Thursday 22 October 2015

Aspirin

Aspirin is just about the only medication I take.  I used to pop vitamin C as we approached Winter but the evidence for its efficacy is so marginal that I decided this time last year that I wouldn't put myself in thrall to 50mg of grass-skirt and maracas.  I was going up to Dublin after work a couple of weeks ago and felt the beginning of a whiff of a headache, so I chewed up one aspirin and before I got to the motorway, the headache was gone.  Call it placebo, but for me it almost always works thus.  But then I only take about one aspirin a year so it's not a  reliably large dataset. I don't do paracetamol [aka acetaminophen phenacetin]: it just wasn't part of our very limited pharmacopoeia when I was growing up.  I've also absorbed the information that death by paracetamol is a particularly grim way to kill yourself because it destroys the liver without, usually, drifting you off to quietus.  By the time symptoms start, and they are horrible, or you have second thoughts, it is too late to administer the antidote.

Aspirin, au contraire, has a chance of precipitating Reye's Syndrome - especially in children.  But that definitely hadn't surfaced as a possibility when I was young.  Reye's is a peculiar disease that triggers liver malfunction and occasionally this upsets some homeostatic balance so that fluid builds up on the brain: even if your kid is not one of the 20% who dies, a trip to intensive care is often indicated and there is a strong likelihood of long-term damage. That is one side of the risk assessment.  The other side is that Reye's is extremely rare: about 6 cases for every million children and that made it difficult to make the association between aspirin and the clatter of characteristic symptoms of encephalopathy which were described by Australian physician Douglas Reye and his colleagues in 1963. The association with aspirin, especially when used to counter the temperatures induced by influenza and other viruses was noted by Dr Karen Starko and others after a case/control study in 1980.  It took 6 years and several other studies to convince the FDA to change the warning labels on aspirin. Sales of aspirin took a hammering after the news got out and those of paracetamol got a complementary boost.  It's a good example of the precautionary principle: better not to use aspirin with children because the adverse consequences, though rare, are really adverse. The incidence of Reye's has collapsed over the last 30 years and is now bumbling along at about 1 case per million.  There are far more likely causes of childhood mortality to worry about - like taking your child to swimming, cello, hip-hop or drama classes in a car.

I thought that was all we had to know about aspirin but last week I came across a 2009 article by Karen Starko [again] in which she claims that aspirin has probable cause for being implicated in the disproportionate death rate among fit young adults during the 1918 influenza pandemic.  This has always been a bit of a mystery: it's usually the very old or very young and/or poorly fed who peg out when there are epidemics. In my own mind, I've explained it (superficially) as getting killed by an over-active inflammatory response to the viral insult. What kills you in cholera is that the toxins produced by Vibrio cholerae trigger an immune response that calls for a dramatic flush-through in the intestine: you die by dehydration.  If you can keep clean fluids up for a couple of days then the bugs calm down and/or go elsewhere and you survive. Dr Starko observes that one of the symptoms of aspirin poisoning is pulmonary oedema: you can't breathe efficiently if your lungs are full of fluid.  Back in 1918, doctors were recommending quite large doses of aspirin to reduce the influenza-driven pain and fever and may, unwittingly, have killed even more of their patients than normal. Could be; hard to test; and we're unlikely to repeat the mistake after all the Reye's brouhaha.

One other bit of murk in the history of aspirin is a controversy about who did what in the laboratories of the German chemical giant Bayer. The standard story is that aspirin was first synthesised by a Bayer chemist called Felix Hoffmann.  This is what Hoffman put about, even citing a specific date - 10 August 1897 - when the protocol was finally sorted out. This was disputed by his line-boss Arthur Eichengrün who maintained that Hoffman was just a pair of hands doing Eichengrün's bidding. Shades of Lemaitre and Hoffmann here: everyone wants to be associated with a success strory. The fact that the older man was trying to defend his reputation writing from the Theresienstadt concentration camp adds a bit of needle to the haystack of claims. Eichengrün was banged up in the camp because he had failed to make it sufficiently clear that he and his company were 'Jewish'. Even without the stuff about aspirin, his reputation would be held up high by his development of protargol in 1897; it was for two generations the drug of choice against gonorrhoea.

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