Taking stock: UK national antidote availability increasing, but further improvements are required.

BACKGROUND: A 2010/2011 audit of the Royal College of Emergency Medicine (RCEM) National Poisons Information Service (NPIS) UK guidelines on antidote availability demonstrated variable stocking of antidotes for the management of poisoned patients; the guidelines were updated and republished in 2013. AIM: To assess if antidote stocking has improved since the 2010/2011 audit and introduction of the 2013 guidelines. METHODS: Questionnaires were sent to Chief Pharmacists at all 215 acute hospitals in England, Wales and Northern Ireland in October 2014. Data were collected on the timing of availability (category A antidotes should be available immediately, category B within 1 h and category C can be held supraregionally) and stock levels. RESULTS: 169 (78.6%) responses were received. Atropine, calcium gluconate and flumazenil (category A) were the only antidotes available in all hospitals within the recommended time and stock levels. Forty-one (24.3%) hospitals held every category A antidote; this increased to 81 (47.9%) for those holding at least one cyanide antidote and all other category A antidotes. The proportion of hospitals stocking category A/B antidotes within the recommended time increased for 20 (90.9%) category A/B antidotes. Fomepizole (category B) availability increased to 62.1% of hospitals from 11.4% in 2010/2011. Other than penicillamine (63.3% hospitals), there was poor availability (2.4%-36.1%) of category C antidotes. CONCLUSIONS: Availability of category A and B antidotes has improved since the 2010/2011 audit and 2013 guidelines. However, there remains significant variability particularly for category C antidotes. More work is required to ensure that those treating poisoned patients have timely access to antidotes focusing particularly on category C antidotes.

Position paper update: ipecac syrup for gastrointestinal decontamination.

CONTEXT: An update of the first position paper on ipecac syrup from 1997 was published by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data. METHODS: A systematic review of the literature from the year 2003 forward. RESULTS: The literature search yielded a limited number of meaningful articles, and there remains no convincing evidence from clinical studies that ipecac improves the outcome of poisoned patients. Furthermore, the availability of ipecac is rapidly diminishing. CONCLUSIONS: The routine administration of ipecac at the site of ingestion or in the emergency department should definitely be avoided. Ipecac may delay the administration or reduce the effectiveness of activated charcoal, oral antidotes, and whole bowel irrigation. There is not sufficient evidence to warrant any change in the previous ipecac position papers. There are, however, insufficient data to support or exclude ipecac administration soon after ingestion of some specific poisons in rare situations.

Position paper update: gastric lavage for gastrointestinal decontamination.

CONTEXT: The first update of the 1997 gastric lavage position paper was published by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists in 2004. This second update summarizes the 2004 content and reviews new data. METHODS: A systematic review of the literature from January 2003 to March 2011 yielded few studies directly addressing the utility of gastric lavage in the treatment of poisoned patients. RESULTS: Sixty-nine new papers were reviewed. Recent publications continue to show that gastric lavage may be associated with serious complications. A few clinical studies have recently been published showing beneficial outcomes, however, all have significant methodological flaws. CONCLUSIONS: At present there is no evidence showing that gastric lavage should be used routinely in the management of poisonings. Further, the evidence supporting gastric lavage as a beneficial treatment in special situations is weak, as is the evidence to exclude benefit in all cases. Gastric lavage should not be performed routinely, if at all, for the treatment of poisoned patients. In the rare instances in which gastric lavage is indicated, it should only be performed by individuals with proper training and expertise.

Thioridazine: the good and the bad.

Thioridazine is a phenothiazine drug which has previously been extensively used for its antipsychotic properties as it is associated with a low risk of extra-pyramidal side-effects. There is good evidence to suggest that, in common with other phenothiazine drugs, thioridazine has important anti-microbial activity and is a potential candidate for development as an anti-microbial drug against multi-resistant organisms, including drug-resistant strains of M. tuberculosis. The clinical pharmacology and toxicity profile of thioridazine are reviewed in this article and the implications for future drug development along with the patent are discussed.

The association between drug related deaths and prior contact with hospital-based services.

UNLABELLED: Reducing drug related deaths has been identified as a health priority by the Scottish Executive. AIMS: This study investigates the association between drug related deaths in the Lothian region and prior contact with hospital-based services in the Edinburgh Royal Infirmary. DESIGN/SETTING: Retrospective analysis of 90 drug related deaths in Lothian from 2003-2005. Hospital episodes within five years of death were identified by searching the electronic patient record system within the Edinburgh Royal Infirmary. FINDINGS: Seventy-five of the 90 drug related deaths occurred in the hospital catchment area. Forty five of these 75 deaths (60%) occurred in patients who had used hospital-based services in the previous five years. The median time from hospital contact to deaths was five months and median number of hospital attendances/admissions was three (range 1 - 26). CONCLUSION: Liaison between emergency departments, clinical toxicology services and community based drug addiction services is important to identify drug misusers at high risk. A hospital-based specialist nurse-led liaison service may be able to fulfil this role.

Factors affecting drug concentrations and QT interval during thioridazine therapy.

The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with >/=1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.

Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.

We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3+/-4.1 ms, P=0.023) and mesoridazine (46.6+/-7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9+/-8.1 ms). The area under the effect-time curve over 8 h following drug administration was similar between the two drugs (129.3+/-22.1 vs 148.3+/-43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval.