Geriatric Anesthesia Research Unit (GARU)
As clinicians and researchers continue to learn more about the basic mechanisms of general anesthesia, they are better able to formulate
safe and effective regimens with which to manage patients
throughout the perioperative period. Because geriatric patients
often have a variety of medical and physiological problems not
present in younger patients, a number of unique clinical challenges
can arise. Due to sophisticated research inquiries in areas such as neuroscience and pharmacology, anesthesiologists have come to
appreciate how older patients are generally affected by the
surgical experience. Indeed, the need for such research continues
to grow as the population ages.
The short-term and long-term effects of general anesthesia on aging
brain function represent a burgeoning area of research interest.
General anesthesia, for instance, has been identified as an important
risk factor for post-operative delirium, a circumstance observed in
15-53% of surgical patients; the elderly seem especially susceptible.
General anesthesia may also contribute to more subtle forms of
postoperative cognitive dysfunction (POCD) that have been observed
one week postoperatively in 27% of a series of 1,218 patients and
three months postoperatively in 10% of the same patient group.
Following coronary artery bypass graft surgery, investigators noted
POCD in 53%, 36%, 24% and 42% of 261 patients at discharge,
at six weeks, six months, and five years, respectively. Because age
is one of several risk factors for POCD, these findings suggest that
the elderly may have a greater risk for persistent cognitive deficits
following anesthesia and surgery. Three separate studies have
shown a mild relationship (an odds ratio of 1.2 to 1.6) between
previous anesthesia/surgery and the onset of Alzheimer's disease
(AD). Further, the age of onset for AD was inversely proportional
to the cumulative exposure to anesthesia before age 50. A recent bservational study reported that patients having coronary artery
bypass graft surgery under general anesthesia were at increased
risk for the emergence of AD as compared to those having
percutaneous transluminal coronary angioplasty under local
anesthesia. These findings implicate general anesthesia and
surgery in postoperative cognitive problems ranging from
common delirium to POCD and even AD. Further research into
the mechanism and effects of general anesthesia is, therefore,
of great importance if we are fully to understand its possible
relationship to these serious sequelae.
Our own laboratory studies have suggested that perioperative factors such as hypoxia, hypocapnia, and anesthetics may contribute to AD neuropathogenesis. Future projects in the Geriatric Anesthesia Research Unit in the Department of Anesthesia, Critical Care and Pain Medicine at Mass General will explore the nature of the relationship between anesthesia and AD, work that may shed more light on AD neuropathogenesis. We will investigate the perioperative factors associated with POCD and attempt to establish a possible association between anesthesia and delirium. Our work proceeds at both the cellular and molecular levels in both mice and in human subjects, and we employ such techniques as somatic gene transfer, genetic modification of animal models, RNA interference, RT-PCR, and immunocytochemistry. We also use various pharmacological tools and behavioral evaluations when these are indicated. These efforts may illustrate whether general anesthesia and surgery can initiate or accelerate the development of AD, POCD and delirium. The results of these studies will ultimately guide clinicians with regard to how to provide the safest anesthesia care for elderly patients, and especially those with AD.