Anesthesia

• 1. Introduction

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  On the 16th of October 1846, a Boston dentist named William Thomas Green Morton stood in a surgical amphitheater and dripped diethyl ether toward a patient's face. The surgeon John Collins Warren then cut a tumor from the neck of a man named Edward Gilbert Abbott, and Abbott did not cry out. The skeptical Warren turned to the room and said, "Gentlemen, this is no humbug." The space where this happened is now called the Ether Dome. Soon after, the physician and writer Oliver Wendell Holmes Sr. wrote to Morton proposing a name for the state Morton had produced: anesthesia. Anesthesia is a controlled, temporary loss of sensation or awareness, induced for medical or veterinary purposes. It can mean relief from pain, muscle relaxation, loss of memory, unconsciousness, or some blend of all four. How can a person be cut open and feel nothing? What does it take to bring someone safely back to consciousness afterward? And who decides which drugs, and how much, for which patient? The answers reach from opium poppies in ancient Mesopotamia to a nurse who recorded thousands of cases without a single anesthetic death.

• 2. Three Routes To Numbness

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  General anesthesia suppresses the central nervous system entirely, producing unconsciousness and a total lack of sensation through injected or inhaled drugs. It is one of three broad categories the source lays out, each reaching the body by a different path. A patient under general anesthesia is unaware and unresponsive, with no memory of the procedure.

  Sedation, sometimes called twilight anesthesia or dissociative anesthesia, dials the nervous system down only partway. It inhibits anxiety and blocks the creation of long-term memories without tipping the patient into unconsciousness. From the outside the person looks sleepy, relaxed and forgetful. From the inside, the experience is general relaxation, loss of memory, and time passing quickly. Because sedatives such as benzodiazepines provide little pain relief on their own, they are usually paired with narcotics or local anesthetics.

  Regional and local anesthesia block nerve impulses from a specific part of the body. With local anesthesia a clinician infiltrates the drug directly onto the area of interest, such as numbing a tooth for dental work. Peripheral nerve blocks target peripheral nerves to anesthetize an isolated part, such as an entire limb. Neuraxial blockade, mainly epidural and spinal anesthesia, reaches into the region of the central nervous system itself. A patient may stay fully conscious under regional anesthesia alone, or it can be combined with general anesthesia or sedation. The choice among these routes turns on a small set of biological goals.

• 3. The Endpoints

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  Hypnosis, analgesia, and muscle relaxation are the three basic goals the source distills anesthesia down to. Hypnosis here carries a technical pharmacological meaning: a temporary loss of consciousness and with it a loss of memory, not the lay idea of an altered mental state. Analgesia is a lack of sensation that also blunts autonomic reflexes. Muscle relaxation is the third. Different techniques reach these endpoints differently. Regional anesthesia affects analgesia, benzodiazepine sedatives favor amnesia, and general anesthetics can touch all of them.

  Hypnosis is produced by drugs acting on nuclei in the brain, in a way similar to the activation of sleep, making people less aware and less reactive to harmful stimuli. Amnesia comes from drugs acting on multiple specific brain regions, interrupting how memories form. Memories are laid down as declarative or non-declarative, across short-term, long-term and long-lasting stages, their strength set by the connections between neurons known as synaptic plasticity. Inhalational anesthetics reliably produce amnesia at doses below those needed to cause loss of consciousness. A drug like midazolam works differently, blocking the formation of long-term memories.

  Not every brain goes fully dark. An estimated 22% of people dream under general anesthesia. One or two cases in a thousand experience some awareness of the procedure despite showing no sign of it, a phenomenon called anesthesia awareness. Whether animals dream under general anesthesia is not known. This uncertainty about the inner experience makes the work of assessing each patient beforehand all the more careful.

• 4. Reading The Patient

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  A well-completed medical history alone arrives at the correct diagnosis 56% of the time, rising to 73% once a physical examination is added. Lab tests, by contrast, help in only 3% of cases, which is why a full history and physical exam come first. Incorrect pre-operative assessment or preparation is the root cause of 11% of all adverse anesthetic events. The detailed history hunts for genetic disorders such as malignant hyperthermia or pseudocholinesterase deficiency, for habits like tobacco, drug and alcohol use, for physical traits such as obesity or a difficult airway, and for coexisting cardiac and respiratory disease.

