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May 2000
Volume 64 |
Number 5
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| Cognitive Function
After Non-Brain Surgery Studied: Second Duke Conference on
Surgery and the Elderly |
Madan M. Kwatra, Ph.D.
It is well known that the elderly population in the United States
is increasing rapidly, and the implications of this trend for
surgery on the elderly are being examined. Five years ago, Duke
University Medical Center established the Gerontological Research
in Anesthesiology and Surgery Program (GRASP) to identify areas
of basic and clinical research that will reduce the incidence
of adverse postsurgical outcomes in the elderly. In addition to
holding monthly meetings and developing research projects, GRASP
organizes biennial conferences on surgery and the elderly. The
second such conference was held at Duke University Medical Center
on September 30, 1999. Titled "Cognitive Function After Surgery:
What Do We Know? What Do We Need to Know?," the conference brought
together anesthesiologists, basic scientists, geriatricians and
surgeons. It was co-hosted by Duke's departments of anesthesiology,
surgery and the Duke Center for the Study of Aging and Human Development.
Funding was provided by the American Geriatrics Society/John A.
Hartford foundation and Abbott Laboratories.
Ronnie Rosenthal, M.D., Yale University, New Haven, Connecticut,
said that the percentage of surgeries performed on people over
the age of 65 (currently at 40 percent) will increase substantially
over the coming decades as the elderly population increases. Although
surgery is beneficial even for octogenarians, the incidence of
adverse outcomes is much higher due to existing co-morbidities.
Dr. Rosenthal provided data implicating nutritional status measured
by serum albumin levels and intraoperative hypothermia as the
two most important factors affecting postoperative outcomes. Further,
she reported that the incidence of major complications including
deaths were significantly higher in patients that have postoperative
delirium.
Paula Trzepacz, M.D., who is affiliated with Eli Lilly, distinguished
delirium from dementia. The hallmarks of delirium are disorientation,
attentional deficits and clouding of consciousness. Demented patients,
on the other hand, can pay attention but cannot remember. Delirium
also develops over a short period of time (hours or a day), whereas
most dementias develop over a longer period. The risk factors
for delirium in the perioperative period include advanced age,
male gender, history of alcoholism, polypharmacy (especially anticholinergic
agents), pre-existing dementia or cognitive impairment, metabolic
disturbances and low serum albumin.
Three presentations focused on cognitive dysfunction after cardiac,
hip and other surgeries. Mark Newman, M.D., Duke University, Durham,
North Carolina, discussed his team's study that followed cognitive
function up to five years after cardiac surgery. Cognitive dysfunction
affected more than half the patients at discharge; this incidence
fell to 20-24 percent at six months, but increased to 42 percent
at five years. The most significant predictor of cognitive dysfunction
at five years was impairment at discharge. To better understand
the mechanism of cognitive dysfunction after cardiac surgery,
a rat model of cardiopulmonary bypass has been developed by Hilary
Grocott, M.D., at Duke University.
Kenneth Koval, M.D., New York University, New York, New York,
presented data on functional outcomes after hip fractures in patients
over the age of 65 who were cognitively intact and lived in community
dwellings. In a sample of 921 hip fracture patients, the incidence
of postoperative delirium was 5 percent, a much lower rate than
that reported by other investigators, possibly reflecting different
definitions used for detecting delirium. The predictors of postoperative
delirium in this population were gender (male) and general anesthesia.
Terri G. Monk, M.D., University of Florida, Gainesville, Florida,
presented details on the International Study of Postoperative
Cognitive Dysfunction (ISPOCD) published in The Lancet
in 1998.1 Postoperative cognitive
dysfunction occurred in 25 percent of patients in the first week
after surgery and in 10 percent of patients within three months
of surgery. More importantly, the ISPOCD study found that patients
over the age of 70 were more susceptible to prolonged cognitive
decline after surgery than those in their early 60s. Dr. Monk
is currently examining whether the multicenter findings apply
to a single institution using ISPOCD methodology, by evaluating
1,500 patients.
