Correspondence

Acetaminophen Treatment Nomogram

N Engl J Med 1994; 330:1907-1908June 30, 1994

Article

To the Editor:

The acetaminophen treatment nomogram is widely used as a guideline for acetylcysteine therapy in patients with an acetaminophen overdose1. However, the potential toxicity of acetaminophen may be underestimated by the nomogram in patients with underlying hepatic dysfunction or long-term alcohol use2.

We recently treated a 21-year-old woman who had attempted suicide by ingesting 25 g of acetaminophen. She had no history of any hepatic abnormality but had consumed large amounts of ethanol for a long period. She presented to her local hospital three hours after ingestion of the acetaminophen. The serum acetaminophen level was 151 μg per milliliter. After gastric lavage (four hours after ingestion), the acetaminophen level was 124 μg per milliliter. According to the acetaminophen treatment nomogram, she was not considered to be at risk for hepatotoxicity. The regional poison-control center did not recommend treatment with acetylcysteine. She was observed overnight and was asymptomatic on discharge from the hospital. Nausea, hematemesis, and abdominal pain in the right upper quadrant subsequently developed. Approximately 50 hours after ingestion of the acetaminophen, she was admitted to our hospital with fulminant hepatic failure. Acetaminophen was undetectable in serum, the prothrombin time was 56.8 seconds (international normalized ratio, 43.9), and she had anuric renal failure. She rapidly became obtunded, requiring tracheal intubation and mechanical ventilation. Twenty-four hours after admission, she became areflexic with fixed and dilated pupils due to massive cerebral edema. A radionuclide study on the fourth hospital day showed an absence of cerebral blood flow.

With therapeutic serum levels, acetaminophen is largely conjugated with sulfate and glucuronide derivatives and excreted renally. The remainder enters the cytochrome P-450 system, where it undergoes oxidation to a toxic intermediate, which in turn undergoes reduction with glutathione. With toxic levels, however, acetaminophen metabolism by the cytochrome P-450 pathway is increased. In alcoholics, glutathione reserves are depleted, resulting in insufficient removal of the toxic intermediate3. If the potential for enhanced toxicity exists in patients with a history of long-term alcohol use despite a presumably safe acetaminophen level, the acetaminophen nomogram becomes an inaccurate predictor of toxicity in such patients. Even therapeutic acetaminophen doses in alcoholics can cause serious hepatotoxicity4.

Because the amount of long-term ethanol consumption required to impair acetaminophen metabolism is not known, acetaminophen levels in alcoholics should be interpreted with caution. We recommend that a careful history of alcohol use be obtained for every patient with an acetaminophen overdose. Toxicity in alcoholics with an acetaminophen overdose may best be prevented or limited with acetylcysteine therapy, regardless of the serum acetaminophen level after the overdose, since acetylcysteine does not appear to have notable adverse effects5.

Lisa Cheung, M.D.
Richard G. Potts, D.O.
Keith C. Meyer, M.D.
University of Wisconsin Clinical Science Center, Madison, WI 53792

5 References

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   Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB. Acetaminophen hepatotoxicity in alcoholics: a therapeutic misadventure. Ann Intern Med 1986;104:399-404
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   Lauterburg BH, Velez ME. Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut 1988;29:1153-1157
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   Miller LF, Rumack BH. Clinical safety of high doses of acetylcysteine. Semin Oncol 1983;10:Suppl 1:76-85
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Citing Articles (12)

Citing Articles

1. 1

   Charles Her. (2008) Acetaminophen-induced, Not Desflurane-induced, Hepatotoxicity. Anesthesiology 109:3, 570-571
   CrossRef

2. 2

   Fahad M. Ali, Edward W. Boyer, Steven B. Bird. (2008) Estimated risk of hepatotoxicity after an acute acetaminophen overdose in alcoholics. Alcohol 42:3, 213-218
   CrossRef

3. 3

   Anne M. Larson. (2007) Acetaminophen Hepatotoxicity. Clinics in Liver Disease 11:3, 525-548
   CrossRef

4. 4

   Duncan Reid, Wayne Hazell. (2003) Paracetamol poisoning: Which nomogram should we use?. Emergency Medicine Australasia 15:5-6, 486-496
   CrossRef

5. 5

   J Brok, N Buckley, C Gluud, Jesper Brok. 2002. Interventions for paracetamol (acetaminophen) overdoses. .
   CrossRef

6. 6

   STEPHEN M. RIORDAN, ROGER WILLIAMS. (2002) Alcohol exposure and paracetamol-induced hepatotoxicity. Addiction Biology 7:2, 191-206
   CrossRef

7. 7

   Laurie F. Prescott. (2000) Paracetamol, alcohol and the liver. British Journal of Clinical Pharmacology 49:4, 291-301
   CrossRef

8. 8

   Harvey E. Finkel. (1996) Wine and health: a review and perspective. Journal of Wine Research 7:3, 157-196
   CrossRef

9. 9

   Daniel R. Douglas, James B. Sholal, Martin J. Smilkstein. (1996) A Pharmacokinetic Comparison of Acetaminophen Products (Tylenol Extended Relief vs Regular Tylenol). Academic Emergency Medicine 3:8, 740-744
   CrossRef

10. 10

    J.A. Vale, A.T. Proudfoot. (1995) Paracetamol (acetaminophen) poisoning. The Lancet 346:8974, 547-552
    CrossRef

11. 11

    (1994) Acetaminophen Poisoning and Liver Function. New England Journal of Medicine 331:19, 1310-1312
    Full Text

12. 12

    &NA;. (1994) Paracetamol overdose. Reactions Weekly &NA;:510, 9
    CrossRef

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