A rare side effect of transesophageal echocardiography: methemoglobinemia from topical benzocaine anesthesia
Department of Internal Medicine, Heart and Vascular Institute, Henry Ford Hospital, 2799 West Grand Boulevard, K-14, Detroit, MI 48202, USA
Received 18 July 2006; received in revised form 30 August 2006; accepted after revision 16 September 2006; online publish-ahead-of-print 3 November 2007.
* Corresponding author. Tel.: +1 313 916 5033; fax: +1 313 916 1249. E-mail address: kananth1{at}hfhs.org (K. Ananthasubramaniam)
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Background: Benzocaine induced methemoglobinemia is an uncommon, potentially fatal condition.
Case report: A 44-year-old woman with a history of hepatitis C and intravenous drug use was referred for transesophageal echocardiography for bacteremia evaluation. During induction of topical anesthesia with benzocaine spray she became cyanotic. Pulse oximetry revealed marked desaturation (75%) but was discordant from arterial blood O2 saturation (99%). Due to clinical suspicion, methemoglobin level was measured and noted to be 69%. The patient was treated with 2 mg/kg of methylene blue intravenously with resolution of her symptoms.
Conclusion: Physicians using topical anesthesia in endoscopic suites should be aware of this rare, potentially life-threatening treatable condition. High clinical suspicion and availability of methylene blue in endoscopy suites will facilitate prompt diagnosis and treatment.
Keywords: Methemoglobinemia; Topical anesthetics; Methylene blue; Transesophageal echocardiography
A 44-year-old woman with a history of hepatitis C and intravenous drug use presented with signs and symptoms of a large chest wall abscess. She subsequently developed necrotizing fasciitis and severe sepsis and was intubated prior to transfer to the intensive care unit. Blood cultures grew methicillin resistant Staphylococcus aureus. As part of the evaluation for possible sources of septic emboli a transesophageal echocardiogram (TEE) was scheduled. Before the procedure, her oxygen saturation using pulse oximetry was 99% on ventilator settings of 40% fractional concentration of inspired oxygen (FiO2). Hemoglobin and hematocrit values were 9 g/dl and 27.2%, respectively. She was given 2 sprays of benzocaine each for 1 second, 2 mg of midazolam and was being administered fentanyl at a rate of 2 mg/h intravenously. Within a few minutes the patient became cyanotic, and her oxygen saturation by pulse oximetry of the fingers progressively dropped to 75%. An arterial blood gas test revealed pH 7.45, pCO2 45 mm of Hg, pO2 368 mm of Hg, O2 saturation 99%, serum bicarbonate 30 mmol/l and a base deficit of 5.6 mmol/l. Due to clinical suspicion for methemoglobinemia (MH) the blood level was measured simultaneously with the blood gas. The methemoglobin level was 69%. She was treated with 2 mg/kg of methylene blue (MB) intravenously. Several hours later her cyanosis completely resolved and her methemoglobin level dropped to 0.9% (Figure 1). Her oxygen saturation by pulse oximetry improved to 97% on 40% FiO2. TEE did not reveal an embolus source. She recovered from sepsis and was eventually discharged.
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Benzocaine induced MH is an uncommon but potentially fatal condition. The incidence ranges from 1 in 3701 to 1 in 70002 in patients who receive a topical anesthetic. In a recent review by Tsigrelis and Weiner a total of 126 cases of MH were found in a literature survey from 1950 to 2004.3 Methemoglobin is formed when the iron in hemoglobin is oxidized from ferrous (Fe + +) to the ferric (Fe + ++ ) state. Once formed, the molecule loses its ability to bind oxygen and also interferes with oxygen delivery to the tissue by shifting the oxygen dissociation curve to the left. It has a brownish to blue color, and patients may appear cyanotic. Cyanosis becomes apparent at levels of 15% and in the absence of cardiopulmonary disease or severe anemia patients generally become symptomatic only when their methemoglobin level exceeds 30%. Common symptoms are anxiety, dyspnea, dizziness, headache, tachycardia, arrhythmias and confusion.4 When the level exceeds 50% of total hemoglobin, syncope, coma, and death can occur.
Controversy remains as to whether benzocaine induced MH is an idiosyncratic or a dose-related response. Knowledge of risk factors predisposing to benzocaine induced MH may help to identify patients at higher risk and hence facilitate closer monitoring.1 Risk factors predisposing to this condition in our patient were severe sepsis, acetaminophen use, recent oropharyngeal instrumentation and an excess dose of benzocaine. The suggested dose by the manufacturer is not more than 2 half-second sprays. Newer metered dose benzocaine dispensers are available to permit more reliable dosing. Other risk factors for MH are advanced age, hypoxia, malnutrition and exposure to oxidizing agents in patients with enzyme deficiency. In addition underlying anemia, cardiac or respiratory diseases may worsen the symptoms associated with MH.
Examination of arterial blood sample in MH reveals a chocolate brown color that does not revert to red when exposed to air. The diagnosis is further confirmed by spectrophotometric measurement of methemoglobin concentration. Pulse oximetry has limitations in evaluating oxygen saturation in the presence of MH. This is the reason for the discordance between abnormal oximetry readings and normal blood gas concentrations of oxygen.
Symptomatic or asymptomatic patients with MH levels of 30% or greater can be treated with 1–2 mg/kg intravenous MB given over 3–10 min. In patients with initial levels of methemoglobin >50% a dose of 2 mg/kg initially is recommended.5 The dose of MB may be repeated if symptoms fail to improve. In patients with concurrent conditions compromising oxygen delivery, lung or heart disease, MB is recommended if the methemoglobin concentration is as low as 10%.6 It is a relatively benign treatment, although at higher doses it may induce hemolysis (maximum cumulative dose is 7 mg/kg) and paradoxically, MH in patients with glucose-6-phosphate dehydrogenase deficiency. In severe cases of MH (levels > 70%) exchange transfusions or dialysis may be necessary.1 It is extremely important to thoroughly search for the offending agent in a patient with MH because simple avoidance may prevent another episode.
Conclusion
This case illustrates a rare but important complication in patients undergoing TEE or other endoscopic procedures who are exposed to topical anesthetics. MH should be suspected in any patient with unexplained cyanosis, low oxygen saturation with a normal arterial oxygen tension, or exposure to a chemical or drug known to cause this disorder. Clinical suspicion and prompt treatment with MB in endoscopy suites may reduce the likelihood of adverse events.
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The authors do not have any financial disclosure or conflict of interest in the preparation of this manuscript. 
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References |
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- 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.[CrossRef][Web of Science][Medline]
- Douglas WW, Fairbanks VF. Methemoglobinemia induced by a topical anesthetic spray (cetacaine). Chest (1977) 71:587–91.[CrossRef][Web of Science][Medline]
- Tsigrelis C, Weiner L. Methemoglobinemia revisited: an important complication after transesophageal echocardiography. Eur J Echocardiogr (2006) 7:470–472.
[Abstract/Free Full Text] - Gupta PM, Lala DS, Arsura EL. Benzocaine-induced methemoglobinemia. South Med J (2000) 93:83–6.[Web of Science][Medline]
- Bradberry SM. Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev (2003) 22:13–27.[CrossRef][Medline]
- Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med (1999) 34:646–56.[CrossRef][Web of Science][Medline]
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