Victorian water pumps and anesthetic neurotoxicity.

Can we learn anything meaningful about disease and causation without direct access to patient records? John Snow, the 18th century father of both Anesthesiology and Epidemiology did just that when he plotted cases of cholera on a map in 1854 and discovered that the disease was not caused by waves of bad air (‘‘miasma’’) coming from the river Thames, but was transmitted by drinking water from a sewagecontaminated well on Broad Street in London. John Snow made his classic discovery without having seen a Vibrio Cholerae specimen through a microscope. In fact, the bacterial cause of cholera was only identified 30 years later during an outbreak in Calcutta. In the same year that Snow was able to eradicate cholera without knowledge of its microbial pathology, a nurse working in a field hospital during the Crimean War, Florence Nightingale, was able to reduce an appalling hospital mortality rate of over 30%—10 times more soldiers died of infectious diseases than died of their war wounds—to less than 2% by radically improving sanitary conditions. Again, no deep knowledge of microbiology was involved. Both Florence Nightingale and John Snow were completely unaware of the microbial cause of high mortality. Both are now regarded as pioneers of epidemiology and medical statistics, because they preferred the use of counting, simple mathematics, and graphing results over ‘‘learned intuition’’ and belief or what we would now call ‘‘eminence-based medicine. ’’ This not only allowed them to draw inferences about causation but also to convince policy makers of their day that radical change was needed. In this issue of J Neurosurg Anesthesiol, DiMaggio and colleagues address the growing concern that exposure to anesthetic drugs during a vulnerable period in the development of the human nervous system may result in neurodegeneration and increase the probability of cognitive and behavioral abnormalities later in life. Although the evidence from laboratory studies is increasing, clinical data are sorely lacking and all we have available at the moment is retrospective data tucked away in many different types of hospital and governmental databases. DiMaggio and colleagues used a typical ‘‘John Snow’’ approach, analyzing only government databases to address the question whether exposure to anesthesia and surgery associates with evidence of neurotoxicity. A cohort of underprivileged children born in the state of New York from parents who were covered under the Medicaid system was selected and the databases were queried both for outcome (delayed development, behavioral disorder, language or speech problems, mental retardation, or a psychiatric diagnosis such as autism) and determinants (an operation for herniorrhaphy within the first 4 years of life and a set of demographic and perinatal data). They then calculated the probability of disturbed neurocognitive development as a function of exposure to herniorrhaphy and a series of other possible determinants. As this is really an ‘‘etiologic’’ question, all determinants other than being exposed to hernia surgery were potential confounders. Epidemiologists intent on uncovering causation often spend a lifetime trying to correct for all possible sources of confounding. Of course, the sobering reality in this clinical domain is that it is simply impossible to account for all possible confounders, because many are either not recorded or because they have not (yet) been considered.