Meals Days Before Surgery May Affect Anesthesia

October 20, 1998

The foods you eat, even several days prior to surgery, may alter how your body will react to anesthesia, report researchers from the University of Chicago Medical Center at the American Society of Anesthesiologists annual meeting in Orlando.

Physicians have long been puzzled why patients respond in surprisingly different and often unpredictable ways to many anesthetics or muscle relaxants. This finding is one of the first to demonstrate a connection between food and the metabolism of anesthetics. (Earlier studies found that chemicals found in grapefruit juice could extend the bioavailability of several drugs, including several sedatives.)

"Our results bring us one step closer to understanding why patients vary so widely in their sensitivity to certain anesthetic drugs," said Jonathan Moss, M.D., Ph.D., professor of anesthesia and critical care at the University of Chicago and director of the study. "We now suspect that much of the variability may be due to diet."

Anesthesiologists make initial dosing decisions based primarily on age, weight and height, liver and kidney function, but "those are only part of the picture," Moss said. "We need to fill in the rest, including genetic, and now, dietary factors. Only then can we predetermine the best dose of drugs to prevent pain and anxiety during an operation but leave the patient awake and alert soon afterwards."

This is becoming increasingly important as more operations shift from inpatient procedures allowing several days for recovery to the outpatient arena with, at most, a few hours to recuperate.

This pre-clinical study suggests that ingesting even small amounts of natural substances found in potatoes, tomatoes and eggplants can markedly delay the metabolism of common anesthetic drugs.

These foods contain compounds called solanaceous glycoalkaloids (SGAs), which act as natural insecticides, protecting plants from the animals, insects or fungi that attack them.

Potatoes, for example, ordinarily produce high levels of SGAs only in their leaves, stems and sprouts. When damaged or exposed to light, however, the edible part -- the tuber -- produces glycoalkaloids. (Tubers exposed to light also produce chlorophyll, which can give the potato a greenish tint, a warning sign of high SGA content.)

Potato SGAs, which are not altered by cooking, have caused serious illness and even death in humans and livestock, notes Moss. Consequently, the U.S. Department of Agriculture monitors glycoalkaloid levels in potato crops and has banned certain potato varieties because of their unsafe levels.

In laboratory experiments, the researchers found that even in tiny amounts, SGAs slow the breakdown of many commonly used anesthetics and muscle relaxants, including established drugs as well as many of the newer short-acting anesthetics.

Glycoalkaloids interfere with anesthesia by inhibiting two important enzymes found in humans, and all vertebrates. The first (butyrylcholinesterase -- BuChE) is found in blood. Although its normal function is unclear, BuChE is responsible for the breakdown of many anesthetic agents, as well as other compounds such as heroin and cocaine.

The other (acetylcholinesterase -- AChE) breaks down a chemical (acetylcholine) used to transmit signals from motor nerves to muscles.

Of the more than 10,000 known toxins produced by plants, SGAs are the only ones that inhibit both AChE and BuChE. These plant toxins appear to be particularly effective at inhibiting BuChE in humans. Moreover, it takes several days for humans to eliminate ingested SGAs. When these two enzymes are inactivated, the body cannot break down and get rid of certain commonly used anesthetics and muscle relaxants, so they continue to act long after they should have worn off.

Moss -- working with colleague Daniel McGehee, Ph.D., assistant professor of anesthesia and critical care, and medical/graduate student Matthew Krasowski -- found that blood levels of SGAs typical after eating moderate amounts of ordinary potatoes days before can significantly block these two human enzymes in the test tube.

"This may help explain why the dosing models of many anesthetic agents are often off by as much as 50 to 100 percent," said Moss. "It also emphasizes the need for skilled anesthesia monitoring of each patient."

Curiously, the presence of SGAs in food appears to have permanently altered some people's response to anesthesia by encouraging the persistence and spread of altered forms of the gene for BuChE.

The current laboratory research grew out of a literature search by Moss and colleagues to prepare a 1997 review article. The review pulled together studies from many labs on an increased frequency of mutant forms of this enzyme in geographic regions that have historically consumed foods high in SGAs. For example, some Middle Eastern ethnic groups that eat a lot of eggplant have a high frequency of variant genes for this enzyme.

Although these variations are less susceptible to SGAs, they are also less effective at breaking down anesthetics. A laboratory test can predict which patients will metabolize drugs slowly because of this genetic shift, but it would not be practical to test patients for SGA levels immediately before surgery, said Moss. He adds, however, that "people who design new medications should begin to look for systems that don't rely on this enzyme to regulate drug metabolism."
-end-


University of Chicago Medical Center

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