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 4-hour nomogram-adjusted level (APAPpl /APAPt ). We conducted a retrospective observational study of all patients (n= 1159) presenting to 2 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= .0329). Although there was a trend towards a lower risk of predefined 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: alanine transaminase >2× upper limit of normal, 7.7 vs. 5.7% (P= .6480); alanine transaminase >1000 IU/L, 2.4 vs. 0% (P= .2145); international normalised ratio >1.3, 8.6 vs. 4.4% (P= .2774); and transfer to tertiary liver unit, 0.2 vs. 0% (P nonsignificant). Our study does not support a change in current clinical practise beyond standard testing at 4 hours or longer post ingestion for mixed low dose paracetamol-opioid overdose.