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17 January 2022 : Case report  USA

Severe Anion Gap Metabolic Acidosis Resulting from Combined Chronic Acetaminophen Toxicity and Starvation Ketosis: A Case Report and Literature Review

Challenging differential diagnosis, Adverse events of drug therapy , Rare coexistence of disease or pathology

Thomas Kalinoski1ABCDEF*

DOI: 10.12659/AJCR.934410

Am J Case Rep 2022; 23:e934410


BACKGROUND: Chronic acetaminophen toxicity has been known to cause an anion gap metabolic acidosis (AGMA) due to accumulation of 5-oxoproline metabolites. This diagnosis requires a high index of suspicion when evaluating a patient with AGMA as occasional acetaminophen use is very common among patients, whom oftentimes are not entirely truthful about the extent of ingestion and have multiple comorbid conditions complicating diagnosis. 

CASE REPORT: A 68-year-old male with multiple medical comorbidities presented to the emergency room with recurrent generalized weakness. On all occasions the patient denies focal weakness or infectious symptoms. The patient also denies ingestions other than his routine prescribed medications, including acetaminophen 325mg as needed, which he describes taking “a couple times” a day. His prior visits were notable for profound anion-gap metabolic acidosis, hypernatremia, acute kidney injury, and positive urine ketones. As the patient’s blood urea nitrogen (BUN), blood sugar, liver function tests, lactic acid, and serum osmolality were normal, the patient received a diagnosis of “starvation ketosis” and received supportive care each time. Further investigation at his final admission revealed an extremely elevated 5-oxoproline level revealing a delayed diagnosis of chronic acetaminophen toxicity

CONCLUSIONS: This report emphasizes the need for a high index of suspicion related to chronic acetaminophen toxicity and other ingestions contributing to a metabolic acidosis in at-risk populations, even when routine history is unrevealing. Furthermore, severe acidosis should prompt more extensive investigation when out of proportion to obvious routine etiologies.

Keywords: Acetaminophen, Acid-Base Equilibrium, ketosis



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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923