Benzocaine-Induced Methemoglobinemia

A Rare, Potentially Fatal Reaction to Common Anesthetics

This is my sixteenth year as an RN and the second year I have worked in the endoscopy lab. During my orientation, I quickly realized that I had a great deal to learn about this interesting and unique area of nursing.

At the hospital where I work, the endoscopy staff assists with both gastrointestinal and pulmonary procedures. Recently I was in the process of being oriented to the technical role of bronchoscopy. As I was preparing the work areas for the scheduled procedure, I noticed a package containing the topical anesthetic that we routinely use had a red warning label attached reading: "Use of this product has been associated with the occurrence of methemoglobinemia." The term methemoglobinemia seemed vaguely familiar, so I discussed it with my co-workers -- some of whom were very familiar with the term. I called the pharmacy and spoke with a pharmacist who understood the condition and how to treat it, but gave a complicated explanation.

I decided to research the topic and put together an informational handout for the benefit of the endoscopy nursing staff. My objective was to present endoscopy nurses with information related to the occurrence of benzocaine-induced methemoglobinemia as documented in literature, the signs and symptoms of the condition, and appropriate nursing assessment, intervention and treatment of this rare but potentially fatal reaction.

The Use of Anesthetics

During upper endoscopy procedures, both intravenous (IV) sedation and topical anesthetic are used to ensure that patients are comfortable and able to tolerate the endoscopic examination. Products containing benzocaine are commonly used to anesthetize the mucus membranes of the oropharynx prior to: esophageal gastric duodenoscopy (EGD), bronchoscopy, transesophageal echocardiograph (TEE), as well as endotracheal intubations. These products are effective in suppressing both the pain sensation and the gag reflex. They are generally safe and well-tolerated by patients. However, literature shows that they have been associated with a complication known as benzocaine-induced methemoglobinemia.

Literature Review

Grum and Rice (1990) reported an acute episode of benzocaine-induced methemoglobinemia in a 59-year-old patient following the administration of a benzocaine 20 percent solution gargle prior to EGD. The patient became cyanotic after the procedure with a methemoglobin level of 67 percent.

Slaughter (1999) reported a 74-year-old developed methemoglobinemia from a topical administration in preparation for a TEE. The patient became somnolent and cyanotic. The methemoglobin level was reportedly near 60 percent.

Stoiber (1999) reported a 71-year-old male received benzocaine prior to bronchoscopy and became cyanotic during the procedure and was diagnosed with benzocaine-induced methemoglobinemia. The methemoglobinemia level was reported as 59.8 percent. The author concluded by saying that this is a rare but potentially fatal adverse effect that must be treated promptly once diagnosed.

Kushner, Chitara, Canfield, Poblete, Cunningham, Sarinas (2000) reported benzocaine-induced methemoglobinemia occurring in a healthy research patient. The research participant developed cyanosis with a reported methemoglobinemia level of 27 percent.

Wurdeman, Mhoiuddin, Holmberg, Shalaby (2000) reported a 69-year-old developed marked cyanosis and became hypotensive during a TEE. The methemoglobin level was reported to be 67.8 percent. The authors concluded by saying, "With the increasing number of outpatient procedures performed under topical anesthesia, measures should be in place to deal with a potential life-threatening adverse reaction such as methemoglobinemia."

H.Y. Abdallah, S.A. Shah (2002) reported a case of benzocaine-induced methemoglobinemia that developed 15 to 20 minutes after an upper endoscopy procedure. While in the recovery room, the patient became short of breath and cyanotic. The methemoglobin level was reported at 14.8 percent.

As seen from the literature review, cases of benzocaine-induced methemoglobinemia are consistently reported. There are many other cases that could be considered, but those selected are representative. Most of the reported information suggests that the patient experiences cyanosis at methemoglobin levels of 15 to 35 percent and that the symptoms worsen as the level increases.

Some of the more serious symptoms -- hypotension, tachycardia and respiratory distress -- were reported to occur at levels greater than 50 percent.

Hematology Update

A review of basic hematology is helpful in understanding how this condition develops. As we recall, hemoglobin is a complex protein-iron compound in the blood that carries oxygen to the cells from the lungs and returns carbon dioxide to the lungs to be exhaled. Each molecule of hemoglobin contains several molecules of heme. Each molecule of heme can carry one molecule of oxygen. Hemoglobin is normally present in the blood at a concentration rage of 12 to 16 gm/dl in women and 14 to 18 gm/dl in men.

