Efficacy of a two bag N-acetylcysteine(NAC) regimen to treat paracetamol overdose (2NAC study).

Paracetamol overdose is the most common pharmaceutical poisoning in developed countries and its incidence is increasing in the developing world. Overdose can lead to liver failure, and in the worst circumstances, death. In overdose, the increased production of N-acetyl para-benzoquinoneimine (NAPQI) depletes hepatic glutathione stores and eventually causes hepatocyte injury. Acetylcysteine is administered as the antidote to prevent hepatotoxicity in overdose. The typical three-bag infusion-dosing regimen in Australia is 150 mg/kg over 1 hour, 50 mg/kg over 4 hours and 100 mg/kg over 16 hours. Despite the safety of this regimen, there remains a significant amount of adverse reactions to acetylcysteine and delays between infusions. To this effect, a recent study of over 200 patients who received a two-bag acetylcysteine regimen was recently undertaken. A 200mg/kg loading dose of NAC was infused over four hours with a further 100 mg/kg infused over 16-hours. The incidence and severity of adverse reactions was significantly reduced, compared to the three-bag regimen, from 10% to 4.3%. A similar two-bag regimen has been adopted by various hospitals around Australia. The efficacy of this new two-bag regimen has not been determined. We aim to compare the rate of acute liver injury using a two-bag acetylcysteine regimen and compare this to the three-bag regimen in the setting of paracetamol overdose.