MCC ICU Topic Deep Dive: Acetaminophen Overdose 

Definition: Intake of acetaminophen, intentional or otherwise, leading to acute liver injury. 

Risk Factors: Chronic acetaminophen ingestion, polypharmacy, underlying preexisting liver disease, suicidal ideation, alcohol abuse.  

Symptoms: Jaundice, confusion, abdominal pain, nausea, vomiting, lethargy to coma, convulsions, diarrhea. 

Pharmacologic Treatment: IV or PO Acetylcysteine 

Nonpharmacologic: Liver Transplant, Molecular Adsorbent Recirculating System (MARS) 

Guidelines: America’s Poison Control Centers (And Three other Toxicology Organizations)                   August 2023

• Obtain a detailed history from the patient with regards to what dose of tablets, how many they believe were taken, and when the pills were ingested. There are IR and ER forms of acetaminophen available. Acute ingestion is defined as 0-24 hours prior to arrival. 

• If ingestion was within 4 hours, consider gastric decontamination with single dose activated charcoal (SDAC) 

• For high risk ingestion, (Considered > 30 grams) of if the acetaminophen concentration is greater than 10 micrograms per milliliter or AST/ALT are abnormal, start acetylcysteine (NAC) 

• Acetylcysteine should be administered for 20-24 hours IV or PO with FDA approved protocol that administers 300 mg/kg over 20-24 hour period. If a loading dose is used, 150 mg/kg loading dose is used, administer over 1 hour. IV NAC rate should be at least 6.25 mg/kg/hr. 

• Draw acetaminophen levels, AST/ALT, and PT/INR every 12-24 hours. 

• NAC stopping criteria included acetaminophen level < 10 micrograms/ml, INR < 2.0, ALT/AST normal for patient or, if elevated, 25-50% decrease from peak, and patient is clinically well. 

• If the offending agent is extended release acetaminophen, activated charcoal may be of benefit beyond the normal 4 hour mark. 

• If the acetaminophen is co-ingested with anticholinergic (Tylenol PM) or opioid agonist medications (Percocet, Vicodin), acetaminophen absorption may be delayed or prolonged. Management is similar except if the first acetaminophen level at 4-24 hours after ingestion is 10 micrograms/ml or less, acetylcysteine is not needed and another acetaminophen level is not needed. If the level is above 10 micrograms/ml at 4-24 hours post ingestion, acetylcysteine is indicated and another measurement should be completed in 4-6 hours. 

• If the patient is pregnant, there is no change in treatment plan 

• For patients > 100 kg, management is the same, but the acetylcysteine level is maxed out and no increase in dose is necessary

• Hemodialysis is recommended in addition to NAC for patients with acetaminophen concentration of 900 micrograms per ml or greater with acidosis or altered consciousness. NAC dosing needs to be at least 12.5 mg/kg per hour during dialysis.

• Consultation with a liver transplant team should be considered with progressive increases in AST and ALT  and coagulation abnormalities.  

Random Dan Advice: 

• Getting a history from a patient is nice…but often useless. You are not really worried about how much tylenol that patient took. You are worried if they are going to go into liver failure. The amount that results in liver failure varies from person to person and the labs will tell you what is happening. The history you get may give a hint as to how worried you should be, but patients can over or underestimate what they took very easily. 

• Consider opening op MDCalc or the medical calculator app of your choice and punch the patient’s labs into King’s College Critieria. This is a prognostic indicator for fulminant hepatic liver failure and from my perspective, if this reads poor prognosis, I am immediately referring this patient to a transplant center 

• It’s always tempting to get more labs, but truly, what are you doing with those results? The guidelines above are pretty specific in the 12-24 hour collections for a reason. 

• The guidelines do not mention MARS (Molecular Adsorbent Recirculating System), likely because not many people have this as an option. As listed below, here is some evidence that this is a good idea in tylenol overdose and Advocate/Aurora St. Luke’s Hospital does have this capability in addition to liver transplant services. Data is not great, but this does seem to make some sense. 

• It is usually not just Tylenol if the overdose was intentional. Don’t get focused on one overdose and miss the other active overdose happening at the same time. 

• If the patient is still dealing with ongoing liver injury after 24 hours, don’t stop the NAC. Keep going until the completion parameters as above are met. 

                       Recent evidence for/against some of the above 

Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement

Project that reviewed 84 guidelines and 278 publications, released in JAMA August 2023 

Author of this project was The America’s Poison Centers.    Doi:10.1001/jamanetworkopen.2023.27739      

Acetaminophen Poisoning. July 2021 Critical Care Clinics. https://doi.org/10.1016/j.ccc.2021.03.005

Acetylcysteine For Acetaminophen Poisoning. New England Journal of Medicine 2008. 

DOI: 10.1056/NEJMct0708278 

Acetaminophen Toxicity. Stats and Pearls from June 2023 National Institutes of Health https://www.ncbi.nlm.nih.gov/books/NBK441917/?report=printable

Use of the Molecular Adsorbent Recirculating System in Acute Liver Failure: Results of a Multicenter Propensity Score-Matched Study. Crit Care Med. 2022. doi: 10.1097/CCM.0000000000005194.