RE: Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity


Dr Christian G. Reiter MD, bene pharmaChem GmbH & Co. KG, R & D, Bayerwaldstrasse 7–9, Geretsried, D-82538, Germany. E-mail:

This article has had a strong following in the German pharmaceutical, medical and life style media, which aroused my interest in this publication.

Unfortunately, the authors failed to mention their previous evaluation of the same data set published in Br J Clin Pharmacol in the spring of 2011 [1]. In this paper the investigated categories were intentional overdose, unintentional overdose and intention unknown. These criteria are very similar to those in the recent publication, namely single time point, staggered overdose pattern and not attributable.

When comparing the numbers given in the abstract it becomes obvious that unintentional together with intention unknown correspond to the category staggered overdose pattern and that intentional corresponds to single time point together with not attributable (Table 1).

Table 1. Comparison of numbers mentioned in the abstract of the actual and a recent article investigated categories overlap almost completely
Overdose pattern and outcome . . .  Staggered overdose pattern . . . 
Br J Clin Pharmacol 2011; 71: 273–282 Br J Clin Pharmacol. 2011; Nov 22. [Epub ahead of print]
Comparing Comparing
Intentional–Unintentional Single time point–Staggered
  • *

    Assuming same mortality for Intention unknown as for Unintentional overdose. Numbers in bold: taken from the abstracts. Numbers in plain text: calculated from other information.

Total patient number 663 663 Total patient number
Intentional 500 450 Single time point
52Not attributable
Intention unknown 53 161 Staggered
Unintentional 110
Intention unknown mortalilty20,24*60Staggered mortality
Unintentional mortality 42
Unintentional mortality38.2% 37.3% Staggered mortality
Intentional mortality25.6% 27.8% Single time point mortality
Intentional mortality 128 125Single time point mortality
Unintentional sensitivity of prognostic criteria 77.8% 77.6% Staggered sensitivity of prognostic criteria

Also, when comparing the percentage numbers given in Table 1 of both papers which show admission clinical and laboratory data it is clear that there is an almost complete overlap of the categories used and the recent paper is nearly a duplication of the former with few additional data.

Nevertheless the recent article has had a much stronger following in the German pharmaceutical, medical and even life style media than the previous with some peculiarities [2–6].

I find it a problem that the term ‘staggered overdose’ is commonly referred to as ‘slightly elevated dosing’, (in German: ‘geringfügig erhöhte Dosis’).

This is made worse by omitting information regarding the highly selective nature of the patient group (admitted to SLTU because of severe liver injury) and also the omission of information as to the low incidence in the total population. For the Scottish population the annual incidence of acute liver failure due to paracetamol overdose is 0.43 cases per 100 000 per year , irrespective ofparacetamol dosing regimen in the years 1992 to 2009 [7].

Journalists readily latch onto the phrase ‘despite lower total ingested paracetamol dose’ in the abstract and ignore the context: low compared with single time overdose.

This is further compounded, albeit inadvertently, through the loose definitions of ‘potentially toxic amount’ and ‘staggered overdose’ together with the unclear definition of a ‘supratherapeutic’ dose. These definitions would include ‘slightly elevated dosing’ but since most patients have taken excessively high doses there are no data that really support the fact that a considerable number of patients have had only slightly elevated dosing.

The authors should be aware that they could be interviewed and cited due to the misleading nature of their articles which could possibly compromise their reputations as scientists [8].

Competing Interests

The author has obtained consulting fees from a paracetamol selling company.