Reported Adverse Event Cases of Methemoglobinemia Associated With Benzocaine Products

Abstract

Health professionals involved in endoscopy, intubation, bronchoscopy, or similar invasive procedures using benzocaine-containing sprays should know that (1) administration may cause MHb with potentially serious consequences, (2) identifying the reaction to benzocaine usually requires cooximetry (although it can be implied by symptoms), and (3) treatment involves immediate intravenous administration of 1 to 2 mg/kg of methylene blue.

A case of almagel-induced methemoglobinemia after pancreatoduodenal resection

“…Methemoglobin is hemoglobin with ferric heme (Fe 3+ ) instead of ferrous (Fe 2+ ) heme, unable to form a bond with oxygen and transport it. Because red blood cells are continuously exposed to various oxidant stresses, blood normally contains approximately 1% methemoglobin levels [2]. The concentration of methemoglobin is kept low by the effect of cytochrome b5 methemoglobin reductase, which is dependent on reduced nicotine adenine dinucleotide (NADH) [5].…”

“…The concentration of methemoglobin is kept low by the effect of cytochrome b5 methemoglobin reductase, which is dependent on reduced nicotine adenine dinucleotide (NADH) [5]. Methemoglobinemia is defined as an abnormal elevation of methemoglobin levels and has 3 different etiologic categories: (1) an autosomal dominant trait that causes production of abnormal hemoglobin; (2) an autosomal recessive trait resulting in decreased activity of methemoglobin reductase, typically resulting in subclinical MHb; and (3) introduction of an external oxidising agent, which overwhelms the reducing capacity of red blood cells (the most common cause of MHb) [2].There are two basic mechanisms of acquired methemoglobinemia: direct or indirect oxidation of the hemoglobin. Direct oxidation can be caused by chlorates, hexavalent chromates, cobalt, and copper salts [6].…”

“…Among 198 reported adverse events of all types associated with benzocaine, in 93.2% of cases the product was a spray, in 1.5%, a benzocaine-containing lozenge, and in 1 case it was gel [2]. Some patients have developed the syndrome with a single 1 s or short spray of 20% solution on mucous membrane: exact dose impossible to determine, anywhere from <76 mg to 212 mg [13].…”

“…Diagnosis of methemoglobinemia is based on: cyanosis of skin and mucosa resistant to treatment with oxygen when there are no other causes (cardiovascular and pulmonary diseases), chocolate brown colour of blood, elevated level of blood metHb, fact of possible poisoning. One can suspect methemoglobinemia when cyanosis of the skin doesn't correlate with dyspnea, while blood gas or pulse oximetry readings can be near normal [2]. Oxygen saturation is non-specific, varying between 50% and 94%, median 85%; a discrepancy between the pulse oximeter saturation (≤90%) and the measured arterial oxygen partial pressure (PaO 2 ≥70 mm Hg) suggests methemoglobinemia [5].…”

“…Normally accounting for about 1% of all circulating hemoglobin, methemoglobin is then reduced back to hemoglobin, mainly by the activity of the cytochrome-b5-methemoglobinemia (MHb) reductase system [2].…”