Here’s another USMLE® Step 2 CK Question of the Day! Today’s case involves a 50-year-old man who took hydrocodone-acetaminophen for his knee pain. He has a history of chronic lower back pain and chronic alcohol use. His partner reported he was less responsive several hours after taking the medication. Can you figure it out?
A 50-year-old man is brought to the emergency department by his partner for evaluation of altered mental status. His partner states the patient woke up today with knee pain, for which he took an “over-the-counter pain reliever” and his prescription hydrocodone-acetaminophen. Several hours later, the partner noticed he was less responsive and unaware of where he was. The patient has a history of chronic lower back pain and chronic alcohol use. On physical examination, the patient is not oriented and responds only to pain. The patient grimaces with palpation of the right upper quadrant. AST and ALT are 2136 and 2467 IU/L, respectively. Which of the following is the most appropriate therapeutic treatment for this patient’s clinical condition?
A. N-Acetylcysteine
B. Activated charcoal
C. Sodium bicarbonate
D. Orogastric lavage
E. Whole bowel irrigation
The correct answer to today’s USMLE® Step 2 CK Question is…
A. N-Acetylcysteine
Before we get to the Main Explanation, let’s see why the answer wasn’t B, C, D, or E. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
Today’s incorrect answers are…
B. Activated charcoal
Incorrect: Activated charcoal may be used to treat acetaminophen overdose when the patient is alert and protecting their airway, and ingestion is within one hour of presentation. Activated charcoal should be avoided in this patient due to the risk of aspiration injury.
C. Sodium bicarbonate
Incorrect: Sodium bicarbonate is an alkaline solution that is used in the treatment of salicylates and tricyclic antidepressants toxicity. It has no role in the management of acetaminophen toxicity.
D. Orogastric lavage
Incorrect: Orogastric lavage is not effective for the treatment of acetaminophen toxicity.
E. Whole bowel irrigation
Incorrect: Whole bowel irrigation, like orogastric lavage, is not effective for the treatment of acetaminophen toxicity.
Main Explanation
This patient presents with altered mental status, right upper quadrant tenderness, and elevated liver enzymes consistent with acute hepatic injury and encephalopathy secondary to acetaminophen overdose. Most cases of acetaminophen toxicity are due to intentional ingestion of large amounts of acetaminophen; however, some patients develop toxicity unintentionally via ingestion of acetaminophen from multiple sources or via underlying hepatic dysfunction (e.g., chronic alcohol use).
Acetaminophen metabolism at therapeutic doses occurs through glucuronidation and sulfation in the liver, which yields non-toxic products that are eliminated through urine. A minimal amount of acetaminophen is converted by CYP450 to the toxic N-acetyl-p-benzoquinone imine (NAPQI); however, this compound is quickly eliminated by combining it with the substrate glutathione.
In case of overdose, glucuronidation and sulfation pathways become saturated, leading to increased metabolism by CYP450 and production of NAPQI. The high amount of NAPQI depletes glutathione, with subsequent NAPQI accumulation, resulting in hepatic necrosis and acute liver failure.
First-line treatment for acetaminophen toxicity is N-acetylcysteine (NAC). NAC is fully protective of the liver; it exerts its protective effects by replenishing glutathione, increasing detoxification of NAPQI, and thus preventing further hepatocyte injury and necrosis.
Major Takeaway
N-acetylcysteine is the first-line treatment of acetaminophen toxicity. It replenishes glutathione in hepatocytes, thus increasing the metabolism of NAPQI and protecting the liver.
References
Agrawal S, Khazaeni B. Acetaminophen Toxicity. [Updated 2020 Sep 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441917/
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