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Toxic methemoglobinemia after topical anesthesia for transesophageal echocardiography
CASE REPORTS
Toxic Methemoglobinemia After Topical Anesthesia for Transesophageal Echocardiography Susan E. Grauer, MD, and George D. Giraud, MD, PhD,
Portland, Oregon
Topical benzocaine spray is an anesthetic agent that is commonly used during transesophageal echocardiography (TEE). This agent is believed to be relatively safe because o f very low systemic absorption. We report a case o f toxic methemoglobinemia induced by benzocaine used for pharyngeal anesthesia during TEE.
Physicians who perform TEE and use benzocaine or other topical anesthetics need to be familiar with this potential complication and have the necessary treatment readily available. (J Am Soc Echocardiogr 1996;9: 874-6.
T r a n s e s o p h a g e a l echocardiography is a relatively safe procedure with a recognized low incidence o f complications, including vomiting, bronchospasm, bleeding, angina, arrhythmias, and esophageal inj u r y ) M a n y echocardiographers, however, may be unaware o f the potential serious complication o f m e t h e m o g l o b i n e m i a , which has been reported to occur after benzocaine anesthesia for other similar procedures. >s We report a case o f initially unrecognized benzocaine-induced toxic m e t h e m o g l o b i n emia associated with transesophageal echocardiography.
stenosis of the left carotid artery, 50% to 60% stenosis of the right carotid artery, and patent vertebral arteries. An electrocardiogram showed evidence of an old anterior myocardial infarction. Transthoracic echocardiography was performed but was technically limited and of poor quality. Because of the concern for a high likelihood ofcardiocmbolic causes for the patient's stroke, a transesophageal echocardiogram was requested by the neurology service. Informed consent was obtained, and transesophageal echocardiography was performed. Blood pressure, heart rate, and pulse oximetry oxygen saturation were monitored during the procedure. Baseline arterial oxygen saturation was 95% on room air. Anesthesia included 4 mg of midazolam administered intravenously in three separate doses and 20% benzocaine spray (Hurricaine ®) administered topically in four sprays of 2 seconds each. Esophageal intubation was uneventful. The oropharynx was suctioned on a regular basis. Approximately 5 minutes into the procedure (approximately 20 minutes after initial benzocaine spray), the pulse oximetry oxygen saturation level began to fall. Despite administration of supplemental oxygen via the nasal cannula, the oxygen saturation continued to decline gradually. The esophageal probe was removed when the saturation reached 86%. The patient was noted to be cyanotic and sleepy but in no respiratory distress. Blood pressure was stable at 110/70 mm Hg, and the heart rate was 80 to 90 beats/rain with frequent premature ventricular complexes. The patient's only complaints were of tingling and dizziness. He was moved to an upright position and stimulated. The oropharynx was suctioned, although there was no evidence of excessive secretions. Flumazenil (0.2 rag) was administered intravenously in an attempt to reverse any remaining benzodiazepine effects. The patient was transferred to the medical intensive care unit where high-flow 100% oxygen was administered. Despite delivery of 100% fraction of inspired oxygen and good respiratory effort, the pulse oximetric oxygen saturation dropped to 70%. After some initial difficulty obtaining arterial blood, an arterial blood gas study was completed that showed an oxygen saturation of 58%, a pH of 7.38, a partial pressure
CASE R E P O R T The patient, a 68-year-old man, was admitted to thc hospital for the elective evaluation of possible stroke. Three months before admission, the patient had a sudden loss of vision. On later evaluation he was found to have a visual field defect. He had a medical history of myocardial infarction, remote partial colectomy for "rupturcd colon," past heavy alcohol use, and current tobacco use. The only medication he was taldng was disulfiram for chronic alcoholism. Physical examination was significant for moderately elevated blood pressure, homonymous hemianopia without other focal neurologic abnormalities, and normal oropharyngeal examination. Evaluation included magnetic resonance imaging of the brain, which showed a right occipital infarct, and carotid ultrasonography, which showed 20% to 49%
