Methemoglobinaemia

Methemoglobinaemia is a condition in which an increased level of methemoglobin, a form of hemoglobin in which iron is in the ferric (Fe3+) state, is present in circulating blood. Methemoglobin cannot bind and transport oxygen effectively, and it also increases the affinity of remaining ferrous iron for oxygen, impairing tissue oxygen delivery. Clinically, the result is reduced oxygen delivery to tissues and cyanosis that does not correct with supplemental oxygen.

Causes are congenital or acquired. Congenital forms result from deficient activity of cytochrome b5 reductase or from variants of hemoglobin M; acquired methemoglobinaemia arises after exposure to oxidizing drugs or chemicals such as nitrates and nitrites, certain anesthetics (benzocaine, lidocaine), dapsone, sulfonamides, aniline dyes, and other oxidants. Neonates are particularly susceptible due to lower erythrocyte reductive capacity and higher fetal hemoglobin.

Symptoms range from mild fatigue and headache to refractory dyspnea and confusion at higher levels. The classic sign is cyanosis disproportionate to oxygen saturation. Pulse oximetry often reads around 85% regardless of oxygen therapy; blood may appear chocolate-brown. Diagnosis is confirmed by co-oximetry measuring methemoglobin percentage; arterial blood gas can show normal PaO2 with decreased oxygen content.

Management includes removing the offending agent and providing supportive oxygen. For moderate to severe methemoglobinaemia, methylene blue is the first-line antidote (typically 1–2 mg/kg IV, repeated if necessary). It is contraindicated in individuals with G6PD deficiency. Alternative treatments include high-dose ascorbic acid and, in life-threatening cases, exchange transfusion or hyperbaric oxygen. In congenital forms, management depends on severity and redox status; some patients require periodic treatment.

The prognosis is generally favorable with prompt recognition and treatment. However, severe or untreated cases can be fatal. Acquired methemoglobinaemia is rare but occurs worldwide; congenital forms are uncommon but lifelong.