Paracetamol toxicity in mild overdose in combination with opioids: a retrospective observational study.

Abstract

Toxicity in paracetamol overdose with opioid co-ingestion is poorly understood. We compared outcomes in both paracetamol-only and paracetamol-opioid overdoses to determine whether toxicity differed significantly between the groups, and to assess the utility of the ratio of measured plasma paracetamol concentration relative to the 4h nomogram-adjusted level (APAPpl /APAPt ). We conducted a retrospective observational study of all patients (N = 1159) presenting to two large UK hospitals between 2005 and 2013 with acute single-dose ingestion paracetamol overdose, with (N = 221) or without (N = 938) opioid co-ingestion. Adverse outcomes included biomarkers of hepatotoxicity and the need for extended treatment. Several outcomes were assessed in relation to the APAPpl /APAPt ratio. Median ingested dose of paracetamol was low in both groups (10g). Statistical comparison of the median APAPpl /APAPt ratios showed a significant difference (0.65 vs 0.56 for the paracetamol-only and paracetamol-opioid groups respectively, p = 0.0329). Although there was a trend towards a lower risk of pre-defined toxic outcomes with opioid co-ingestion, statistical analysis did not show a significant difference, with outcomes for the paracetamol-only and paracetamol-opioid groups including the following: ALT > 2x ULN, 7.7% vs 5.7% (p = 0.6480); ALT > 1000 IU/L, 2.4% vs 0 (p = 0.2145); INR > 1.3, 8.6% vs 4.4% (p = 0.2774); and transfer to tertiary liver unit, 0.2% vs 0 (p NS). Our study does not support a change in current clinical practise beyond standard testing at four hours or longer post ingestion for mixed low dose paracetamol-opioid overdose.