Copyright © 2005, The European Society of Cardiology
Methemoglobinemia revisited: An important complication after transesophageal echocardiography
Department of Internal Medicine, UMDNJ-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, MEB 486, New Brunswick, NJ 08903, USA
Received 19 June 2005; received in revised form 29 September 2005; accepted after revision 29 September 2005.
weinerle{at}umdnj.edu
* Corresponding author. Tel.: +1 732 235 7742 (work), +1 732 672 5215 (mobile); fax: +1 732 235 7427. tsigreco{at}umdnj.edu dr_tsigrelis{at}yahoo.com
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Abstract |
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 TopNotes Abstract Case presentationDiscussionReferences |
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Methemoglobinemia induced by the use of benzocaine-containing topical anesthetics is a rare, but potentially lethal complication after transesophageal echocardiography (TEE). We report a patient who developed methemoglobinemia after TEE. A review of the literature was performed and the majority of cases of benzocaine-induced methemoglobinemia reported thus far have occurred in patients undergoing TEE, endotracheal intubation, esophagogastroduodenoscopy, and bronchoscopy. All of these procedures have become more frequent than before, and there is a need to reemphasize the potential problem and to reconsider the need for further use of topical anesthetics.
Keywords: Methemoglobinemia; Benzocaine; Transesophageal echocardiography
1 Tel.: +1 201 320 6262 (mobile). 
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Case presentation |
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TopNotesAbstractCase presentationDiscussionReferences |
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An 82-year-old female with type 2 diabetes mellitus, hypertension, and hypercholesterolemia developed dysarthria after left hip surgery. Magnetic resonance imaging of the brain showed multiple areas of infarction, and the patient was scheduled for TEE to rule out a cardiac source of emboli. The patient received midazolam 1mg IV and fentanyl 25µg IV for sedation, and the oropharynx was anesthetized with 2 half-second sprays of Cetacaine® spray (benzocaine 14%, butyl aminobenzoate 2%, tetracaine 2%, and benzalkonium chloride 0.5%; Cetylite Industries Inc, Pennsauken, NJ). Prior to the procedure, the patient's pulse oximetry reading was 100% on room air. After the procedure the patient became cyanotic, and an arterial blood gas with cooximetry showed a partial pressure of oxygen of 77mmHg (inspired oxygen of 40%), arterial oxygen saturation of 68.3%, and a methemoglobin level of 29.1%. The patient was transferred to the intensive care unit and 90mg of methylene blue IV was administered. The patient's cyanosis resolved and a repeat arterial blood gas 1h later showed a partial pressure of oxygen of 88.8mmHg (inspired oxygen of 3L nasal cannula), arterial oxygen saturation of 95.6%, and a methemoglobin level of 1.6%.
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Discussion |
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We report a patient with benzocaine-induced methemoglobinemia after TEE, an important and potentially lethal reaction caused by benzocaine-containing topical anesthetics. Methemoglobinemia can be caused by many drugs and chemicals including benzocaine.1 Methemoglobin is formed from hemoglobin when iron of the heme group is oxidized from the ferrous to the ferric state, which interferes with its ability to bind to oxygen. Cyanosis may occur when the methemoglobin level reaches 10–15%. Malaise, headache, dyspnea, and tachycardia can occur once the methemoglobin level reaches 30%. At higher levels of methemoglobinemia, impairment of consciousness and death may occur. Diagnosis is made by performing an arterial blood gas with cooximetry to detect methemoglobin. Treatment involves the use of methylene blue 1–2mg/kg IV which causes a reduction in methemoglobinemia within 1h. Generally, methylene blue is indicated when methemoglobin levels are in excess of 30%, or if the patient shows overt signs of tissue hypoxia, central nervous system depression, or cardiovascular instability.
