Researchers are trying to figure out the mechanisms behind anesthesia. In doing so, they hope to develop better drugs used in the process.
People undergo anesthesia all the time during surgery. Even though being “put under” is quite common, there’s still plenty that doctors don’t know about it.
Having a better understanding of how anesthesia works could improve drugs used during the process.
That’s what Bruno van Swinderen, PhD, an associate professor from the University of Queensland in Australia, set out to do in a recent study published in Cell Reports.
He said his team has found that propofol, a common drug used in anesthesia — the one involved in Michael Jackson’s death — goes beyond simply putting a person to sleep.
“Propofol anesthesia is extremely safe, as is most general anesthesia today,” van Swinderen told Healthline. “However, knowing this alternate mechanism might help us understand why recovery from general anesthesia is slow and sometimes problematic. You can keep people under with propofol safely for a long time, so my feeling is that we’ve hit on a drug that works pretty well,” he noted.
“Propofol is the sedative of choice given to first knock you out. Usually, other anesthetics are then given to keep you under,” van Swinderen added.
What exactly does propofol do?
Van Swinderen’s team examined the impact of propofol on the synaptic release in rats. Synaptic release is how neurons or nerve cells communicate with each other.
Doctors had known propofol impacts the brain’s sleep system similar to a sleeping pill, but van Swinderen said his team discovered that it disturbs presynaptic mechanisms as well.
This probably affects communication between neurons throughout the brain in a way that’s different than being asleep.
“In this way, it is very different than a sleeping pill,” he said in a statement.
The researchers found that propofol restricted the movement of a key protein — syntaxin1A — that’s required at the synapses of all neurons. That lowers communication between brain neurons.
This could explain why patients typically are groggy after surgery, van Swinderen said.
“We think that widespread disruption to synaptic connectivity — the brain’s communication pathways — is what makes surgery possible, although effective anesthetics such as propofol do put you to sleep first,” he said.
The discovery could explain why general anesthesia can be problematic for younger and older patients, they said.
Van Swinderen said that the challenge in studying the response to anesthesia is to find out how countless small effects during the presynapse phase lead to major changes in how the brain works.
“That is difficult to study in humans,” he said. “It is also difficult to line up a super-resolution microscope onto cells in a human brain.”
There’s a great value in using animal models because the synaptic release infrastructure in animals and humans is almost identical. Humans just have more brain cells, he said.
A drug that provides better control of the immobilization (or remobilization) of syntaxin1A at the presynapse would give physicians better control of how and when to keep the brain unresponsive, van Swinderen said. If such drugs were developed, they could be used in combination with classical sedatives.
Complications and dangers
Long-term harms or complications of anesthesia aren’t well understood and are debated in the field.
“General anesthesia is extremely safe, but we just don’t know whether some of the complications [lasting cognitive deficits in some patients, for example] result from this potentially brain-wide effect,” he said.
“Human brains have a trillion synapses,” van Swinderen explained. “If syntaxin1A mobility is impaired in each one, you could imagine how that might lead to lasting changes in the long run. But this is still just a hypothesis that needs to be tested.”
Waking up during surgery — something known as intraoperative awareness — is rare, according to James Lozada, DO, a fellow in obstetrical anesthesiology at the Northwestern University Feinberg School of Medicine in Illinois.
This occurs in 1 or 2 of about 1,000 procedures, according to The American Society of Anesthesiologists. Other reports state that 1 out of every 19,000 patients experiences intraoperative awareness during a procedure.
Lozada said it can be more common in procedures when the patient is unstable such as trauma-related surgeries, emergency cesarean section operations, or those that require lower doses of medication to safely treat the patient.
A 2013 report found better monitoring can help prevent the phenomenon.
As for the age-old question about why people need to fast during anesthesia, Lozada said that they should do what their doctors advise.
Fasting guidelines vary depending on the type of procedure and patient, but generally patients cannot eat solid foods for six to eight hours. Many places have become more relaxed about allowing a small-to-moderate amount of clear liquids up to two hours before the procedure, Lozada said.
“You can absolutely risk your health by not fasting,” he explained.
When under anesthesia, the muscles of the stomach and throat relax and that makes it easier to vomit. Because the patient is asleep and cannot protect their airway, vomit can go into the lungs and cause damage during a process known as aspiration pneumonitis.
The research sheds light on the mechanisms behind how anesthetics work, though physician anesthesiologists generally understand that, Lozada said.
“The work shows propofol stops some normal cell function, which the authors suggest could lead to general anesthesia,” Lozada said. “More work is needed to definitively show this.”
Choosing which medications are used during a surgery is made by doctors on an individual basis. Factors that go into the selection include heart and lung function, vital signs, overall health, history of anesthesia response, and allergies.
That said, once a patient uses propofol once, it doesn’t necessarily mean they medically can receive it again, he said.
“This is what physician anesthesiologists are trained to assess, and in their hands, it is generally tolerated well,” he said.
Van Swinderen doesn’t want his study to alarm patients.
“People should not be worried about general anesthesia — it works very well. It is just important to know how the drugs we use work, and it is surprising that we still are confused about how this extremely common procedure makes us unconscious and unresponsive,” he said. “Knowing more will help us better solve any side effects.”