Benzocaine is a common topical anesthetic found in over-the-counter products like oral gels, sprays, and lozenges used for temporary pain relief, such as for sore gums or a sore throat. Benzocaine carries a rare but serious risk of causing a life-threatening blood disorder called methemoglobinemia, which can cause the skin to turn a blue or gray color.
Understanding Methemoglobinemia
Methemoglobinemia is a condition that severely reduces the blood’s ability to transport oxygen throughout the body. The condition arises when the concentration of methemoglobin in the red blood cells becomes abnormally high. Normal blood has less than one percent methemoglobin, but a spike above this level quickly impairs oxygen delivery to tissues.
Methemoglobin is an altered form of the oxygen-carrying molecule, hemoglobin. When this altered form dominates, the blood appears a dark, chocolate-brown color instead of the bright red of healthy, oxygenated blood. This change causes the skin, lips, and nail beds to take on a pale, gray, or blue tint, a sign known as cyanosis. The body suffers from a cellular oxygen deficit due to the blood’s inability to release oxygen effectively.
The Physiological Mechanism
The process begins when benzocaine is absorbed into the bloodstream and metabolized by the body. One of the metabolites created during this breakdown is an oxidizing agent that acts directly on the iron atom located at the center of the hemoglobin molecule.
Normally, the iron in hemoglobin is in the ferrous state (Fe2+), which allows it to bind oxygen molecules reversibly for transport. Benzocaine’s metabolite oxidizes this ferrous iron, converting it into the ferric state (Fe3+). This ferric iron is the defining characteristic of methemoglobin. Once the iron is converted to the ferric state, it loses its capacity to bind and carry oxygen effectively.
The presence of methemoglobin also affects remaining normal hemoglobin molecules, increasing their affinity for oxygen. This causes functional hemoglobin to hold onto oxygen rather than releasing it to the tissues. This dual effect creates a severe systemic oxygen deficit.
Recognizing Symptoms and High-Risk Groups
The signs of methemoglobinemia often appear quickly, usually within minutes to one or two hours after using a benzocaine product. The most noticeable symptom is the blue, gray, or pale discoloration of the skin, lips, and nail beds, reflecting the circulation of oxygen-deprived blood. This change is often accompanied by general signs of oxygen deprivation, such as headache, lightheadedness, and profound fatigue.
As the condition worsens, individuals may experience shortness of breath and a rapid heart rate as the body attempts to compensate for the lack of oxygen delivery. Confusion or other changes in mental status can also occur in severe cases. Symptoms can appear after the first use of a product or after repeated applications.
High-Risk Groups
Certain populations face a higher risk of developing this condition. Infants and children under two years old are particularly vulnerable because their natural enzyme systems, which would normally convert methemoglobin back to functional hemoglobin, are not fully developed. Because of these serious risks, the Food and Drug Administration (FDA) issued a strong warning in 2018, urging manufacturers to stop marketing over-the-counter benzocaine products for teething pain in children younger than two years old.
Adults with pre-existing conditions are also at greater risk for complications if they develop methemoglobinemia. This includes individuals with heart disease, asthma, bronchitis, emphysema, or other breathing problems, as their bodies are already compromised in their ability to handle reduced oxygen levels. Additionally, people with a rare genetic deficiency in the glucose-6-phosphate dehydrogenase (G6PD) enzyme may be more susceptible.
Immediate Steps and Recovery
Methemoglobinemia is a medical emergency that requires immediate attention. If any of the symptoms, particularly the blue or gray skin discoloration and difficulty breathing, occur after using a benzocaine product, stop using the product immediately and seek emergency medical care. Prompt recognition and treatment are paramount for a positive outcome.
In the hospital setting, treatment typically begins with the administration of supplemental oxygen to maximize the delivery of oxygen by the remaining functional hemoglobin. The definitive treatment for significant or symptomatic methemoglobinemia is the intravenous administration of a medication called methylene blue.
Methylene blue acts as an antidote by assisting the body’s natural mechanisms to convert methemoglobin back into functional hemoglobin. This medication works by accelerating the reduction of the ferric iron (Fe3+) back to the ferrous iron (Fe2+) state, rapidly restoring the blood’s oxygen-carrying capacity. Most patients respond quickly to methylene blue treatment, and full recovery is usually achieved with prompt intervention.