Amlodipine Toxicity in Children Less Than 6 Years of Age: A Dose-Response Analysis Using National Poison Data System Data. Benson BE et al. J Emerg Med August 2010;39:186-193.

Abstract

The authors analyzed 1251 cases entered into the computerized database of the National Poison Data Collection System as single-agent amlodipine ingestions in children < 6 years of age. The goal was to determine a dose-response relationship for the drug in this population.  On the basis of their data, they conclude (surprise!) that as the dose of amlodipine increases, so do effects.  In addition, they imply that children in this age group who reportedly ingest less than 2.5 mg of amlodipine can be managed at home.Unfortunately, this paper has fatal — even gruesome — methodological flaws. In fact, no such conclusions can reasonably be drawn from retrospective analysis of this database.  Interestingly, in this age of the 24-hour news cycle and instant response, an excellent “Letter to the Editor” by Lugassy et al critiquing the study has already appeared on JEM‘s website. The authors of this letter make the following points:

• These 1251 cases really represent amlodipine exposures, since no testing was done to confirm actual ingestion. As the letter states: “Exposures do not equal ingestions.”
• The doses recorded in the database are just estimates, based on unconfirmed reports at least three times removed.  Again, to quote the letter: “As such, it is a critical error for the authors to suggest that a dose-response relationship could be created from these data.”
• By using the adult definition for hypotension (systolic < 90 mm Hg) the paper may have misclassified some children as having a “clinically important response”.

I agree with the authors of the letter that ” . . .until more reliable data are available, all patients under the age of 6 years who might have ingested amlodipine should be evaluated in the emergency department regardless of the reported dose.”

By the way, several years ago one of the authors of this “Letter to the Editor”, Robert S. Hoffman, published a superb editorial discussing the limitations of using poison center data in retrospective studies.  We will have more on that editorial at a later date.

Clinical characteristics of mephedrone toxicity reported to the UK National Poisons Information Service. James D et al. Emerg Med J [Published online August 25, 2010 in advance of print]

Full Text

Mephedrone (4-methylmethcathinone, 4-MMC) is a synthetic stimulant with structural similarities to both methamphetamine and the alkaloid cathinone. Although mephedrone seems to act as a stimulant, there have been almost no scientific studies into its physiologic and toxicologic effects.  To my knowledge, there has been only one report of confirmed mephedrone exposure.

This paper, from the National Poisons Information Service in the U.K., purports to collate and describe clinical features seen in 131 cases of exposure to mephedrone (alone or combined with alcohol) on which the service was consulted.  This would seem to be very valuable data indeed.  Unfortunately, the entire paper is nullified by the same problem that plagues many studies based on poison center data — we have no idea what these 131 people were actually exposed to.  The authors try to fast-step their way around this problem, stating:

The data analysed relies on user and healthcare professionals knowing and providing accurate information on the agents involved since toxicological confirmation is not generally available.

There is, of course, no way such accurate information could be known or provided, and it is rather disingenuous to publish a paper relying on the medical equivalent of hearsay.

Saxitoxin is a heat-stable neurotoxin that blocks sodium channels and impairs conduction in excitable nerve, muscle, and myocardial cells.  Mollusks filter and concentrate dinoflagellates — primarily Alexandrium catanella — that actually produce the toxin.  These small organisms proliferate during red tide blooms. Non-traditional (that is, non-filter-feeding) vectors of saxitoxin have been identified, including crustaceans and some fish.

The clinical condition caused by saxitoxin is paralytic shellfish poisoning (PSP). Within an hour of ingesting affected mollusks, patients develop facial paresthesias and bulbar palsy, with dysarthria and dysphagia.  Muscle weakness spreads to the extremities and eventually results in respiratory paralysis.  Cognition remains clear.  Since saxitoxin generally does not cause initial gastrointestinal symptoms, there is no self-decontamination.  There is no antidote for saxitoxin; the mainstay of treatment is support care with mechanical ventilation if needed.

A just-published comprehensive review of PSP is well worth reading for anyone with an interest in the topic.