From the Department of Medicine, Oregon Health Sciences University and Portland Veterans Administration Medical Center. Reprint requests: Susan E. Grauer, MD, Cardiology Section, 111 B, Portland VA Medical Center, P.O. Box 1034, Portland, OR 97207. Copyright © 1996 by the American Society of Echocardiography. 0894-7317/96 $5.00 + 0 27/4/71486 874
Journal of the AmericanSocietyof Echocardiography Volume 9 Number 6
of carbon dioxide of 44 mm Hg, and a partial pressure of oxygen of 425 mm Hg. The blood contained 47.2% methemoglobin. Methylene blue was administered intravenously (100 rag or approximately 1 mg/kg as a 1% solution over 5 minutes). Within 15 to 20 minutes, the oximetric oxygen saturation had risen to 90%. After 20 minutes, arterial blood gas study results revealed an oxygen saturation of 89%, a pH of 7.32, a partial pressure of carbon dioxide of 44 mm Hg, and a partial pressure of oxygen of 426 mm Hg, with a methemoglobin level of 12.3%. By 4 hours after administration of methylene blue, thc oxygen saturation was 96% and the methemoglobin level was 1.7%. The blood was also tested for nicotinamide adenine dinucleotide (NADH) methemoglobin reductase, which was found to be in the normal range (11.9 IU/gm hemoglobin with expected values of 10.1 to 19.4 IU/gm hemoglobin). DISCUSSION
Transesophageal echocardiography is a frequently performed procedure that has a lowincidence o f complications. ~Local anesthetic agents are usually administered topically before esophageal intubation; benzocaine spray is a commonly used agent, which is available as a 14% spray (Cetacaine ®) and a 20% spray (Hurricaine®). Toxic methemoglobinemia, a rare complication o f local anesthetics including benzocaine, has been reported to be associated with procedures including endoscopy, 2°4'6 tracheal intubation, 3'7'8 bronchoscopy, a'4,ga° and dental procedures.S Because patients undergoing transesophageal echocardiography are also at risk for this rare complication, cardiologists who perform this procedure also need to be aware o f this disorder and its treatment. Methemoglobin, which is normally present as approximately 1% o f an individual's hemoglobin, is formed when hemoglobin is oxidized from the ferrous form to the ferric form. This oxidized hemoglobin is incapable o f binding oxygen) 1 Normally, methemoglobin is reduced quickly back to the ferrous form by the action o f N A D H methemoglobin reductase (also known as N A D H diaphorase or cytochrome b5 reductase). The condition o f methemoglobinemia occurs when the rate of oxidation exceeds the rate o f reduction and the amount o f oxidized hemoglobin or methemoglobin reaches abnormal levels. T M This can occur in the following situations: (1) when increased rates o f oxidation produced by drugs or toxins overwhelm the normal reducing capacity (toxic or acquired methemoglobinemia), (2) when a decrease in the reducing capacity o f red blood ceils results from a deficiency o f the enzyme N A D H methemoglobin reductase, or (3)
Grauer and Giraud
875
when an abnormal globin moiety (hemoglobin M) renders hemoglobin resistant to reduction, n-13 Both of the latter two conditions are congenital. Hemoglobin M is associated with cyanosis in the first 6 months o f lifc12; N A D H methemoglobin reductase dcficiency may be asymptomatic in the absence of oxidant stress or may be associated with cyanosis, depending on the baseline lcvels o f methemoglobin, n Drug-induced or toxic methemoglobinemia occurs in normal individuals 4'7'8 and in patients with decreased reducing capacity as a result ofmethemoglobin rcductasc deficiency.2 Agents that arc capable o f greatly increasing the rate o f h c m e oxidation include nitrites, nitrates, sulfonamidcs, aniline dyes, and local anesthetics, n i~ This reaction to local anesthetics may be dose related, as in the case ofprilocaine, or it may bc sporadic, as in the casc o f lidocaine. Based on chemical structure, it is postulated that benzocaine may cause a dose-related responsc. 