Pain Relief Overload

"She looked physically blue. It's the kind of thing that sticks with you [having seen one other patient in a similar medical predicament during his decades-long career]."
"These products [with benzocaine in their list of ingredients] carry serious risks and provide little to no benefits for treating oral pain, including sore gums in infants due to teething."
"This is a medicine that is commonly used with no problem all the time. [However], there's certain people out there who have this idiosyncratic reaction, and you won't know it until it happens."                                                        "People have no idea that something very specific and very dangerous can happen. It is not a mild side effect."
Dr. Otis Warren, emergency medicine physician, Department of Emergency Medicine, Brown University, Providence, Rhode Island

(Photo credit: CNN via The New England Journal of Medicine)

When the 25-year-old woman whose name has been withheld for privacy reasons looked at herself in her bathroom mirror the morning after she applied a topical pain medication to soothe a toothache, she was instantly alarmed. So much so that she took herself immediately to the emergency department. She was dizzy, experiencing shortness of breath, and felt extremely weak. The admitting doctor focused immediately on her appearance, not so much the symptoms.

Her skin and nails had a distinct blue blush. Physicians interpret this as a sign the body is being starved of oxygen, turning blood unusually dark. The event has turned up in a report published in the most recent issue of the New England Journal of Medicine. It was the young woman's good fortune that the attending physician at emergency knew precisely how to respond, because he know exactly what had gone wrong.

All the presenting symptoms indicated a rare but potentially fatal condition named acquired methemoglobinernia. Exposure to particular chemicals in medicines in some people can alter the shape of a person's hemoglobin molecules leading to the condition. This causes blood to no longer release oxygen into the surrounding tissue, explained Dr. Warren. Tissues become blue, and blood is now "selfishly holding on to the oxygen" becoming dark, transformed from a "bright brilliant red colour" to a "chocolatey brown".

The condition can be inherited, but in fact that form of methemoglobinemia is quite rare. The onset of the woman's 'acquired' condition had been caused when she reacted to a topical pain medication which contained benzocaine, the active ingredient in a number of over-the-counter anesthetic ointments. Doctors and nurses commonly use benzocaine during medical procedures to numb areas on a patient's body about to undergo a medical process.

According to the U.S. Food and Drug Administration, over 400 cases of benzocaine-associated methemoglobinemia have been reported since 1971. Through a long medical career in emergency medicine, only one other such case had ever presented itself in Dr. Warren's experience, and it was so unusual that the memory of it was immediately triggered when the woman presented herself at the emergency center, stating, "I am blue".

Once it became clear that this was a diagnosis of benzocaine involvement doctors administered the antidote; methylene blue which works to return the altered hemoglobin to its normal state, restoring the ability of blood to deliver oxygen normally and returning the young woman to a healthy condition. Later laboratory results confirmed the diagnosis when it was revealed that 44 percent of the hemoglobin in the woman's body had been affected.

This is significant since patients with levels of over 50 percent have the potential risk of heat failure, coma, and possibly death. "She was on that precipice, for sure", affirmed Dr. Warren. In 2018 the FDA had noted that 119 reports of the condition had been identified in the past decade, leading the agency to make an announcement relating to the danger of benzocaine products.

Most of those reported cases were serious, requiring immediate treatment.  Moreover, of those cases, four people failed to recover, among them an infant; all died.

Benzocaine, an ingredient in Orajel which is used for toothaches, 

can in some rare cases lead to methemoglobinemia. 

 (AP Photo/Stephanie Nano) ASSOCIATED PRESS

Causing the federal agency to warn that any oral drugs containing benzocaine should never be utilized in the treatment of infants and children under two years of age, considered a demographic particularly susceptible to the blood disorder.

After receiving two doses of methylene blue through an IV and responding well, the woman's treatment was successful in restoring her to health.

What is methemoglobinemia?

Methemoglobinemia is a blood disorder in which too little oxygen is delivered to your cells.
Oxygen is carried through your bloodstream by haemoglobin, a protein that’s attached to your red blood cells.
Normally, haemoglobin then releases that oxygen to cells throughout your body.
However, there’s a specific type of haemoglobin known as methemoglobin that carries oxygen through your blood but doesn’t release it to the cells.
If your body produces too much methemoglobin, it can begin to replace your normal haemoglobin. This can lead to not enough oxygen getting to your cells.
Source: Healthline