL FEATURES Methaemoglobinaemia is characterized by cyanosis in the absence of cardiac or pulmonary disease, and refractory to oxygen administration. A typically greyish cyanosis is observed when levels of methaemoglobin exceed 1.5 g/dL, about 10% of the total haemoglobin in a normal individual. At this level, the patient may be otherwise asymptomatic. Symptoms related to impaired oxygen delivery including headache, weakness, tachycardia and breathlessness develop progressively as concentrations of methaemoglobin exceed 20%. Concentrations > 50% result in severe hypoxaemia and CNS depression. Concentrations > 70% may be incompatible with life. Presence of anaemia, cardiac failure or pulmonary disease may produce symptoms of hypoxia at lower percentage levels of methaemoglobin. A blood sample of a patient with more than 15% methaemoglobinaemia has a chocolate brown colour which does not change when exposed to air. DIFFERENTIAL DIAGNOSIS Sulphaemoglobinaemia. Cyanosis due to other causes (e.g. hypoxia). RELEVANT INVESTIGATIONS Arterial blood gases. The p02 is normal while the measured oxygen saturation is decreased. Blood methaemoglobin concentration Pulse oximeters are not accurate in the presence of methaemoglobinaemia. TREATMENT Oxygen. High flow oxygen should be administered Identification of offending agent and prevention of further exposure. This measure alone is usually adequate for mild cases. Gastrointestinal or skin decontamination may be necessary. Methylene blue. This specific antidote is indicated in any patient with symptoms and/or signs of hypoxia (mental changes, tachycardia, dyspnoea, chest pain). Initial dose of methylene blue: 1 to 2 mg/kg not exceeding 4 mg/kg (maximum 7 mg/kg) as a 1% solution intravenously over 5 minutes. In cases not responding to methylene blue or where methylene blue is contraindicated (G6PD deficiency), the following measures may be considered: Exchange transfusion Hyperbaric oxygenation CLINICAL COURSE AND MONITORING Clinical improvement as a result of methylene blue therapy should be observed within one hour. Methaemoglobin levels should be subsequently monitored to document adequacy of response and/or recurrent methaemoglobinaemia. In these cases, further doses of methylene blue are indicated. POTENTIAL SEQUELAE Hypoxic organ injury if treatment is delayed or inadequate. AUTHOR(S)/REVIEWERS Author: Prof. Ad N.P. van Heijst, Bosch en Duin, Netherlands. Peer Review: Cardiff 3/95, Berlin 10/95: V. Danel, T. Meredith, L. Murray, J. Pronczuk.