As a 20-year-old college student, Mark Rosen was once given general anesthesia for chest surgery but was far from knocked out.
"I knew something was wrong, feeling them cutting," he told ABCNews.com in a 2008 interview. "I remember wanting to push away but you're paralyzed. You can't move, you can't open your eyes … the fright of being locked in."
He is now Dr. Rosen and vice chairman of anesthesiology at the University of California San Francisco Children's Hospital and places complete faith in modern anesthesia; a medical advancement that researchers are only beginning to understand fully.
His experience is rare, and doctors have since developed brain monitors that can gauge levels of consciousness, which underscores the complex science of keeping patients free from consciousness and pain without killing them.
The use of general anesthesia is a routine part of surgical operations at hospitals and medical facilities around the world, but the precise biological mechanisms of the drugs' effects on the brain are only now being analyzed.
In a review article published this week in the New England Journal of Medicine, scientists have for the first time used a range of disciplines, including neuroscience and sleep medicine, to lay the groundwork for better understanding of how anesthesia actually works.
Armed with the new information, doctors can speak more frankly and knowledgeably to patients.
"The biggest concern among patients is, "Am I going to wake up?" said lead study author Dr. Emery Brown, an anesthesiologist at Massachusetts General Hospital and professor at Massachusetts Institute of Technology.
"That happens extremely rarely but it's a fear everyone has. I think the way to assuage the fear is to know what we are doing. But we can't continue to comfort people if it's a black box and I assure you it's not going to go wrong."
This research may also shed light on treatments for neurological disorders such as depression, schizophrenia, Parkinson's disease and chronic pain syndrome. And, they say, it may also help doctors bring patients out of comas.
General anesthesia is a reversible coma, not sleep, Brown said, although doctors often tell their patients they are putting them to sleep in hopes of scaring them less.
"From a laymen's standpoint, you want to come in to surgery and basically know you are going to be well taken care of," Brown said. "We try to give patients the impression we understand what is going on, but we say you are going off to sleep when it turns out it's not sleep, it's more like a state of coma."
Anesthesia Is Medicine's 'Greatest Gift'
Modern anesthesia, which has been around for about 160 years, has long been considered one of medicine's greatest gift and it had its beginnings at Massachusetts General Hospital.
Historically, herbal extracts or alcohol was used to dull pain as patients underwent surgery. But in 1831, Englishman James Young Simpson discovered the sleep-inducing properties of chloroform. Its use spread and it was even administered when Queen Victoria gave birth to Prince Leopold in 1853. But because it was used by untrained practitioners, chloroform lead to many deaths.
On Oct. 16, 1846, Boston dentist Dr. William T.G. Morton demonstrated the use of ether during surgery. Using a specially designed glass inhaler containing an ether-soaked sponge, he administered the anesthetic to Gilbert Abbott, a printer who needed treatment for a vascular tumor on his jaw. After several minutes, Abbott was rendered unconscious and the surgeon was able to surgically remove the tumor.
Upon wakening, Abbott informed the physicians and medical students in the theater that he had experienced no pain. The surgeon reportedly remarked, "Gentlemen, this is no humbug."
News of the discovery spread quickly and, within months, it was hailed as the "greatest gift ever made to suffering humanity."
The goal of general anesthesia is to rid the patient of pain and to awaken with a clear head and no side effects, such as nausea. That is now possible by inducing sedation with a wide variety of drugs in a controlled manner.
Controlled Coma Aids Surgery
Brown and his co-authors -- Ralph Lydic, a sleep expert from the University of Michigan, and Dr. Nicholas Schiff, a coma expert from Weill Cornell Medical College in New York -- compared the physical signs and electroencephalogram (EEG) patterns of general anesthesia to those of sleep.
While it is common to describe general anesthesia as going to sleep, there actually are significant differences between the states, with only the deepest stages of sleep being similar to the lightest phases of anesthesia induced by some kinds of agents.
While natural sleep normally cycles through a predictable series of phases, general anesthesia involves the patient being taken to and maintained at the phase most appropriate for the procedure, and the phases of general anesthesia at which surgery is performed are most similar to states of coma.
"People have hesitated to compare general anesthesia to coma because the term sounds so harsh, but it really has to be that profound or how could you operate on someone?" Brown said.
"The key difference is this is a coma that is controlled by the anesthesiologist and from which patients will quickly and safely recover."
One of the most widely used drugs, Propofol -- the drug abused as a sleeping aid by pop singer Michael Jackson -- has been around since 1990. "It is extremely potent and very powerful," he said.
The drug "goes everywhere," Brown said, to the arousal centers in the brain stem, decreasing the levels of excitatory neurons; in the thalamus, the neural control center; in the cortex, the part of the brain that controls memory and consciousness; and then down the body to suppress action in the muscles and respiratory center.
"There are six areas of the brain where one drug is working," Brown said.
Only about 0.1 to 0.2 percent of all patients -- about 20,000 to 40,000 a year out of 21 million surgeries in the United States -- are aware of what's happening during the procedure, according to the Joint Commission, a regulatory committee that monitors safety at hospitals.
"Basically, there are three cases [where awareness happens]," Brown said. "A woman comes in for an emergency Caesarian section and you try not to give as much anesthesia to the mother so it doesn't go to the baby, because it crosses the placenta.
"And in a major trauma gunshot wound. You give as little of the drug as possible because the drug suppresses blood flow."
Anesthesia Study May Help in Brain Disorders
The third scenario is a medical mistake, when the patient is inadvertently moved or whose position is changed and the medication is turned off.
Brain disorders show similar neurological shutdowns on EEGs as those created by anesthesia, suggesting this research may help discover new treatments.
Ketamine, for example, a drug used for anesthesia, has shown promise in smaller doses in the treatment of depression. "If we can turn the brain on and off, maybe we can also turn off chronic pain syndrome," he said.
Ambien, a widely used sleep drug, also works in some of the same ways as anesthesia, turning down internal brain activity and allowing the natural sleeping mechanism to take over.
With 40 million Americans who have some kind of insomnia and 60 million with some form of sleep disorder, the research could also provide more answers about the natural oscillations of sleep.
Brown and his colleagues described the case of a brain-injured patient in a minimally conscious state who actually recovered some functions through administration of Ambien or zolpidem.
It mirrors a common occurrence called paradoxical excitation, in which patients in the first stage of general anesthesia may move around or vocalize. The authors describe how zolpidem's suppression of the activity of a brain structure called the globus pallidus -- which usually inhibits the thalamus -- stimulates activity in the thalamus.
"Anesthesiology has long been viewed as a mystery," Brown said. "We can now muster something we can understand in neuroscientific terms."