A month after open heart surgery, 74-year-old William Riley was re-admitted to the hospital with atrial fibrillation. His
cardiologist ordered a transesophageal echocardiogram (TEE), performed at the bedside. Mr. Riley received 1 mg of midazolam
(Versed) intravenously for sedation and several sprays of benzocaine (Cetacaine, Hurricaine) orally as a topical anesthetic.
Several hours later, the patient was fully awake and joking with the staff. Since he had to miss breakfast because of the
TEE, he told his nurse he hoped his lunch would come by special delivery. She noted that his vital signs were stable. Still,
the nurse realized that something wasn't right.
Closer examination revealed that Mr. Riley's pulse oximeter reading (SpO2) was normal at 96%. And he denied any shortness of breath or discomfort. Yet his lips and nail beds were becoming dusky.
The nurse started him on nasal oxygen and called the cardiologist, who ordered a stat arterial blood gas (ABG) and chest X-ray.
She continued to monitor him closely. Despite the additional oxygen, Mr. Riley's cyanosis increased and his pulse oximetry
readings began to fall. He was also becoming lethargic. Suddenly, his SpO2 dropped from 92% to 69%—and he could barely be aroused.
What was happening?
The respiratory therapist who drew the ABG noticed that the blood sample was a dark brownish-red color. This prompted her
to wonder if Mr. Riley had developed methemoglobinemia and, if so, why.
When hemoglobin can't transport O2
Methemoglobin is a form of hemoglobin that's unable to combine with and transport oxygen.1 It's normally absent or present in minute amounts, making up no more than 1.5 % of the total circulating hemoglobin.2 Higher levels are referred to as methemoglobinemia.
How to spot trouble
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Naturally occurring methemoglobinemia is caused by congenital abnormalities and is very rare. Acquired methemoglobinemia is
more common and results from exposure to a chemical that accelerates methemoglobin formation.2 Increased methemoglobin production leaves less hemoglobin available to combine with oxygen. As a result, blood oxygen levels
fall, causing hypoxia, which in turn decreases the amount of oxygen delivered to the tissues.3Signs and symptoms vary depending upon the amount of methemoglobin present and the severity of the resulting hypoxia. Cyanosis
is often the only sign of early methemoglobinemia (levels of 10% – 15%)—despite a normal oxygen saturation.4-6 At levels between 15% and 30% patients experience fatigue, headache, weakness, anxiety, nausea and vomiting.4-6 Mental changes such as lethargy and confusion usually start to appear with levels of 30% – 50%, and increasing signs of hypoxia
such as tachycardia, and increased respiratory rate.2,4-6 Severe methemoglobinemia (levels above 50%) can cause acidosis, cardiac dysrhythmias, seizures, and coma,4-6 and levels above 60% can be fatal.2,6
An abnormal amount of methemoglobin turns blood a brownish red, which accounts for the sudden appearance of cyanosis without
any of the other symptoms you'd expect to accompany it. The elevated level of methemoglobin also makes pulse oximeter readings
inaccurate and unreliable indicators of the severity of the problem.7 The more methemoglobin present, the greater the color change. In addition, high levels of methemoglobin give a distinct chocolate
brown cast to the cyanotic skin and mucous membranes.8
A diagnosis of methemoglobinemia must be confirmed with ABG analysis by CO-oximeter, a machine that measures levels of the
different forms of hemoglobin in arterial blood.4 Mr. Riley's results showed a methemoglobin level of 61.9%, indicating severe methemoglobinemia. His nurse increased his oxygen
to 100% by mask and transferred him to the ICU for further treatment and closer monitoring.
A condition caused by topical anesthetic
Drug triggers
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What set this chain of events into motion? Researchers have found that benzocaine spray, the topical anesthetic Mr. Riley
received to decrease swallowing and blunt his gag reflex during the TEE, is the most common cause of methemoglobinemia in
hospitalized patients, but there are other drug triggers.1 (See the box.)
Although it's not clear why some patients develop this reaction while others do not, previous exposure to a drug like benzocaine,
anemia, and a history of cardiac or pulmonary disorders increase the risk.1 Mr. Riley had all three risk factors: postop anemia, cardiac disease, and previous exposure to benzocaine spray during a
preop TEE.
Research also shows that the severity of methemoglobinemia is directly related to the amount of spray used.9,10 The manufacturer's recommended dose is one spray lasting no more than one second.9 But Mr. Riley received three to four sprays during the procedure. This combined with his risk factors resulted in severe
methemglobinemia.