14 Factors besides N A D H reductase deficiency, which may predispose a patient to methemoglobinemia after use of local anesthetics, include mucosal or skin breakdown leading to systemic absorption, administration o f a higher than usual dose, and concomitant usc o f other agents that may cause this r e a c t i o n . 4"6"a°'ls The signs and symptoms o f methemoglobinemia are those o f tissue hypoxia and arc typically most serious in patients with existing cardiopulmonary disease)* Decreased oxygen delivery to tissues results from the inability ofmethcmoglobin to bind oxygen, but there is evidence that methemoglobinemia also alters the oxygen affinity o f normal hemoglobin, shifting the oxygen dissociation curve to the left) 6 Methemoglobin levels of 10% to 25% are usually associated with cyanosis. Headache, fatigue, dizziness, dyspnea, and tachycardia may occur at levels o f 35% to 40%. Levels o f 60% may cause arrhythmias, seizures, lethargy, and stupor, and levels o f greater than 70% may result in vascular collapse and death.n-13 Severe toxic methemoglobinemia requires prompt treatment. The offending agent should be discontinued, and high-flow oxygen should be administ e r e d ) °a3 The antidote o f choice is the intravenous administration of methylene blue (1 to 2 m g / k g ) given as a 1% solution over 5 minutes. The dose may be repeated if cyanosis does not clear within 1 hour. 11'z3"17In the presence ofnicotinamide adenine dinucleotide phosphate (NADPH), methylene blue is converted to leukomethylene blue, which results in the nonenzymatic reduction ofmethemoglobin, a2,~8 Because the action o f methylene blue requires an intact pentose phosphate pathway for regeneration o f N A D P H , methylene blue may have no effect on
876
Graucr and Giraud
methemoglobin levels in patients with glucose-6phosphate dehydrogenase deficiency and may actually induce hemolysis in those patients. 12'1s Excessivc doses of methylene blue should be avoided in all patients because further production ofmethemoglobin can be induced. 13 The monitoring of therapy may be complicated by inaccurate pulse oximetric readings caused by methylene bluc and methemoglobin itself. 19 Therefore direct measurement of arterial oxygen saturation may be necessary in the initial assessment and evaluation ofthcrapy. Finally, if methylene blue therapy is ineffective at adequately reducing methemoglobin, alternate treatments include exchange transfusion 13 and possibly hyperbaric oxygen therapy. 13a4 Our patient responded quicldy to treatment with methylene blue, with a decrease in methemoglobin levels and an improvement in oxygen saturation. The only possible predisposing factor for this complication identified in this case was the dose of benzocaine administered. The recommended dose by the manufacturers of Hurricaine (Beutlich, Inc., Niles, Ill.) is a 1/2-second spray that may bc repeated. The manufacturers ofCetacaine (Cetylite Industries, Inc., PennSankcn, N.J.) recommend a spray of 1 second or less with a maximum application of 2 seconds. 2° It is likely that these doses are frequently exceeded in routine pharyngeal anesthesia for transcsophageal echocardiography. This patient did not have evident breakdown in the mucosal barrier or enzyme deficiency to predispose him to this reaction. He was taking disulfiram, but this agent has not been reported to cause methemoglobinemia. Many other reported cases of benzocaine-induced methemoglobinemia have occurred in the absence of predisposing factors and after doses within the recommended range. ~'4'7'~ Although toxic methemoglobinemia is a rare complication of local anesthesia, it is potentially lifethreatening and its rare occurrence is unavoidable. It is very important then that cardiologists who use topical anesthetic agents for transcsophageal echocardiography be aware of this potential complication, so recognition of this cause of rapidly developing cyanosis can be identified and prompt therapy can be initiated. REFERENCES 1. Daniel WG, Erbel R, gasper W, et al. Safety of transesophageal echocardiography: a multicenter survey of 10,419 examinations. Circulation 1991;83:817-21.
