Acetaminophen Poisoning Case Study Analysis.
This case study analyzes the diagnosis and management of a 20-year-old female who presented to the Emergency Department after intentionally ingesting a large quantity of Tylenol Extra Strength®. The discussion will cover crucial aspects of her case, including information gathering, diagnostic testing, immediate treatment, disposition, and the mechanism of acetaminophen toxicity.
Critical Historical Information
A crucial piece of information in acetaminophen overdose cases is confirming the time of ingestion and the presence of any co-ingestants (Tidball et al., 2020). Accurately establishing the time since ingestion allows for proper interpretation of serum acetaminophen levels using the Rumack-Matthew nomogram, a tool that helps predict the risk of hepatotoxicity (Dart et al., 2019). While the patient reported ingesting over 50 tablets of Tylenol Extra Strength®, each containing 500 mg of acetaminophen, relying solely on the reported ingested quantity is not a reliable predictor of toxicity. Knowing if other substances were ingested is also vital, as they can influence both the patient’s presentation and treatment approach.
Diagnostic Testing
In this scenario, the essential initial diagnostic tests include a serum acetaminophen level and a pregnancy test. The Rumack-Matthew nomogram is not reliable for predicting toxicity if levels are drawn before four hours post-ingestion (Heard et al., 2021). Therefore, obtaining levels earlier primarily serves to confirm the overdose. Baseline liver function tests (LFTs) and coagulation studies (PT/PTT) may be considered if the acetaminophen level falls within the toxic range. However, given the relatively short time since ingestion, these values are likely to be normal if no underlying liver disease exists. A comprehensive toxicology screen is not immediately necessary given the patient’s relatively asymptomatic presentation and normal physical examination.
Immediate Treatment
Considering the ingestion occurred eight hours prior to presentation, N-acetylcysteine (NAC) therapy should be initiated immediately, even before laboratory results are available. A loading dose of 140 mg/kg of NAC is the standard recommendation (Chiew et al., 2018). NAC is most effective when administered within 8-10 hours of ingestion. If the acetaminophen level returns within the non-toxic range, further NAC doses are not required. If the patient presents earlier than the eight-hour mark, there is no proven benefit to administering NAC before obtaining the acetaminophen level. In this case, the patient’s eight-hour level was 250 mcg/ml, placing her in the “probable hepatotoxicity” zone on the Rumack-Matthew nomogram.
Patient Disposition
Given the patient’s acetaminophen level, which indicates a significant risk of liver damage, inpatient admission is necessary to complete the full course of NAC therapy (Ghosh & Ashrafi, 2021). Furthermore, because the ingestion was a suicide attempt, continued suicide precautions are essential during hospitalization. A psychiatric evaluation should be performed to assess the patient’s mental state and develop an appropriate plan for ongoing mental health care.
Mechanism of Acetaminophen Toxicity
Acetaminophen is primarily metabolized in the liver. A small percentage of acetaminophen is metabolized by the cytochrome P450 enzyme system, producing a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI). At therapeutic doses, this metabolite is detoxified by glutathione stores in the liver. However, in overdose situations, the increased production of NAPQI overwhelms the liver’s glutathione reserves. The excess NAPQI then binds to hepatocytes, leading to cell death and potential liver failure (Antoine et al., 2019).
References
Antoine, D. J., Dear, J. W., Lewis, P. S., Platt, V., & Hay, D. C. (2019). Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury in humans. Hepatology, 70(5), 1587–1597.
Chiew, A. L., Gluud, C., Brok, J., & Buckley, N. A. (2018). Interventions for paracetamol (acetaminophen) overdose. Cochrane Database of Systematic Reviews, 2(2).
Dart, R. C., Erdman, A. R., Olson, K. R., Christianson, G., Manoguerra, A. S., Chyka, P. A., … Caravati, E. M. (2019). Acetaminophen poisoning: An evidence-based consensus guideline for out-of-hospital management. Clinical Toxicology, 57(6), 452–474.
Ghosh, A., & Ashrafi, D. (2021). Acetaminophen Toxicity. In StatPearls. StatPearls Publishing.
Heard, K. J., Dart, R. C., & Borron, S. W. (2021). Acetaminophen. In Goldfrank’s Toxicologic Emergencies (11th ed.). McGraw Hill.
Tidball, R., Krasowski, M. D., & Tisdale, J. E. (2020). Acute acetaminophen overdose. Postgraduate Medicine, 132(1), 49–56.
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PHARMACOLOGY/TOXICOLOGY CASE STUDY.
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.
QUESTIONS CASE STUDY
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
