Severe Methemoglobinemia Detected by Pulse Oximetry

Annabi, Emil H. MD; Barker, Steven J. PhD, MD

Anesthesia & Analgesia:
doi: 10.1213/ane.0b013e318172af73
Technology, Computing, and Simulation: Case Report
Chinese Language Editions

An elderly surgical patient acquired a life-threatening methemoglobinemia as a result of topical benzocaine spray to the oropharynx in preparation for awake endotracheal intubation. A new multiwavelength pulse oximeter, the Masimo Rad-57, detected this methemoglobinemia an hour before it was confirmed by laboratory CO-oximetry. The Rad-57 monitored the patient's methemoglobin levels during diagnosis and treatment with methylene blue, and the values it provided (as high as 33%) were very close to those of the laboratory CO-oximeter. The new pulse oximeter gave continuous readings of methemoglobin level at the bedside, whereas the laboratory values were delayed by up to an hour. This case demonstrates the clinical application of a multiwavelength pulse oximeter in the diagnosis and treatment of a life-threatening dyshemoglobinemia.

In Brief

IMPLICATIONS: This case report demonstrates that life-threatening, drug-induced methemoglobinemia can be diagnosed and monitored using a new multiwavelength pulse oximeter, the Masimo Rad-57. This new device can detect methemoglobin without the delays inherent in laboratory blood analysis, and it can monitor the effectiveness of treatment.

Author Information

From the Department of Anesthesiology, University of Arizona, Tucson, Arizona.

Accepted for publication February 4, 2008.

Dr. Barker is chairman of Masimo's scientific advisory board, and is a community member of the board of directors. He does not receive salary or consulting fees. Masimo has provided support for research done in Dr. Barker's department.

Address correspondence and reprint requests to Steven J. Barker, PhD, MD, Professor and Head, Department of Anesthesiology, University of Arizona College of Medicine, P.O. Box 245114, Tucson, AZ 85724-5114. Address e-mail to

Article Outline

Methemoglobinemia can be a serious problem in perioperative and critical care patients who receive a number of drugs that induce methemoglobin (MetHb). A retrospective study suggested that all patients in critical care units should be screened for MetHb toxicity.1 Until now, this disease could be diagnosed only by sending blood specimens to the laboratory for CO-oximetry analysis of MetHb levels. This in vitro testing is laborious, expensive, and can cause significant delays in starting life-saving treatment. Conventional pulse oximetry is of no use in this regard, as it can neither detect MetHb nor even accurately measure Spo2 in the presence of significant MetHb levels.2

A recently developed “pulse CO-oximeter” (Rad-57 “Rainbow,” Masimo Inc., Irvine, CA) uses eight wavelengths of light rather than the two wavelengths used by conventional pulse oximeters. The Rad-57 can noninvasively measure both MetHb and carboxyhemoglobin, as well as conventional Spo2. We report a surgical case wherein a patient suffered a life-threatening methemoglobinemia caused by topical benzocaine spray. The Rad-57 was used to monitor MetHb levels and guide treatment.

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A 69-yr-old woman was scheduled for debridement of a facial squamous cell carcinoma. Because of a small mouth opening, awake intubation was performed using fiberoptic laryngoscopy. Cetacaine™ (14% benzocaine, 2% tetracaine) was sprayed into the oropharynx for topical anesthesia, and during this process, the patient was observed to inspire once. The surgical procedure proceeded routinely for about 1 h, at which time the conventional pulse oximeter reading gradually decreased to 85%, and the patient's skin appeared dusky. Because of the known behavior of conventional pulse oximetry in the presence of MetHb2 and the well documented risks of benzocaine, the Masimo Rad-57 pulse oximeter was connected to the patient. It immediately provided an SpMet (pulse oximeter estimate of MetHb%) value of 13%. A radial arterial cannula was then inserted for blood sampling and CO-oximetry analysis. After an additional 30 min, the SpMet reading increase to 33% and methylene blue (2 mg/kg) was given by IV bolus. The first two hospital laboratory CO-oximeter MetHb results were reported as “off-scale,” until a reading of 26% was reported from the laboratory on the third sample, more than an hour after the first Rad-57 reading of toxic MetHb levels. The patient responded promptly to methylene blue therapy, and MetHb% decreased to 4% within an hour. The surgical procedure was successfully completed, and the patient suffered no permanent sequelae.

