IV Acetadote only requires a 21 hr dosing regimen as opposed to PO NAC which traditionally requires 72 h hour dosing
Keep in mind that when you get 2 Toxicologists talking about the "correct" treatment of acetaminophen, there is a good chance you will get 3 opinions.
The 21 hour dosing protocol is controversial subject. Personally, I don't use it as a "set it and forget it" way of doing things. I can also say that I have not treated for 72 hours with oral in a simple, uncomplicated, acetaminophen ingestion ever. I've always chosen a patient tailored approach. When using the 21 hour protocol, you kind of "get away with it," where as with the 72 hour oral, you are clearly using too much.
What do I mean:
It requires an understanding of what is going on physiologically: APAP goes to NAPQI which conducts an electrophilic attack on membranes. Glutathione quenches. As the amount of APAP ingested goes up, the amount of NAPQI produced also goes up, especially as other mechanisms of detoxification are swamped.
Seems simple, but it is unfortunately more complex than that. As time progresses from t=0, the injured liver membranes start an inflammatory cascade. Additionally, the membrane components can also become reactive (similarly to free radical propagation). There is growing evidence that some of the liver injury comes not from from the direct attack of NAPQI, but from products of the attack and the induced inflammation.
So, what does that mean? From a simplistic approach, if 1 mol of APAP forms 1 mol of NAPQI, you need 1 mol of NAC to regenerate 1 mol of glutathione to quench it. On a mg-mg basis, you need about 8% more NAC than APAP for a 1-1 quench. So the Acetadote protocol provides 300 mg/kg of NAC, so it can cover pretty much any ingestion of 275 mg/kg or more is covered. Plus, we know that a liver can realistically take 150 mg/kg (probably closer to 200 mg/kg) without resulting in transplantation. So, the Acetadote protocol, in the most simplistic form, should cover an ingestion up to 425 mg/kg. That very simplistic however.
More realistically however, an early presenting patient (< 8 hours) with normal LFT and otherwise normal protoplasm can probably be treated with the simplistic Acetadote as long as they haven't taken a massive dose. What is massive? I dunno. Maybe less than 300-350 mg/kg. Above those amounts, and, based on half life calculations, you run out of NAC before you run out of APAP. Theoretically you should have normal glutathione stores at this point and can absorb 150mg/kg of APAP without concern. One need only go to the North American Congress of Clinical Toxiciology meeting to see at least one or two posters each year on "Acetadote Failures" (heck, I think I even did one of those as a fellow). Although, usually "treatment failure" is defined as an LFT bump and the patients have an uneventful course after "failing."
There are also other poorly understood mechanisms related to APAP toxicity. Patients who have truly massive ingestions (> 1000 mg/kg) die very early, like on day 1 or 2. They don't die from liver failure but instead develop a severe lactic acidosis and refractory organ failure.
So what do my ramblings mean? Hard to say. For most early, uncomplicated APAP ingestions, you can get away with using the Acetadote protocol: there is probably enough NAC in there to neutralize the generated NAPQI, as most people don't take more than 300 mg/kg, and even if they have an LFT bump, it is unlikely to result in liver failure. If you don't check, you don't find it. The problem is that you can't rely on the protocol if the patient isn't early presenting, uncomplicated or if they took a lot. Outside of those limits and you have to worry about the other issues.
For most ingestions, using either the oral or IV, I check the LFTs and APAP at ~20 hours after treatment was started. If the LFTs are flat and the APAP < 10, I'm done. If there LFTs are rising or the APAP is detectable, I'm going to keep going for another 12-24 hours with either. Using the oral product, even with several doses of Zofran, is way cheaper than the IV.
On NAC vomiting: It is rare that a patient can't drink the NAC. The stuff has minimal taste and it is the smell that really does it. The other thing people forget is that NAC is around 1500 mosm. You put that in to the stomach undiluted and it will be returned to sender based on the osmolarity alone. Dilute that 4:1 in something cold and sweet combined with nose holding, a covered cup, straw and zofran and it almost always goes down.