Pamela Williams-Russo, M.D., Cornell University, Ithaca, New
York, addressed the question of anesthetic technique and cognitive
outcome. Because patients undergoing regional anesthesia are alert
and awake during and immediately after surgery, it is likely that
regional anesthesia could result in less postoperative cognitive
dysfunction than general anesthesia. However, the available literature
does not provide a clear answer to this hypothesis. Dr. Williams-Russo
presented data on a randomized trial of the effects of epidural
versus general anesthesia on cognitive dysfunction in 262 older
adults (85 percent over the age of 60 and 50 percent over the
age of 70) undergoing elective primary total knee replacement.2
The two anesthesia groups were compared for change in neurocognitive
function prior to surgery to six months after surgery using a
comprehensive neuropsychologic testing battery. No significant
difference in the incidence of postoperative dysfunction was detected
between the two groups.
Alexis Carmer, M.D., Duke University, Dunham, North Carolina,
discussed an abstract (presented by Stephan A. Schug, M.D., at
the 1999 meeting of the American Society of Regional Anesthesia
and Pain Medicine) on a meta-analysis comparing regional versus
general anesthesia in 107 different trials consisting of more
than 8,000 patients. Regional anesthesia patients had a one-third
less mortality rate and a significant decrease in the incidence
of deep venous thrombosis, pulmonary embolism, pneumonia and respiratory
depression. These differences in outcomes, Dr. Carmer suggested,
could affect cognitive dysfunction. The group consensus, however,
was that anesthesia type does not seem to influence the incidence
of cognitive dysfunction, but a larger prospective randomized
controlled trial focusing on older patients is warranted to definitively
answer this crucial question.
Dr. Trzepacz focused on the cholinergic mechanisms of postoperative
delirium. She reviewed the brain areas involved in delirium and
highlighted a key role of acetylcholine in the REM sleep, arousal,
mood and memory changes seen in delirium.3
Anticholinergic drugs are known to cause delirium. Dopamine may
also cause delirium through acetylcholine because it acts through
D2 receptors and reduces acetylcholine levels.
Opiates also cause delirium as they are known to reduce acetylcholine
and increase dopamine. Madan M. Kwatra, Ph.D., presented biochemical
information on the enzymes and receptors involved in the function
of acetylcholine and how the various components of the cholinergic
system are affected with age and anesthetics. Muscarinic receptors,
a key target through which acetylcholine produces its action,
become desensitized with age.4 Further,
anesthetics are known to disrupt muscarinic receptor-G protein
coupling.5 Whether the cholinergic
system of elderly patients is more susceptible to the detrimental
effects of anesthetics is an important question that needs to
be addressed.
Lively discussions following the talks identified three key
problems. First, the very term "cognitive dysfunction" is confusing.
Is it delirium or dementia or both? Precise standard definitions
are sorely needed. Second, researchers have used a variety of
instruments to detect cognitive dysfunction. Standardization of
instruments is needed so that studies from different institutions
can be adequately compared. The group consensus was that a standardized
and validated delirium score be developed for use in all surgical
patients. Finally, many studies have focused on populations consisting
of a large portion of patients who are 60 or 65 years old. Since
this age group is relatively healthy, more trials should be performed
on patients over the age of 75. This group will present the greatest
challenge to anesthesiologists.
References:
1. Moller JT, et al. Long-term postoperative
cognitive dysfunction in the elderly. ISPOCDI study. Lancet.
1998; 351:857-861.
2. Williams-Russo P, Sharock NE, Mattis S,
et al. Cognitive effects after epidural vs. general anesthesia
in older adults. A randomized trial. JAMA. 1995; 274(1):44-50.
3. Trzepacz PT. Anticholinergic model for
delirium. Semin Clin Neuropsychiatry. 1996; 1(4):294-303.
4. Anson RM, Cutler R, Joseph JA, et al.
The effects of aging on muscarinic receptor/G-protein coupling
in the rat hippocampus and striatum. Brain Res. 1992; 598:302-306.
5. Anthony BL, Dennison RL, Aronstam RS.
Disruption of muscarinic receptor-G protein coupling is a general
property of liquid volatile anesthetics. Neurosci Lett.
1989; 99:191-196.
Madan M. Kwatra, Ph.D., is Associate Professor
of Anesthesiology and Assistant Professor of Pharmacology and
Cancer Biology at Duke University. He is also Coordinator of the
Gerontological Research in Anesthesia and Surgery Program (GRASP)
and Senior Fellow of the Center for the Aging and Human Development,
Duke University Medical Center, Durham, North Carolina.
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