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Wednesday, February 6, 2019

Anesthesia

From Wikipedia, the free encyclopedia

Anesthesia
Preoxygenation before anesthetic induction.jpg
A child being prepared to go under anesthesia
Pronunciation/ˌænɪsˈθziə, -siə, -ʒə/
MeSHE03.155
MedlinePlusanesthesia
eMedicine1271543

Anesthesia or anaesthesia (from Greek "without sensation") is a state of controlled, temporary loss of sensation or awareness that is induced for medical purposes. It may include analgesia (relief from or prevention of pain), paralysis (muscle relaxation), amnesia (loss of memory), or unconsciousness. A patient under the effects of anesthetic drugs is referred to as being anesthetized.

Anesthesia enables the painless performance of medical procedures that would otherwise cause severe or intolerable pain to an unanesthetized patient, or would otherwise be technically unfeasible. Three broad categories of anesthesia exist:
  • General anesthesia suppresses central nervous system activity and results in unconsciousness and total lack of sensation.
  • Sedation suppresses the central nervous system to a lesser degree, inhibiting both anxiety and creation of long-term memories without resulting in unconsciousness.
  • Regional and local anesthesia, which block transmission of nerve impulses from a specific part of the body. Depending on the situation, this may be used either on its own (in which case the patient remains conscious), or in combination with general anesthesia or sedation. Drugs can be targeted at peripheral nerves to anesthetize an isolated part of the body only, such as numbing a tooth for dental work or using a nerve block to inhibit sensation in an entire limb. Alternatively, epidural or spinal anesthesia can be performed in the region of the central nervous system itself, suppressing all incoming sensation from nerves outside the area of the block.
In preparing for a medical procedure, the clinician chooses one or more drugs to achieve the types and degree of anesthesia characteristics appropriate for the type of procedure and the particular patient. The types of drugs used include general anesthetics, local anesthetics, hypnotics, sedatives, neuromuscular-blocking drugs, narcotics, and analgesics.

Risks during and following anesthesia are difficult to quantify, since many may be related to a variety of factors related to anesthesia itself, the nature of the procedure being performed and the patient's medical health. Examples of major risks include death, heart attack and pulmonary embolism whereas minor risks can include postoperative nausea and vomiting and hospital readmission. Of these factors, the person's health prior to the procedure(stratified by the ASA physical status classification system) has the greatest bearing on the probability of a complication occurring. Patients typically wake within minutes of anesthesia being terminated and regain their senses within hours.

Medical uses

The purpose of anesthesia can be distilled down to three basic goals or endpoints:
  • hypnosis (a temporary loss of consciousness and with it a loss of memory. In a pharmacological context, the word hypnosis usually has this technical meaning, in contrast to its more familiar lay or psychological meaning of an altered state of consciousness not necessarily caused by drugs).
  • analgesia (lack of sensation which also blunts autonomic reflexes)
  • muscle relaxation
Different types of anesthesia affect the endpoints differently. Regional anesthesia, for instance, affects analgesia; benzodiazepine-type sedatives (used for sedation, or "twilight anesthesia") favor amnesia; and general anesthetics can affect all of the endpoints. The goal of anesthesia is to achieve the endpoints required for the given surgical procedure with the least risk to the patient. 

The anesthetic area of an operating room
 
To achieve the goals of anesthesia, drugs act on different but interconnected parts of the nervous system. Hypnosis, for instance, is generated through actions on the nuclei in the brain and is similar to the activation of sleep. The effect is to make people less aware and less reactive to noxious stimuli.

Loss of memory (amnesia) is created by action of drugs on multiple (but specific) regions of the brain. Memories are created as either declarative or non-declarative memories in several stages (short-term, long-term, long-lasting) the strength of which is determined by the strength of connections between neurons termed synaptic plasticity. Each anesthetic produces amnesia through unique effects on memory formation at variable doses. Inhalational anesthetics will reliably produce amnesia through general suppression of the nuclei at doses below those required for loss of consciousness. Drugs like midazolam produce amnesia through different pathways by blocking the formation of long-term memories.