Methemoglobin is a form of hemoglobin in which the iron component has been oxidized from the ferrous to the ferric state. Methemoglobin cannot carry oxygen and thereby contributes nothing to the oxygen-transporting capacity of the blood. Methemoglobin is a product of various oxidative reactions as is found in the blood in trace amounts.⁵

Benzocaine-induced methemoglobinemia is considered an acquired or toxic form of methemoglobinemia. There is also a form of hereditary methemoglobinemia that is due to a NADH-cyochrome b5 reductase deficiency. This condition is rare and occurs most often in Navajo and Alaskan Native Americans, Puerto Ricans, North Africans, Arabs, Hindus, Chinese, Japanese and Siberians. These individuals are functionally normal with cyanosis dating from birth that is especially pronounced around the lips. Patients with this type or any other form of hemoglobin variance are at greater risk of developing methemoglobinemia in the presence of benzocaine.⁴

Benzocaine is an active ingredient found in the topical anesthetics that are commonly used prior to endoscopic procedures. Benzocaine appears to induce an increase in the level of methemoglobin by acting as an indirect oxidant, causing the hemoglobin in the red blood cells to undergo oxidation. This oxidation alters the cell membrane, resulting in the heme iron converting from the ferrous to the ferric form, leaving the hemoglobin unable to bind with oxygen. As the level of the methemoglobin increases, it can result in symptoms such as: dyspnea, tachycardia, stupor, coma and death.⁴

Diagnosis

The symptoms of this condition are likely to occur 45 to 60 minutes after the application of the benzocaine-containing product. Blood drawn from a patient with increased levels of methemoglobin may appear as a chocolate brown color. The most accurate lab values are measured by a co-oximeter. A co-oximeter is a spectrometer that measures light absorbance at four wavelengths.¹

The elevation of the methemoglobin above the normal 1 to 2 percent, or a trace amount in the presence of symptoms, will result in the diagnosis of benzocaine-induced methemoglobinemia.

Treatment

The treatment of benzocaine-induced methemoglobinemia is the IV administration of methylene blue. Methylene acts as a reducing agent that stabilizes the oxidation process that occurred with the absorption of the benzocaine. The recommended dose is 1 mg/kg given during a five-minute time period. The dose can be repeated up to 7 mg/kg. If the patient's condition continues to worsen, a blood transfusion may be required to increase the patient's level of functioning hemoglobin.⁴

Assessment and Intervention

The endoscopy nurse will want to screen patients pre-procedure for any history of reactions to benzocaine or hemoglobin disorders. When a product containing benzocaine is used, remember to follow product instructions carefully. The most common products used in endoscopy have specific instructions indicating that the length of time the product is sprayed equals the dosage applied. Most of the benzocaine sprays suggest an application that does not exceed two seconds. The endoscopy nurse will want to carefully assess the patient for cyanosis both during and after the procedure. Most upper endoscopy procedures are relatively short, so the development of methemoglobinemia may occur after the completion of the endoscopic procedure.

The nurse should include discharge instructions related to the use of benzocaine-containing products. The patient may need to know that if he feels short of breath, his heart rate increases or if he notices any cyanosis, he should call or return to the patient care facility. This is especially important if the patient is discharged form the endoscopy area less than one hour after the application of the benzocaine-containing product.

If the patient should develop symptoms of methemoglobinemia, the nurse should immediately inform the physician of the patient's condition. Continuing assessment and support of the patient's respiratory, cardiac and mental status should be provided.

The nurse can expect that the doctor may order labs drawn, and to treat the condition with Methylene Blue IV. If the patient's condition does not improve with the administration of methylene blue, a blood transfusion may be indicated to increase the patient's level of functioning hemoglobin. The patient will most likely be admitted to an area of the hospital where he or she can be closely monitored for complications and for worsening symptoms. Benzocaine-induced methemoglobinemia rarely occurs, but when it does, effective treatment depends on prompt diagnosis. Careful nursing assessment can make the difference.

Endoscopy nursing is a special kind of nursing. The patients arrive at the endoscopy suite fearful of both the discomfort of the test and the results that the test might bring. It is our ultimate goal to provide them with a safe and comfortable experience.

Cynthia R. King, RN, BSN, CCRN, has worked at the Nashville VA Medical Center for 10 years. She has worked eight years in the MICU and the last two in the endoscopy lab. She lives in Franklin, Tenn., with her husband and two children.

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