May 11, 1999 DURHAM, N.C. -- In a finding that has perplexed researchers, women appear to wake up almost twice as fast as men when general anesthesia is discontinued after surgery.
This may mean that women are less sensitive than men to anesthetic drugs that promote unconsciousness and could need more anesthesia during surgery, say researchers at Duke University Medical Center, who led the study, which was conducted at Duke, the University of North Carolina at Chapel Hill, Emory University and Massachusetts General Hospital in Boston. The finding may also help explain why three times more women than men have complained of being conscious during surgery, the investigators say. The research findings are published in the May issue of the journal Anesthesiology.
"This is the first time we have seen a difference in how men and women wake up after anesthesia is withdrawn, and that gender effect is both unexpected and strong," said Duke anesthesiologist Dr. Tong Gan, who co-authored the study. "It shows that women have a higher chance of being aware during surgery than men, and indicates women may need significantly more anesthesia than men to keep them asleep."
"No one ever thought gender would be a variable in delivering anesthetics to patients, but we now need to consider adding a patient's sex into the equation," added the other Duke co-author, anesthesiologist Dr. Peter Glass.
Currently, doses are based on body size, which means that women are typically given less anesthesia than men, although drug levels are often adjusted during the operation if a patient shows signs of returning consciousness. Anesthesiologists participating in this study, however, used a new standardized technique that delivered the same concentration of an anesthetic drug to patients -- enough to ensure they were asleep during the operation -- and then monitored their level of consciousness and how quickly they awoke after the drug was stopped.
The phenomenon of patients being aware during surgery is rare because many physicians "tend to give more anesthetics than is needed to make sure the patient is asleep. But when it happens, it is devastating, especially if their pain medication also is not adequate," Gan said. "Our commitment to our patients is to keep them asleep during surgery, and this information on the level of sedation should help us do that."
Gan and the research team did not answer the question of why such a difference exists. "We can only guess," Gan said. "It could be that women are less sensitive to these anesthetics than men, or that they metabolize them faster. Or both."
Furthermore, the research highlights the issue of the effectiveness of other pharmaceutical agents on the female brain, Glass said. "We really need to have a hard look at gender differences in sensitivity to anesthetics, and follow up with more research."
The study was initially undertaken in 1997 to test the effectiveness of "bispectral index monitoring," dubbed BIS, a device that interprets brain wave patterns and assigns a numerical score to a patient's degree of unconsciousness. The scale ranges from 0 (a dead brain) to 100 (fully awake). The 1997 Duke study, supported in part by the manufacturer of the device, Aspect Medical Systems of Natick, Mass., was the first to test BIS with human surgery patients. Based on the findings of that research, as well as other studies, anesthesiologists determined that the optimal range of "consciousness" for patients during surgery to be between 45-60. At 70 and above, according to Gan, patients are emerging from the anesthesia, and below 35, they may be too deeply anesthetized.
The BIS monitor was approved by the Food and Drug Administration in 1996 and is used in many tertiary academic medical centers, but is not standard equipment in many operating rooms, perhaps because of its expense, Gan said.
Instead, many physicians monitor their patients for signs of consciousness by checking their blood pressure and heart rate, and looking for such signs as movement, changes in the size of their eye pupils and sweating. Anesthesiologists constantly maintain a delicate balance of keeping patients asleep, but as lightly sedated as possible, for fear of developing such side effects as repressed blood pressure from heavy sedation.
Using Duke funds, the research team then re-examined the data culled from their original study of 274 patients in an effort to determine the BIS score that best determines how quickly a patient will wake up after anesthetics were withdrawn. Faster recovery would not only benefit a patient, but would save healthcare dollars, Gan said, because patients who are asleep must be attended by an anesthesiologist. Once they are awake, they can be moved to a less intensive, therefore lower cost, recovery area.
Participating in the study were 96 men and 178 women who were scheduled for either general surgery, gynecologic, urologic, ENT (ear nose or throat), or orthopedic procedures. They were all given the same doses of an hypnotic drug called propofol, which affects consciousness, along with a painkiller called alfentanil and nitrous oxide, which also mediates pain and awareness. These drugs are commonly used.
Through analyzing wake-up times, the researchers discovered that female patients woke up in an average of about seven minutes, compared to more than 11 minutes for men in the study, even though there was no difference in the dose of anesthetic used between both groups. The study was designed to keep range of BIS between 45 and 60, and while that was accomplished, Gan said it is possible that the women had a higher BIS score than the men overall. That means the same level of anesthesia produced a "lighter" sedation in women than men, although it was certainly adequate, Gan said.
Glass agreed with the theory, citing a previous study that he conducted which demonstrated that women had consistently higher BIS scores than men, even though the concentration of anesthetic in their blood was the same. Although the women were less deeply asleep, they still were anesthetized enough not to remember the surgery or feel pain.
"We discovered a large and unexpected difference in the recovery times of men and women," Gan said. "The difference was significant at four separate institutions and occurred despite the use of a highly standardized anesthetic technique."
Working with Gan on the study was Duke anesthesiologist Dr. Peter Glass; Dr. Jeff Sigl, from Aspect Medical Systems; Dr. Peter Sebel and Patricia Embree, at Grady Health System, Emory University; Dr. Frederick Payne, of the University of North Carolina at Chapel Hill; and Dr. Carl Roscow at Massachusetts General Hospital and Harvard University.
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