Posted: July 23rd, 2023

Acetaminophen Overdose: Management and Treatment Considerations

Acetaminophen Overdose: Management and Treatment Considerations

Acetaminophen overdose is a significant medical emergency that requires prompt and appropriate intervention. This paper examines a case study of a 16-year-old female who ingested a toxic dose of acetaminophen, focusing on the assessment, treatment options, and potential complications associated with this common yet potentially life-threatening poisoning.

Initial Assessment and Management

Upon presentation to the emergency department, the primary focus is on rapid assessment and initiation of appropriate treatment. The patient’s history of ingesting 25 tablets (500 mg each) of acetaminophen approximately three hours prior to arrival is crucial information. The physical examination findings, including stable vital signs and normal neurological status, are reassuring but do not preclude the need for aggressive management.

Gastric decontamination measures, such as gastric lavage, are not recommended in this case. Research has shown that gastric lavage is of limited benefit in acetaminophen overdose, especially when more than one hour has elapsed since ingestion (Chiew et al., 2018). Instead, the focus should be on administering activated charcoal and obtaining necessary laboratory tests.

Activated charcoal is an effective adsorbent for acetaminophen and can be administered up to four hours post-ingestion. While its impact on clinical outcomes remains uncertain, it is generally considered a safe intervention that may reduce drug absorption. The standard dose is 1 g/kg body weight, given orally or via nasogastric tube (Juurlink, 2016).

Laboratory testing is crucial in guiding treatment decisions. The most important test is the serum acetaminophen level, ideally drawn at four hours post-ingestion. This timing allows for complete absorption of the drug and accurate plotting on the Rumack-Matthew nomogram, which predicts the risk of hepatotoxicity (Heard, 2008).

Treatment Decisions Based on Acetaminophen Levels

The patient’s acetaminophen level at four hours post-ingestion was 224 mcg/mL, which falls above the treatment line on the Rumack-Matthew nomogram. This level indicates a high risk of hepatotoxicity and necessitates immediate treatment with N-acetylcysteine (NAC), the antidote for acetaminophen poisoning.

NAC can be administered either orally or intravenously. The oral protocol involves a loading dose of 140 mg/kg followed by 70 mg/kg every four hours for 17 doses, totaling 72 hours of treatment. The intravenous protocol, which has gained popularity due to its shorter duration and ability to treat patients with persistent vomiting, consists of a loading dose of 150 mg/kg over 15-60 minutes, followed by 12.5 mg/kg/hr for 4 hours, and then 6.25 mg/kg/hr for 16 hours (Zed et al., 2022).

The choice between oral and intravenous NAC depends on factors such as the patient’s ability to tolerate oral medication, the severity of the overdose, and institutional protocols. In this case, given the patient’s history of vomiting, the intravenous route might be preferable to ensure complete administration of the antidote.

Interaction Between Activated Charcoal and N-acetylcysteine

A common concern in the management of acetaminophen overdose is the potential interaction between activated charcoal and NAC. Theoretically, activated charcoal could adsorb orally administered NAC, reducing its effectiveness. However, clinical evidence suggests that this interaction is not clinically significant when the treatments are appropriately timed (Green et al., 2020).

For patients receiving oral NAC, it is recommended to administer activated charcoal first, followed by NAC after a short interval. This approach maximizes the benefits of both treatments without significant compromise. For patients receiving intravenous NAC, there is no concern about interaction with activated charcoal.

In conclusion, the management of acetaminophen overdose requires a systematic approach based on timely assessment, appropriate use of the antidote N-acetylcysteine, and supportive care. While gastric decontamination with activated charcoal may be considered in early presentations, the mainstay of treatment remains NAC administration guided by serum acetaminophen levels and clinical presentation. Ongoing monitoring and supportive care are essential to manage potential complications and ensure optimal outcomes.

Keywords: Acetaminophen overdose, N-acetylcysteine, Rumack-Matthew nomogram

References

Chiew, A. L., Isbister, G. K., Duffull, S. B., & Buckley, N. A. (2018). Evidence for the changing regimens of acetylcysteine. British Journal of Clinical Pharmacology, 84(6), 1379-1389.

