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Letters to the Editor: Letters & Announcements

Banana Blues

Guay, Joanne MD, FRCPC

Editor(s): Saidman, Lawrence

Author Information
doi: 10.1213/ANE.0b013e3181c3c924
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In Response:

Drs. Marcucci and Bourke1 disagree that the use of benzocaine should be abandoned. Based on a fraction of the number of episodes reported (54 of 159) and the sales of some benzocaine products, they estimate that methemoglobinemia related to benzocaine would be an extremely rare event with an incidence of 1 in 1 million. Case reports are sent to medical journals by authors and accepted for publication by reviewers and editors only if they think that those cases can bring new knowledge or interesting educational reminders. Therefore, the number of episodes published has nothing to do with the true incidence of methemoglobinemia related to benzocaine. An incidence is best calculated from a large prospective study. Unfortunately, this is rarely available. Retrospective studies are our second best tool. From a high-volume transesophageal echocardiography laboratory, Novaro et al.2 calculated that the incidence of methemoglobinemia related to benzocaine is 0.115% (95% confidence interval 0.037%–0.269% or 1 in 370 to 1 in 2700) for a first exposure and 0.345% (95% confidence interval 0.376%–3.531% or 1 in 28 to 1 in 266) if there are 2 exposures within 1 wk.

A large dose of benzocaine is not necessary to produce methemoglobinemia in susceptible individuals. Although some individuals will tolerate a large dose of benzocaine without ill effects, susceptible individuals (and it is not possible to know in advance who they are) may develop methemoglobinemia with the smallest dose that can be administered, which is a single spray. In my review, I identified 4 cases of methemoglobinemia occurring after a single spray, and this was also noted when the cases reported to the United States Food and Drug Administration were reviewed by Moore et al.3–7 The exact amount of benzocaine administered is impossible to determine because it varies with the canister orientation and its residual volume.8 Therefore, there is no “safe dose” in susceptible individuals. The amount of methemoglobinemia produced with this minimal dose has been as high as 40%.5

The effects of methemoglobinemia should not be taken lightly. Apart from rendering a fraction of the circulating amount of hemoglobin ineffective for oxygen transport, methemoglobinemia will affect the oxygen-hemoglobin dissociation curve of the residual hemoglobin further limiting the amount of oxygen available to tissues.9 The heme in methemoglobin would be more likely to dissociate from the pocket in the protein, and heme release may trigger some inflammatory processes thus producing organ and tissue damage by mechanisms other than hypoxemia alone.10 Catastrophic outcomes may occur from methemoglobinemia even in previously normal individuals. A good example is the case reported by Ash-Bernal et al.11 A 52-yr-old man investigated for dyspnea on exertion developed methemoglobinemia after the administration of benzocaine spray. Despite tracheal intubation and methylene blue administration, multiple organ failure and death ensued.

The question is, do we still really need benzocaine? The real efficacy of this drug can be seriously challenged by at least 2 randomized controlled trials in which benzocaine was either ineffective or no more potent than clove gel.12,13 I wrote: “Because it is impossible to predict which individuals will be susceptible to develop methemoglobinemia after benzocaine exposure, and also because there is no therapeutic window (between the doses required to produce a therapeutic effect and those producing toxicity) in susceptible individuals, the clinical use of benzocaine should be abandoned.” And I maintain my statement.14

Joanne Guay, MD, FRCPC

Department of Anesthesiology

Maisonneuve-Rosemont Hospital

University of Montreal

Montreal, Quebec, Canada

[email protected]


1. Marcucci C, Bourke DL. Banana blues. Anesth Analg 2010;110:259–60
2. Novaro GM, Aronow HD, Militello MA, Garcia MJ, Sabik EM. Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory. J Am Soc Echocardiogr 2003;16:170–5
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6. Sachdeva R, Pugeda JG, Casale LR, Meizlish JL, Zarich SW. Benzocaine-induced methemoglobinemia: a potentially fatal complication of transesophageal echocardiography. Tex Heart Inst J 2003;30: 308–10
7. Moore TJ, Walsh CS, Cohen MR. Reported adverse event cases of methemoglobinemia associated with benzocaine products. Arch Intern Med 2004;164: 1192–6
8. Khorasani A, Candido KD, Ghaleb AH, Saatee S, Appavu SK. Canister tip orientation and residual volume have significant impact on the dose of benzocaine delivered by Hurricane spray. Anesth Analg 2001;92:379–83
9. Darling RC, Roughton FJW. The effect of methemoglobin on the equilibrium between oxygen and hemoglobin. Am J Physiol 1942;137:56–68
10. Umbreit J. Methemoglobin—it's not just blue: a concise review. Am J Hematol 2007;82:134–44
11. Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore) 2004;83: 265–73
12. Alqareer A, Alyahya A, Andersson L. The effect of clove and benzocaine versus placebo as topical anesthetics. J Dent 2006;34:747–50
13. Fukayama H, Suzuki N, Umino M. Comparison of topical anesthesia of 20% benzocaine and 60% lidocaine gel. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:157–61
14. Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth Analg 2009;108:837–45
© 2010 International Anesthesia Research Society