  The American Society of Anesthesiologists built a six-tier scale to capture a patient's pre-operative state, the ASA physical status classification. ASA 1 is a healthy person and ASA 2 someone with mild systemic disease. ASA 3 marks severe systemic disease, ASA 4 severe disease that constantly threatens life, and ASA 5 a moribund person not expected to survive without the operation. ASA 6 is a declared brain-dead person whose organs are being removed for donation. An E suffix is added for emergency procedures.

  Specific surgical situations layer on extra considerations. Anesthesia during childbirth must account for both mother and baby. Cancers and tumors that occupy the lungs or throat create special challenges for general anesthesia. Of all the factors that shape anesthetic risk, the patient's own health carries the greatest weight, a fact the safety statistics bear out in stark numbers.

• 5. Building General Anesthesia

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  Harvey Cushing solved a problem that had been quietly killing surgical patients. Early anesthetics could reliably deliver the first two goals of general anesthesia, paralysis and unconsciousness, letting surgeons operate, yet patients still died because the extremes of blood pressure and pulse from the surgical insult proved harmful. Cushing injected local anesthetic before hernia repairs to blunt that stress response, and the recognition of this third goal led to other drugs that lowered surgical mortality.

  Inhaled general anesthetics remain the most common route to those endpoints. Each has a potency tied to its solubility in oil, because the drugs bind directly into cavities in proteins of the central nervous system. Their effects split across the body: the immobilizing effect comes from action on the spinal cord, while sedation, hypnosis and amnesia involve sites in the brain. Potency is measured by minimum alveolar concentration, or MAC, the percentage dose that prevents a response to painful stimulus in half of subjects. The higher the MAC, generally the less potent the drug.

  In the 1930s physicians began augmenting inhaled anesthetics with intravenous ones, which improved the risk profile and sped recovery. A combination of drugs was later shown to lower the odds of dying in the first seven days after an anesthetic. One modern sequence uses propofol to start, fentanyl to blunt the stress response, midazolam to ensure amnesia, and inhaled sevoflurane to maintain the effects through the procedure. Newer intravenous drugs now let inhaled anesthetics be avoided entirely when desired, though delivering any of this safely depends on machinery built to fail safely.

• 6. Machines And Monitors

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  Vaporizers, ventilators, a breathing circuit, a waste gas scavenging system and pressure gauges make up the anesthetic machine at the core of inhalational delivery. Its job is to supply anesthetic gas at constant pressure, deliver oxygen, and carry away carbon dioxide and waste gases. Because inhalational anesthetics are flammable, checklists confirm the machine is ready, its safety features active and electrical hazards removed. Intravenous anesthetic arrives instead by bolus doses or an infusion pump. The common thread running through this equipment is fail-safe design that reduces the odds of catastrophic misuse.

  Continuous physiological monitoring guards every patient under general anesthesia. In the United States the American Society of Anesthesiologists set minimum standards covering electrocardiography, heart rate, blood pressure, inspired and expired gases, blood oxygen saturation by pulse oximetry, and temperature. In the United Kingdom the Association of Anaesthetists set its own minimum guidelines. For minor surgery these include heart rate, oxygen saturation, blood pressure, and the inspired and expired concentrations of oxygen, carbon dioxide and inhalational agents. More invasive surgery can add temperature, urine output, central venous pressure, pulmonary artery pressures, cardiac output, cerebral activity and neuromuscular function. The operating room itself is watched too, for ambient temperature and humidity and for any buildup of exhaled anesthetic gases that could harm the staff who breathe that air every day.

• 7. Blocking The Nerve

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  Spinal anesthesia is a single one-shot injection into the subarachnoid space, giving rapid onset and deep sensory anesthesia at low doses, usually with loss of muscle control alongside. Epidural anesthesia instead uses larger doses fed through an indwelling catheter, which can be topped up if the effect begins to fade, and it typically leaves muscle control intact. Caudal anesthesia reaches the tail end of the spinal cord. These central neuraxial techniques deliver analgesia to the abdomen, pelvis or lower extremities. Because they cause arterial and venous vasodilation, a drop in blood pressure is common, driven largely by the venous side that holds 75% of the circulating blood volume. The effect grows much greater when the block sits above the 5th thoracic vertebra.

