To the Editor:
In the letter, the particular Danish practice of treating all patients without any risk stratification is questioned. In most countries, the decision to treat with N-acetylcysteine (NAC) is based on modifications of the plasma concentration versus time since overdose nomogram originally suggested by Prescott and Rumack.Citation1 However, use of the nomogram is not without problems.
Firstly, the information from the patient regarding the time of the overdose needs to be accurate in order to estimate the risk correctly. Secondly, the choice of treatment line (‘standard’ or ‘high-risk’) is based on knowledge of individual risk factors that are believed to enhance the patient's risk of liver damage. These risk factors typically include regular alcohol abuse, ingestion of enzyme-inducing drugs, malnutrition, and HIV infection. Whereas the basis for some of these risk factors is rather theoretic, other potentially important factors (e.g. age) have not been included, and extreme genetic variation is not considered.Citation2 Thirdly, the nomogram may be misinterpreted causing NAC to be withheld in patients meeting the treatment requirements. In one study, this was the case in as many as 142 out of 560 patients (25%).Citation3 Another study described 11 fatal cases in which NAC was incorrectly withheld.Citation4 Fourthly, even with correct use of the nomogram, liver injury regularly develops in ‘low risk’ patients.Citation1 One study has even described four deaths (one following liver transplantation) in ‘low risk’ patients, all of which would have been completely preventable if a relevant and timely course of NAC had been administered.Citation5
Based on the above considerations, I conclude that use of the nomogram is associated with otherwise preventable fatality, either because the nomogram is imperfect or because it is misapplied. In Denmark, the use of the nomogram has been considered obsolete since 1996, and the official recommendation is to treat all patients regardless of risk estimation. Even though this point has recently been debated in Denmark, it was still decided that treating all patients was the only way to absolutely ensure that no one develops acute liver failure from paracetamol overdose due to withheld or unnecessarily delayed NAC treatment. In further favour of the Danish recommendation, NAC treatment is simpler and safer, and the costs involved are less when compared to the costs of treating patients with acute liver failure or the cost of liver transplantation.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
- Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. Clin Toxicol2002; 40:3–20.
- Schmidt LE. Age and paracetamol self-poisoning. Gut2005; 54: 686–690.
- Makin AJ, Wendon J, Williams R. A 7-year experience of severe acetaminophen-induced hepatotoxicity. Gastroenterology1995; 109:1907–1916.
- Read RB, Tredger JM, Williams R. Analysis of factors responsible for continuing mortality after paracetamol overdose. Hum Toxicol1986; 5:210–206.
- Bridger S, Henderson K, Glucksman E, Ellis AJ, Henry JA, Williams R. Deaths from low dose paracetamol poisoning. BMJ1998; 316:1724–1725.