Methemoglobin

Methemoglobin is a form of hemoglobin in which the iron in the heme group is ferric (Fe3+), rendering it unable to bind oxygen. In healthy individuals, a small amount is continuously produced and rapidly reduced back to ferrous iron by methemoglobin reductase; the normal fraction of methemoglobin is usually less than 1-2% of total hemoglobin.

Acquired methemoglobinemia results from exposure to oxidizing agents, including certain drugs and chemicals. Common culprits are nitrates and nitrites, benzocaine, lidocaine, dapsone, sulfonamides, phenazopyridine, aniline dyes, and contaminated drinking water or formula in infants. Congenital forms arise from defects in the enzyme NADH-cytochrome b5 reductase or from abnormal hemoglobin variants (Hb M), leading to higher baseline methemoglobin levels.

Clinical features reflect tissue hypoxia despite normal arterial oxygen tension. Patients often have cyanosis that does not improve with oxygen, and may experience headache, dizziness, fatigue, shortness of breath, tachycardia, or weakness. Chest pain and altered mental status can occur at higher levels. Blood typically appears chocolate-brown. Pulse oximetry readings may plateau around the mid-80s, while arterial blood gas often shows a normal PaO2 with reduced oxygen saturation on co-oximetry.

Diagnosis is made by co-oximetry, which directly measures methemoglobin levels. Normal levels are 1-2%; symptoms usually emerge as methemoglobin rises above 10-20%, with severe danger above 50-70%.

Treatment focuses on removing the offending agent and reducing methemoglobin. The antidote is methylene blue (1-2 mg/kg IV, may be repeated once); it requires functioning glucose-6-phosphate dehydrogenase and NADPH. In G6PD deficiency or refractory cases, ascorbic acid or exchange transfusion may be used. Prognosis is good with prompt treatment.