Methemoglobiner

Methemoglobiner are oxidized forms of hemoglobin in which the iron of the heme group is ferric (Fe3+) rather than ferrous (Fe2+). Methemoglobin cannot reversibly bind oxygen, so its accumulation reduces the blood’s oxygen-carrying capacity. A small amount occurs normally as a metabolic byproduct and is kept at low levels by red blood cell reductive systems.

Under normal conditions, methemoglobin levels are maintained below about 1% by endogenous reducing pathways, principally NADH-dependent cytochrome b5 reductase, with a smaller contribution from NADPH-dependent systems. When oxidant exposure or genetic defects overwhelm these pathways, methemoglobinemia develops, causing tissue hypoxia despite adequate arterial oxygen tension.

Causes include acquired factors such as nitrates and nitrites, aniline dyes, dapsone, benzocaine, lidocaine, and other oxidants; and congenital forms due to cytochrome b5 reductase deficiency or abnormal hemoglobins (hemoglobin M). Newborns are particularly susceptible.

Clinical features range from mild cyanosis to severe dyspnea, headache, tachycardia, dizziness, and altered mental status as methemoglobin levels rise. Blood may appear chocolate-brown. Pulse oximetry often underestimates oxygen saturation, while arterial blood gas analysis shows a normal PaO2.

Diagnosis is by co-oximetry demonstrating elevated methemoglobin percentage. Treatment involves removing the oxidant source; mild cases may resolve spontaneously. The antidote is methylene blue (1–2 mg/kg IV) when not contraindicated, notably in individuals without G6PD deficiency. In severe cases or with G6PD deficiency or methylene blue failure, alternatives include high-dose ascorbic acid, exchange transfusion, or hyperbaric oxygen therapy. Prevention focuses on limiting exposure to known oxidants, especially in at-risk populations such as newborns.