Double NAC trial: Investigation of increased N-acetylcysteine dosing in patients treated for paracetamol overdose.

INTERVENTION: N‐acetylcysteine (NAC) given intravenously 200mg/kg over 4 hours, followed by 200mg/kg over 16 hours CONDITION: Injuries and Accidents ‐ Poisoning paracetamol overdose; ; paracetamol overdose PRIMARY OUTCOME: The primary outcomes will be the rate of “hepatic injuryâ€? (defined to be alanine transaminase (ALT) doubling and peak ALT >100IU/L measured at 20 hrs after the commencement of NAC infusion) and need for further antidote. ALT is assessed by serum assay. This is a composite primary outcome[0 and 20 hours post initiation of NAC] SECONDARY OUTCOME: Adverse reactions to N‐acetylcysteine. These may include angioedema, rash, hypotension, vomiting, nausea, wheeze. Determined by clinical examination[Up to 20 hours post initiation of N‐acetylcysteine.] Development of fulminant hepatic failure. Determined by bedside/clinical assessment.[During hospital admission (up to 2 weeks)] Mortality. Determined by Bedside assessment.[During hospital admission (anytime up to 4 weeks post admission)] Peak INR>2. Measured by blood test.[During hospital admission (up to 2 weeks)] These will include development of hepatotoxicity (defined as ALT >1000 IU/L). ALT measured by serum assay.[0,20 hours post initiation and every 12 hrs till ALT peaked and downtrending] INCLUSION CRITERIA: Patients requiring NAC following single acute or staggered overdose with abnormal liver function tests on presentation (ALT>40 U/L), or paracetamol concentration more than double the nomogram treatment line, modified‐release paracetamol paracetamol ingestions.