Letter in response to Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose

To the Editor:

We read with interest the recent paper discussing early treatment with NAC in patients with paracetamol [APAP] poisoning based on reported ingestion dose.¹ We agree that the need to treat patients with single acute ingestions above the Rumack–Matthew nomogram in a timely fashion is critical as delays to NAC significantly affect outcome.² Also, it is worth reinforcing that since adverse events related to IV NAC are inversely related to APAP concentration,³ there is an additional potential benefit to initiate treatment as early as possible.

Duffull and Isbister state that the reported paracetamol ingestion dose is a reliable predictor of patients being above the nomogram's treatment line and that such a metric could be used to empirically initiate antidotal therapy before the APAP concentration is known. The authors conclude that at a reported dose of 50 g, over 90% of patients require NAC treatment and, thus, this value could be used as a “cut-off” to initiate early treatment. We are hesitant to accept these conclusions based on two simple concepts. First, the median reported ingestion was 10 g with an interquartile range of 6–16 g. Thus, with 75% of the data points below the 16 g dose and an unknown distribution between 16 and 100 g, this conclusion is based on very limited data. More importantly, it is fairly universally accepted that NAC should be started if the APAP concentration cannot be determined within 8 h of ingestion.² Additionally, there are reasonable data to suggest that there is no change in outcome when NAC is started incrementally earlier than 8 h after ingestion of APAP. Smilkstein et al., in a study examining NAC efficacy in APAP overdose, demonstrated that there was no statistically significant difference in the incidence of hepatotoxicity between patients treated between 0 and 4 h post-ingestion and those treated 4–8 h post-ingestion.² Therefore with no defined benefit of early initiation of therapy, the added cost of therapy, and potential adverse effects of NAC, we see no benefit to early empiric therapy if the APAP concentration can be determined within 8 h post-ingestion.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.