MetHb

Methemoglobin (MetHb) is an oxidized form of hemoglobin in which the iron in the heme group is ferric (Fe3+) rather than ferrous (Fe2+). Ferric heme cannot bind oxygen effectively, so MetHb reduces the blood’s oxygen-carrying capacity and impairs oxygen delivery to tissues. The presence of MetHb also alters the oxygen affinity of the remaining normal hemoglobin, often leading to reduced oxygen unloading in tissues. Clinically, blood can appear chocolate-brown, and pulse oximetry frequently reads around 85% regardless of PaO2, which is typically normal on arterial blood gas analysis.

Causes of methemoglobinemia include congenital and acquired factors. Congenital forms arise from deficiencies in the enzymes that reduce MetHb back to Hb, notably cytochrome b5 reductase, or from hemoglobin variants (HbM). Acquired methemoglobinemia occurs after exposure to oxidizing agents such as nitrates and nitrites (including certain food additives and contaminated water), aniline dyes, benzocaine or lidocaine sprays, dapsone, sulfonamides, and some other drugs. Neonates and individuals with reduced enzyme activity are at higher risk.

Diagnosis relies on co-oximetry to measure the fraction of MetHb; standard pulse oximetry is unreliable. Arterial blood gas typically shows a normal PaO2 with a reduced oxyhemoglobin saturation. Treatment includes removing the oxidant source and providing 100% oxygen. The main antidote is methylene blue (1–2 mg/kg IV over several minutes); a repeat dose can be given if there is no response, with a typical maximum total dose around 7 mg/kg. Methylene blue is contraindicated in G6PD deficiency due to risk of hemolysis and poor response; alternatives include high-dose ascorbic acid, exchange transfusion, or hyperbaric oxygen in severe cases. In congenital forms or HbM variants, management focuses on supportive care and avoidance of oxidants; methylene blue may be less effective.

With prompt recognition and treatment, prognosis is favorable, though severe or untreated cases can be life-threatening.