Tied closely to the concepts of amnesia and hypnosis is the concept of consciousness. Consciousness is the higher order process that synthesizes information. For instance, the "sun" conjures up feelings, memories and a sensation of warmth rather than a description of a round, orange warm ball seen in the sky for part of a 24‑hour cycle. Likewise, a person can have dreams (a state of subjective consciousness) during anesthetic or have consciousness of the procedure despite having no indication of it under anesthetic. It is estimated that 22% of people dream during general anesthesia and 1 or 2 cases per 1000 have some consciousness termed "awareness during general anesthesia".

Techniques

Safe anesthesia care depends greatly on well-functioning teams of highly trained healthcare workers. The medical specialty centred around anesthesia is called anesthesiology, and medical doctors who practise it are termed anesthesiologists. Non-medical healthcare workers involved in anesthesia provision have varying titles and roles depending on the jurisdiction, and include nurse anesthetists, anesthetic nurses, anesthesiologist assistants, anaesthetic technicians, physicians' assistants (anaesthesia), operating department practitioners and anesthesia technologists. International standards for the safe practice of anesthesia, jointly endorsed by the World Health Organization and the World Federation of Societies of Anaesthesiologists, highly recommend that anesthesia should be provided, overseen or led by anesthesiologists, with the exception of minimal sedation or superficial procedures performed under local anesthesia. A trained, vigilant anesthesia provider should continually care for the patient; where the provider is not an anesthesiologist, they should be locally directed and supervised by an anesthesiologist, and in countries or settings where this is not feasible, care should be led by the most qualified local individual within a regional or national anesthesiologist-led framework. The same minimum standards for patient safety apply regardless of the provider, including continuous clinical and biometric monitoring of tissue oxygenation, perfusion and blood pressure; confirmation of correct placement of airway management devices by auscultation and carbon dioxide detection; use of the WHO Surgical Safety Checklist; and safe onward transfer of the patient's care following the procedure.

Anesthesia is unique in that it is not a direct means of treatment; rather, it allows others to do things that may treat, diagnose, or cure an ailment which would otherwise be painful or complicated. The best anesthetic, therefore, is the one with the lowest risk to the patient that still achieves the endpoints required to complete the procedure. The first stage in anesthesia is the pre-operative risk assessment consisting of the medical history, physical examination and lab tests. Diagnosing a person's pre-operative physical status allows the clinician to minimize anesthetic risks. A well completed medical history will arrive at the correct diagnosis 56% of the time which increases to 73% with a physical examination. Lab tests help in diagnosis but only in 3% of cases, underscoring the need for a full history and physical examination prior to anesthetics. Incorrect pre-operative assessments or preparations are the root cause of 11% of all adverse anesthetic events.

ASA physical status classification system
ASA class Physical status
ASA 1 Healthy person
ASA 2 Mild systemic disease
ASA 3 Severe systemic disease
ASA 4 Severe systemic disease that is a constant threat to life
ASA 5 A moribund person who is not expected to survive without the operation
ASA 6 A declared brain-dead person whose organs are being removed for donor purposes
E Suffix added for patients undergoing emergency procedure

One part of the risk assessment is based on the patients' health. The American Society of Anesthesiologists has developed a six-tier scale that stratifies the patient's pre-operative physical state. It is called the ASA physical status. The scale assesses risk as the patient's general health relates to an anesthetic.

The more detailed pre-operative medical history aims to discover genetic disorders (such as malignant hyperthermia or pseudocholinesterase deficiency), habits (tobacco, drug and alcohol use), physical attributes (such as obesity or a difficult airway) and any coexisting diseases (especially cardiac and respiratory diseases) that might impact the anesthetic. The physical examination helps quantify the impact of anything found in the medical history in addition to lab tests.

Aside from the generalities of the patients health assessment, an evaluation of specific factors as they relate to the surgery also need to be considered for anesthesia. For instance, anesthesia during childbirth must consider not only the mother but the baby. Cancers and tumors that occupy the lungs or throat create special challenges to general anesthesia. After determining the health of the person undergoing anesthetic and the endpoints that are required to complete the procedure, the type of anesthetic can be selected. Choice of surgical method and anesthetic technique aims to reduce risk of complications, shorten time needed for recovery and minimise the surgical stress response.

