Correspondence

Methemoglobinemia and Topical Pharyngeal Anesthesia

N Engl J Med 2003; 348:85-86January 2, 2003

Article

To the Editor:

Methemoglobinemia results from oxidation of ferrous iron (Fe²⁺) to ferric iron (Fe³⁺), which renders the hemoglobin molecule unavailable for oxygen transport, resulting in potentially life-threatening hypoxemia. This disorder may be triggered by topical anesthetics1 used in endoscopic procedures. However, reports on the safety of transesophageal echocardiography in more than 25,000 patients2,3 and upper endoscopy in more than 500,000 patients4,5 do not list methemoglobinemia as a potential complication. We recently observed two cases of methemoglobinemia during transesophageal echocardiography within a three-month period. These cases underscore the importance of familiarity with the expected findings on physical examination, pulse oximetry, and arterial blood gas analysis for rapid diagnosis and therapy.

Case 1 involved a 68-year-old man who underwent transesophageal echocardiography before elective cardioversion. Pulse oximetry showed that the arterial oxygen saturation was 99 percent with nasal oxygen delivered at a rate of 2 liters per minute. Topical pharyngeal anesthesia was established with the use of 20 percent benzocaine spray with midazolam and fentanyl for conscious sedation. During transesophageal echocardiography, the patient's arterial oxygen saturation dropped to 88 percent, and his lips appeared cyanotic. After completion of the study, 100 percent oxygen delivered by face mask did not change the arterial oxygen saturation. Arterial blood gas and hemoglobin analysis by co-oximetry revealed the following values: pH, 7.47; partial pressure of oxygen, 292 mm Hg; partial pressure of carbon dioxide, 32 mm Hg; bicarbonate, 24 mEq per liter; and arterial oxygen saturation, 67 percent. The methemoglobin level was 31 percent. The patient was treated with intravenous methylene blue (1 mg per kilogram of body weight) and recovered promptly.

Case 2 involved a 59-year-old woman who was referred for transesophageal echocardiography because of fever, atrial fibrillation, and dyspnea one month after renal transplantation. Topical pharyngeal anesthesia and conscious sedation were accomplished as described above. At the conclusion of the procedure, the arterial oxygen saturation fell from 98 to 80 percent and was unresponsive to 100 percent oxygen delivered through a face mask. The patient appeared cyanotic and tachypneic. Arterial blood gas and hemoglobin analysis revealed the following values: pH, 7.45; partial pressure of oxygen, 208 mm Hg; partial pressure of carbon dioxide, 40 mm Hg; bicarbonate, 29 mEq per liter; and arterial oxygen saturation, 70 percent. The methemoglobin level was 29 percent by co-oximetry. The patient was treated with ascorbic acid (600 mg given orally four times a day) and had an uneventful recovery.

Methemoglobinemia is a rare but potentially fatal complication of oxidizing agents such as the topical anesthetic benzocaine. Major findings include marked cyanosis and inaccurate readings on pulse oximetry (not reflecting the true oxygen saturation). Co-oximetry of the blood gas sample can be performed to determine the methemoglobin level and confirm the diagnosis. Treatment should be initiated promptly with antioxidant drugs such as methylene blue (1 to 2 mg per kilogram of body weight, given over a five-minute period) or, in less severe cases, ascorbic acid.

Franz C. Aepfelbacher, M.D.
Patrick Breen, M.D.
Warren J. Manning, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215
wmanning@caregroup.harvard.edu

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Citing Articles (8)

Citing Articles

1. 1

   Deya N. Jourdy, Ashutosh Kacker. (2010) Regional Anesthesia for Office-based Procedures in Otorhinolaryngology. Anesthesiology Clinics 28:3, 457-468
   CrossRef

2. 2

   Saurabh S. Dhawan. (2009) Methemoglobinemia-A Rare Complication of Transesophageal Echocardiography. Clinical Cardiology 32:6, E101-E101
   CrossRef

3. 3

   Melinda J Throm, Margie Dale Stevens, Carol Hansen. (2007) Benzocaine-Induced Methemoglobinemia in Two Patients: Interdisciplinary Collaboration, Management, and Near Misses. Pharmacotherapy 27:8, 1206-1214
   CrossRef

4. 4

   Sushmitha Kurapati, Atul C. Mehta, Prasoon Jain. (2007) Benzocaine-induced Methemoglobinemia. Journal of Bronchology 14:1, 41-44
   CrossRef

5. 5

   Swarnalatha BheemReddy, Frank Messineo, Debasish Roychoudhury. (2006) Methemoglobinemia Following Transesophageal Echocardiography: A Case Report and Review. Echocardiography 23:4, 319-321
   CrossRef

6. 6

   Jens Meier, Andreas Pape, Patrick Lauscher, Bernhard Zwiler, Oliver Habler. (2005) Hyperoxia in lethal methemoglobinemia: Effects on oxygen transport, tissue oxygenation, and survival in pigs*. Critical Care Medicine 33:7, 1582-1588
   CrossRef

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   Arthur E Weyman. (2004) The year in echocardiography. Journal of the American College of Cardiology 43:1, 140-148
   CrossRef

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   &NA;. (2003) Benzocaine. Reactions Weekly &NA;:934, 7
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