Anesthesia: A medical mainstay re-examined

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Anesthesia: A medical mainstay re-examined

http://www.latimes.com/features/health/la-he-

anesthesia14may14,1,7233408.story

Some worry about brain cell death in studies of young animals. Human

trials are planned.

By Chandra Shekhar, Special to The Times

Anesthesia has been ranked in the top five medical advances of

recent times. You are asleep on the table, surrounded by beeping

monitors and people in white, unaware of the tube down your throat

and the slice of the surgeon's knife. You wake a few hours later, as

if from deep slumber — and, thanks to the miracle of anesthesia,

remember nothing.

Back to normal — or so it has long been assumed.

The use of anesthetics dates back at least 150 years to when a

traveling dentist reported using laughing gas on a patient. Today,

anesthesia is an integral part of modern medicine: A survey by the

British Medical Journal earlier this year ranked it among the five

most important medical advances in recent times.

But recently, a few scientists and clinicians have raised concerns

about its possible long-term effects. They suspect, based on studies

in animals and lab dishes as well as some preliminary human data,

that for patients who are very young, old or sick, anesthesia might

have longer-term consequences.

" Anesthesia was thought to be something that lasted a few hours, and

any consequences would be gone within a day, " says Dr.

Sessler, an anesthesiologist and chair of the outcomes research

department at the Cleveland Clinic in Ohio. " There is increasing

evidence that it is not the case. "

It is a minority viewpoint: Most anesthesiologists and surgeons,

citing the millions of people the world over who live long, healthy

lives after surgery, say there is no call for worry.

But the possibility has led Sessler and others to start human trials

to examine the issue. The Food and Drug Administration is also

taking notice. In March, it convened a panel of experts to look into

the long-term safety of pediatric anesthesia.

Those worried about long-term effects cite several possible risks.

Sessler suggests that general anesthesia might weaken the body's

ability to kill tumor cells released into the bloodstream during

cancer surgery, making the disease more likely to return. Other

researchers fear that anesthesia could trigger an inflammatory

response in the body, eventually leading to atherosclerosis and

other serious conditions.

But the biggest concern is the effect of anesthetic drugs upon brain

cells, especially in infants.

In 2003, Dr. Olney, professor of psychiatry and neuropathology

at the Washington University School of Medicine in St. Louis,

reported that an anesthetic mix commonly used on children caused

significant loss of brain cells in infant rats. (The cause: a sharp

increase in a kind of cell death that naturally occurs during brain

development.) Olney and other researchers have also found that

anesthetized baby rodents develop memory and learning problems — as

measured by skills such as maze navigation — in adulthood.

" The chances are pretty strong that the same effect can occur in

humans, " Olney says.

Researchers at the FDA have repeated Olney's experiments with rhesus

monkeys, which live longer than rats — about 20 years — and are

biologically more similar to humans. They also found that 24 hours

of anesthesia caused unborn and 5-day-old rhesus monkeys to lose

brain cells, although not as many as the rats did. The cell death

didn't happen, however, with shorter periods of anesthesia or in

older monkeys.

Crosby, associate professor of anesthesia at Harvard Medical

School and Brigham and Women's Hospital in Boston, has found effects

on older animals. In 2004, he reported that aged rats given two

hours of general anesthesia did more poorly in a maze-running test

two weeks later. He also detected abnormalities in the rats'

hippocampus — the part of the brain linked to spatial reasoning and

memory formation.

Mental confusion after surgery has been reported in humans: For

example, in 1998, a study in Lancet found that about 10% of elderly

surgery patients had a worse score in cognitive tests three months

after the operation. But it's not clear if the real culprit for this

condition, called post-operative cognitive dysfunction, is

anesthesia or the surgery itself.

Many clinical anesthesiologists question the relevance of the animal

studies. " Human babies are not large rat pups, " says Dr. Sulpicio

Soriano, associate professor of anesthesia at Harvard Medical School

and senior associate in anesthesia at Children's Hospital Boston. In

his own experiments, he says, he had to anesthetize the baby rodents

for at least six hours to trigger brain cell death: equivalent to

giving several weeks-worth of anesthesia to a human patient. " That

is a very artificial condition, " he says.

If human infants need major surgery, " we should not be delaying that

because of this very preliminary result in rats, " says Dr.

, first vice president of the Park Ridge, Ill.-based American

Society of Anesthesiologists and chair emeritus of the Deborah Heart

and Lung Center in Brown Mills, N.J.

A group of researchers including anesthesiologist Dr.

son of the Royal Children's Hospital in Melbourne, Australia,

is planning a multinational study of the long-term outcomes of

infants undergoing hernia surgery. The patients will get either

general anesthesia or spinal anesthesia, which, in theory, has less

effect on the brain. The researchers will assess the mental

development of the children at two and five years after surgery to

see if those who got general anesthesia suffered any long-term

effects.

" The study can be regarded as a safety trial, " son says. " We'd

like to show that anesthesia is safe in babies and doesn't cause

injuries. "

If any of the concerns turns out to be true, what then? Some

researchers suggest postponing elective surgery for infants — such

as cleft lip repair — until about 3 years of age. Most surgeries on

newborns, however, are emergency life-saving operations. " We are not

giving anesthesia for fun, " Soriano says.

Olney suggests developing a drug that interrupts the cascade of

biochemical changes by which anesthetics might destroy brain cells.

By giving this hypothetical drug along with the anesthetic, " you can

have the benefits of anesthesia " without the unwelcome side effects,

he says.

Crosby says he has found, in as-yet-unpublished work, that one

commonly used anesthetic is less harmful to lab animals than the

others he has tested. Maybe, he says, some of the potentially

harmful effects of anesthesia could be avoided by changing the

cocktail of anesthetic drugs administered to patients.

An already available option is regional anesthesia — in which only a

region of the body is numbed instead of making the patient fully

unconscious. In February, Sessler started a clinical trial to

compare the cancer recurrence rate of about 1,100 women undergoing

breast cancer surgery with either general or regional anesthesia. He

hopes to show the latter is more benign.

In another clinical trial, he's investigating the long-term outcomes

of patients undergoing vascular surgery whose dose of general

anesthetic is optimized based on their level of consciousness, as

measured by a brain monitor. The idea is to give just enough

medication to keep the patient unconscious, he says. A preliminary

study of 1,064 patients published in 2005 suggested that this

technique could reduce the likelihood of death in the year after

vascular surgery.

Results of such studies are likely to be subtle, all

agree. " Obviously, " Crosby says, " we are not rotting out people's

brains in a big way or you'd have known that a hundred years ago. "