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

Aims: 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). Methods: 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. Results: Median ingested dose of paracetamol was low in both groups (10 g). 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]