Journal of the AmericanSocietyof Echocardiography November-December 1996
2. Collins JF. Methemoglobinemia as a complication of 20% benzocaine spray for cndoscopy. Gastroenterology 1990;98: 211-3. 3. Douglas WW, Fairbanks Vfa. Methemoglobinemia induced by a topical anesthetic spray (Cetacaine). Chest 1977;71:58791. 4. Dinneen SF, Mohr DN, Fairbanks VF. Methemoglobinemia from topically applied anesthetic spray. Mayo Clin Proc 1994; 69:886-8. 5. Ludwig SC. Acute toxic methemoglobinemia following dental analgesia. Ann Emerg Med 1981;10:265-6. 6. Ferraro L, Zeichner S, Greenblott G, Groeger JS. Cetacaineinduced acute methemoglobinemia. Anesthesiology 1988; 69:614-5. 7. Olson ML, McEvoy GK. Methemoglobinemia induced by local anesthetics. Am } Hosp Pharm 1981;38:89-93. 8. O'Donohue WJ, Moss LM, Angelillo VA. Acute methemoglobinemia induccd by topical benzocaine and lidocaine. Arch Intern Med 1980;140:1508-9. 9. Sandza IG, Robcrts RW, Shaw RC, Connors JR Symptomatic methemoglobinemia with a commonly used topical anesthetic, Cetacaine. Ann Thorac Surg 1980;30:187-90. 10. Vessely MB, Zitsch 112. Topical anesthetic-induced methemoglobinemia: a case report and review of the literature. Otolaryngol Head Neck Surg 1993;108:763-7. 11. Beutler E. Methemoglobinemia and sulfhemoglobinemia. In: Williams WJ, Beutler E, Erslev A]-, Lichtman MA, eds. Hematology. New York: McGraw-Hill, 1990:743-6. 12. Lukens JN. Methemoglobinemia and other disorders accompartied by cyanosis. In: Lee RG, Bithell TC, Foerster J, Athens JW, Lukens JN, eds. Wintrobe's clinical hematology. Philadelphia: Lea & Febiger, 1993:1262-71. 13. Donovan JW. Nitrates, nitrites, and other sources of methemoglobinemia. In: Haddad LM, Winchester JF, eds. Clinical management of drug overdose. Philadclphia: WB Saunders, 1990:1419-31. 14. Smith RP, Olson MV. Drug-induced methemoglobinemia. Semin Hematol 1973;10:253-68. 15. Muchmore EA, Dahl BJ. One blue man with mucositis. N Engl I Med 1992;327:133. 16. Darling RC, Roughton FJW. The effect of methemoglobin on the equilibrium between oxygen and hcmoglobin. Am J Physiol 1942;137:56-66. 17. MansouriA, Lurie AA. Concise review: methemoglobinemia. Am J Hematol 1993;42:7-12. 18. Beutler E, Baluda MC. Methemoglobin reduction: studies of the interaction between cell populations and of the role of methylene blue. Blood 1963;22:323-33. 19. Alexander CM, Teller LE, Gross JB. Principles of pulse oximetry: theoretical and practical considerations. Anesth Analg 1989;68:368-76. 20. Physician's desk reference. 49th ed. Montvale, New Jersey: Medical Economics Data Production Company, 1995:863.
Toxic Methemoglobinemia After Topical Anesthesia for Transesophageal Echocardiography Susan E. Grauer, MD, and George D. Giraud, MD, PhD,
Portland, Oregon
Topical benzocaine spray is an anesthetic agent that is commonly used during transesophageal echocardiography (TEE). This agent is believed to be relatively safe because o f very low systemic absorption. We report a case o f toxic methemoglobinemia induced by benzocaine used for pharyngeal anesthesia during TEE.
Physicians who perform TEE and use benzocaine or other topical anesthetics need to be familiar with this potential complication and have the necessary treatment readily available. (J Am Soc Echocardiogr 1996;9: 874-6.
T r a n s e s o p h a g e a l echocardiography is a relatively safe procedure with a recognized low incidence o f complications, including vomiting, bronchospasm, bleeding, angina, arrhythmias, and esophageal inj u r y ) M a n y echocardiographers, however, may be unaware o f the potential serious complication o f m e t h e m o g l o b i n e m i a , which has been reported to occur after benzocaine anesthesia for other similar procedures. >s We report a case o f initially unrecognized benzocaine-induced toxic m e t h e m o g l o b i n emia associated with transesophageal echocardiography.
