If you’ve ever had surgery, your anesthesiologist has likely told you to count back from 100. You don’t get too far before you’ve drifted off. Hours later, you wake up from the “reversible coma” often unaware of whatever happened during the surgery. But what happens when the body, specifically the brain, goes through this procedure, and why are we unable to feel pain or remember anything?

Anesthesia Dosage

In the U.S., 40 million anesthetics are administered to patients every year, yet many questions still surround the drugs and their effects. Anesthesia, as a procedure, is considered successful when a patient has successfully experienced amnesia, analgesia, muscle relaxation, and loss of consciousness. However, going with a dose that’s too low or too high has also caused patients to wake up in the middle of surgery, while others have experienced postoperative cognitive decline.

For surgery, the recommended dose of general anesthesia is at least 1 minimum alveolar concentration (MAC) — the standard measure signifying the concentration of anesthesia in vapor. Fifty percent of people who inhale 1 MAC of anesthesia don’t move in response to a pain stimulus, and studies suggest it takes lower concentrations of anesthetic to induce unconsciousness than it does to prevent movement in response to surgery.

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Dosing is contingent on two factors: the patient’s health profile and the anesthetics and sedatives that are used. Anesthesiologists use a combination of drugs, including xenon gas, sevoflurane, propofol, and midazolam to achieve an anesthetic state — they must also be on hand at all times to constantly monitor patients’ vital signs. So far, through research involving functional magnetic resonance imaging (fMRI), researchers have learned that different drugs and doses cause different effects in the brain. Here’s what they do.

Infusion pump
Anesthesiologists use infusion pumps to deliver medications. Smithpie, CC BY-SA 3.0

Your Brain On Sevoflurane

Sevoflurane is often used to induce or maintain unconsciousness in patients undergoing surgery, and doses lower than 1 MAC of the inhaled anesthetic agent are enough to affect memory-related regions of the brain. These regions include the primary visual cortex and its association cortex, which translates the information gathered into complex representations.

A 2007 study published in the journal Anesthesia and Analgesia, for example, found that only 0.25 MAC sevoflurane could increase levels of cerebral blood flow (CBF) in the brain’s occipital lobe, where the visual processing centers reside. This increased CBF influences how brain cells try to survive as well as the way they perform their designated tasks, such as thinking, ultimately slowing everything down.

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Another study from 2008 arrived at similar results. After administering 0.5 MAC of sevoflurane, researchers saw changes in CBF within the frontal and parietal lobes, which house brain regions responsible for memory and sensory functions. This in turn brings more oxygenated blood to the brain, which researchers speculate results in memory loss. However, so much oxygen can also overflood the region and damage neural tissue.

These findings are consistent with what researchers already know about the effects of general anesthetics. Sevoflurane and other anesthetics trigger a nerve impulse when they make contact with the synapses in the brain. Under normal circumstances, these signals would then be sent from the primary regions to the secondary, and finally to the tertiary regions where multiple types of stimuli are combined and processed. However, when that signal comes from an anesthetic, the anesthetic is believed to build on each synapse it passes throughout this chain, eventually affecting all regions with a larger effect.

Your Brain on Propofol and Ketamine

The widely used anesthetic propofol (a hypnotic drug) not only causes unconsciousness but amnesia too. Researchers believe propofol binds to GABA receptors, which are involved in controlling sleep and alertness.

A 2011 study published in the European Journal of Anesthesiology suggested that rather than suddenly switching off, consciousness actually fades away. The study found consciousness resides in the connections between multiple parts of the brain, not just one single region, and that an anesthetized brain was first affected in the midbrain where there’s an abundance of GABA receptors. Once propofol binds to these receptors, it mimics and enhances the effects of GABA, thus inhibiting cellular activity. Consciousness fades as the drug spreads outward to different regions of the brain.

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Along with propofol, anesthetists often give patients anesthetics with an analgesic effect. While these are sometimes opioid painkillers, other times they’re the drug ketamine. While in lower doses, this drug turns the brain highly active, in higher doses it’ll have the opposite effect. Ketamine is a dissociative anesthetic, which means it doesn’t make patients completely unconscious. Rather, it inhibits their senses, judgement, and coordination for up to 24 hours.

Ketamine doesn’t induce amnesia or forgetfulness, Dr. Theodore Henderson, founder of the Neuro-Laser Foundation and Neuro-Luminance in Denver, Colo., told Medical Daily in an email. He said the drug blocks NMDA receptors, which are critical to learning, memory, locomotion and neural plasticity.

Together these drugs work on patients by sedating them and providing painkilling benefits.

Drug ampoules
Drug ampoules contain small amounts of medications. Smithpie, CC BY-SA 3.0

The Developing Brain On Anesthetics

Children who are exposed to anesthesia only once can be at a higher risk of neurodevelopmental problems and changes in brain structure. A recent review published in the journal Pediatrics found children under 4 years old who received general anesthesia prior to undergoing surgery were more likely to experience problems with language comprehension; have a lower IQ; and exhibit decreased gray matter density in regions toward the back of their brains — specifically in the occipital lobe and cerebellum, which coordinates and regulates muscular activity. The drugs used on these kids, some of whom underwent multiple early-life surgeries, included sevoflurane, isoflurane, and halothane.

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Another study from 2012 found children who underwent anesthetic surgeries before age 3 were also twice as likely to develop learning disabilities, including long-term language and reasoning deficits before the age of 10. However, the researchers saw there weren’t any observed differences when it came to behavior, visual tracking, attention, or fine and gross motor function.

In all, these studies highlight the need to look for better methods for administering anesthesia for children — researchers are working on it.

The Aging Brain On Anesthesia

Those who undergo surgery later in life most often do so for health-related issues more often than cosmetic. But with age also comes a longer recovery time. Older patients can take up to six months to recover from anesthesia following a surgery, according to a 2013 study. In part, this recovery takes so long because elderly patients are more likely to experience slight changes in their mental capacity, which may place them at higher risk for dementia — as much as 35 percent higher, the study found. Researchers believe this is because anesthesia causes inflammation to neural tissues. In turn, this increases a person’s chances of developing postoperative cognitive dysfunction (POCD) or precursors to Alzheimer’s disease, such as beta-amyloid plaques.

These findings suggest the elderly could use a lower dose of anesthesia before undergoing surgery. After all, they’re more prone to other health conditions, such as hypertension, diabetes, and heart disease, and might even be taking drugs to treat these conditions. Complications could arise from either of these factors when a person is put under.

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The Future Of Anesthesia

Researchers have gotten loads of insight regarding the effects of anesthetics on the brain thanks to fMRI. Yet despite knowing they can reliably put someone to sleep during surgery, without causing pain, they still don’t know every detail regarding how anesthetic drugs work. This compilation of studies suggests the brain undergoes changes in an anesthetic state, and that these drugs — if not used properly — can be harmful to patients. But until further research is completed to map the brain under anesthesia, we won’t know the best approach to dealing with them.