Correspondence

A 20-Hour Treatment for Acute Acetaminophen Overdose

N Engl J Med 2003; 348:2471-2472June 12, 2003

Article

To the Editor:

The only treatment approved by the Food and Drug Administration for acute acetaminophen poisoning is a 72-hour protocol of oral N-acetylcysteine administration. Clinical experience suggests that this protocol may be excessive for many episodes of acute acetaminophen poisoning. Hepatotoxicity from such poisoning is preventable when intravenous administration of N-acetylcysteine is initiated within 8 to 10 hours after ingestion and continued for 20 hours.1,2

We investigated the use of a 20-hour protocol of oral N-acetylcysteine for the management of acute ingestion of an acetaminophen product (except sustained-release preparations) between 1996 and 1999. The investigation was approved by our institutional review board. The inclusion criteria were a precise and reliable history of the time of ingestion, a serum acetaminophen concentration above the possible-hepatotoxicity line (the line joining the plots of 150 μg per milliliter [992 μmol per milliliter] at four hours and 80 μg per milliliter [529 μmol per milliliter] at eight hours on the Rumack–Matthew nomogram), normal base-line levels of aspartate aminotransferase and alanine aminotransferase, and a normal base-line international normalized ratio (INR). Oral and written informed consent was obtained from the patients or their parents. The oral loading dose of N-acetylcysteine was 140 mg per kilogram of body weight, administered within eight hours after acetaminophen ingestion; the oral maintenance dose was 70 mg per kilogram, given every four hours for five additional doses. Hence a total of six doses were given in a 20-hour period. Laboratory studies were performed initially and 16, 36, and 48 hours after the administration of the acetaminophen loading dose.

A total of 34 patients (29 females and 5 males) were enrolled in the study. There were two children, 13 and 14 years old; both were girls. One child's acetaminophen level was above the possible-hepatotoxicity line, and the other was above the line joining the plots of 200 μg per milliliter (1323 μmol per milliliter) at four hours and 100 μg per milliliter (662 μmol per milliliter) at eight hours on the nomogram (i.e., the probable-hepatotoxicity line). The 32 adults (27 women and 5 men) were 18 to 48 years old. One adult was withdrawn from the study because of a treatment-protocol violation. Of the remaining 33 patients, 4 had an acetaminophen level above the probable-hepatotoxicity line, and 29 had a level above the possible-hepatotoxicity line. The peak ranges of the INR and of the aspartate aminotransferase and alanine aminotransferase levels in the group with possible hepatotoxicity were 1.0 to 1.5 U per liter, 16 to 41 U per liter, and 15 to 54 U per liter, respectively; the peak ranges in the group with possible hepatotoxicity were 1.2 to 1.3 U per liter, 18 to 28 U per liter, and 12 to 19 U per liter, respectively. All the patients were discharged from the hospital in good condition.

Thus, a 20-hour protocol of oral N-acetylcysteine was effective in preventing hepatic injury after an acute acetaminophen overdose when the loading dose was initiated within 8 hours after ingestion, especially in patients with an acetaminophen level below the probable-hepatotoxicity line. Further prospective studies will be needed to validate and refine this protocol.

Luke Yip, M.D.
Richard C. Dart, M.D., Ph.D.
Rocky Mountain Poison and Drug Center, Denver, CO 80230
luke.yip@rmpdc.org

2 References

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   Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J 1979;2:1097-1100
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   Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet 1977;2:432-434
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Citing Articles (10)

Citing Articles

1. 1

   Steven R. Offerman. (2011) The Clinical Management of Acetaminophen Poisoning in a Community Hospital System: Factors Associated with Hospital Length of Stay. Journal of Medical Toxicology 7:1, 4-11
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2. 2

   David P. Betten, Elizabeth E. Burner, Stephen C. Thomas, Christian Tomaszewski, Richard F. Clark. (2009) A retrospective evaluation of shortened-duration oral N-acetylcysteine for the treatment of acetaminophen poisoning. Journal of Medical Toxicology 5:4, 183-190
   CrossRef

3. 3

   Heard, Kennon J., . (2008) Acetylcysteine for Acetaminophen Poisoning. New England Journal of Medicine 359:3, 285-292
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4. 4

   David P. Betten, F. Lee Cantrell, Stephen C. Thomas, Saralyn R. Williams, Richard F. Clark. (2007) A Prospective Evaluation of Shortened Course Oral N-Acetylcysteine for the Treatment of Acute Acetaminophen Poisoning. Annals of Emergency Medicine 50:3, 272-279
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5. 5

   Stephen J. Wolf, Kennon Heard, Edward P. Sloan, Andy S. Jagoda. (2007) Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department With Acetaminophen Overdose. Annals of Emergency Medicine 50:3, 292-313
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6. 6

   Neeral L. Shah, Fredric D. Gordon, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein. (2007) N -acetylcysteine for acetaminophen overdose: When enough is enough. Hepatology 46:3, 939-941
   CrossRef

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   Ernesto A. Pretto. (2006) Perioperative Management of the Recipient of the Extended Criteria Cadaveric Donor Liver (ECDL). International Anesthesiology Clinics 44:4, 79-96
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   2006. Paracetamol. , 2679-2693.
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   Aline Charabaty Pishvaian, Bradley W. Trope, James H. Lewis. (2004) Drug-induced liver disease in 2003. Current Opinion in Gastroenterology 20:3, 208-219
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       . (2003) Paracetamolintoxicatie bij kinderen: snel en lang behandelen. Medisch-Farmaceutische Mededelingen 41:8, 240-240
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