When emergency doctors drew arterial blood from an 80-year-old woman who could not get enough oxygen, the sample came out chocolate brown instead of bright red.
The likely culprit, according to a new case report, was a combination painkiller she had been taking on and off for about two months. One of its ingredients, phenacetin, was withdrawn from the U.S. market in 1983.
The report, published Aug. 10 in Frontiers in Pharmacology by emergency physicians at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine in Jinan, China, describes drug-induced methemoglobinemia, a condition that leaves blood unable to carry oxygen properly.
Oxygen Numbers That Didn’t Add Up
The woman had a long list of health problems, including peripheral artery disease, coronary artery disease, high blood pressure, chronic kidney insufficiency, an underactive thyroid, and atrial fibrillation. She was admitted after two months of worsening leg swelling and pain, followed by altered consciousness the day before.
Her pulse oximeter reading hovered around 85%. Doctors suspected respiratory failure and gave oxygen, but her oxygenation did not meaningfully improve, and her lungs sounded unremarkable.
An arterial blood gas test on March 10 deepened the puzzle. Her partial pressure of oxygen was 271 mmHg, a markedly high value, even as the fingertip sensor kept showing low saturation. Clinicians call this mismatch a saturation gap, and it is a key diagnostic clue.
The explanation lies in chemistry. In methemoglobinemia, iron inside hemoglobin is oxidized from its normal ferrous state to a ferric state that cannot carry oxygen. Methemoglobin normally stays below 1%, according to the report. Hers measured 22.4%.
The California Poison Control System notes that standard pulse oximeters are not calibrated to detect methemoglobin, making their readings unreliable in these cases, and that affected blood takes on a chocolate-brown color that does not turn red when exposed to air.
An Old Painkiller Formula with Oxidizing Ingredients
When doctors revisited her medication history, they learned she had been taking compound aminopyrine-phenacetin tablets, sold as Qutong tablets, for chronic leg pain. Each tablet contained aminopyrine, phenacetin, caffeine, and phenobarbital. She usually took one a day but sometimes more during bad flare-ups.
Both phenacetin and aminopyrine are broken down in the liver into reactive compounds that can oxidize hemoglobin. A toxicology screen covering 252 compounds found aminopyrine, phenacetin, and phenobarbital in her plasma above the laboratory’s reference limits.
Phenacetin has a long, troubled history in the U.S. A federal Report on Carcinogens profile from the National Toxicology Program notes that the drug was used extensively in painkiller mixtures until it was implicated in kidney disease linked to analgesic abuse, and that it was withdrawn from the U.S. market in 1983. Phenacetin itself is listed as reasonably anticipated to be a human carcinogen, and painkiller mixtures containing it are listed as known human carcinogens. The case report’s authors noted that the compound tablets have declined in use in many regions but remain accessible in certain settings.
Using a standard scoring tool, the team rated the reaction a probable adverse drug reaction. They also raised a possibility they could not prove: phenobarbital, which ramps up certain liver enzymes, might increase production of the oxidizing byproducts. They explicitly described that mechanism as a hypothesis.
Blue Medicine, Green Urine, and a Rapid Turnaround
Doctors stopped the painkiller and gave methylene blue, the standard antidote, along with vitamin C, on March 10 and again on March 11. Her urine turned dark green, an expected effect of methylene blue, and her blood gradually shifted from brown back to bright red.
Her methemoglobin level fell to 6.0% on March 11 and to 0.6% on March 12, with marked improvement in her oxygen levels and overall condition.
What makes the case notable is the pattern of exposure. Many published cases involve acute or high-dose exposure, and a 2025 Chinese report described acute poisoning with the same type of tablets. This one involved irregular, intermittent use by an older patient with several chronic diseases, suggesting that clinically significant methemoglobinemia can occur without a clearly defined overdose.
What Remains Uncertain
The authors listed several limitations. They could not pin down her total dose or the timing of her last pill. A test for G6PD deficiency, a genetic condition that can make methylene blue risky, was not available before treatment, although no obvious breakdown of red blood cells was observed. Related blood disorders such as sulfhemoglobinemia were not fully excluded with dedicated testing, and the toxicology results document exposure rather than proving toxic accumulation.
For U.S. readers, phenacetin is not the main concern, but oxidizing drugs still sold here can cause the same condition. The FDA has warned that benzocaine, a common numbing ingredient, can cause methemoglobinemia that may be life-threatening. In 2018, the agency urged companies to stop marketing over-the-counter oral benzocaine products for teething in children younger than 2 and to add methemoglobinemia warnings to oral benzocaine products for older children and adults.
The practical lesson is to tell clinicians about every pain reliever, including over-the-counter, imported, or traditional products. The FDA advises seeking medical attention immediately for pale, gray, or blue-colored skin, lips, or nail beds, as well as shortness of breath, fatigue, confusion, headache, lightheadedness, or a rapid heart rate.
Key Questions Answered
What is methemoglobinemia?
It is a condition in which iron in hemoglobin is oxidized into a form that cannot carry oxygen, starving tissues of oxygen even when the lungs work normally.
Why was the woman’s blood brown?
High levels of methemoglobin give blood a characteristic chocolate-brown color. Her level was 22.4%, compared with a normal level below about 1%.
What is a saturation gap?
It is a mismatch between a low pulse oximeter reading and a high oxygen level on an arterial blood test. It is a major clue that an abnormal form of hemoglobin is present.
Is phenacetin sold in the United States?
No. Phenacetin was withdrawn from the U.S. market in 1983 and is no longer used in U.S. drug products, according to the National Toxicology Program.
How was she treated?
Doctors stopped the painkiller and gave methylene blue with vitamin C. Her methemoglobin level dropped to 0.6% within two days.
