ANESTHESIA, like the rest of medicine, has always been a mixture of art and science. I have always told my trainees that anesthesia, like cooking, is best done “to taste,” because no two patients responses are exactly alike. However, despite that caution, there have been occasions in my practice when the taste was very unexpected and led to an extraordinarily undesired outcome for my patient. In every case, these outcomes were examined to determine whether they could have been avoided. In almost all of these cases, the undesirable outcomes were found to be impossible to predict. In an ideal world, this would not be the case, and in this ideal world, patient care would be improved and medical costs would be decreased. In this issue, Palmer et al. 1present an outstanding review of old, new, and future ways of making the dream of being able to better predict each patient’s responses to the drugs we use every day become a reality.
The response of any given patient to anesthetic drugs is a classic example of the interaction of genes and environment. It depends on a complex formula including their individual genetic makeup, their endocrine and emotional states, and environmental factors that they have been exposed to in both their immediate and perhaps distant past. Anesthesiologists, even recently trained anesthesiologists, may have been briefly exposed to the “wonders” of modern molecular biology and the human genome project. However, for the most part anesthesiologists as a group tend to be unaware of how they are interacting with this branch of science in their everyday practice. The review of Palmer et al. will help to increase this awareness. It first provides an excellent guide to understanding the gobbledygook and alphabet soup that make up the language of geneticists, molecular biologists, and bioinformaticians who are the bulk of the experts in this field. Then, it discusses genetic conditions and interactions between genes an environment that are both relevant and important to every practicing anesthesiologist. These include the classic examples of pseudocholinesterase deficiency, halothane hepatitis, and malignant hyperthermia susceptibility as well as lesser-known traits associated with the duration of benzodiazepine action, opiate and nonsteroidal antiinflammatory drug action, and the perception of pain. The bibliography is extensive and a useful starting point for the reader to extend his or her knowledge base in this important area.
In their conclusions, Palmer et al. discuss some of the medical realities associated with taking advantage of these 21st century techniques, such as cost:benefit ratios and whether patients should be tested before or after a therapeutic problem. However, they sidestep the dilemma of the ethical problems of genetic testing and how we will manage the information after the “genie” is out of the bottle.
More importantly, this review points out a new opportunity for our specialty to take the lead in doing medical research that is directly relevant to our clinical practice. One example of the practical importance of such studies might include being able to predict who would develop bleeding and who would develop graft thrombosis after coronary artery bypass grafting. With such predictive capability, we might alter our intraoperative management of the first group and give the second one larger doses of postoperative anticoagulants. A second example not discussed in the review but equally important is transcriptional profiling with the goal of silencing or induction of certain genes before anesthesia and surgery, e.g. , we may be able to alter gene expression in the elderly to prevent postanesthesia cognitive deficits and confusion. Or before surgery that would result in an ischemic injury, we may be able to induce genes responsible for defense mechanisms (e.g. , genes responsible for antiinflammation and resolution, the genes responsible for superoxide dismutase, catalase, or both). Lastly, understanding the genetic basis for pharmacogenetic disorders may be the backbone for creating gene therapy treatments to correct the disorder. We as anesthesiologists are in an ideal position with our intensive patient contact to initiate and facilitate the prospective sufficiently powered gene association studies that are critical for making these discoveries. In addition, because of our detailed preoperative evaluation, we are also in the ideal position to make certain that these studies include detailed patient demographics and carefully defined and measurable outcomes. If we do this, anesthesiologists will be in the position to both evaluate the clinical significance of various gene associations to our everyday practice and to put our specialty in the lead as contributors to this critically important area of medical discovery.
Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, Massachusetts. allen@zeus.bwh.harvard.edu
