ORGANIC NITRNrE-INDllCED METHEMOGLOBINEMIA

ABSTRACT: Metabolism of organic nitrates results in the format ion of inorganic nitrites that can oxidize hemoglobin to methemoglobin. Clinical tr ials have investigated the risk of developing methem oglobinemia during the therapeutic use of organic nitrates. Based on the results of these trials, organic nitrate use does appear to increase methemoglobin content but not to a clinically significant exten t. The se elevations may be related to do se but stud y design prevents determination of an y dose-respon se relationship. Despite these result s, several case reports of patients experiencing clinicall y significant methemoglobinemia can be found in the literature. Th ese pat ients generally received organic nitrates at doses greater than tho se used in the clinical tr ials, and several were diagnosed earl y during coronary surgery. Renal dysfunction and concurrent use of methemoglobin inducers may be contributing factors. Patients receiving organic nitrates should be monitored for symptoms suggestive of methemoglobinemia, especially while receiving large dose s. Treatment of nitrate-induced methemoglobinemia con sists of discont inu ing the medication and, when necessary, administering methylene blue. otcr 1989;23:283·8. METHEMOGLOBINEMIA occurs when an excessiveamount of hemoglobin containing iron in the oxidized state (Fe 3 +), known as methemoglobin, is present in the blood. Normally, 99 percent of the total hemoglobin in the blood contains iron in a reduced state (Fe2+). The remaining I percent consists of naturally occurring met-hemoglobin. This small amount of methemoglobin is continuously recycled to normal hemoglobin by one of several pathways, the most predominant involving nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase. Minor pathways involve nicotinamide adenine dinucleotide phosphate (NADPH)-dependent methemoglobin reductase, reduced glutathione, or ascorbic acid. I Methemoglobinemia results in decreased oxygen delivery to the tissues by two mechanisms. First, methe-moglobin is not capable of binding with oxygen