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A Review of Acetaminophen
Poisoning
Michael J. Hodgman,

MD

a,b,

*, Alexander R. Garrard,

PharmD

a

KEYWORDS
 Acetaminophen poisoning  Acetaminophen overdose  N-acetylcysteine
 Hepatotoxicity  Fulminant hepatic failure  Liver transplant  Paracetamol
KEY POINTS
 Acetaminophen is the leading cause of acute liver failure in the United States. Liver
toxicity may resultfrom an acute overdose as well as from chronic excessive ingestion.
 N-acetyl cysteine (NAC) is an effective antidote for acetaminophen overdose. Early treatment with NAC prevents the formation of a toxic metabolite that leads to hepatic injury.
NAC is also an effective therapy to aid in the recovery of the hepatic injury as a consequence of acetaminophen.
 Obtaining an accurate time ofingestion is essential to interpreting an acetaminophen
level in an acute exposure on the Rumack-Matthews Nomogram line. The nomogram
line cannot be used to assess the risk of hepatotoxicity in a chronic acetaminophen
exposure.
 The King’s College Hospital criteria is the most often used to determine which patients
are to die from fulminant hepatic failure. Other criteria have been proposedincluding
phosphate, lactate, and a MELD score.

Acetaminophen (APAP) is a safe and effective analgesic and antipyretic.1 It is widely
available as a single-component medication and also as a component of a plethora
of combination over-the-counter and prescription medications. More than 28 billion
doses of APAP-containing products were dispensed in 2005.2 With more than 89
million prescriptions,hydrocodone/APAP was the most commonly dispensed medication in 2003.3 Despite its safety when used properly, APAP is one of the more common
overdoses reported to poison centers. Serious toxicity results in hepatic injury, which
may progress to fulminant hepatic failure (FHF) and death.4 In 2009, the American Association of Poison Control Centers’ National Poison Data System reported 401 deathscaused by APAP or an APAP combination product.5 APAP is the most common cause
of acute liver failure (ALF) in the United States, accounting for nearly half of the cases of

The authors have no financial disclosures or conflicts of interest to disclose.
a
Department of Emergency Medicine, Upstate New York Poison Center, SUNY Upstate Medical
University, Suite 202, 250 Harrison Street,Syracuse, NY 13202, USA; b Emergency and Trauma
Services, Bassett Medical Center, Cooperstown, NY 13326, USA
* Corresponding author.
E-mail address: hodgmanm@upstate.edu
Crit Care Clin 28 (2012) 499–516
http://dx.doi.org/10.1016/j.ccc.2012.07.006
criticalcare.theclinics.com
0749-0704/12/$ – see front matter Ó 2012 Elsevier Inc. All rights reserved.

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ALF in the USAcute Liver Failure Study Group.6,7 Additionally, a significant number of
cases of ALF of unknown cause may be unrecognized APAP toxicity, suggested by the
presence of APAP protein adducts.8 In children, APAP is much less frequently the
cause of acute liver failure.9
APAP toxicity may be the consequence of either an acute overdose or from
repeated excessive dosing (repeated supratherapeuticingestion [RSTI]).10 Unintentional toxicity may also occur from the concurrent use of several different medications
that each contains APAP. The Acute Liver Failure Study Group found nearly equal
proportions of patients with APAP hepatotoxicity caused by intentional versus unintentional overdose. Unintentional overdoses were often caused by RSTI and tended
to present later with signs of hepaticinjury apparent on presentation.11 Concerns
that combination APAP-opioid products are a risk factor for APAP hepatotoxicity
from RSTI led the Food and Drug Administration to recently request that manufacturers of prescription drugs limit the APAP content of each unit dose to 325 mg.
They have until early 2014 to comply with this requirement.12 Earlier this year, in an
effort to avoid dosing...