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Figure 1 shows a plot of SpMet and Spo2 displayed by the Rad-57, as well as MetHb% values from the hospital laboratory CO-oximeter as functions of time. The Rad-57 SpMet values were in good agreement with contemporaneous values from the laboratory, even after the injection of methylene blue. The bias (mean error) was +1.0 and the precision (standard deviation of error) was 3.31.

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Acquired methemoglobinemia can be a serious problem in perioperative patients, and the diagnosis has often been missed.1 Barker et al. showed in 1989 that the Spo2 values of conventional two-wavelength pulse oximeters are forced towards 85% in the presence of high MetHb levels.2 This is consistent with the behavior of the conventional pulse oximeter used at the beginning of the present case, which in fact displayed an Spo2 of 85% shortly after the induction of anesthesia. As shown again in this patient, conventional pulse oximetry can neither detect MetHb nor accurately determine Spo2 in its presence.

The Masimo Rad-57 pulse oximeter, introduced in 2005, uses 8 wavelengths of light to measure percentage levels of MetHb as well as carboxyhemoglobin. Barker et al. have shown that Rad-57 measures MetHb% levels with an uncertainty of about 0.5% within the range of 0%–12% in healthy volunteers.3 This case report has shown that the Rad-57 also functions well at much higher MetHb levels (33%), and that it can quickly diagnose this life-threatening problem in the perioperative setting. Somewhat surprisingly, the Rad-57 SpMet values continued to agree with MetHb% values from the laboratory CO-oximeter after the injection of methylene blue, which dramatically changes the light absorbance characteristics of blood.

The current version of the Rad-57 uses the conventional two-wavelength “red to infrared ratio” to determine its Spo2 values. The eight-wavelength algorithm is used only for the determination of SpMet and SpCO. Therefore, the Spo2 from Rad-57 is subject to the same dyshemoglobin errors as conventional pulse oximetry.2 This can be seen in Figure 1, which shows Rad-57 reading Spo2 values of 87% during the period of high MetHb levels.

Finally, this case reminds us again of the potential toxicity of benzocaine topical sprays, particularly when used in the oropharynx. If a patient inspires during oral spraying, the IV absorption from the trachea and lungs may be very rapid. In fact, intratracheal benzocaine spray was the method used to produce MetHb% levels of more than 60% in the Barker 1989 study.2 Despite numerous case reports of MeHb toxicity from benzocaine, physicians continue to use it for oropharyngeal topicalization.4–6 We make two recommendations when using topical benzocaine: (1) use extreme caution to avoid inspiration of the spray, limiting the dose as recommended by the manufacturer, and (2) monitor the patient for developing methemoglobinemia. The Masimo Rad-57, a new bedside tool for the continuous, noninvasive monitoring of MetHb levels, was valuable in the care of this patient.

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1. Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine 2004;83:265–73
2. Barker SJ, Tremper KK, Hyatt J. Effects of Methemoglobinemia on pulse oximetry and mixed venous oximetry. Anesthesiology 1989;70:112–17
3. Barker SJ, Curry J, Redford D, Morgan S. Measurement of carboxyhemoglobin and methemoglobin by pulse oximetry. Anesthesiology 2006;105:892–7
4. Anderson ST, Hajduczek J, Barker SJ. Benzocaine-induced methemoglobinemia in an adult: accuracy of pulse oximetry with methemoglobinemia. Anesth Analg 1988;67:1099–101
5. Seibert RW, Seibert JJ. Infantile methemoglobinemia induced by a topical anesthetic, Cetacaine. Laryngoscope 1984;94:816–7
6. Kellet PB, Copeland CS. Methemoglobinemia associated with benzocaine-containing lubricant. Anesthesiology 1983;59:463–4
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