LAUSR

From its first use in paracetamol (Acetaminophen, APAP) overdose, oral acetylcysteine (NAC) was controversial [1,2]. Intravenous (IV) NAC was initially no less provocative [3,4]. Yet, over a few short years both the 72-h oral, and the 20-h IV protocols rapidly became standard practices. Three facts likely hampered altering these regimens: (1) The case-fatality rate in untreated patients was very low. (2) The casefatality rate in NAC-treated patients was even lower, suggesting efficacy. (3) Although some patients developed hepatotoxicity despite NAC, recovery was generally complete and uneventful. Additionally, legitimate concerns that delayed or prolonged methionine exacerbated hepatotoxicity prevented extending the IV protocol for over a decade [5]. Even when prolonged NAC was accepted for patients with fulminant hepatic failure, the initial protocols remained static. NAC therapy, however, is not benign. The foul-smelling oral protocol commonly produced nausea and emesis, and the IV therapy caused more concerning anaphylactoid reactions. Combined with the complexity of the 3-bag IV protocol these adverse effects led to countless interruptions and premature terminations of care. Small changes occurred over time such as extending the 20-h protocol to 21 h in an attempt to the limit anaphylactoid events. Also, although discussions regarding tailoring NAC regimens to various patient scenarios arose, they rarely gained traction. The nature of APAP overdose also evolved as preparations that combined APAP with anticholinergics or opioids as well as modified release products were introduced. This added complexity as delayed peak concentrations, multiple peak concentrations, patients who crossed from below treatment thresholds to above, and prolonged elimination phases were all recognized. Treatment decisions were further complicated by the introduction of multiple variations of Rumack Matthew nomogram [6] notwithstanding the fact that it was nearly flawless in thousands of cases.