General anesthesia

A vaporizer holds a liquid anesthetic and converts it to gas for inhalation (in this case sevoflurane)
 
Anesthesia is a combination of the endpoints (discussed above) that are reached by drugs acting on different but overlapping sites in the central nervous system. General anesthesia (as opposed to sedation or regional anesthesia) has three main goals: lack of movement (paralysis), unconsciousness, and blunting of the stress response. In the early days of anesthesia, anesthetics could reliably achieve the first two, allowing surgeons to perform necessary procedures, but many patients died because the extremes of blood pressure and pulse caused by the surgical insult were ultimately harmful. Eventually, the need for blunting of the surgical stress response was identified by Harvey Cushing, who injected local anesthetic prior to hernia repairs. This led to the development of other drugs that could blunt the response leading to lower surgical mortality rates

The most common approach to reach the endpoints of general anesthesia is through the use of inhaled general anesthetics. Each anesthetic has its own potency which is correlated to its solubility in oil. This relationship exists because the drugs bind directly to cavities in proteins of the central nervous system, although several theories of general anesthetic action have been described. Inhalational anesthetics are thought to exact their effects on different parts of the central nervous system. For instance, the immobilizing effect of inhaled anesthetics results from an effect on the spinal cord whereas sedation, hypnosis and amnesia involve sites in the brain. The potency of an inhalational anesthetic is quantified by its minimum alveolar concentration or MAC. The MAC is the percentage dose of anesthetic that will prevent a response to painful stimulus in 50% of subjects. The higher the MAC, generally, the less potent the anesthetic. 

Syringes prepared with medications that are expected to be used during an operation under general anesthesia maintained by sevoflurane gas: 

- Propofol, an hypnotic
- Ephedrine, in case of hypotension
- Fentanyl, for analgesia
- Atracurium, for neuromuscular blockade
- Glycopyrronium bromide (here under trade name "Robinul"), reducing secretions

The ideal anesthetic drug would provide hypnosis, amnesia, analgesia, and muscle relaxation without undesirable changes in blood pressure, pulse or breathing. In the 1930s, physicians started to augment inhaled general anesthetics with intravenous general anesthetics. The drugs used in combination offered a better risk profile to the person under anesthesia and a quicker recovery. A combination of drugs was later shown to result in lower odds of dying in the first 7 days after anesthetic. For instance, propofol (injection) might be used to start the anesthetic, fentanyl (injection) used to blunt the stress response, midazolam (injection) given to ensure amnesia and sevoflurane (inhaled) during the procedure to maintain the effects. More recently, several intravenous drugs have been developed which, if desired, allow inhaled general anesthetics to be avoided completely.

Equipment

The core instrument in an inhalational anesthetic delivery system is an anesthetic machine. It has vaporizers, ventilators, an anesthetic breathing circuit, waste gas scavenging system and pressure gauges. The purpose of the anesthetic machine is to provide anesthetic gas at a constant pressure, oxygen for breathing and to remove carbon dioxide or other waste anesthetic gases. Since inhalational anesthetics are flammable, various checklists have been developed to confirm that the machine is ready for use, that the safety features are active and the electrical hazards are removed. Intravenous anesthetic is delivered either by bolus doses or an infusion pump. There are also many smaller instruments used in airway management and monitoring the patient. The common thread to modern machinery in this field is the use of fail-safe systems that decrease the odds of catastrophic misuse of the machine.

Monitoring

An anesthetic machine with integrated systems for monitoring of several vital parameters.

