Frontiers in pharmacology · 2026
Case Report: Methemoglobinemia associated with compound aminopyrine-phenacetin tablets supported by toxicological evidence.
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Liu Yang, Zhao Xue, Li Wenqiang, Shao Xupeng, Fan Kailiang, Kong Li, Wei Zekun
Аннотация
BACKGROUND: Methemoglobinemia (MetHb) is characterized by the oxidation of ferrous iron (Fe2+) in hemoglobin to the ferric state (Fe3+), resulting in impaired oxygen-carrying capacity and subsequent tissue hypoxia. Acquired methemoglobinemia is most commonly induced by drugs or chemical agents; however, it remains relatively rare in clinical practice and is frequently misdiagnosed.
CASE PRESENTATION: We report a case of drug-induced methemoglobinemia associated with compound aminopyrine-phenacetin tablets (Qutong tablets). An 80-year-old woman with chronic lower limb pain had intermittently used this analgesic prior to admission. She presented with unexplained hypoxemia that was refractory to oxygen therapy. Arterial blood gas analysis revealed a markedly elevated PaO2 (271 mmHg) despite persistently low pulse oximetry saturation, indicating a significant oxygen saturation gap. The MetHb level was 22.4%. Toxicological testing detected plasma aminopyrine and phenacetin concentrations above the laboratory reference limits, documenting relevant drug exposure and supporting the clinical attribution in the context of the medication history, saturation gap, elevated MetHb level, and treatment response. Following discontinuation of the suspected agent and administration of methylene blue combined with vitamin C, MetHb levels rapidly normalized and hypoxemia significantly improved.
CONCLUSION: This case highlights that chronic, irregular exposure to oxidant drugs may be associated with clinically significant methemoglobinemia even in the absence of a clear acute overdose. Clinicians should maintain a high index of suspicion in patients with hypoxemia unresponsive to oxygen therapy and evidence of an oxygen saturation gap. Careful medication history, co-oximetry, and toxicological testing may help document exposure and support diagnostic attribution in clinically compatible cases. Keywords: methemoglobinemia; phenacetin; aminopyrine; methylene blue; drug toxicity; toxicological evidence.
CASE PRESENTATION: We report a case of drug-induced methemoglobinemia associated with compound aminopyrine-phenacetin tablets (Qutong tablets). An 80-year-old woman with chronic lower limb pain had intermittently used this analgesic prior to admission. She presented with unexplained hypoxemia that was refractory to oxygen therapy. Arterial blood gas analysis revealed a markedly elevated PaO2 (271 mmHg) despite persistently low pulse oximetry saturation, indicating a significant oxygen saturation gap. The MetHb level was 22.4%. Toxicological testing detected plasma aminopyrine and phenacetin concentrations above the laboratory reference limits, documenting relevant drug exposure and supporting the clinical attribution in the context of the medication history, saturation gap, elevated MetHb level, and treatment response. Following discontinuation of the suspected agent and administration of methylene blue combined with vitamin C, MetHb levels rapidly normalized and hypoxemia significantly improved.
CONCLUSION: This case highlights that chronic, irregular exposure to oxidant drugs may be associated with clinically significant methemoglobinemia even in the absence of a clear acute overdose. Clinicians should maintain a high index of suspicion in patients with hypoxemia unresponsive to oxygen therapy and evidence of an oxygen saturation gap. Careful medication history, co-oximetry, and toxicological testing may help document exposure and support diagnostic attribution in clinically compatible cases. Keywords: methemoglobinemia; phenacetin; aminopyrine; methylene blue; drug toxicity; toxicological evidence.