stenosis of the left carotid artery, 50% to 60% stenosis of the right carotid artery, and patent vertebral arteries. An electrocardiogram showed evidence of an old anterior myocardial infarction. Transthoracic echocardiography was performed but was technically limited and of poor quality. Because of the concern for a high likelihood ofcardiocmbolic causes for the patient's stroke, a transesophageal echocardiogram was requested by the neurology service. Informed consent was obtained, and transesophageal echocardiography was performed. Blood pressure, heart rate, and pulse oximetry oxygen saturation were monitored during the procedure. Baseline arterial oxygen saturation was 95% on room air. Anesthesia included 4 mg of midazolam administered intravenously in three separate doses and 20% benzocaine spray (Hurricaine ®) administered topically in four sprays of 2 seconds each. Esophageal intubation was uneventful. The oropharynx was suctioned on a regular basis. Approximately 5 minutes into the procedure (approximately 20 minutes after initial benzocaine spray), the pulse oximetry oxygen saturation level began to fall. Despite administration of supplemental oxygen via the nasal cannula, the oxygen saturation continued to decline gradually. The esophageal probe was removed when the saturation reached 86%. The patient was noted to be cyanotic and sleepy but in no respiratory distress. Blood pressure was stable at 110/70 mm Hg, and the heart rate was 80 to 90 beats/rain with frequent premature ventricular complexes. The patient's only complaints were of tingling and dizziness. He was moved to an upright position and stimulated. The oropharynx was suctioned, although there was no evidence of excessive secretions. Flumazenil (0.2 rag) was administered intravenously in an attempt to reverse any remaining benzodiazepine effects. The patient was transferred to the medical intensive care unit where high-flow 100% oxygen was administered. Despite delivery of 100% fraction of inspired oxygen and good respiratory effort, the pulse oximetric oxygen saturation dropped to 70%. After some initial difficulty obtaining arterial blood, an arterial blood gas study was completed that showed an oxygen saturation of 58%, a pH of 7.38, a partial pressure
CASE R E P O R T The patient, a 68-year-old man, was admitted to thc hospital for the elective evaluation of possible stroke. Three months before admission, the patient had a sudden loss of vision. On later evaluation he was found to have a visual field defect. He had a medical history of myocardial infarction, remote partial colectomy for "rupturcd colon," past heavy alcohol use, and current tobacco use. The only medication he was taldng was disulfiram for chronic alcoholism. Physical examination was significant for moderately elevated blood pressure, homonymous hemianopia without other focal neurologic abnormalities, and normal oropharyngeal examination. Evaluation included magnetic resonance imaging of the brain, which showed a right occipital infarct, and carotid ultrasonography, which showed 20% to 49%
From the Department of Medicine, Oregon Health Sciences University and Portland Veterans Administration Medical Center. Reprint requests: Susan E. Grauer, MD, Cardiology Section, 111 B, Portland VA Medical Center, P.O. Box 1034, Portland, OR 97207. Copyright © 1996 by the American Society of Echocardiography. 0894-7317/96 $5.00 + 0 27/4/71486 874
Journal of the AmericanSocietyof Echocardiography Volume 9 Number 6
of carbon dioxide of 44 mm Hg, and a partial pressure of oxygen of 425 mm Hg. The blood contained 47.2% methemoglobin. Methylene blue was administered intravenously (100 rag or approximately 1 mg/kg as a 1% solution over 5 minutes). Within 15 to 20 minutes, the oximetric oxygen saturation had risen to 90%. After 20 minutes, arterial blood gas study results revealed an oxygen saturation of 89%, a pH of 7.32, a partial pressure of carbon dioxide of 44 mm Hg, and a partial pressure of oxygen of 426 mm Hg, with a methemoglobin level of 12.3%. By 4 hours after administration of methylene blue, thc oxygen saturation was 96% and the methemoglobin level was 1.7%. The blood was also tested for nicotinamide adenine dinucleotide (NADH) methemoglobin reductase, which was found to be in the normal range (11.9 IU/gm hemoglobin with expected values of 10.1 to 19.4 IU/gm hemoglobin). DISCUSSION
Transesophageal echocardiography is a frequently performed procedure that has a lowincidence o f complications. ~Local anesthetic agents are usually administered topically before esophageal intubation; benzocaine spray is a commonly used agent, which is available as a 14% spray (Cetacaine ®) and a 20% spray (Hurricaine®). Toxic methemoglobinemia, a rare complication o f local anesthetics including benzocaine, has been reported to be associated with procedures including endoscopy, 2°4'6 tracheal intubation, 3'7'8 bronchoscopy, a'4,ga° and dental procedures.S Because patients undergoing transesophageal echocardiography are also at risk for this rare complication, cardiologists who perform this procedure also need to be aware o f this disorder and its treatment. Methemoglobin, which is normally present as approximately 1% o f an individual's hemoglobin, is formed when hemoglobin is oxidized from the ferrous form to the ferric form. This oxidized hemoglobin is incapable o f binding oxygen) 1 Normally, methemoglobin is reduced quickly back to the ferrous form by the action o f N A D H methemoglobin reductase (also known as N A D H diaphorase or cytochrome b5 reductase). The condition o f methemoglobinemia occurs when the rate of oxidation exceeds the rate o f reduction and the amount o f oxidized hemoglobin or methemoglobin reaches abnormal levels. T M This can occur in the following situations: (1) when increased rates o f oxidation produced by drugs or toxins overwhelm the normal reducing capacity (toxic or acquired methemoglobinemia), (2) when a decrease in the reducing capacity o f red blood ceils results from a deficiency o f the enzyme N A D H methemoglobin reductase, or (3)
