Organic nitrate-induced methemoglobinemia

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.