LAUSR

Dear Editor, We have with interest read the recently published commentary by Isbister and Chiew in which current approaches for the treatment of paracetamol poisoning with N-acetylcysteine (NAC) were described. While we appreciate the authors' valuable comments on the challenges in managing this common poisoning, we noticed the omission of the Danish NAC regimen. NAC has been established as a highly efficient antidote in preventing paracetamol-induced hepatotoxicity when administered within 8 h of paracetamol ingestion. Treatment delays because of pending laboratory results do not harmfully affect the outcome if NAC is administered within 8 h. However, it is frequent occurring that patients get treated beyond that time in, for example, the United Kingdom, thus potentially decreasing the efficacy of NAC. In Denmark, a 20-h two-bag regime has been used for more than 7 years. All patients suspected of poisoning with more than 6 g of paracetamol are treated with NAC without risk stratification according to a nomogram. Patients deliberately poisoning themselves with paracetamol may not report reliable information of the time of ingestion and dose of paracetamol. If a nomogram is used without an accurate time of ingestion, the estimation of the risk of hepatotoxicity is unreliable. It is well documented that patients have been withheld treatment with NAC due to misinterpretation of the nomogram resulting in hepatotoxicity. Concomitant overdosing of several drugs that delay the time to peak paracetamol concentration is common and may result in crossing from below to above the treatment line leaving line crossers who required treatment untreated. The same is relevant in cases of massive paracetamol overdosing alone (drug bezoar) or poisonings with extended-release paracetamol formulations (late paracetamol peak). Furthermore, it is well-known that the half-life of paracetamol in liver injury exceeds the expected 4 h used for treatment decision in the nomogram, thus further questioning the reliability of the nomogram as a risk stratification tool for patients suffering from liver diseases. Although the Danish regime further reduces the risk of hepatoxicity, because of incorrectly withheld or delayed NAC treatment compared with other regimes based on a nomogram, it comes at a cost of more patients being treated. We believe that all approaches deserve mention in order to identify the most effective and safe approach to this poisoning. Therefore, we should consider the effectiveness, duration, and safety of choice of treatment including the incidence of anaphylactoid reactions to NAC while assuring that nobody is wrongly withhold NAC treatment. Not to mention that the abovementioned approach is associated with a comparable incidence of anaphylactoid reactions when compared with other approaches. It is worth mentioning that the primary factor limiting a faster delivery of the antidote is the development of anaphylactoid reactions. It is to be shown if pre-administrations of antihistamines can reduce the dose-dependent side-effect leading to development of faster NAC regimes.