Skip to main content
SpringerLink
Log in

Evaluation and Management of Acquired Methemoglobinemia Associated with Topical Benzocaine Use

  • Review Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Benzocaine is a widely used topical oropharyngeal anesthetic and has been reported to cause methemoglobinemia. We discuss benzocaine-induced methemoglobinemia and review the causes, presentation, and management of this serious complication. Treatment with methylene blue will result in reversal of methemoglobinemia and clinical recovery in most cases but needs to be used at appropriate doses in carefully selected individuals. Physicians who perform procedures involving the application of benzocaine for topical anesthesia need to rapidly identify and treat methemoglobinemia to avoid significant associated morbidity and mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Olson ML, McEvoy GK. Methemoglobinemia induced by local anesthetics. Am J Hosp Pharm. 1981;38(1):89–93.

    CAS  PubMed  Google Scholar 

  2. Spielman FJ, Anderson JA, Terry WC. Benzocaine-induced methemoglobinemia during general anesthesia. J Oral Maxillofac Surg. 1984;42(11):740–3.

    Article  CAS  PubMed  Google Scholar 

  3. Marcovitz PA, Williamson BD, Armstrong WF. Toxic methemoglobinemia caused by topical anesthetic given before transesophageal echocardiography. J Am Soc Echocardiogr. 1991;4(6):615–8.

    CAS  PubMed  Google Scholar 

  4. Ho RT, et al. Benzocaine-induced methemoglobinemia—two case reports related to transesophageal echocardiography premedication. Cardiovasc Drugs Ther. 1998;12(3):311–2.

    Article  CAS  PubMed  Google Scholar 

  5. Fisher MA, et al. Toxic methemoglobinemia: a rare but serious complication of transesophageal echocardiography. Can J Cardiol. 1998;14(9):1157–60.

    CAS  PubMed  Google Scholar 

  6. Grauer SE, Giraud GD. Toxic methemoglobinemia after topical anesthesia for transesophageal echocardiography. J Am Soc Echocardiogr. 1996;9(6):874–6.

    Article  CAS  PubMed  Google Scholar 

  7. Guerriero SE. Methemoglobinemia caused by topical benzocaine. Pharmacotherapy. 1997;17(5):1038–40.

    CAS  PubMed  Google Scholar 

  8. Sachdeva R, et al. Benzocaine-induced methemoglobinemia: a potentially fatal complication of transesophageal echocardiography. Tex Heart Inst J. 2003;30(4):308–10.

    PubMed  Google Scholar 

  9. Bernstein BM. Cyanosis following use of anesthesin; case report. Rev Gastroenterol. 1950;17(2):123.

    CAS  PubMed  Google Scholar 

  10. Weiss-Smith S, et al. The FDA drug safety surveillance program: adverse event reporting trends. Arch Intern Med. 2011;171(6):591–3.

    Article  PubMed  Google Scholar 

  11. Kane GC, et al. Benzocaine-induced methemoglobinemia based on the Mayo Clinic experience from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors. Arch Intern Med. 2007;167(18):1977–82.

    Article  CAS  PubMed  Google Scholar 

  12. Haymond S, et al. Laboratory assessment of oxygenation in methemoglobinemia. Clin Chem. 2005;51(2):434–44.

    Article  CAS  PubMed  Google Scholar 

  13. Umbreit J. Methemoglobin—it’s not just blue: a concise review. Am J Hematol. 2007;82(2):134–44.

    Article  CAS  PubMed  Google Scholar 

  14. Posthumus MD, van Berkel W. Cytochrome b5 reductase deficiency, an uncommon cause of cyanosis. Neth J Med. 1994;44(4):136–40.

    CAS  PubMed  Google Scholar 

  15. Ferraro-Borgida MJ, et al. Methemoglobinemia from perineal application of an anesthetic cream. Ann Emerg Med. 1996;27(6):785–8.

    Article  CAS  PubMed  Google Scholar 

  16. Ganesan S, et al. Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol. 2009;241(1):14–22.

    Article  CAS  PubMed  Google Scholar 

  17. El-Husseini A, Azarov N. Is threshold for treatment of methemoglobinemia the same for all? A case report and literature review. Am J Emerg Med. 2010;28(6):748 e5–748 e10.

    Google Scholar 

  18. Guertler AT, Pearce WA. A prospective evaluation of benzocaine-associated methemoglobinemia in human beings. Ann Emerg Med. 1994;24(4):626–30.

    Article  CAS  PubMed  Google Scholar 

  19. Novaro GM, et al. Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory. J Am Soc Echocardiogr. 2003;16(2):170–5.

    Article  PubMed  Google Scholar 

  20. Udeh C, Bittikofer J, Sum-Ping ST. Severe methemoglobinemia on reexposure to benzocaine. J Clin Anesth. 2001;13(2):128–30.

    Article  CAS  PubMed  Google Scholar 

  21. Moore TJ, Walsh CS, Cohen MR. Reported adverse event cases of methemoglobinemia associated with benzocaine products. Arch Intern Med. 2004;164(11):1192–6.

    Article  PubMed  Google Scholar 

  22. Boran P, Tokuc G, Yegin Z. Methemoglobinemia due to application of prilocaine during circumcision and the effect of ascorbic acid. J Pediatr Urol. 2008;4(6):475–6.

    Article  PubMed  Google Scholar 

  23. Kaendler L, Dorszewski A, Daehnert I. Methaemoglobinaemia after cardiac catheterisation: a rare cause of cyanosis. Heart. 2004;90(9):e51.

