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We don't usually think of caffeine as a drug, but it's one of the most widely used drugs in the world. Its ability to make people feel more awake and alert are undisputed, and now researchers from the University of Chicago are testing to see if it can be used to help people wake up from a deeper kind of "sleep" than your usual 6:00 am wake up call: general anesthesia.
Scientists aren't sure exactly how anesthetics work. We use the common metaphor of sleep to describe patients who are under general anesthesia, but some researchers suggest that it puts people in a reversible coma-like state.
"We don't quite understand the mechanism of anesthesia, even though we've been using it every day for a long time," said Zheng (Jimmy) Xie, MD, PhD, associate professor of anesthesia & critical care. "With a patient, you basically try to wash out the anesthetic agent by turning it off and letting them breathe it out. There is no reversal, so some patients can stay there a long time without waking up."
Anesthetic agents like isofluorane and propofol target a lot of different receptors and neurons in the brain and spinal cord, but their mechanisms of action aren't clear. One thought is that they inhibit the release of neurotransmitters that relay signals between nerve cells in the brain. If this is true, then drugs that increase neurotransmitter release, such as caffeine, which is part of a family of compounds that elevate levels of a cellular messenger molecule called cyclic adenosine monophosphate, or cAMP, might be able to reverse the overall effects of anesthetics.
To test this, Xie and his UChicago colleagues, Qiang Wang, Robert Fong, Peggy Mason and Aaron Fox looked at caffeine and two other drugs that raise cAMP levels, forskolin and theophylline. In a study published recently in the Journal of Neurophysiology, they found that when injected into rats that had been put under with isofluorane and propofol, all three drugs decreased waking times. Caffeine performed the best, accelerating recovery time by more than 60 percent.
Fox, a professor in the Department of Pharmacological and Physiological Sciences and one of the authors on the study, said that if the same results hold for human patients, giving patients a shot of caffeine as they wake up from anesthesia could become common practice.
"Caffeine is so innocuous, and is so inexpensive that I think it's completely possible in 10 years it will become the standard procedure if it works in humans like it does in rats," he said. "We could just give it to everybody because it's really safe."
The researchers saw significant shortening of waking time at all doses of caffeine without significant blood pressure and heart change in the rats. All three drugs not only reduced waking times, but normalized them as well. In other words, there was wide variation in how long it took the rats to wake up from anesthesia normally. But when given caffeine or one of the other drugs, they woke up at a more consistent time.
Xie and Fox are working with the FDA to get permission to test this in humans next, using 1, 5, 10 mg/kg doses of caffeine, which are equivalent to 1-4 small cups of Starbucks coffee (or "tall" in Starbucks-speak) in a person of average weight. Rats usually require higher concentrations of anesthetics to go to sleep than humans do, so Xie and Fox said they wouldn't be surprised if the required dose of caffeine to wake up humans is lower than in rats.
They will monitor the waking time and potential side effects of caffeine, paying special attention to see if caffeine can help patients recover from some of the cognitive impairment (feeling tired, groggy, etc.) that can linger for hours after general anesthesia too. Making recovery times after surgery more predictable would be a boon for hospitals, helping staff schedule procedures and move patients to their rooms or outpatient care more quickly.
"If you could wake up everybody reproducibly and quickly, and relieve the cognitive problems that are associated with anesthetics, it might change everyday medicine," said Fox. "We haven't cured cancer, but it would be very useful."