metahemoglobinemia

Metahemoglobinemia is a blood disorder characterized by an elevated fraction of methemoglobin, the ferric (Fe3+) form of hemoglobin that cannot bind oxygen. Methemoglobin is formed continually but is normally reduced back to functional hemoglobin by enzymatic systems, primarily the NADH-dependent cytochrome b5 reductase, with a secondary NADPH-dependent pathway. When production of methemoglobin exceeds the capacity of these reductive mechanisms, methemoglobin accumulates and impairs oxygen delivery despite a normal arterial oxygen tension.

Causes include both congenital and acquired factors. Congenital methemoglobinemia results from defects in red cell methemoglobin reductase (Types I and II) or from abnormal hemoglobin M variants. Acquired methemoglobinemia arises after exposure to oxidant drugs and chemicals (such as nitrites and nitrates, benzocaine, lidocaine/prilocaine, dapsone, nitrofurantoin, and aniline dyes), well-water contaminants, tobacco smoke, and certain anesthetic agents.

Clinical features range from mild to life-threatening. Patients commonly present with cyanosis and headaches, along with dyspnea and fatigue. Blood may appear chocolate-brown. At higher methemoglobin levels, symptoms can progress to confusion, tachycardia, seizures, coma, arrhythmias, and potentially death.

Diagnosis is based on co-oximetry demonstrating elevated methemoglobin, with a normal PaO2 on arterial blood gas but reduced oxygen saturation on standard pulse oximetry (often around 85%). Congenital cases may require enzymatic studies for definitive diagnosis.

Treatment focuses on removing the offending agent and reversing methemoglobinemia. Acute therapy typically uses methylene blue (1-2 mg/kg IV), with reassessment and possible repetition. Methylene blue is contraindicated or used with caution in individuals with glucose-6-phosphate dehydrogenase deficiency and may interact with serotonergic medications. Ascorbic acid can serve as an adjunct. Severe or refractory cases, including some congenital forms, may require exchange transfusion or hyperbaric oxygen. Prognosis is generally favorable with prompt management; prevention centers on avoiding known oxidants and contaminated sources.