Analysis of an 8-hour acetylcysteine infusion protocol for repeated supratherapeutic ingestion (RSTI) of paracetamol

Objectives: In Australia, the treatment guideline for patients with repeated supratherapeutic ingestion (RSTI) of paracetamol recommends an abbreviated acetylcysteine regimen if the paracetamol concentration is low (<10 mg/L) and alanine aminotransferase (ALT) is normal or static after 8 hours of infusion. There are currently no studies of this recommendation. Method: A retrospective review of paracetamol overdose presentations from October 2009 to August 2016 in two hospital toxicology networks was performed. All cases of RSTI treated with acetylcysteine were extracted. Results: Of the 2249 paracetamol overdose presentations, 91 cases of RSTI were treated with acetylcysteine. Median time to initial blood tests was 6 hours post-last paracetamol dose (IQR 4–6). Sixty-three (69%) presentations had an initial detectable paracetamol concentration, median 30 mg/L (IQR 18–60). Median ALT on presentation was 48 IU/L (IQR 18–109). After 8 hours of acetylcysteine infusion, median ALT was 34 IU/L (IQR 16–71) in those receiving abbreviated treatment and 74 IU/L (IQR 40–231) in those continuing acetylcysteine. Thirty-nine presentations (43%) had an abbreviated regimen. Nine (10%) patients had an initial ALT ≥50 IU/L and subsequently developed hepatotoxicity (ALT >1000 IU/L). No patients with an initial ALT <50 IU/L developed hepatotoxicity. Median duration of acetylcysteine infusion for those receiving a non-abbreviated regimen was 20 hours (IQR 20–25) vs. 10.4 hours (IQR 4.8–12.0) who received an abbreviated regimen. There were no re-presentations with hepatotoxicity. Conclusions: An 8-hour acetylcysteine infusion regimen for treatment of paracetamol RSTI may be safe and is likely to reduce length of stay for patients at low risk of hepatotoxicity. Larger prospective studies are needed to examine the efficacy of this abbreviated acetylcysteine protocol.