Green, J. L., Heard, K. J., Reynolds, K. M., & Albert, D. (2020). Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis. Western Journal of Emergency Medicine, 21(3), 600-610.

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

Juurlink, D. N. (2016). Drug-Induced Liver Injury. New England Journal of Medicine, 374(9), 899.

References
Chiew, A. L., Isbister, G. K., Duffull, S. B., & Buckley, N. A. (2018). Evidence for the changing regimens of acetylcysteine. British Journal of Clinical Pharmacology, 84(6), 1379-1389.
Goldfrank, L. R., Flomenbaum, N., Lewin, N. A., Weisman, R. S., & Hoffman, R. S. (2022). Goldfrank’s toxicologic emergencies (11th ed.). McGraw-Hill Medical.
Green, J. L., Heard, K. J., Reynolds, K. M., & Albert, D. (2020). Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis. Western Journal of Emergency Medicine, 21(3), 600-610.
Heard, K. (2008). Acetylcysteine for Acetaminophen Poisoning. New England Journal of Medicine, 359(3), 285-292.
Juurlink, D. N. (2016). Drug-Induced Liver Injury. New England Journal of Medicine, 374(9), 899.

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PHARMACOLOGY/TOXICOLOGY CASE STUDY
History: A 16-year-old woman presents to your emergency department with her
boyfriend. She admits to having taken 25 acetaminophen tablets (500 mg
each) approximately three hours prior to arrival. She has had three
episodes of emesis in the past 30 minutes.

Physical Examination:
T: 98.6°F HR: 80 bpm RR: 16 breaths per minute BP: 110/60 mm Hg
General: Alert and oriented.
HEENT: Pupils 3 mm bilaterally and reactive.
Pulmonary: Clear to auscultation.
CV: Regular rate and rhythm, without murmur.
Abdomen: Soft, nontender, no masses palpable.
Neurologic: GCS 15.
QUESTIONS CASE STUDY #32
1. Should treatment with gastric lavage be used this patient? What treatment, if any,
would you administer? What testing, if any, should be ordered?
2. The patient’s acetaminophen level at four hours post-ingestion is 224 mcg/ml.
What treatment, if any, is indicated now? How would you give it?
3. If administered on the patient’s initial presentation, would charcoal interfere with
the activity of the antidote?

CASE STUDY: ACETAMINOPHEN POISOINING
1. No. Gastric lavage is not indicated in cases of isolated acetaminophen overdose
because of the efficacy of N-acetyl cysteine for treatment. Activated charcoal
effectively adsorbs acetaminophen and its administration is generally
recommended for up to four hours post ingestion, but its ability to influence
outcome has not yet been proven.
An acetaminophen (APAP) level should be checked four hours after ingestion.
There is little value to stat acetaminophen levels in these patients, except
possibly to substantiate their claim of acetaminophen ingestion.
Based on the Rumack-Matthew nomogram, a level equal to or greater than 150
mg/dL at four hours is considered a potentially toxic dose and should be treated
with N-acetyl cysteine (NAC).
2. The patient should be given N-acetyl cysteine (NAC) by either the oral or
intravenous route. The protocol for oral NAC is 72 hours in length and is
administered with a loading dose of 140 mg/kg followed by 70 mg/kg every four
hours for seventeen doses. More recently, intravenous NAC has been used in
the United States and its protocol is 21 hours in length. Intravenous NAC is
administered with a loading dose of 150 mg/kg IV over fifteen to 60 minutes.
After the loading dose, an infusion of 12.5 mg/kg/hr is continued for four hours,
after which 6.25 mg/kg/hr is administered for sixteen hours. Starting NAC
anytime within the first eight hours appears to be equally effective. Antiemetics
(e.g. ondansetron) may be needed.
3. Theoretically, the administration of activated charcoal could interfere with gastric
absorption of NAC. However, in practice, this effect is probably clinically
insignificant, and charcoal can be administered in patients who will receive NAC.

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