An accidental overdose of N-acetylcysteine during treatment for acetaminophen toxicity

To the Editor:

Acetylcysteine is the established antidote for acetaminophen toxicity; however, its overdose is associated with several adverse effects. In 2010, a 20-year-old black woman ingested ten 500-mg acetaminophen tablets in a reported suicide attempt at 4 am. She presented to an outside hospital at 10 am with complaints of epigastric pain, nausea, and vomiting, and was started on an acetylcysteine infusion in the emergency department. At 4 pm, her serum acetaminophen concentration was 24.2 mcg/mL, raising concern that she had ingested more than the reported dose. Over the next 2 days, her transaminase levels rose dramatically and her synthetic function rapidly declined; she was then transferred to a tertiary care facility for a liver transplant evaluation. Upon arrival, her aspartate transaminase (AST) and alanine transaminase (ALT) levels were 9,388 and 7,472 IU/L, international normalized ratio (INR) was 4.1, and lactate level was 3.4 mmol/L. At the time of admission, she had an acetylcysteine infusion of 67 mL/hr without documentation of the dose or concentration.

The admitting team discussed the case with Poison Control who recommended administering acetylcysteine IV 100 mg/kg over 16 h since the patient had already received the 150 mg/kg loading dose and 50 mg/kg 2nd dose. A data-entry error resulted in her weight being entered as 439.0 kg instead of 43.9 kg requiring an infusion containing 42,390 mg of acetylcysteine. Upon nursing shift change, it was noted that the patient's weight was incorrectly entered into the computer; this prompted the immediate discontinuation of the infusion. It was determined that the patient received over 14 h of the infusion for a total dose of approximately 38,400 mg.

The patient was monitored closely, but did not exhibit any significant signs or symptoms of acetylcysteine overdose although her nausea and vomiting, that had been present since her admission, persisted. Her laboratory results revealed evidence of hemolysis with a total bilirubin level of 6.4 mg/dL and an indirect bilirubin level of 2.9 mg/dL; however, her hemoglobin level remained stable. Her INR trended downward but remained elevated at 2.0; she did not meet any King's College Criteria, given her normal arterial serum pH, INR < 6.5, creatinine level < 3.4 mg/dL, and no evidence of encephalopathy. While the patient was given 10 times the recommended dose of acetylcysteine, the total dose administered was over 8 times the approved dosage since the patient only received the infusion for 14 h. Her liver function test results continued to improve and 4 days after transfer to a tertiary care facility, her AST and ALT levels were 139 and 1,349 IU/L and her INR was 1.2.

Acetylcysteine is the established antidote for acetaminophen overdose. However, given its complicated dosing regimen, it has a high potential for medication-related errors.¹ The effects of acetylcysteine overdose have been reported in several instances and include hemolysis, cerebral edema, status epilepticus, and death.^2–5 The patient's laboratory results did demonstrate evidence of hemolysis, which might have been secondary to hepatic injury or acetylcysteine toxicity. Despite this, the patient did not experience any significant adverse effects, survived this hospital admission, and was discharged home.

Funding

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Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.