The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases.

OBJECTIVE: The use of the standard procedure for managing overdoses with immediate release (IR) paracetamol is questionable when applied to overdoses with modified release (MR) formulations. This study describes the pharmacokinetics of paracetamol and the clinical outcomes following overdoses with a MR formulation. METHODS: Medical records including laboratory analyses concerning overdoses of MR paracetamol from 2009 to 2015 were collected retrospectively. Inclusion criteria were ingestion of a toxic dose, known time of intake and documented measurements of serum paracetamol and liver function tests. Graphical analysis, descriptive statistics and population pharmacokinetic modelling were used to describe data. RESULTS: Fifty-three cases were identified. Median age was 26 years (range 13-68), median dose was 20 g (range 10-166) and 74% were females. The pharmacokinetic analysis showed a complex, dose dependent serum versus time profile with prolonged absorption and delayed serum peak concentrations with increasing dose. Ten patients had persistently high serum levels for 24 h or more, six of them had a second peak 8-19 h after ingestion. Seven of 34 patients receiving N-acetylcysteine (NAC) within 8 h had alanine aminotransferase (ALT) above reference range. Three of them developed hepatotoxicity (ALT >1000 IU/l). DISCUSSION AND CONCLUSIONS: The pharmacokinetic and clinical analysis showed that the standard treatment protocol, including risk assessment and NAC regimen, used for IR paracetamol poisoning not appear suitable for MR formulation. Individual and tailored treatment may be valuable but further studies are warranted to determine optimal regimen of overdoses with MR formulation.

[Overdose of modified-release paracetamol calls for changed treatment routines. New guidelines from the Swedish Poisons Information Centre]. / Överdosering av paracetamol med modifierad frisättning ökar - Etablerad behandlingsregim med N-acetylcystein otillräcklig ­ Giftinformationscentralen ger ut nya behandlingsråd.

Overdose of modified-release paracetamol calls for changed treatment routines. New guidelines from the Swedish Poisons Information Centre  The sales of modified-release paracetamol tablets are steadily increasing in Sweden as are the number of overdose cases with this formulation. The Swedish Poisons Information Centre has noted that the standard treatment protocol with N-acetylcysteine (NAC), which is based on overdoses with immediate-release paracetamol formulations, is often inadequate in this setting. In this paper, an adult who overdosed on 66.5 grams of modified-release paracetamol tablets and developed severe liver impairment (max ALT 6,660 U/l) despite timely and rigorous NAC treatment is presented. The patient's peak S-paracetamol of 2,800 µmol/l was delayed to 19 hours post-ingestion. Moreover, a pharmacokinetic and clinical study of similar cases showed that seven (21%) of the 34 patients who received NAC treatment within 8 hours after ingestion developed liver impairment. Finally, new Swedish guidelines for management of these cases are presented. The guidelines are also available on www.giftinfo.se.

A nationwide study of Vipera berus bites during one year-epidemiology and morbidity of 231 cases.

OBJECTIVES: To describe clinical course, influence of treatment, and epidemiology of Vipera berus envenomation in a defined population, and to compare the results with those of a similar, nationwide study in 1975. Design. Retrospective case review study. SETTING AND SUBJECTS: Case records regarding all patients treated in Swedish hospitals during 1995 for bites by the common European adder, V. berus, were studied. A severity grading was applied. Possible dropout was fewer than 10 patients. RESULTS: A total of 231 inpatients were treated for V. berus bites in Sweden in 1995. Children less than 10 years old were overrepresented and there was a slight predominance for males. Maximum severity of envenomation was none in 11%, minor in 47%, moderate in 29%, and severe in 13% of the cases. A few patients with initially minor or moderate symptoms eventually met the criteria of severe envenomation. Less commonly reported features were pulmonary edema, generalized plasma leakage, seizures, deep venous thrombosis, compartment syndrome, numbness and paraesthesia, and myocardial infarction. Treatment included antivenom in 42 patients [ovine Fab in 30 and equine F(ab')2 in 12 cases]. Systemic symptoms resolved during or shortly after the antivenom infusion. Extensive edema involving the trunk occurred in 5% of the cases in 1995, whereas 14% of the patients had extensive swelling in 1975. CONCLUSIONS: Incidence and other epidemiological data were similar to those 20 years ago, whereas the clinical course was more benign. It seems reasonable to believe that this is due to the introduction of effective antivenoms.