OT: Aspirin in 1918 Pandemic, Another Possible Killer

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October 13, 2009

In 1918 Pandemic, Another Possible Killer: Aspirin By NICHOLAS BAKALAR

 

http://www.nytimes.com/2009/10/13/health/13aspirin.html?8au & emc=au

 

The 1918

flu<http://health.nytimes.com/health/guides/disease/the-flu/overview.html?inline\

=nyt-classifier>epidemic

was probably the deadliest plague in human history, killing more

than 50 million people worldwide. Now it appears that a small number of the

deaths may have been caused not by the virus, but by a drug used to treat

it: aspirin.

 

Dr. Karen M. Starko, author of one of the earliest papers connecting aspirin

use with Reye’s syndrome, has published an

article<http://www.journals.uchicago.edu/doi/abs/10.1086/606060>suggesting

that overdoses of the relatively new “wonder drug” could have

been deadly.

 

What raised Dr. Starko’s suspicions is that high doses of aspirin, amounts

considered unsafe today, were commonly used to treat the illness, and the

symptoms of aspirin

overdose<http://health.nytimes.com/health/guides/poison/aspirin-overdose/overvie\

w.html?inline=nyt-classifier>may

have been difficult to distinguish from those of the

flu<http://health.nytimes.com/health/guides/disease/the-flu/overview.html?inline\

=nyt-classifier>,

especially among those who died soon after they became ill.

 

Some doubts were raised even at the time. At least one contemporary

pathologist working for the Public Health Service thought that the amount of

lung damage seen during autopsies in early deaths was too little to

attribute to viral

pneumonia<http://health.nytimes.com/health/guides/disease/viral-pneumonia/overvi\

ew.html?inline=nyt-classifier>,

and that the large amounts of bloody, watery liquid in the lungs must have

had some other cause.

 

Dr. Starko acknowledged that she did not have autopsy reports or other

documents that could prove that aspirin was the problem. “There was a lot of

chaos in these places,” she said, “and I’m not sure if there are good

records anywhere.”

 

But of the many factors that might have influenced the outcome in any

particular case, Dr. Starko wrote, aspirin overdose stands out for several

reasons, including a confluence of historical events.

 

In February 1917, Bayer lost its American patent on aspirin, opening a

lucrative drug market to many manufacturers. Bayer fought back with copious

advertising, celebrating the brand’s purity just as the epidemic was

reaching its peak.

 

Aspirin packages were produced containing no warnings about toxicity and few

instructions about use. In the fall of 1918, facing a widespread deadly

disease with no known cure, the surgeon general and the United States

Navy<http://topics.nytimes.com/top/reference/timestopics/organizations/n/us_navy\

/index.html?inline=nyt-org>recommended

aspirin as a symptomatic treatment, and the military bought

large quantities of the drug.

 

The Journal of the American Medical Association suggested a dose of 1,000

milligrams every three hours, the equivalent of almost 25 standard

325-milligram aspirin tablets in 24 hours. This is about twice the daily

dosage generally considered safe today.

 

Dr. Starko’s paper, published in the Nov. 1 issue of Clinical Infectious

Diseases, has stirred some interest, if not enthusiastic endorsement, among

other experts.

 

“I think the paper is creative and asking good questions,” said John M.

Barry, author of a book on the 1918 flu titled “The Great Influenza.” “But

we don’t know how many people actually took the doses of aspirin discussed

in the article.”

 

The pharmacology of aspirin is complex and was not fully understood until

the 1960s, but dosage is crucial. Doubling the dose given at six-hour

intervals can cause a 400 percent increase in the amount of the medicine

that remains in the body. Even quite low daily doses — six to nine standard

aspirin pills a day for several days — can lead to dangerously high blood

levels of the drug in some people.

 

Peter A. Chyka, a professor of pharmacy at the University of

Tennessee<http://topics.nytimes.com/top/reference/timestopics/organizations/u/un\

iversity_of_tennessee/index.html?inline=nyt-org>,

said he found Dr. Starko’s theory “intriguing.” Little was known about safe

dosages at the time, he said, and doctors often simply raised the amount

until they saw signs of toxicity.

 

“In the context of what we know today about aspirin and aspirinlike

products, Starko has made an interesting effort to put this together,” Dr.

Chyka said. “There are things other than flu that can complicate a disease

like this.”

 

Although he doubted that more than a small number of deaths could be

attributed to aspirin overdose, Dr. David M. Morens, an epidemiologist with

the National Institutes of

Health<http://topics.nytimes.com/top/reference/timestopics/organizations/n/natio\

nal_institutes_of_health/index.html?inline=nyt-org>,

said the paper was valuable in that “it makes an attempt to look at

environmental or host factors that may be involved.” He said, “We haven’t

been able to explain all the deaths in young adults with the virus itself.”

 

Dr. Starko was hesitant to estimate how many deaths aspirin overdose could

have caused, but suggested that military archives might be one place to

look. “I’m hoping others will follow up,” she said, “by examining available

treatment records.”

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New York Times Company <http://www.nytco.com/>