Edward Tabor
Bethesda, Maryland, United States

All physicians get phone calls from time to time from friends asking for medical advice. I received one of these calls from a pharmacologist I knew. A few weeks prior, his wife had begun having memory loss and difficulty walking. The day before he called me, she began losing consciousness and was admitted to the hospital.

This pharmacologist, Jack, was a remarkable man. He had an amazing memory, and he could always remember details about any adverse drug reaction that had been published in the past decade. In many discussions, he would jump up, saying, “I’ll be right back,” and he would return with an article or a file describing an adverse reaction from five or ten years earlier.

Jack said the neurologists at the hospital had not yet found any cause for his wife’s illness. In his anxiety, he kept saying over and over in a shaky voice, “My wife is my best friend.” Although I was unable to offer any medical suggestions, I tried to reassure him.

At our next phone call, Jack described how he had been sitting by his wife’s hospital bed, watching her slip back and forth between mild coma and deep coma, when he looked in her bedpan and saw a black stool.

If he had been a physician, he probably would have thought it was either melena (caused by blood in the stool) or due to ingestion of iron supplements, which can also cause stools to be black. These are common causes of black stools, and physicians have been taught to look for common causes; in medical school they were taught the aphorism, “When you hear hoofbeats, think horses, not zebras.”

However, as a pharmacologist, Jack was focused on adverse reactions to medications, including uncommon reactions. He remembered a rare pharmacologic cause of black stools—bismuth. It was only then that he also remembered that his wife had been taking bismuth subsalicylate (Pepto-Bismol) for a year to self-treat her indigestion.

Because he was Jack, he immediately went to the hospital library to verify his recollection about bismuth, even though it was late in the evening. He somehow gained admission even though he was not on the hospital staff, and within a few minutes found two case reports of bismuth toxicity that sounded just like his wife’s case. He telephoned his wife’s attending physician, whose response was, “Wow.”

After his wife stopped taking bismuth subsalicylate, her symptoms resolved. Later that month, she went home from the hospital with only a small residual memory loss. She was able to perform all of her usual daily activities.

Bismuth subsalicylate (two of its well-known brands being Pepto-Bismol and Kaopectate) has been sold over-the-counter for many years to treat nausea, indigestion, and diarrhea, and to prevent traveler’s diarrhea.¹ In more recent times, it has been used in conjunction with other drugs to treat Helicobacter pylori infection² and collagenous colitis.³

Ninety-nine percent of ingested bismuth is excreted in the feces, and black stools result when bismuth reacts with bacterial sulfides to form bismuth sulfide.⁴ Neurologic toxicity as a result of taking bismuth at too high a dose or for too long can include impaired cognition, ataxia, falls, tremor, seizures, somnolence, and coma.³ Bismuth can accumulate in tissues even from the recommended oral dose if taken for longer than six weeks. With high doses, neurotoxicity can occur after as few as seven days.³ At least seven cases of neurotoxicity due to oral bismuth subsalicylate have been reported in patients who took it in high doses or for a long duration.³

In the end, Jack himself made the correct diagnosis. Most likely he had been able to do this because he was a pharmacologist and not a physician. Most physicians have never heard about neurotoxicity due to bismuth subsalicylate. Bismuth toxicity is given only two sentences in a major pharmacology textbook used in medical schools,⁴ with no mention of neurotoxicity. Even the website of the Centers for Disease Control and Prevention (CDC) makes no mention of neurotoxicity in its discussion of bismuth.^1,2

This case underlines the importance of asking patients about over-the-counter medications they are taking. It also shows the importance of knowing about obscure causes of symptoms, because occasionally the sound of “hoofbeats” can be caused by “zebras.”

References

1. Centers for Disease Control. “Travelers’ Diarrhea.” CDC Yellow Book 2024. https://wwwnc.cdc.gov/travel/yellowbook/2024/preparing/travelers-diarrhea.
2. Centers for Disease Control. “Helicobacter pylori.” CDC Yellow Book 2024. https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/helicobacter-pylori.
3. Hogan DB, Harbidge C, Duncan A. “Bismuth toxicity presenting as declining mobility and falls.” Can Geriatr J 2018;21:307-309. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281375/.
4. Brunton LL, Lazo JS, and Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, eleventh edition. New York: McGraw-Hill, 2006, page 996.