  Nerve blocks work farther out, around a larger nerve that carries sensation from an entire region. Dentists use them when the mandibular nerve is blocked for work on the lower teeth. For larger nerves, such as the interscalene block for upper limbs or the psoas compartment block for lower limbs, ultrasound or electrical stimulation locates the nerve and needle. Evidence supports ultrasound guidance, alone or with peripheral nerve stimulation, as superior for better sensory and motor block with fewer complications. Nerve blocks carry a lower risk of neurologic complications than the more central epidural or spinal blocks.

  Regional anesthesia may also ease pain long after surgery. A 2018 Cochrane review found moderate-quality evidence that it can reduce persistent postoperative pain from 3 to 18 months after thoracotomy and from 3 to 12 months after caesarean. The same review found only low-quality evidence 3 to 12 months after breast cancer surgery. Managing pain in this preemptive way can shape the body's whole response, because pain itself is not fixed but learned.

• 8. Counting The Risk

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  1:185,056 is the rate of death attributed to anesthesia alone, set against 1:870 for deaths attributed entirely to the patient's health and 1:2,860 for surgical factors. The single greatest driver of anesthetic mortality, those numbers show, is the health of the patient. Compare them to the first such study from 1954, which reported death from all causes at 1:75 and from anesthesia alone at 1:2,680. The source cautions that comparisons across time and country are unreliable because risk factors are stratified differently, though anesthetics have clearly grown safer by some uncertain degree. It was two years after ether was introduced that the first death directly tied to anesthesia was reported.

  Risk is reported through multipliers rather than a flat rate. A patient aged 60 to 79 faces 2.3 times the risk of someone under 60, and a patient over 80 faces 3.3 times. An ASA score of 3, 4 or 5 multiplies risk 10.7 times over a score of 1 or 2. Emergencies carry 4.4 times the risk, females a lower 0.8, and a less experienced operator 1.1 times. Regional anesthetics run lower risk than general ones. Obstetric patients, the very young and the very old all warrant extra precaution.

  On the 14th of December 2016 the Food and Drug Administration warned that repeated or lengthy use of general anesthetic and sedation drugs in children under 3, or in pregnant women in their third trimester, may affect children's brain development. The American College of Obstetricians and Gynecologists criticized the warning, noting the absence of direct evidence in pregnant women and the danger of dissuading needed care. Patient advocates countered that a randomized trial would be unethical, that the injury mechanism is well established in animals, and that multiple anesthetic exposures raised the risk of learning disabilities in young children, with a hazard ratio of 2.12. Recovery from this state carries its own quieter hazards, which surface only as the brain finds its way back.

  Emergence is the name for the immediate time after anesthesia, and it demands careful monitoring because complications still lurk. Nausea and vomiting are reported at 9.8%, varying with the anesthetic and procedure. Airway support is needed in 6.8% of cases and hypotension in 2.7%, while urinary retention is more common in those over 50. Hypothermia, shivering and confusion are frequent too, because the lack of muscle movement during surgery means little body heat is produced. A rarer outcome in this period is functional neurological symptom disorder.

  Andrew Hudson, an assistant professor in anesthesiology, describes recovery as something more active than a drug simply fading. Working from a study at the David Geffen School of Medicine at UCLA, he found the brain navigates a series of activity clusters, or hubs, on its way back to consciousness. "Recovery from anesthesia is not simply the result of the anesthetic 'wearing off,'" Hudson states, "but also of the brain finding its way back through a maze of possible activity states to those that allow conscious experience. Put simply, the brain reboots itself."

  Postoperative cognitive dysfunction, known as POCD, is a disturbance in cognition after surgery. It spans emergence delirium, early dysfunction in the first postoperative week, and a long-term form. The presence of delirium afterward predicts early POCD, though neither appears linked to the long-term version. Long-term POCD is a subtle decline lasting weeks, months or longer. Relatives often report lost attention and memory, and a fading interest in things once dear, such as crosswords. There is good evidence it follows cardiac surgery, where the major cause is the formation of microemboli. It appears after non-cardiac surgery too, where older age is a known risk factor.

