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If you’ve had surgery, you might remember starting to count backwards from ten, nine, eight, and then waking up with the surgery already over before you even got to five. And it might seem like you were asleep, but you weren’t. You were under anesthesia, which is much more complicated. You were unconscious, but you also couldn’t move, form memories, or, hopefully, feel pain. Without being able to block all those processes at once, many surgeries would be way too traumatic to perform. Ancient medical texts from Egypt, Asia and the Middle East all describe early anesthetics containing things like opium poppy, mandrake fruit, and alcohol. Today, anesthesiologists often combine regional, inhalational and intravenous agents to get the right balance for a surgery. Regional anesthesia blocks pain signals from a specific part of the body from getting to the brain. Pain and other messages travel through the nervous system as electrical impulses. Regional anesthetics work by setting up an electrical barricade. They bind to the proteins in neurons’ cell membranes that let charged particles in and out, and lock out positively charged particles. One compound that does this is cocaine, whose painkilling effects were discovered by accident when an ophthalmology intern got some on his tongue. It’s still occasionally used as an anesthetic, but many of the more common regional anesthetics have a similar chemical structure and work the same way. But for major surgeries where you need to be unconscious, you’ll want something that acts on the entire nervous system, including the brain. That’s what inhalational anesthetics do. In Western medicine, diethyl ether was the first common one. It was best known as a recreational drug until doctors started to realize that people sometimes didn’t notice injuries they received under the influence. In the 1840s, they started sedating patients with ether during dental extractions and surgeries. Nitrous oxide became popular in the decades that followed and is still used today. although ether derivatives, like sevoflurane, are more common. Inhalational anesthesia is usually supplemented with intravenous anesthesia, which was developed in the 1870s. Common intravenous agents include sedatives, like propofol, which induce unconsciousness, and opioids, like fentanyl, which reduce pain. These general anesthetics also seem to work by affecting electrical signals in the nervous system. Normally, the brain’s electrical signals are a chaotic chorus as different parts of the brain communicate with each other. That connectivity keeps you awake and aware. But as someone becomes anesthetized, those signals become calmer and more organized, suggesting that different parts of the brain aren’t talking to each other anymore. There’s a lot we still don’t know about exactly how this happens. Several common anesthetics bind to the GABA-A receptor in the brain’s neurons. They hold the gateway open, letting negatively charged particles flow into the cell. Negative charge builds up and acts like a log jam, keeping the neuron from transmitting electrical signals. The nervous system has lots of these gated channels, controlling pathways for movement, memory, and consciousness. Most anesthetics probably act on more than one, and they don’t act on just the nervous system. Many anesthetics also affect the heart, lungs, and other vital organs. Just like early anesthetics, which included familiar poisons like hemlock and aconite, modern drugs can have serious side effects. So an anesthesiologist has to mix just the right balance of drugs to create all the features of anesthesia, while carefully monitoring the patient’s vital signs, and adjusting the drug mixture as needed. Anesthesia is complicated, but figuring out how to use it allowed for the development of new and better surgical techniques. Surgeons could learn how to routinely and safely perform C-sections, reopen blocked arteries, replace damaged livers and kidneys, and many other life-saving operations. And each year, new anesthesia techniques are developed that will ensure more and more patients survive the trauma of surgery.