Metabolism of organic
nitrates results in the formation of inorganic
nitrites that can oxidize
hemoglobin to
methemoglobin. Clinical trials have investigated the risk of developing
methemoglobinemia 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 extent. These elevations may be related to dose but study design prevents determination of any dose-response relationship. Despite these results, several case reports of patients experiencing clinically significant
methemoglobinemia can be found in the literature. These patients generally received organic
nitrates at doses greater than those used in the clinical trials, and several were diagnosed early 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 doses. Treatment of
nitrate-induced
methemoglobinemia consists of discontinuing the medication and, when necessary, administering
methylene blue.