Treatment of methemoglobinemia depends on the severity of the patient's symptoms. Those with mild methemoglobinemia usually
require only supplemental oxygen and monitoring. In addition to oxygen, patients with moderate and severe methemoglobinemia
will receive methylene blue (Urolene blue) IV to accelerate the breakdown of methemoglobin. A patient's weight determines
the dose (1 – 2 mg/kg).
Side effects of methylene blue include chest pain, anxiety, dysuria, and blue urine, so patients receiving it need careful
monitoring and reassurance. The drug usually acts rapidly, with methemoglobin dropping to normal levels within 20 – 60 minutes.10 In severe cases, however, additional doses—up to a maximum total of 7 mg/kg—may be necessary to bring methemoglobin levels
back to normal. One caveat: In doses >15 mg/kg, methylene blue can cause methemoglobinemia.5
When this therapy is not effective, a patient who has severe methemoglobinemia may require exchange transfusion therapy, ventilatory
support, hemodialysis, and even hyperbaric oxygen therapy.4,5,11
Fortunately, that wasn't the case with Mr. Riley. He weighed 75 kg and received an initial dose of 75 mg of methylene blue
IV over five minutes. After 15 minutes, his methemoglobin level had not decreased so the physician ordered a second dose of
75 mg. Half an hour later, the patient's methemoglobin level was down, and he was more responsive. Within an hour, his methemoglobin
level had fallen to 30%. Four hours later, it was back to normal.
Mr. Riley was transferred to a med/surg unit the next morning and discharged two days later. As part of his discharge teaching,
the nurse emphasized the need to alert all his healthcare providers, including his dentist, to his reaction to benzocaine
spray. She warned him, too, that he should never be given this drug again.
Mr. Riley's experience offers a valuable lesson to all nurses caring for patients undergoing endoscopic procedures. Always
ask the physician if benzocaine spray was used and if so, how much. Pay close attention to any changes in skin color after
the procedure. If you detect any change, give supplemental oxygen and report the cyanosis immediately. And, if you work in
a short-stay unit or outpatient area, include information about the signs and symptoms of methemoglobinemia in discharge instructions
for patients who have had an endoscopic procedure.
With the number of patients undergoing bronchoscopy, gastroscopy, and transesophageal echocardiography on the rise, concern
about benzocaine-induced methemoglobinemia is increasing.6,8 Indeed, some clinicians have begun questioning the need for this topical anesthetic in patients who receive conscious sedation.9 But as long as benzocaine is still used, your knowledge of which patients are at risk and when to take action can make all
the difference.
REFERENCES
1. Novaro, G. M., Aronow, H. D., et al. (2003). Benzocaine-induced methemoglobinemia: Experience from a high volume transesophageal
echocardiography laboratory. J Am Soc Echocardiogr, 16(2), 170.
2. Ash-Bernal, R., Wise, R., & Wright, S. (2004). Acquired methemoglobinemia: A retrospective series of 138 cases at 2 teaching
hospitals. J Med, 83(5), 265.
3. Benz, E. (2005). Hemoglobinopathies. In D. Kasper, E. Braunwald, et al. (Eds), Harrison's principles of internal medicine (16th ed.), (pp. 598 – 599). New York: McGraw-Hill.
4. Baynard, M., Farrow, J., & Tudiver, F. (2004). Acute methemoglobinemia after endoscopy. J Am Board Fam Pract, 17(3), 227.
5. Konig, M. W., & Dolinski, S. Y. (2003). Pulmonary and critical care pearls: A 74-year-old woman with desaturation following
surgery. Chest, 123(2), 613.
6. Gupta, P. M., Lala, D. S., Arsura, E. L. (2000). Benzocaine-induced methemoglobinemia. South Med J, 93(1), 83.
7. Groeper, K., Katcher, K., & Tobias, J. (2003). Anesthetic management of a patient with methemoglobinemia. South Med J, 96(5), 504.
8. Sharma, V., & Haber, A. (2002). Acquired methemoglobinemia: A case report of benzocaine-induced methemoglobinemia and a
review of the literature. Clin Pulm Med, 9(1), 53.
9. Byrne, M., Michell, R., et al. (2004). The need for caution with topical anesthesia during endoscopic procedures, as liberal
use may result in methemoglobinemia. J Clin Gastroenterol, 38(3), 225.
10. Wright, R., Lewander, W., & Woolf, A. (1999). Methemoglobinemia: Etiology, pharmacology, and clinical management. Ann Emerg Med, 34(5), 646.
11. Margulies, D., & Manookian, C. (2002). Methemoglobinemia as a cause of respiratory failure. J Trauma, 52(4), 796.
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