Benzocaine Can Give A Whole New Meaning to “Blue Blood”

When a 25-year-old woman showed up in a Rhode Island emergency room reporting that she was fatigued, weak, and short of breath—and that her skin had turned a shade of blue overnight not normally associated with living people—medical personnel on call knew something was very wrong. One quick-witted physician had fortunately seen the condition before, early in his training, and once the patient’s recent medication history was taken, all became rapidly clear.

She had applied benzocaine for a toothache the night before.

And like at least 400 other known people since 1971 in the United States, she had developed acute, acquired methemoglobinemia—a serious and potentially fatal blood disorder that reduces the amount of oxygen that can be transported by the blood. The most noticeable symptom is that red blood cells, normally bright red with oxygen, turn a chocolatey brown as they are starved of oxygen; through the skin, the affected person’s appearance becomes “cyanotic” (so-called for cyan, or blue).

The Rhode Island patient was lucky to have arrived at a health care facility where someone recognized her symptoms; at the time she was treated and had blood drawn, her hemoglobin oxygen saturation was diminished enough to place her in the danger zone. Advanced cases can progress beyond headaches, dizziness and fatigue to seizures, coma, and death.

Blue Blood Disorder: Risks and Causes

The risk of medication-associated methemoglobinemia is serious enough that in 2018, the FDA issued a warning not to administer drugs containing benzocaine to children under two years of age. But that over-the-counter preparation, which so many people reach for without a second thought to bridge the gap between making a dental appointment and getting to the office, is not the only medication known to produce the complication.

In fact, various drug classes that result in oxidative stress can produce acute methemoglobinemia, and health care professionals should be aware of the potential for this side effect in patients of any age:

  • antibiotics(trimethoprim, sulfonamides, dapsone)
  • local anesthetics (benzocaine, articaine, prilocaine, lidocaine)
  • anilinedyes
  • metoclopramide
  • rasburicase
  • chlorates
  • bromates

In some susceptible people, drinking well water containing high levels of nitrates can produce symptoms as well.

The good news is “Blue Blood” is treatable once health care professionals understand what they are looking at—literally—with a simple intravenous drug.

Ironically, its name is as appropriate as the malady: Methylene Blue.

Blue People of Kentucky Unlocked the Blood Disorder’s Mysteries

Quite apart from the acute, dangerous form of methomoglobinemia, an inherited form is also possible to acquire when two parents with copies of a recessive gene have offspring. Such was the case of an isolated rural Kentucky family, the so-called “Blue Fugates of Kentucky,” who all descended from a French orphan who settled near the evocatively named Troublesome Creek. Misunderstood, shunned, and with many children born blue and even purple, the clan lived with the condition from the 1820s until the 1960s.

Then Dr. Madison Cawein III, a hematologist at the University of Kentucky’s Lexington Medical Clinic, encountered the family and, using the family’s charts and blood samples, enlisted their unique genetics to help humanity better understand the genetic disorder.

“Blue People of Troublesome Creek,” published in 1982 by the University of Indiana’s Cathy Trost, is a fascinating exploration of how even today, when we have unlocked the keys to Saturn and the Moon, we are still working on unraveling some of the deepest mysteries of the human body.

For dentists and hygienists, the major takeaway is awareness: The reaction that causes methemoglobinemias is acute, tied to oral numbing agents, and can strike at any age (although babies, toddlers, and children seem especially susceptible). Discuss side effects of these OTC agents with patients and make sure parents, especially, are aware of the warning signs and dangers