There are a number of risk factors which may predispose a patient to develop methemoglobinemia when exposed to benzocaine. These include elderly age, excessive dose of benzocaine, enzyme deficiencies that increase susceptibility to oxidizing agents, hypoxia, malnutrition, mucosal erosion/damage, recent oropharyngeal instrumentation, and sepsis.2 In our patient, advanced age may have played a role by increasing susceptibility to oxidizing agents due to inefficient enzyme function.2 In addition, our patient underwent endotracheal intubation for hip surgery 9 days prior to the index TEE, and laryngoscopy for assessment of dysphasia 8 days prior to the index TEE. These 2 procedures involving oropharyngeal instrumentation may have caused mucosal damage which may have increased the systemic absorption of benzocaine.2 The patient was not given other medications or chemicals within the previous 10 days known to cause methemoglobinemia, such as nitrates or dapsone.1 An excessive dose of Cetacaine® spray may also predispose to methemoglobinemia. The Cetacaine® package insert describes an average dose of 200mg of Cetacaine® from each 1-s expulsion of spray, and recommends that sprays of 1-s or less be applied. Sprays in excess of 2s are contraindicated. Our patient received 2 half-second sprays which is within the manufacturer's recommended dosage. One final predisposing factor that deserves mention is genetic deficiency of nicotinamide adenine dinucleotide-dependent methemoglobin reductase, which is an enzyme that normally reduces naturally occurring methemoglobin levels in humans.2 This deficiency, particularly the heterozygous form, may predispose to methemoglobinemia upon exposure to various oxidizing agents and should be considered in all patients.
The incidence of benzocaine-induced methemoglobinemia associated with TEE in clinical practice has recently been assessed. In a retrospective study by Novaro et al.,2 the incidence of benzocaine-induced methemoglobinemia associated with TEE in their institution was estimated to be 0.115%, which appears to be higher than previously reported. We performed a literature search to assess the number of cases of benzocaine-induced methemoglobinemia reported to date, as well as the types of procedures associated with each case. Since the first case reported by Bernstein3 in 1950, 126 cases of methemoglobinemia were noted. This number likely underestimates the true number of cases, as many cases may go unreported. Fig. 1 displays the number of cases of methemoglobinemia stratified by the type of benzocaine exposure. The majority of the cases reported thus far have occurred in patients undergoing TEE (26 cases), endotracheal intubation (24 cases), esophagogastroduodenoscopy (17 cases), and bronchoscopy (14 cases). Transesophageal echocardiography and other procedures that utilize topical benzocaine have become more frequent than before and there is a need to reemphasize the potential problem.
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There is also a need to reconsider the use of benzocaine-containing topical anesthetics before TEE. The benefit of adding topical benzocaine anesthesia to intravenous sedation has been evaluated in patients undergoing upper endoscopy, and the results are inconclusive.4 Further randomized trials are needed to evaluate the efficacy of topical anesthesia before TEE and other endoscopic procedures. In the meantime, in patients who receive benzocaine-containing topical anesthetic prior to TEE, rapid recognition of methemoglobinemia is essential and treatment can be lifesaving.
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Notes |
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TopNotesAbstractCase presentationDiscussionReferences |
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1 Tel.: +1 201 320 6262 (mobile).
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References |
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TopNotesAbstractCase presentationDiscussionReferences |
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- Osterhoudt K.C. Methemoglobinemia. In: Ford: clinical toxicology (2001) 1st ed. Philadelphia: W.B. Saunders Company. 211–217.
- Novaro G.M., Aronow H.D., Militello M.A., Garcia M.J., Sabik E.M. Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory. J Am Soc Echocardiogr (2003) 16:170–175.[CrossRef][Web of Science][Medline]
- Bernstein B.M. Cyanosis following use of anesthesin (ethyl-amino-benzoate). Rev Gastroenterol (1950) 17:123–124.[Medline]
- Gunaratnam N.T., Vazquez-Sequeiros E., Gostout C.J., Alexander G.L. Methemoglobinemia related to topical benzocaine use: is it time to reconsider the empiric use of topical anesthesia before sedated EGD? Gastrointest Endosc (2000) 52:692–693.[CrossRef][Web of Science][Medline]
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