Methemoglobinemia is a condition in which ferrous iron within hemoglobin is oxidized to ferric iron resulting in impaired oxygen and carbon dioxide transport leading to cyanosis. This ferric state leads to the formation of methemoglobin that causes brownish discoloration of the blood. In healthy normal children, the ferric iron is reduced to ferrous state by the aid of cytochrome b5 oxidase (methemoglobin reductase) along with other systems such as NADH reductase, glutathione reductase and Glucose-6-phosphate dehydrogenase (G-6-PD). Normal concentration of methemoglobin is maintained below 1% in healthy individuals by these enzyme systems.

Methemoglobinemia occurs as an acquired or congenital variant. Acquired methemoglobinemia is more common and occurs from exposure to oxidizing agents such as nitrates, nitrites, aniline dyes and medications such as lidocaine, prilocaine antimalarials. Pyridium etc. It is seen more commonly in premature infants and infants younger than 4 months of age due to presence of fetal hemoglobin and decreased levels of NADH reductase at that age group. Congenital methemoglobinemia is due to either presence of altered hemoglobin (Hemoglobin M) or NADH reductase deficiency. Patients with congenital methemoglobinemia are generally asymptomatic other than cyanosis from birth. Acquired methemoglobinemia is usually mild but can be severe depending upon the cause and can present with cyanosis, dyspnea, lethargy-headache, dizziness and deterioration of mental functioning. A history of exposure to a known toxin or drug may be elicited.

Methemoglobinemia can be easily diagnosed by pulse oximetry. The severity of cyanosis does not correspond to the pulse oximetry reading. The patient may appear extremely cyanotic but have a pulse oximetry reading in the high 80s. The arterial blood sample will show a normal PaO2 though the blood is chocolate brown. This blood when exposed to 100% oxygen continues to remain brown while deoxygenated blood changes to bright red. The diagnosis and severity of methemoglobinemia can be determined by methemoglobin levels. Methemoglobin levels greater than 1% are normal and symptomatic individuals usually have levels greater than 40-50%.