Acetaminophen Poisoning Case Study Analysis.
Acetaminophen Toxicity: A Case Study and Review of Management Strategies
Acetaminophen (APAP), also known as paracetamol, is a widely used over-the-counter analgesic and antipyretic medication. Despite its relative safety at therapeutic doses, APAP overdose remains a significant cause of acute liver failure in many countries (Yoon et al., 2016). This paper presents a case study of acetaminophen poisoning and discusses the critical aspects of its management.
Case Presentation
A 20-year-old female presented to the Emergency Department (ED) eight hours after ingesting over 50 tablets of Tylenol Extra Strength® in a suicide attempt. The patient denied coingestants and complained of nausea. Her past medical history was unremarkable. Physical examination revealed a tearful female in no acute distress, with vital signs showing mild tachycardia (heart rate 90 beats per minute) but otherwise within normal limits.
Key Management Considerations
Historical Information
In cases of suspected acetaminophen overdose, obtaining accurate historical information is crucial. The most critical data points include the time of ingestion and the presence of coingestants (Heard, 2008). The time of ingestion is particularly important as it allows for proper interpretation of serum acetaminophen levels using the Rumack-Matthew nomogram, a tool used to assess the risk of hepatotoxicity (Rumack, 2002).
Diagnostic Testing
The primary diagnostic test in acetaminophen overdose is the serum acetaminophen level. In this case, the patient’s eight-hour level was 250 mcg/mL, placing her in the “probable hepatotoxicity” category on the Rumack-Matthew nomogram. Additionally, a pregnancy test should be performed in all women of childbearing age presenting with overdose. Baseline liver function tests and coagulation studies may be considered, although they are typically normal in the early stages of toxicity (Chun et al., 2009).
Immediate Treatment
N-acetylcysteine (NAC) is the antidote of choice for acetaminophen poisoning. Its efficacy is highest when administered within the first 8-10 hours after ingestion (Smilkstein et al., 1988). Consequently, in this case, NAC should be initiated immediately, even before laboratory results are available. The standard protocol begins with a loading dose of 140 mg/kg, followed by maintenance doses.
Patient Disposition
Given the toxic acetaminophen level and the suicide attempt, this patient requires hospital admission for continued NAC therapy and psychiatric evaluation. Inpatient management allows for close monitoring of liver function and the development of potential complications (Bunchorntavakul & Reddy, 2013).
Mechanism of Toxicity
Understanding the mechanism of acetaminophen toxicity is essential for comprehending its management. At therapeutic doses, acetaminophen is primarily metabolized through glucuronidation and sulfation pathways. However, a small portion is metabolized by the cytochrome P450 system, producing a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Normally, NAPQI is rapidly detoxified by glutathione. In overdose situations, the glucuronidation and sulfation pathways become saturated, leading to increased NAPQI production. This overwhelms glutathione stores, resulting in the accumulation of NAPQI, which causes hepatocellular damage through oxidative stress and mitochondrial dysfunction (McGill & Jaeschke, 2013).
Conclusion
This case study highlights the importance of prompt recognition and treatment of acetaminophen poisoning. Key elements in management include accurate history taking, timely diagnostic testing, and early administration of N-acetylcysteine. Understanding the mechanism of toxicity provides insight into the rationale behind current treatment strategies and may guide future therapeutic approaches.
References
Bunchorntavakul, C., & Reddy, K. R. (2013). Acetaminophen-related hepatotoxicity. Clinics in Liver Disease, 17(4), 587-607.
Chun, L. J., Tong, M. J., Busuttil, R. W., & Hiatt, J. R. (2009). Acetaminophen hepatotoxicity and acute liver failure. Journal of Clinical Gastroenterology, 43(4), 342-349.
Heard, K. J. (2008). Acetylcysteine for acetaminophen poisoning. New England Journal of Medicine, 359(3), 285-292.
McGill, M. R., & Jaeschke, H. (2013). Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharmaceutical Research, 30(9), 2174-2187.
Rumack, B. H. (2002). Acetaminophen hepatotoxicity: the first 35 years. Journal of Toxicology: Clinical Toxicology, 40(1), 3-20.
Smilkstein, M. J., Knapp, G. L., Kulig, K. W., & Rumack, B. H. (1988). Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. New England Journal of Medicine, 319(24), 1557-1562.
Yoon, E., Babar, A., Choudhary, M., Kutner, M., & Pyrsopoulos, N. (2016). Acetaminophen-induced hepatotoxicity: A comprehensive update. Journal of Clinical and Translational Hepatology, 4(2), 131-142.
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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