Grauer and Giraud
875
when an abnormal globin moiety (hemoglobin M) renders hemoglobin resistant to reduction, n-13 Both of the latter two conditions are congenital. Hemoglobin M is associated with cyanosis in the first 6 months o f lifc12; N A D H methemoglobin reductase dcficiency may be asymptomatic in the absence of oxidant stress or may be associated with cyanosis, depending on the baseline lcvels o f methemoglobin, n Drug-induced or toxic methemoglobinemia occurs in normal individuals 4'7'8 and in patients with decreased reducing capacity as a result ofmethemoglobin rcductasc deficiency.2 Agents that arc capable o f greatly increasing the rate o f h c m e oxidation include nitrites, nitrates, sulfonamidcs, aniline dyes, and local anesthetics, n i~ This reaction to local anesthetics may be dose related, as in the case ofprilocaine, or it may bc sporadic, as in the casc o f lidocaine. Based on chemical structure, it is postulated that benzocaine may cause a dose-related responsc. 14 Factors besides N A D H reductase deficiency, which may predispose a patient to methemoglobinemia after use of local anesthetics, include mucosal or skin breakdown leading to systemic absorption, administration o f a higher than usual dose, and concomitant usc o f other agents that may cause this r e a c t i o n . 4"6"a°'ls The signs and symptoms o f methemoglobinemia are those o f tissue hypoxia and arc typically most serious in patients with existing cardiopulmonary disease)* Decreased oxygen delivery to tissues results from the inability ofmethcmoglobin to bind oxygen, but there is evidence that methemoglobinemia also alters the oxygen affinity o f normal hemoglobin, shifting the oxygen dissociation curve to the left) 6 Methemoglobin levels of 10% to 25% are usually associated with cyanosis. Headache, fatigue, dizziness, dyspnea, and tachycardia may occur at levels o f 35% to 40%. Levels o f 60% may cause arrhythmias, seizures, lethargy, and stupor, and levels o f greater than 70% may result in vascular collapse and death.n-13 Severe toxic methemoglobinemia requires prompt treatment. The offending agent should be discontinued, and high-flow oxygen should be administ e r e d ) °a3 The antidote o f choice is the intravenous administration of methylene blue (1 to 2 m g / k g ) given as a 1% solution over 5 minutes. The dose may be repeated if cyanosis does not clear within 1 hour. 11'z3"17In the presence ofnicotinamide adenine dinucleotide phosphate (NADPH), methylene blue is converted to leukomethylene blue, which results in the nonenzymatic reduction ofmethemoglobin, a2,~8 Because the action o f methylene blue requires an intact pentose phosphate pathway for regeneration o f N A D P H , methylene blue may have no effect on
876
Graucr and Giraud
methemoglobin levels in patients with glucose-6phosphate dehydrogenase deficiency and may actually induce hemolysis in those patients. 12'1s Excessivc doses of methylene blue should be avoided in all patients because further production ofmethemoglobin can be induced. 13 The monitoring of therapy may be complicated by inaccurate pulse oximetric readings caused by methylene bluc and methemoglobin itself. 19 Therefore direct measurement of arterial oxygen saturation may be necessary in the initial assessment and evaluation ofthcrapy. Finally, if methylene blue therapy is ineffective at adequately reducing methemoglobin, alternate treatments include exchange transfusion 13 and possibly hyperbaric oxygen therapy. 13a4 Our patient responded quicldy to treatment with methylene blue, with a decrease in methemoglobin levels and an improvement in oxygen saturation. The only possible predisposing factor for this complication identified in this case was the dose of benzocaine administered. The recommended dose by the manufacturers of Hurricaine (Beutlich, Inc., Niles, Ill.) is a 1/2-second spray that may bc repeated. The manufacturers ofCetacaine (Cetylite Industries, Inc., PennSankcn, N.J.) recommend a spray of 1 second or less with a maximum application of 2 seconds. 2° It is likely that these doses are frequently exceeded in routine pharyngeal anesthesia for transcsophageal echocardiography. This patient did not have evident breakdown in the mucosal barrier or enzyme deficiency to predispose him to this reaction. He was taking disulfiram, but this agent has not been reported to cause methemoglobinemia. Many other reported cases of benzocaine-induced methemoglobinemia have occurred in the absence of predisposing factors and after doses within the recommended range. ~'4'7'~ Although toxic methemoglobinemia is a rare complication of local anesthesia, it is potentially lifethreatening and its rare occurrence is unavoidable. It is very important then that cardiologists who use topical anesthetic agents for transcsophageal echocardiography be aware of this potential complication, so recognition of this cause of rapidly developing cyanosis can be identified and prompt therapy can be initiated. REFERENCES 1. Daniel WG, Erbel R, gasper W, et al. Safety of transesophageal echocardiography: a multicenter survey of 10,419 examinations. Circulation 1991;83:817-21.
