PHILADELPHIA – University of Pennsylvania School of Medicine researchers have answered long-running questions about the way that anesthetics act on the body, by showing that the cellular pathway for emerging from anesthesia is different from the one that drugs take to put patients to sleep during operations. The findings are published this month in Proceedings of the National Academy of Sciences.
The research focuses on orexins, the small, specialized fraction of the brain’s 100 billion neurons that play a key role in regulating the body’s wakeful state. Studying mice whose orexin systems had been genetically destroyed – a state similar to humans suffering from narcolepsy, a neurological condition that causes unusual daytime sleepiness – Max B. Kelz, MD, PhD, an assistant professor in Penn’s Department of Anesthesiology and Critical Care and the Mahoney Institute of Neurological Sciences, found that these mice took much longer to emerge from general anesthesia than those with normal orexin signaling systems. However, the mice with faulty orexin systems did not appear to fall asleep faster during anesthesia, which suggests that different processes are at play when transitioning to and from the anesthetized stated.
“The modern expectation is that anesthesiologists can simply flip a consciousness switch as easily as we might turn the room lights on or off,” Kelz says. “However, what patients do not realize is that despite 160 years of widespread clinical use, the mechanisms through which the state of anesthesia arises and dissipates remain unknown.”
Kelz became interested in these questions after treating a narcoleptic patient who took more than six hours to regain consciousness after anesthesia, compared to the typical six minutes or so. By probing what’s different about the narcoleptic brain, the Penn study has established for the first time that the process of entry into and exit from the anesthetized state are not mirror images of one another.
Kelz and his colleagues, including Sigrid Veasey, MD, associate professor in the Department of Medicine’s Sleep Medicine division, hope that further research on the brain’s neural signaling systems will lead to novel ways to administer anesthesia and “jump start” a speedy, safe return to consciousness – particularly among patients who struggle to wake up or in patient groups that may be more prone to anesthesia side effects such as the elderly and patients with neurodegenerative disorders. The findings might also be used to create designer anesthetic agents that “hijack” the body’s natural sleep cycles to mimic a state closer to natural sleep than a chemically-induced coma, Kelz says.
Funding for this research was provided by the Foundation for Anesthesia Education and Research, the National Institues of Health, and the Department of Anesthesiology and Critical Care at the Penn School of Medicine.
Editor’s note: In addition to Penn researchers involved in the study, a narcoleptic patient who recently experienced a delayed emergence from anesthesia is also available for interviews.
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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year.
The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided $500 million to benefit our community.