Case Presentation: A 21 year old woman presented with confusion, nausea and vomiting over 24 hours after attempting suicide by ingesting 50 g of acetaminophen (APAP). Initial labs showed INR 1.5, ALT 141, T bili 1.7, APAP level 97. Her LFTs peaked at AST 15266, ALT 10566 on hospital day 2. After consulting Poison Control, the primary team chose to treat her with IV N-acetyl-cysteine (NAC) every 4 hours until both AST and ALT were below 1000, which took approximately 7 days; upon discharge, her LFTs had fallen to AST 67, ALT 956 and her APAP level was undetectable by day 4 post-ingestion. She did not develop any encephalopathy while admitted, only experiencing mild nausea/vomiting that quickly resolved. She was then transferred to Psychiatry for further management of her suicidality.
Discussion: APAP is one of the most common causes of medication-related poisoning and death and has gained popularity among young adults for use in suicide attempts due to its potential for hepatic and renal toxicity. Current standard of care for liver injury secondary to APAP is treatment with NAC. The exact mechanism of action of NAC is unclear, but it is thought to replenish the hepatic glutathione stores necessary for conjugation and excretion of APAP. The modified Rumack-Matthew nomogram uses serum APAP concentration and time since ingestion to guide clinicians on whether asymptomatic patients should receive NAC; any patient with hepatotoxicity is treated empirically. While the nomogram is a useful tool, it is limited as it cannot be applied to patients with a staggered overdose or that present more than 24 hours post-ingestion.
The appropriate duration of NAC therapy is controversial; the FDA has only approved time-based therapies (20 and 72 hours), but some clinicians use an approach based on clinical endpoints, such as decreasing transaminases, resolution of INR abnormalities and a normal serum APAP. This patient was deemed stable by the clinical endpoints approach days before Poison Control recommended stopping treatment with NAC. While her case is unique given the massive dose of APAP she consumed, she may have been over-treated at the expense of delaying psychiatric treatment for her suicidality. Unfortunately, there is currently no reliable way to predict which patients with APAP toxicity will develop acute liver failure, therefore standardization of the duration of NAC treatment has not yet been achieved. Given the unpredictable nature of APAP toxicity, a multidisciplinary approach with input from Medicine, Hepatology, Psychiatry and Poison Control may better allow for modification of protocols to best fit the needs of individual patients.
Conclusions: The current standard of treatment for APAP toxicity is NAC, an effective antidote against hepatotoxicity. However, the decisions to start or continue NAC therapy are not standardized for all patients. A multidisciplinary approach to these patients may prevent over- or under-treatment moving forward.