In 1918 Pandemic, Another Possible Killer: Aspirin
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 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.
In May 1918, usual but highly contagious influenza was publicized in Spain (hence, “Spanish influenza”). In June, after 6 weeks of usual influenza in Europe, serious pulmonary lesions and deaths increased in those “admitted to the special inf luenza centres,” especially those with an “old-standing renal lesion”. In July, increased mortality of young Londoners was documented.
In summary, just before the 1918 death spike, aspirin was recommended in regimens now known to be potentially toxic and to cause pulmonary edema and may therefore have contributed to overall pandemic mortality and several of its mysteries. Young adult mortality may be explained by willingness to use the new, recommended therapy and the presence of youth in regimented treatment settings (military).
Aspirin usually is not recommended during pregnancy unless you have certain medical conditions.
Conclusion: Using aspirin during pregnancy is associated with increased postpartum bleeding and postpartum hematoma. It may also be associated with neonatal intracranial hemorrhage. When offering aspirin during pregnancy, these risks need to be weighed against the potential benefits.
The Effects of the 1918–1919 Influenza Pandemic on Infant and Child Health in Derbyshire
The well-established increased risk to pregnant women is likely to have been heightened during 1918–19 due to the unusual age structure of influenza in this particular epidemic, and there is evidence that influenza infection may also have precipitated foetal loss. In England and Wales the death rate from spontaneous abortion in 1917 was 0.16 per thousand (one in 6,302 pregnancies), whereas during the epidemic the death rate from only those miscarriages linked to influenza was ten times greater at 1.60 per thousand (one in 624 pregnancies). If influenza could provoke this level of increase in such deaths, it is likely that it was responsible for a great many more non-fatal spontaneous abortions. In the USA, pregnancy was interrupted in 26 per cent of uncomplicated cases of influenza and in 52 per cent of cases complicated by pneumonia. Foetal loss and premature delivery may also have generated a higher number of stillbirths and premature live infants during or shortly after the pandemic. This is corroborated by evidence that higher rates of early neonatal mortality after four of the five influenza epidemics between 1948 and 1971 were due to an increase in the prematurity rate, probably as a result of infection to mothers in the first or second trimesters. However there has been little other evidence to support the effect of influenza on the premature termination of pregnancy or stillbirth.
A confluence of events created a “perfect storm” for widespread salicylate toxicity. The loss of Bayer's patent on aspirin in February 1917 allowed many manufacturers into the lucrative aspirin market. Official recommendations for aspirin therapy at toxic doses were preceded by ignorance of the unusual nonlinear kinetics of salicylate (unknown until the 1960s), which predispose to accumulation and toxicity; tins and bottles that contained no warnings and few instructions; and fear of “Spanish” influenza, an illness that had been spreading like wildfire.
The high case-fatality rate—especially among young adults—during the 1918–1919 influenza pandemic is incompletely understood. Although late deaths showed bacterial pneumonia, early deaths exhibited extremely “wet,” sometimes hemorrhagic lungs. The hypothesis presented herein is that aspirin contributed to the incidence and severity of viral pathology, bacterial infection, and death, because physicians of the day were unaware that the regimens (8.0–31.2 g per day) produce levels associated with hyperventilation and pulmonary edema in 33% and 3% of recipients, respectively. Recently, pulmonary edema was found at autopsy in 46% of 26 salicylate-intoxicated adults. Experimentally, salicylates increase lung fluid and protein levels and impair mucociliary clearance. In 1918, the US Surgeon General, the US Navy, and the Journal of the American Medical Association recommended use of aspirin just before the October death spike. If these recommendations were followed, and if pulmonary edema occurred in 3% of persons, a significant proportion of the deaths may be attributable to aspirin.
