To the editor:
 

—A 5-month-old African girl was brought to the emergency department (ED) with a chief complaint of fever and lethargy. Four days before admission, she was seen by her private physician because of fever and a mass in her right groin. He prescribed amoxicillin and acetaminophen. Two days later she began having vomiting and diarrhea. She appeared to be well on the night before admission, but in the morning she became progressively lethargic.

On examination, vital signs were temperature 97°F (36.1°), heart rate 140 beats/min and respiration 42 breaths/min. Her weight was 7.4 kg. She was lethargic and listless but cried with sternal rub. Her scleras were anicteric. She had dry mucous membranes with poor peripheral perfusion. There were no signs of head trauma. A palpable liver was noted 2-cm below the costal margin. A tender fluctuant mass consistent with abscess was palpated in the right inguinal area. Her peripheral pulses were weak. Her skin was mottled, cool, and clammy but there was no jaundice and no rashes.

While the patient was being evaluated and stabilized, she began having a generalized seizure. Her dextrostix was 29 mg/dL. This was immediately corrected with intravenous glucose and the seizure stopped but the patient remained lethargic.

Laboratory data included hemoglobin of 11.5 gm/dL, hematocrit 33.7 %, white blood cell count 29,700 cell/mm³ with 67% neutrophils, and the platelet count was 676,000/mm³. Serum sodium was 134 mEq/L, potassium 5.0 mEq/L, chloride 112 mEq/L, bicarbonate 18 mEq/L, BUN 8 mg/dL, creatinine 0.5 mg/dL, and glucose 30 mg/dL. In view of the hepatomegaly, liver function tests were also obtained. Results revealed: total protein of 4.6 g/dL. Albumin 3.1 g/dL, alanine transaminase (ALT) 455 U/L, aspartate transaminase (AST) 1907 U/L and alkaline phosphatase 603 U/L. The total bilirubin was 2.7 mg/dL with conjugated bilirubin of 1.9 mg/dL. The ammonia was 135mcmol/L. The prothrombin time (PT) was 53.5 seconds, and the partial thromboplastin time (PTT) was 75 seconds. INR was 2.5. Urinalysis revealed a specific gravity of 1.037, the bilirubin was negative, and the rest of the examination was unremarkable. A room air blood gas revealed the pH to be 7.29, the PCO₂ to be 24 and PO₂ was 71.

Because of the patient's history of acetaminophen administration, a blood level was performed and it was 78.5 µg/mL. On further questioning the patient's mother reported giving 2 mL of acetaminophen 80 mg/0.8 mL (200 mg/dose) every 4-hours. The infant probably received a total dose of 162 mg/kg/day of acetaminophen for several days. It appeared that because of a language barrier, she misunderstood the doses and switched the medication doses of acetaminophen and amoxicillin. She inadvertently gave her infant an overdose of acetaminophen. She has received last dose of acetaminophen night before the visit (approximately 10 hours). The child was given a loading dose of N-acetylcysteine (NAC) and transferred to the regional transplant center. She was treated with acetylcysteine for a total of 18 doses. Clinical recovery was rapid and progressive. The liver enzymes returned to near normal by the fifth hospital day and she made a complete recovery over 3 weeks.

Acetaminophen is a safe and effective antipyretic/analgesic for children when administered in appropriate dosages.¹ Hepatotoxicity has been well described in cases of acute overdosage.² Hepatotoxicity results from the formation of N-acetyl-benzoquinoneimine (NAPQI) by the cytochrome P-450 mixed function oxidase pathway.

Acute ingestion in an adult of greater than 140 mg/kg (7.5 g or more in a “normal” sized adult) or > 150 mg/kg in a child is a potentially toxic dose of acetaminophen. The most reliable method to assess risk of toxicity after an acute single ingestion of acetaminophen is to determine the plasma acetaminophen concentration. Our patient's plasma acetaminophen level of 78.5 µg/mL approximately 96 hours after the first dose would be in the toxic range if the Rumack and Matthew³ nomogram for a single dose were to be extrapolated out to 96 hours. Our patient's plasma acetaminophen level of 78.5 g/mL cannot be applied to the nomogram as it was the result of chronic, supratherapeutic dosing rather than a single acute ingestion. NAC is indicated for all toxic ingestions above the “possible toxicity line” on the nomogram. In the U.S., the only approved NAC treatment is oral: 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 doses (total of 18 doses equaling 1,330 mg/kg in 68 hours).⁴

Several prognostic factors have been identified in patients with severe liver damage, and used as predictors of the need for liver transplantation. These include elevated prothrombin time >37 seconds 48 hours postingestion; pH <7.3 at 24 hour after the ingestion of an overdose, creatinine >3 mg/dL, grade 3 or 4 encephalopathy, hypophosphatemia and elevated bilirubin.⁵ Our patient had 4 of these criteria. This case shows all the manifestations of severe acetaminophen toxicity, including protracted vomiting followed by acute hepatic failure causing hypoglycemia, coagulopathy, and encephalopathy. Acetaminophen toxicity should be considered in any child presenting with a febrile illness, lethargy, and protracted vomiting to whom an antipyretic is being administered.

Copyright 2003, Elsevier Science (USA). All rights reserved.

doi:10.1053/ajem.2003.50022

Muhammad Waseem, MD
Scott Bomann, DO
Joel Gernsheimer, MD
Heidi Pinkert, MD
Department of Emergency Medicine, Lincoln Medical and Mental Health Center, Bronx, NY


References

1.  American Academy of Pediatrics Committee on Drugs: Commentary on acetaminophen. Pediatrics 1978;61:1-5

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2.  Zimmerman HJ: Effects of aspirin and acetaminophen on the liver. Arch Intern Med 1981;141:333-342

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3.  Rumack BH, Matthew H: Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871-6

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4.  Rumack BH, Peterson RG, Koch GG, et al: Acetaminophen overdose: 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med 1981;141:380-385

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5.  Vale JA, Proudfoot AT: Paracetamol poisoning. Lancet 1995;346:547-552

MEDLINE