Journal of the AmericanSocietyof Echocardiography November-December 1996
2. Collins JF. Methemoglobinemia as a complication of 20% benzocaine spray for cndoscopy. Gastroenterology 1990;98: 211-3. 3. Douglas WW, Fairbanks Vfa. Methemoglobinemia induced by a topical anesthetic spray (Cetacaine). Chest 1977;71:58791. 4. Dinneen SF, Mohr DN, Fairbanks VF. Methemoglobinemia from topically applied anesthetic spray. Mayo Clin Proc 1994; 69:886-8. 5. Ludwig SC. Acute toxic methemoglobinemia following dental analgesia. Ann Emerg Med 1981;10:265-6. 6. Ferraro L, Zeichner S, Greenblott G, Groeger JS. Cetacaineinduced acute methemoglobinemia. Anesthesiology 1988; 69:614-5. 7. Olson ML, McEvoy GK. Methemoglobinemia induced by local anesthetics. Am } Hosp Pharm 1981;38:89-93. 8. O'Donohue WJ, Moss LM, Angelillo VA. Acute methemoglobinemia induccd by topical benzocaine and lidocaine. Arch Intern Med 1980;140:1508-9. 9. Sandza IG, Robcrts RW, Shaw RC, Connors JR Symptomatic methemoglobinemia with a commonly used topical anesthetic, Cetacaine. Ann Thorac Surg 1980;30:187-90. 10. Vessely MB, Zitsch 112. Topical anesthetic-induced methemoglobinemia: a case report and review of the literature. Otolaryngol Head Neck Surg 1993;108:763-7. 11. Beutler E. Methemoglobinemia and sulfhemoglobinemia. In: Williams WJ, Beutler E, Erslev A]-, Lichtman MA, eds. Hematology. New York: McGraw-Hill, 1990:743-6. 12. Lukens JN. Methemoglobinemia and other disorders accompartied by cyanosis. In: Lee RG, Bithell TC, Foerster J, Athens JW, Lukens JN, eds. Wintrobe's clinical hematology. Philadelphia: Lea & Febiger, 1993:1262-71. 13. Donovan JW. Nitrates, nitrites, and other sources of methemoglobinemia. In: Haddad LM, Winchester JF, eds. Clinical management of drug overdose. Philadclphia: WB Saunders, 1990:1419-31. 14. Smith RP, Olson MV. Drug-induced methemoglobinemia. Semin Hematol 1973;10:253-68. 15. Muchmore EA, Dahl BJ. One blue man with mucositis. N Engl I Med 1992;327:133. 16. Darling RC, Roughton FJW. The effect of methemoglobin on the equilibrium between oxygen and hcmoglobin. Am J Physiol 1942;137:56-66. 17. MansouriA, Lurie AA. Concise review: methemoglobinemia. Am J Hematol 1993;42:7-12. 18. Beutler E, Baluda MC. Methemoglobin reduction: studies of the interaction between cell populations and of the role of methylene blue. Blood 1963;22:323-33. 19. Alexander CM, Teller LE, Gross JB. Principles of pulse oximetry: theoretical and practical considerations. Anesth Analg 1989;68:368-76. 20. Physician's desk reference. 49th ed. Montvale, New Jersey: Medical Economics Data Production Company, 1995:863.