Patients under general anesthesia must undergo continuous physiological monitoring to ensure safety. In the US, the American Society of Anesthesiologists (ASA) has established minimum monitoring guidelines for patients receiving general anesthesia, regional anesthesia, or sedation. These include electrocardiography (ECG), heart rate, blood pressure, inspired and expired gases, oxygen saturation of the blood (pulse oximetry), and temperature. In the UK the Association of Anaesthetists (AAGBI) have set minimum monitoring guidelines for general and regional anesthesia. For minor surgery, this generally includes monitoring of heart rate, oxygen saturation, blood pressure, and inspired and expired concentrations for oxygen, carbon dioxide, and inhalational anesthetic agents. For more invasive surgery, monitoring may also include temperature, urine output, blood pressure, central venous pressure, pulmonary artery pressure and pulmonary artery occlusion pressure, cardiac output, cerebral activity, and neuromuscular function. In addition, the operating room environment must be monitored for ambient temperature and humidity, as well as for accumulation of exhaled inhalational anesthetic agents, which might be deleterious to the health of operating room personnel.

Sedation

Sedation (also referred to as dissociative anesthesia or twilight anesthesia) creates hypnotic, sedative, anxiolytic, amnesic, anticonvulsant, and centrally produced muscle-relaxing properties. From the perspective of the person giving the sedation, the patient appears sleepy, relaxed and forgetful, allowing unpleasant procedures to be more easily completed. Sedatives such as benzodiazepines are usually given with pain relievers (such as narcotics, or local anesthetics or both) because they do not, by themselves, provide significant pain relief.

From the perspective of the person receiving a sedative, the effect is a feeling of general relaxation, amnesia (loss of memory) and time passing quickly. Many drugs can produce a sedative effect including benzodiazepines, propofol, thiopental, ketamine and inhaled general anesthetics. The advantage of sedation over a general anesthetic is that it generally does not require support of the airway or breathing (no tracheal intubation or mechanical ventilation) and can have less of an effect on the cardiovascular system which may add to a greater margin of safety in some patients.

Regional anesthesia

Sonography guided femoral nerve block
 
Backflow of cerebrospinal fluid through a spinal needle after puncture of the arachnoid mater during spinal anesthesia

When pain is blocked from a part of the body using local anesthetics, it is generally referred to as regional anesthesia. There are many types of regional anesthesia either by injecting into the tissue itself, a vein that feeds the area or around a nerve trunk that supplies sensation to the area. The latter are called nerve blocks and are divided into peripheral or central nerve blocks. 

The following are the types of regional anesthesia:
  • Infiltrative anesthesia: a small amount of local anesthetic is injected in a small area to stop any sensation (such as during the closure of a laceration, as a continuous infusion or "freezing" a tooth). The effect is almost immediate.
  • Peripheral nerve block: local anesthetic is injected near a nerve that provides sensation to particular portion of the body. There is significant variation in the speed of onset and duration of anesthesia depending on the potency of the drug (e.g. Mandibular block).
  • Intravenous regional anesthesia (also called a Bier block): dilute local anesthetic is infused to a limb through a vein with a tourniquet placed to prevent the drug from diffusing out of the limb.
  • Central nerve blockade: Local anesthetic is injected or infused in or around a portion of the central nervous system (discussed in more detail below in Spinal, epidural and caudal anesthesia).
  • Topical anesthesia: local anesthetics that are specially formulated to diffuse through the mucous membranes or skin to give a thin layer of analgesia to an area (e.g. EMLA patches).
  • Tumescent anesthesia: a large amount of very dilute local anesthetics are injected into the subcutaneous tissues during liposuction.
  • Systemic local anesthetics: local anesthetics are given systemically (orally or intravenous) to relieve neuropathic pain

Nerve blocks

When local anesthetic is injected around a larger diameter nerve that transmits sensation from an entire region it is referred to as a nerve block or regional nerve blockade. Nerve blocks are commonly used in dentistry, when the mandibular nerve is blocked for procedures on the lower teeth. With larger diameter nerves (such as the interscalene block for upper limbs or psoas compartment block for lower limbs) the nerve and position of the needle is localized with ultrasound or electrical stimulation. The use of ultrasound may reduce complication rates and improve quality, performance time, and time to onset of blocks. Because of the large amount of local anesthetic required to affect the nerve, the maximum dose of local anesethetic has to be considered. Nerve blocks are also used as a continuous infusion, following major surgery such as knee, hip and shoulder replacement surgery, and may be associated with lower complications. Nerve blocks are also associated with a lower risk of neurologic complications compared to the more central epidural or spinal neuraxial blocks.

