EM@3AM – Acute APAP Toxicity

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 14 year-old male with a history of major depressive disorder presents to the emergency department following a toxic ingestion. The patient reports consumption of approximately 40 extra strength Tylenol caplets (500mg each), two hours prior to arrival. The patient is nauseated and covered in non-bloody gastric contents. Upon initial examination: GCS 15. VS: HR 132, BP 128/84, RR 18, SpO2 98% on room air.

What is the patient’s diagnosis? What’s the next step in your evaluation and treatment?

Answer: Acute Acetaminophen Toxicity^1-3

• Recommended dosing: 3-4g QD; toxic dose: 150mg/kg

• Presentation varies according to stage of toxicity:
  • Stage 1 (0.5-24 hrs): mild nausea, emesis, weakness
  • Stage 2 (24-72 hrs): hepatotoxicity +/- nephrotoxicity => RUQ abdominal pain
  • Stage 3 (72-96 hrs): hepatotoxicity peaks => nausea, vomiting, jaundice, coagulopathy
  • Stage 4 (4 days -2 wks): recovery or decompensation resulting in death

• Evaluation:
  • Use the Rumack-Matthew nomogram for single ingestions occurring <24 hours prior to arrival:
    • Obtain AST level at 4 hours s/p ingestion: utilize nomogram to determine the appropriateness of N-acetylcysteine (NAC) treatment
  • If the time of ingestion is unknown:
    • Obtain AST level and a serum acetaminophen level => if AST is elevated or serum acetaminophen concentration >10mcg/mL = initiate NAC^2,3

• Treatment:
  • If patient presents within one hour of toxic ingestion, consider NG lavage if no contraindications.
  • NAC Loading dose: 150 mg/kg IV (max 15g) infused over 1 hr or 140 mg/kg PO

• Pearls:
  • Rumack-Matthew nomogram should not be employed in the setting of unknown time of ingestion or chronic acetaminophen therapy.
  • NAC is most effective if initiated within 8 hours of acetaminophen ingestion.
  • Evaluate for co-ingestions: serum salicylate, serum ETOH; calculate an anion gap and an osmolar gap as appropriate. Consider UDS.
  • End point of NAC treatment: AST <100 U/L and acetaminophen <10mcg/mL or if extended therapy required: normalization of INR, resolution of encephalopathy, and decreasing AST (<1,000 U/L).³

References:

1. Tintinalli J, Kelen G, Stapczynski J, Ma O, Cline D, et al. Tintinalli’s Emergency Medicine. 8^th ed. New York: McGraw-Hill; 2016. Chapter 190, Acetaminophen.
2. Heard K. Acetylcysteine for acetaminophen poisoning. N Engl J Med. 2008; 359(3):285-292.
3. Mottram A, Kumar A. Focus On: Acetaminophen Toxicity and Treatment. American College of Emergency Physicians Clinical and Practice Management. Available from: https://www.acep.org/Clinical—Practice-Management/Focus-On–Acetaminophen-Toxicity-and-Treatment/