Toxicology Case Study: Acetaminophen Poisoning

Toxicology Case Study: Acetaminophen Poisoning
History: A 20-year-old female presents to the Emergency Department after
ingesting over 50 tablets of Tylenol Extra Strength® eight hours prior to
arrival in a suicide attempt. She denies coingestants and complains of
nausea.
PMH: None.
Physical Examination:
T: 99 °F HR: 90 bpm RR: 12 breaths per minute BP: 120/72 mm Hg
General: Tearful female in no acute distress.
HEENT: Pupils 4 mm and reactive, moist mucus membranes.
Pulmonary: Clear to auscultation.
CV: Tachycardic with regular rhythm.
Abdomen: Normal bowel sounds, nontender to palpation.
Neurologic: Unremarkable.

Pharmacology Case Study Questions
1. What is the most important historical information that should be obtained?
2. What diagnostic testing, if any, would you perform?
3. What treatment, if any, should be initiated immediately?
4. What is the appropriate disposition of this patient?
5. Explain the mechanism of toxicity of acetaminophen.

Case Study: Acetaminophen Poisoning
1. The presence of coingestants and confirmation of the time of ingestion is the most
important historical information to obtain. The time of ingestion should be
determined so that accurate plotting of the level on the Rumack-Matthew
nomogram can be accomplished to determine the risk of toxicity. Tylenol Extra
Strength® contains 500 mg of acetaminophen (APAP) per tablet; however there is
no reliable way to predict toxicity based on the patient’s report of the quantity
ingested.
2. The only initial laboratory tests that should be obtained are a serum APAP level
and a pregnancy test. Because the Rumack-Matthew nomogram does not risk
stratify patients based on levels obtained prior to four hours after ingestion,
obtaining acetaminophen levels prior to this time is not useful except possibly to
substantiate a claim of overdose. One may consider ordering baseline LFTs and
PT/PTT if the APAP level is in the toxic range, but this early after the ingestion,
one would expect those to be normal if the patient has no underlying disease. A
toxicology screen would not be useful because the patient is relatively
asymptomatic and has a normal exam.
3. Because the ingestion occurred eight hours earlier, N-acetylcysteine (loading dose
140 mg/kg) should be administered prior to the laboratory results. The antidote is
most effective if administered within the first 8-10 hours. If the level is non-toxic,
further doses are not indicated. If the patient presents prior to the eight hour
mark, there is no known advantage to administering NAC before the level returns.
In this patient, the eight hour level is 250 mcg/ml.
4. Because the patient’s eight hour acetaminophen level places her in the “probable
hepatotoxicity” category, she should be admitted for the full course of NAC.
Suicide precautions should be continued as an inpatient.
5. Hepatic metabolism of acetaminophen occurs via the cytochrome p450 system
and produces a highly reactive metabolite called N-acetyl-p-benzoquinone imine,
(NAPQI). In therapeutic doses, approximately 4% of APAP is metabolized via the
P450 system and the resultant NAPQI is detoxified by the glutathione stores in the
liver. In the presence of toxic doses, the amount of acetaminophen metabolized
by the cytochrome p450 system increases, subsequently depleting glutathione
stores and leading to an increased amount of NAPQI. NAPQI acts to cause
toxicity by binding to the hepatocyte and resulting in cell death.