    Article  CAS  PubMed  Google Scholar 

  24. Coleman MD, Coleman NA. Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf. 1996;14(6):394–405.

    Article  CAS  PubMed  Google Scholar 

  25. Birchem SK. Benzocaine-induced methemoglobinemia during transesophageal echocardiography. J Am Osteopath Assoc. 2005;105(8):381–4.

    PubMed  Google Scholar 

  26. Tantisattamo E, et al. Atypical presentations of methemoglobinemia from benzocaine spray. Hawaii Med J. 2011;70(6):125–6.

    PubMed  Google Scholar 

  27. Tsigrelis C, Weiner L. Methemoglobinemia revisited: an important complication after transesophageal echocardiography. Eur J Echocardiogr. 2006;7(6):470–2.

    Article  PubMed  Google Scholar 

  28. Lu HC, et al. Pseudomethemoglobinemia: a case report and review of sulfhemoglobinemia. Arch Pediatr Adolesc Med. 1998;152(8):803–5.

    Article  CAS  PubMed  Google Scholar 

  29. Allegaert K, et al. Methemoglobinemia and hemolysis after enteral administration of methylene blue in a preterm infant: relevance for pediatric surgeons. J Pediatr Surg. 2004;39(1):E35–7.

    Article  CAS  PubMed  Google Scholar 

  30. Bradberry SM. Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev. 2003;22(1):13–27.

    Article  CAS  PubMed  Google Scholar 

  31. Sass MD, Caruso CJ, Axelrod DR. Mechanism of the TPNH-linked reduction of methemoglobin by methylene blue. Clin Chim Acta. 1969;24(1):77–85.

    Article  CAS  PubMed  Google Scholar 

  32. DiSanto AR, Wagner JG. Pharmacokinetics of highly ionized drugs. II. Methylene blue–absorption, metabolism, and excretion in man and dog after oral administration. J Pharm Sci. 1972;61(7):1086–90.

    Article  CAS  PubMed  Google Scholar 

  33. Hegedus F, Herb K. Benzocaine-induced methemoglobinemia. Anesth Prog. 2005;52(4):136–9.

    Article  PubMed  Google Scholar 

  34. BheemReddy S, Messineo F, Roychoudhury D. Methemoglobinemia following transesophageal echocardiography: a case report and review. Echocardiography. 2006;23(4):319–21.

    Article  PubMed  Google Scholar 

  35. Rodriguez LF, Smolik LM, Zbehlik AJ. Benzocaine-induced methemoglobinemia: report of a severe reaction and review of the literature. Ann Pharmacother. 1994;28(5):643–9.

    CAS  PubMed  Google Scholar 

  36. Foltz LM, et al. Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine. Am J Hematol. 2006;81(3):210–1.

    Article  PubMed  Google Scholar 

  37. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med. 1999;34(5):646–56.

    Article  CAS  PubMed  Google Scholar 

  38. Jansen T, et al. Isobutyl-nitrite-induced methemoglobinemia; treatment with an exchange blood transfusion during hyperbaric oxygenation. Acta Anaesthesiol Scand. 2003;47(10):1300–1.

    Article  CAS  PubMed  Google Scholar 

  39. Golden PJ, Weinstein R. Treatment of high-risk, refractory acquired methemoglobinemia with automated red blood cell exchange. J Clin Apher. 1998;13(1):28–31.

    Article  CAS  PubMed  Google Scholar 

  40. Dunne J, et al. Ascorbate removes key precursors to oxidative damage by cell-free haemoglobin in vitro and in vivo. Biochem J. 2006;399(3):513–24.

    Article  CAS  PubMed  Google Scholar 

  41. Tanen DA, LoVecchio F, Curry SC. Failure of intravenous N-acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: a randomized controlled trial. Ann Emerg Med, 2000; 35(4):369–73.

    Google Scholar 

  42. Gunaratnam NT, et al. Methemoglobinemia related to topical benzocaine use: is it time to reconsider the empiric use of topical anesthesia before sedated EGD? Gastrointest Endosc. 2000;52(5):692–3.

    Article  CAS  PubMed  Google Scholar 

  43. Dahshan A, Donovan GK. Severe methemoglobinemia complicating topical benzocaine use during endoscopy in a toddler: a case report and review of the literature. Pediatrics. 2006;117(4):e806–9.

    Article  PubMed  Google Scholar 

  44. Evans LT, et al. Pharyngeal anesthesia during sedated EGDs: is “the spray” beneficial? A meta-analysis and systematic review. Gastrointest Endosc. 2006;63(6):761–6.

    Article  PubMed  Google Scholar 

  45. Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med. 2001;37(6):635–41.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Drs. MT, ZA, SV, and JT have declared no conflicts of interest that might be relevant to the contents of this review.

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, University of Toledo Medical Center, 3000 Arlington Avenue, Toledo, OH, 43614, USA

    Mohammed Taleb, Zubair Ashraf, Shahul Valavoor & Jodi Tinkel

Authors
  1. Mohammed Taleb
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zubair Ashraf
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shahul Valavoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jodi Tinkel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jodi Tinkel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taleb, M., Ashraf, Z., Valavoor, S. et al. Evaluation and Management of Acquired Methemoglobinemia Associated with Topical Benzocaine Use. Am J Cardiovasc Drugs 13, 325–330 (2013). https://doi.org/10.1007/s40256-013-0027-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-013-0027-2

Keywords

Search

Navigation