Benzocaine-induced methemoglobinemia: Experience from a high-volume transesophageal echocardiography laboratory

doi:10.1067/mje.2003.5

Journal of the American Society of Echocardiography

Volume 16, Issue 2, February 2003, Pages 170-175

https://doi.org/10.1067/mje.2003.5 Get rights and content

Abstract

Benzocaine (ethyl aminobenzoate), a topical anesthetic widely used before transesophageal echocardiography, has been reported to cause acquired methemoglobinemia. The incidence of benzocaine-induced methemoglobinemia in clinical practice, however, has been difficult to estimate. After systematic review of our institutional experience for clinically recognized cases of benzocaine-induced methemoglobinemia in patients undergoing transesophageal echocardiography, we report an estimated incidence of 0.115% (95% confidence interval 0.037-0.269). This report also provides the largest analysis of the incidence of methemoglobinemia in readministration cases. Although controversy remains as to whether this is an idiosyncratic versus dose-related response, a description of purported patient risk factors is included. (J Am Soc Echocardiogr 2003;16:170-5.)

Section snippets

Study population

Patients who underwent TEE between January 1999 and August 2001 were identified from the Cleveland Clinic Foundation echocardiographic database. Patients undergoing intraoperative TEE were excluded, as preprocedural oropharyngeal topical anesthetics are not used in this setting. Methylene blue administration and increased methemoglobin levels were identified by cross-referencing the above patients with our institutional pharmacy and laboratory databases, respectively. Data regarding topical

Patient characteristics

During the 32-month study period, a total of 4336 TEE examinations were performed. Of these, 5 patients were identified who met criteria for benzocaine-induced methemoglobinemia, resulting in an estimated incidence of 0.115% (95% confidence interval 0.037-0.269). In other words, the incidence of clinically significant methemoglobinemia ranged from approximately 1 in 370 to 1 in 2700. All 5 patients were hospital inpatients; there were no cases that occurred in the outpatient setting. The mean

Discussion

Benzocaine-induced methemoglobinemia is an uncommon occurrence in clinical practice, yet knowledge of this life-threatening condition is vital. Since its first description in the literature in 1950,⁴ at least 60 cases have been reported. This investigation reports on another 5 cases of clinically significant benzocaine-induced methemoglobinemia in patients undergoing TEE. We estimated the incidence of this complication to be approximately 0.115%. Our study constitutes the only systematic

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Cited by (61)

Causes of acquired methemoglobinemia – A retrospective study at a large academic hospital
2024, Toxicology Reports
Methemoglobinemia is a potentially life-threatening condition caused by the formation of methemoglobin, a form of hemoglobin that cannot bind oxygen. While there are some rare congenital causes of methemoglobinemia, most cases are acquired from the effects of specific drugs or environmental exposures. In this retrospective study, we analyzed a large data set of whole blood samples analyzed for methemoglobin at an academic medical center in Midwestern United States that provides both pediatric and adult services. For a 14 year timeframe (May 2009- June 2023), we performed detailed chart analysis of all patients with a methemoglobin concentration of 3.1 % or higher. For an earlier 13 year timeframe (January 1996-April 2009), we performed chart review for all patients with a methemoglobin concentration of 10.0 % or higher. For the 2009–2023 data, dapsone was the most frequent cause of methemoglobinemia (methemoglobin 3.1 % or higher) in both pediatric (73.3 %, 115 clinical encounters, 105 unique patients) and adult (65.3 %, 195 clinical encounters, 190 unique patients) populations. Inhaled nitric oxide as medical therapy was the next most frequent cause in both pediatric (18.1 %) and adult (13.2 %) populations. Causes associated with two or more unique episodes with methemoglobin concentrations of 10.0 % and higher included the following: dapsone (n = 40 episodes), benzocaine (n = 10), recreational use of amyl or isobutyl nitrite (n = 3), suicide attempt with sodium nitrite (n = 3 with 1 fatality; all 3 cases within last 3 years), food contaminated with nitrates (n = 2), and sepsis (n = 2). A total of 18 patients received treatment with methylene blue including 5 cases associated with benzocaine and all of the cases associated with amyl nitrite, isobutyl nitrite, sodium nitrite, and contaminated food. Only 3 patients with dapsone-associated methemoglobinemia received methylene blue, reflecting primary management by dose reduction or discontinuation of drug. Overall, our data reinforce previous studies showing dapsone, inhaled nitric oxide, and nitrites as common agents causing methemoglobinemia in a patient population seen at a medical center. Our data also are consistent with recent epidemiology trends showing increase in suicide attempts using sodium nitrite.
Nursing Staff Administered Topical Lidocaine Anesthesia in Transesophageal Echocardiography: Impact on Quality, Delivery of Care, and the Rates of Methemoglobinemia
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Guidelines for performing a comprehensive transesophageal echocardiographic examination: Recommendations from the american society of echocardiography and the society of cardiovascular anesthesiologists
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Citation Excerpt :
The physician-patient interaction and efficacy of verbal sedation should not be underestimated. The risk for methemoglobinemia with excess use of benzocaine is rare (0.07%–0.12%) and possibly related to a number of clinical factors, including age, dose of medication, enzyme deficiencies, malnutrition, mucosal erosion, hospitalization, sepsis, and anemia.43,44 Signs and symptoms of methemoglobinemia (methemoglobin level > 1.5%) include dyspnea, nausea, tachycardia, cyanosis, and a drop in oxygen saturation by pulse oximetry.
Preparation of the Patient for Awake Intubation
2013, Benumof and Hagberg's Airway Management
Preparation of the Patient for Awake Intubation
2012, Benumof and Hagberg's Airway Management: Third Edition
Severe methemoglobinaemia due to benzocaine-containing 'burn cream': Two case reports in an adult and in a child
2011, Burns

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^*: Reprint requests: Ellen Mayer Sabik, MD, Section of Cardiovascular Imaging, Desk F15, 9500 Euclid Ave, Cleveland, OH 44195 E-mail: [email protected]).

^**: 0894-7317/2003/$30.00 + 0

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Original ArticlesBenzocaine-induced methemoglobinemia: Experience from a high-volume transesophageal echocardiography laboratory*,**

Abstract

Section snippets

Study population

Patient characteristics

Discussion

Chest

Am J Med Sci

Ann Thorac Surg

J Clin Anesth

Ann Emerg Med

Fundam Appl Toxicol

Am J Med

Hereditary methemoglobinemias associated with abnormalities in the metabolism of erythrocytes

Am J Med

Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam

N Engl J Med

Drug- and chemical-induced methaemoglobinaemia: clinical features and management

Med Toxicol

Cyanosis following use of anesthesia (ethylaminobenzoate)

Rev Gastroenterol

Original Articles
Benzocaine-induced methemoglobinemia: Experience from a high-volume transesophageal echocardiography laboratory*,**