 Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. Methemoglobin is a form of hemoglobin that does not bind oxygen. When its concentration is elevated in red blood cells, anemia and tissue hypoxia can occur. Both 4 percent amides solutions articaine and prilocaine commonly used in dental procedures as a local anesthetic may produce methemoglobin especially in elderly and medically compromised patients but can be a problem in younger people with the congenital disorder. Such biotransformation of a metabolite into o-toluidine is dose related and can manifest itself within 3 to 6 hours, long after administration and long after the patient has left the operatory. The problem follows a set process where the body's ferrous iron is oxidized into ferric iron, thereby blocking the enzyme methemoglobin reductase pathways. Symptoms and signs will vary with the concentration blood levels of methemoglobin, but typically the patient will be fatigue, lethargic and a noticeable degree of hypoxia and respiratory distress. The skin assumes a pale grey pallor as a result of reduced amount of oxyhemoglobin in skin or mucous membrane and nail beds will appear cyanotic. In most cases since the patient is no longer in the office, if paramedics are called Ironically, administration of 100 percent oxygen does not significantly improve the situation because the now ferric cannot surrender oxygen to tissue. If a sample of gingival (venous blood) is taken it may have the color of dark chocolate brown. It will not assume the bright red even when oxygen is infused. This is no time to be a hero. The course of action is to call 911. Methylene blue is the preferred course of action, however by the time you have located it (assuming you have it) maybe too late. However for your wall chart of emergency actions, methylene blue 1 percent should be administered via slow I.V. (1.5mg/kg or roughly 0.7 mg /lb. This dose can be repeated q4h if cyanosis is still evident. The mode of action of methylene blue is to convert ferric back to ferrous atoms. A word of caution, if you are in an isolated area and time is against you may try a parenteral (either I.M or I.V) administration of ascorbic acid (100 -- 200 mg/day). Ascorbic acid can hasten the metabolic pathways that produce ferrous atoms. Be aware that methylene blue administered in excess unfortunately can itself cause methemoglobinemia. Prilocaine or any of the 4 percent local anesthetic solutions should not cause undue concern unless given in excess of their absolute maximum dose. The presence of congenital methemoglobinemia remains a relative contraindication of either articaine or prilocaine. Editorial Note: Prilocaine is a lidocaine homologue and the only secondary amine local anesthetic that remains in clinical use. Prilocaine is biotransformed by hepatic amidase to aminophenol metabolites (i.e., ortho-toluidine and N-propylalanine), which subsequently can oxidize hemoglobin to methemoglobin. Administration of prilocaine in doses exceeding 400 mg has been associated with methemoglobinemia in adults. Proportionately lower doses may cause this problem in children (1). Methemoglobin levels above 10 percent may result in clinical anoxia (2), and levels above 60 percent can cause stupor, coma, and death. The findings in this report indicate that doses of prilocaine only slightly exceeding the recommended therapeutic dose have the potential to cause methemoglobinemia. The manufacturer's package insert for prilocaine recommends a therapeutic dose of 4 mg/lb * (8 mg/kg) for "normal healthy adults," with a maximum dose of 600 mg indicated for persons weighing 150 lbs (68 kg) or more.For persons weighing less than 150 lbs (68 kg), the maximum dose must be accurately adjusted for body weight to reduce the risk for adverse effects. The Food and Drug Administration (FDA) has investigated the incidents in this report and recommends that the manufacturer update the package insert for prilocaine to emphasize the importance of adjusting dosage for body weight, particularly for persons weighing less than 150 lbs (68 kg). During January 1992-September 1993, FDA received nine reports of prilocaine-induced methemoglobinemia. However, methemoglobinemia may be underreported because 1) some persons may develop only mild symptoms that do not require medical care, 2) some cases may not be recognized as prilocaine-induced, and 3) only drug manufacturers are required by law to report these events. Oral surgeons and other health practitioners should use accurate body weight information to calculate safe doses of prilocaine and should know that doses exceeding 4.0 mg per pound (8 mg/kg) of body weight pose a risk to healthy adults. The risk for adverse effects associated with prilocaine use is increased for infants, persons with underlying health problems (i.e., anemia or diseases affecting the respiratory or cardiovascular systems), persons with hereditary deficiencies of glucose-6-phosphate dehydrogenase and methemoglobin reductase, and persons taking other oxidant drugs (e.g., nitrite-containing medications, sulfonamides, antimalarials, or acetaminophen). ReferencesAstra Pharmaceutical Products, Inc. Brief summary of prescribing information: Citanest Plain{Registered} and Citanest{Registered} Forte {Package insert}. Westborough, Massachusetts: Astra Pharmaceutical Products, Inc, 1992. National Academy of Sciences. The health effects of nitrate, nitrite, and N-nitroso compounds. Washington, DC: National Academy Press, 1981. Disclaimer All MMWR HTML versions of articles are electronic conversions from ASCII text into HTML. This conversion may have resulted in character translation or format errors in the HTML version. Users should not rely on this HTML document, but are referred to the electronic PDF version and/or the original MMWR paper copy for the official text, figures, and tables. An original paper copy of this issue can be obtained from the Superintendent of Documents, U.S. Government Printing Office (GPO), Washington, DC 20402-9371; telephone: (202) 512-1800. Contact GPO for current prices. Comments to localanesthetics@yahoo.ca M.Sc. PharmD. CCPE Please visit WWW.AnestheticNews.comAuthor: M.Sc. PharmD.
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