Spinal, epidural and caudal anesthesia

Central neuraxial anesthesia is the injection of local anesthetic around the spinal cord to provide analgesia in the abdomen, pelvis or lower extremities. It is divided into either spinal (injection into the subarachnoid space), epidural (injection outside of the subarachnoid space into the epidural space) and caudal (injection into the cauda equina or tail end of the spinal cord). Spinal and epidural are the most commonly used forms of central neuraxial blockade. 

Spinal anesthesia is a "one-shot" injection that provides rapid onset and profound sensory anesthesia with lower doses of anesethetic, and is usually associated with neuromuscular blockade (loss of muscle control). Epidural anesthesia uses larger doses of anesthetic infused through an indwelling catheter which allows the anesthetic to be augmented should the effects begin to dissipate. Epidural anesthesia does not typically affect muscle control. 

Because central neuraxial blockade causes arterial and vasodilation, a drop in blood pressure is common. This drop is largely dictated by the venous side of the circulatory system which holds 75% of the circulating blood volume. The physiologic effects are much greater when the block is placed above the 5th thoracic vertebra. An ineffective block is most often due to inadequate anxiolysis or sedation rather than a failure of the block itself.

Acute pain management

A patient-controlled analgesia infusion pump, configured for epidural administration of fentanyl and bupivacainefor postoperative analgesia

Pain that is well managed during and immediately after surgery improves the health of patients (by decreasing physiologic stress) and the potential for chronic pain. Nociception (pain sensation) is not hard-wired into the body. Instead, it is a dynamic process wherein persistent painful stimuli can sensitize the system and either make pain management difficult or promote the development of chronic pain. For this reason, preemptive acute pain management may reduce both acute and chronic pain and is tailored to the surgery, the environment in which it is given (in-patient/out-patient) and the individual patient.

Pain management is classified into either pre-emptive or on-demand. On-demand pain medications typically include either opioid or non-steroidal anti-inflammatory drugs but can also make use of novel approaches such as inhaled nitrous oxide or ketamine. On demand drugs can be administered by a clinician ("as needed drug orders") or by the patient using patient-controlled analgesia (PCA). PCA has been shown to provide slightly better pain control and increased patient satisfaction when compared with conventional methods. Common preemptive approaches include epidural neuraxial blockade or nerve blocks. One review which looked at pain control after abdominal aortic surgery found that epidural blockade provides better pain relief (especially during movement) in the period up to three postoperative days. It reduces the duration of postoperative tracheal intubation by roughly half. The occurrence of prolonged postoperative mechanical ventilation and myocardial infarction is also reduced by epidural analgesia.

Risks and complications

Risks and complications as they relate to anesthesia are classified as either morbidity (a disease or disorder that results from anesthesia) or mortality (death that results from anesthesia). Quantifying how anesthesia contributes to morbidity and mortality can be difficult because a person's health prior to surgery and the complexity of the surgical procedure can also contribute to the risks.

Anesthesia-related deaths by ASA status
 
Prior to the introduction of anesthesia in the early 19th century, the physiologic stress from surgery caused significant complications and many deaths from shock. The faster the surgery was, the lower the rate of complications (leading to reports of very quick amputations). The advent of anesthesia allowed more complicated and life-saving surgery to be completed, decreased the physiologic stress of the surgery, but added an element of risk. It was two years after the introduction of ether anesthetics that the first death directly related to the use of anesthesia was reported.

Morbidity can be major (myocardial infarction, pneumonia, pulmonary embolism, renal failure/insufficiency, postoperative cognitive dysfunction and allergy) or minor (minor nausea, vomiting, readmission). There is usually overlap in the contributing factors that lead to morbidity and mortality between the health of the patient, the type of surgery being performed and the anesthetic. To understand the relative risk of each contributing factor, consider that the rate of deaths totally attributed to the patient's health is 1:870. Compare that to the rate of deaths totally attributed to surgical factors (1:2860) or anesthesia alone (1:185,056) illustrating that the single greatest factor in anesthetic mortality is the health of the patient. These statistics can also be compared to the first such study on mortality in anesthesia from 1954, which reported a rate of death from all causes at 1:75 and a rate attributed to anesthesia alone at 1:2680. Direct comparisons between mortality statistics cannot reliably be made over time and across countries because of differences in the stratification of risk factors, however, there is evidence that anesthetics have made a significant improvement in safety but to what degree is uncertain.