  3400 BCE is roughly when the Sumerians are said to have cultivated the opium poppy, Papaver somniferum, in lower Mesopotamia. Alcohol, one of the oldest known sedatives, was used in ancient Mesopotamia thousands of years ago. The ancient Egyptians had crude analgesics and sedatives, possibly including an extract from the mandrake fruit. In China, the legendary internist and surgeon Bian Que, around 300 BCE, reportedly used general anesthesia, though historians treat the physician Hua Tuo as the first verifiable figure to develop an anesthetic mixture, his recipe still not fully discovered.

  The soporific sponge, soaked in opium, mandragora, hemlock juice and other substances, then dried and later moistened and held under a patient's nose, carried this knowledge through medieval Europe. Arabic physicians used it, the Salerno school of medicine introduced it to Europe in the late 12th century, and Theodoric Borgognoni, who lived from 1205 to 1298, described it. In Inca civilization, shamans chewed coca leaves and spat into skull wounds to anesthetize them. Cocaine was later isolated as the first effective local anesthetic, used in eye surgery in 1884 by Karl Koller at the suggestion of Sigmund Freud. German surgeon August Bier first used cocaine for intrathecal anesthesia in 1898.

  On the 14th of November 1804, Hanaoka Seishu, a Japanese doctor, became the first person to successfully perform surgery under general anesthesia, using a formula he named tsusensan that combined Korean morning glory with other herbs. Before his death in 1835 he performed more than 150 operations for breast cancer, yet the Tokugawa shogunate's isolation policy kept his work hidden from the world until 1854. In the West, Crawford Long gave general anesthesia in Jefferson, Georgia, operating on James Venable on the 30th of March 1842 after noticing friends felt no pain under ether, though Long did not announce it until 1849.

  Chloroform soon challenged ether, which suffered from vomiting and explosive flammability. Scottish obstetrician James Young Simpson first demonstrated chloroform's anesthetic properties on humans in 1847, and by 1895 Britain used 750,000 doses weekly. John Snow administered it to Queen Victoria during the birth of Prince Leopold in 1853, and she called the experience "delightful beyond measure." Yet on the 28th of January 1848 Hannah Greener became the first fatality directly attributed to chloroform, one of many to follow from untrained handling. That toll convinced surgeons they needed a dedicated, trained anesthetist.

  Alice Magaw, born in November 1860 and often called "The Mother of Anesthesia," recorded her cases with rare thoroughness. As the personal anesthesia provider for William and Charles Mayo, she reviewed more than 14,000 surgical anesthetics in one publication and reported not a single anesthetic-related death. In another article she wrote, "We have administered an anesthetic 1,092 times; ether alone 674 times; chloroform 245 times; ether and chloroform combined 173 times. I can report that out of this number, 1,092 cases, we have not had an accident." In his 1905 article William Mayo praised his reliance on nurse anesthetists, saying regular anaesthetists let him devote his entire attention to the surgical work.

  The specialty itself acquired a literature and a structure. The first comprehensive textbook on the subject, titled Anesthesia, was written in 1914 by anesthesiologist Dr. James Tayloe Gwathmey and chemist Dr. Charles Baskerville, and it stood as the standard reference for decades. International standards endorsed by the World Health Organization and the World Federation of Societies of Anaesthesiologists recommend that anesthesia be provided, overseen or led by anesthesiologists, except for minimal sedation or superficial local procedures. The same minimum safety standards apply to every provider, including continuous monitoring of tissue oxygenation, perfusion and blood pressure, confirmation of airway device placement by auscultation and carbon dioxide detection, and use of the WHO Surgical Safety Checklist.

  Who actually delivers the drug varies widely by country. In the United Kingdom, Australia, New Zealand, Hong Kong and Japan, all anesthetics are administered by doctors. Nurse anesthetists administer anesthesia in 109 nations. In the United States, about 35% of anesthetics come from physicians in solo practice, roughly 55% from anesthesia care teams in which anesthesiologists direct certified registered nurse anesthetists or anesthesiologist assistants, and about 10% from nurse anesthetists in solo practice. Of the first famous anesthetics, only nitrous oxide is still widely used today, while chloroform and ether have given way to safer general anesthetics and cocaine to local anesthetics with less abuse potential.