4. Methemoglobinemia
In approximately 3% of the body's hemoglobin, the ferrous iron in heme is oxidized upon deoxygenation, creating methemoglobin. Most of this naturally occurring methemoglobin is reduced to hemoglobin through the methemoglobin reductase enzyme system. Methemoglobinemia, characterized by excess production of methemoglobin, causes impairment in the transport of oxygen. Methemoglobinemia can be congenital (due to defects in enzymatic reduction of hemoglobin) or acquired. Patients present with symptoms of anoxia, cyanosis, reduced oxygen saturation, and chocolate-brown arterial blood. Confirmation of the diagnosis is made by measurement of methemoglobin on arterial blood gas sampling.
Drugs that induce methemoglobinemia either directly oxidize hemoglobin or are metabolically activated to an oxidizing species [7]. Phenazopyridine, used for relief of cystitis, can cause oxidative hemolysis [8]. Dapsone, used for leprosy, dermatitis herpetiformis, and prophylaxis for pneumocystis carinii, is metabolized to a hydroxylamine derivative [9]. It was the most common cause of methemoglobinemia in one recent series [10]. Primaquine and local anesthetics, such as topical or spray benzocaine (used prior to upper endoscopic procedures) and prilocaine, can cause methemoglobinemia [11–13]. Amyl nitrite and isobutyl nitrite have been implicated also [7]. Treatment includes cessation of the inducing agent, oxygen, and methylene blue.