Lifting
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Anesthesia

Learning why current anesthetics are so potent and sometimes dangerous will lead to a new generation of safer targeted drugs without unwanted side effects

By Beverley A. Orser
A Hollywood thriller due out this year

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COPYRIGHT 2007 SCIENTIFIC AMERICAN, INC.

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centers on a young man who awakens while undergoing open-heart surgery but is unable to move or cry out. The film’s plot will undoubtedly take many more dramatic turns from there, but its early premise is, sadly, not entirely far-fetched. Episodes of intraoperative awareness while under general anesthesia are reported by one or two of every 1,000 patients. In reality, such incidents are usually brief and generally do not involve pain or distress, but they do highlight one of several ways that even the newest generation of anesthetic drugs can sometimes leave much to be desired.
Indeed, the medical specialty of anesthesiology has evolved into a sophisticated art form because scientific understanding of how anesthetic drugs actually work, and how to make them better, has lagged behind most other areas of drug development.
Many of the modern anesthetics, in fact, share structural properties and clinical effects with ether, whose application as an anesthetic was first successfully demonstrated in public by Boston dentist William Morton in 1846. Since then, the use of general anesthesia has expanded to 40 million patients each year in North America alone. Yet advances in anesthetic care since Morton’s day have come largely from the development of complex drug delivery systems and strategies for managing anesthesia’s dangers and side effects.
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Today’s general anesthetics are the death during an operation than the surmost potent depressors of nervous sys- gical procedure itself. And because antem activity used in medicine. They even esthesia-related mortality has plateaued affect regulation of breathing and heart at a rate of approximately one patient in function. As a result, the drugs have a 13,000 for the past 15 years, it appears fairly narrow margin of safety, which is that anesthesiologists may have reached the difference between the therapeutic the limits of our ability to deliver these dose and a dose that is toxic, even lethal. toxins safely. Moreover, severe side efThat is one reason why individuals fects — ranging from loss of airway conwhose lung or cardiovascular function trol to memory and cognitive problems is already unstable — such as trauma vic- after general anesthesia— may also stem tims undergoing emergency operations from the broad yet poorly understood or patients in the midst of heart sur- influence that current anesthetics exert gery— must receive a lighter than nor- on the central nervous system. mal dose of anesthesia, which could
Science should be able to do much make them susceptible to brief aware- better, and very recent research is beginness incidents, as in the movie. ning to reveal how it can.
Although radical improvements in the care of people under general anes- Pulling Out the Plugs thesia have laid the foundation for com- a l l of t oday ’s general anesthetic plicated procedures such as organ trans- drugs were developed empirically, plants and open-heart surgery, the pow- which is to say, they were tested for their erful neurodepressive effects of these ability to produce the desirable effects drugs make them more likely to cause that define the anesthetized state. Anesw w w. s c ia m . c o m

COPYRIGHT 2007 SCIENTIFIC AMERICAN, INC.

thesia’s main components are sedation, unconsciousness (also sometimes called hypnosis), immobility, absence of pain
(analgesia) and absence of memory for the anesthetized period (amnesia). By studying the mechanisms through which anesthetics achieve these end points, many groups, including my own at the University of Toronto, are beginning to tease those effects apart. Such studies are revealing that the