Tim Vo, MD
Acetaminophen poisoning some background it’s one of the most common causes of acute liver failure and the us alone it causes over 300,000 hospitalizations per year it’s one of the most common medications that we see both in the hospital and out of the hospital and this is something that is very important to know about so how does it cause liver injury normally it’s
Metabolized through glucuronidation in sulfation or it’s excreted unchanged in the urine about 5% of a therapeutic ingestion is metabolized through cytochrome 450 to e1 to the toxic metabolite any pqi or nap key normally nap key is bound by intracellular glutathione and then it’s excreted harmlessly however in super therapeutic ingestions more and more substrate
Is metabolized by the sip 450 pathway this creates more and more nap key which overruns the cells glutathione stores it can then bind indiscriminately to macromolecules it causes reactive oxygen species formation mitochondrial damage and then eventually cell death so you’re either worried that your patient has liver injury or your patient does have liver injury
What can we do about it we have an antidote it’s called n-acetylcysteine or nak the way works is it repeats glutathione stores thereby decreasing the amount of free nap key that can run around in the cell and cause problems it comes in pio and iv form it’s very cheap and there are very few side effects so when should we use it should we give it to everyone back
In the 1970s to toxicologists room and matthew developed a nomogram to help determine when nat should be used in the initial studies all the patients who develop liver injury were found to have acetaminophen concentration correlating to a level of at least 200 micrograms per milliliter at four hours after ingestion so somewhat arbitrarily the people who made the
Guideline said you know what let’s be safe and treat everyone with a level greater than a hundred and fifty milligram micrograms per milliliter at four hours that way we can be sure we’re picking up everyone with clinically important ingestion in order to use it you plot the acetaminophen concentration against time you reference the 150 line which is the line that
Shows what the concentration would have been at a given time with a hypothetical level of a hundred and fifty micrograms per milliliter at four hours if the concentration is greater than the 150 line you treat with nak if not you don’t some caveats you need to use a 4-hour level and no earlier why four hours that is when you would reasonably expect an oral low to
Be fully absorbed and in the serum if you measure a level before then you potentially would miss some load that would be in the gi system and not in the serum yet second caveat is that the time of ingestion must be known let’s say you measure the concentration to be 50 but the time is unknown at the time of ingestion is four hours ago then no treatment is indicated
But if it was 12 hours ago you would treat so let’s say you have a patient with an unknown time of ingestion with some level of acetaminophen in their serum should you treat or not it’s well it’s hard to say this gets into the realm of regional practice variation and expert opinion which we’re gonna be covering in part two so some take-home points acetaminophen
Poisoning does not have an acute toxic drum in most clinical settings and however it can be very deadly nak is the antidote for acetaminophen poisoning it works by repeating glutathione stores thereby scavenging nap ki the toxic metabolite the room at matthew nomogram shows when to reasonably expect liver injury to occur and therefore when nak should be given you
Use it by plotting the serum concentration versus the time of ingestion two major caveats the time of ingestion must be known and the time of ingestion must be greater than four hours but you’ve given in time mortality mortality and morbidity can be significantly reduced
Transcribed from video
Acetaminophen overdose By Timothy Vo
