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Topical anesthetic-induced methemoglobinemia

From the June 4,1997 Issue

Problem: Healthcare professionals know the hazards associated with the use of intravenous or inhaled anesthetics but tend to consider topical anesthetics relatively innocuous substances. That topical anesthetics like benzocaine, dyclonine and lidocaine are widely available in many over-the-counter products, such as Cepacol® Anesthetic Troches and Sucrets® Maximum Strength Lozenges, only increases the perception of their safety. However, methemoglobinemia, a serious, and sometimes fatal adverse drug reaction, may occur.

A hospital recently reported two cases of methemoglobinemia due to topically applied anesthetics to FDA's medWatch Program. In the first case, a day-old infant was scheduled for circumcision. An hour before surgery, EMLA® cream (eutectic mixture: lidocaine 2.5%, prilocaine 2.5%) was applied. Three days later, the baby exhibited circumoral cyanosis, and oxygen saturation (O2 sat) was noted to be 89-91% (normal 95-99%). ABGs revealed a methemoglobin (metHb) level of 15.9% (normal <1.5% of total hemoglobin). After treatment with 0.3 mL of 1% methylene blue IV over 5 minutes, the baby stabilized.

In the second case, a 67-year-old patient was scheduled for bronchoscopy due to recurrent respiratory problems. Prior to the procedure, the patient received three sprays of Hurricane" ® Spray (benzocaine 20%) and approximately 3 mL of topical lidocaine 1%. Post-procedure, his O2 sat fell to 80%. Blood tests revealed a markedly elevated metHb of 45%. With appropriate treatment his metHb level had decreased to 2.6% by day 3.

MetHb concentrations greater than 10 to 15 percent of total hemoglobin will cause cyanosis,1 and at levels >70%, patients have died.2 Methemoglobinemia occurs when iron in hemoglobin is oxidized to its ferric form.3 Unlike hemoglobin, methemoglobin binds so firmly with oxygen that less of it is available to tissues. It can be hereditary, but methemoglobinemia is typically acquired from drugs and chemicals, such as nitrites and aniline derivatives, which includes virtually all local anesthetics.1

A recent study assessed the safety and efficacy of EMLA cream for neonatal circumcision.4 The methemoglobin concentrations of the neonates who received EMLA did not differ significantly from those of the control group, but methemoglobinemia has been reported previously with the use of EMLA cream.5.6 Methemoglobinemia has also occurred when an OTC vaginal cream was used to treat an infant's diaper rash.7


Safe Practice Recommendation: Because methemoglobinemia is easily treated, it is important to recognize the possibility of it when topical anesthetics are used. Tell patients not to use topical anesthetics in high doses, on excoriated skin. Use with caution in infants or geriatric patients, some of whom may be less likely to tolerate them.


References: 1. Jacobs DS, editor et al. Laboratory Test Handbook. Lexi-Comp Inc. 1996, Cleveland, OH, 642-3; 2. Wintrobe MM. Methemoglobinemia and other disorders usually accompanied by cyanosis. Clinical Hematology. Philadelphia, Lea and Febiger. 1974:1009-1016; 3. Dinneen SF et al. Methemoglobinemia from topically applied anesthetic spray. Mayo Clin Proc 1994; 69: 886-8. 4. Taddio A et al. Efficacy and safety of lidocaine-prilocaine cream for pain during circumcision. N Engl J Med 1997;336:1197-201. 5. Tse S et al. Methemoglobinemia associated with prilocaine use in neonatal circumcision. Am J Perinatol 1995;12:331-2; 6. Frayling IM, Addison GM, Chattegee K et al. Methaemoglobinaemia in children treated with prilocaine-lignocaine cream. Br Med J 1990; 301: 153-4; 7. Tush GM et al. Methemoglobinemia induced by an OTC medication. Ann Pharmacother 1996;30:1251-4.

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