Rather than stating a flat rate of morbidity or mortality, many factors are reported as contributing to the relative risk of the procedure and anesthetic combined. For instance, an operation on a person who is between the ages of 60–79 years old places the patient at 2.3 times greater risk than someone less than 60 years old. Having an ASA score of 3, 4 or 5 places the person at 10.7 times greater risk than someone with an ASA score of 1 or 2. Other variables include age greater than 80 (3.3 times risk compared to those under 60), gender (females have a lower risk of 0.8), urgency of the procedure (emergencies have a 4.4 times greater risk), experience of the person completing the procedure (less than 8 years experience and/or less than 600 cases have a 1.1 times greater risk) and the type of anesthetic (regional anesthetics are lower risk than general anesthetics). Obstetrical, the very young and the very old are all at greater risk of complication so extra precautions may need to be taken.

On 14 December 2016 the Food and Drug Administration issued a Public Safety Communication warning that "repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains." The warning was criticized by the American College of Obstetricians and Gynecologists, which pointed out the absence of direct evidence regarding use in pregnant women and the possibility that "this warning could inappropriately dissuade providers from providing medically indicated care during pregnancy."  Patient advocates noted that a randomized clinical trial would be unethical, that the mechanism of injury is well-established in animals, and that studies had shown exposure to multiple uses of anesthetic significantly increased the risk of developing learning disabilities in young children, with a hazard ratio of 2.12 (95% confidence interval, 1.26–3.54).

Recovery

The immediate time after anesthesia is called emergence. Emergence from general anesthesia or sedation requires careful monitoring because there is still a risk of complication. Nausea and vomiting are reported at 9.8% but will vary with the type of anesthetic and procedure. There is a need for airway support in 6.8%, there can be urinary retention (more common in those over 50 years of age) and hypotension in 2.7%. Hypothermia, shivering and confusion are also common in the immediate post-operative period because of the lack of muscle movement (and subsequent lack of heat production) during the procedure.

Postoperative cognitive dysfunction (also known as POCD and post-anesthetic confusion) is a disturbance in cognition after surgery. It may also be variably used to describe emergence delirium (immediate post-operative confusion) and early cognitive dysfunction (diminished cognitive function in the first post-operative week). Although the three entities (delirium, early POCD and long-term POCD) are separate, the presence of delirium post-operatively predicts the presence of early POCD. There does not appear to be an association between delirium or early POCD and long-term POCD. According to a recent study conducted at the David Geffen School of Medicine at UCLA, the brain navigates its way through a series of activity clusters, or "hubs" on its way back to consciousness. Dr. Andrew Hudson, an assistant professor in anesthesiology states, "Recovery from anesthesia is not simply the result of the anesthetic 'wearing off,' 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."

Long-term POCD is a subtle deterioration in cognitive function, that can last for weeks, months, or longer. Most commonly, relatives of the person report a lack of attention, memory and loss of interest in activities previously dear to the person (such as crosswords). In a similar way, people in the workforce may report an inability to complete tasks at the same speed they could previously. There is good evidence that POCD occurs after cardiac surgery and the major reason for its occurrence is the formation of microemboli. POCD also appears to occur in non-cardiac surgery. Its causes in non-cardiac surgery are less clear but older age is a risk factor for its occurrence.

History

The first attempts at general anesthesia were probably herbal remedies administered in prehistory. Alcohol is one of the oldest known sedatives and it was used in ancient Mesopotamia thousands of years ago. The Sumerians are said to have cultivated and harvested the opium poppy (Papaver somniferum) in lower Mesopotamia as early as 3400 BC.

The ancient Egyptians had some surgical instruments, as well as crude analgesics and sedatives, including possibly an extract prepared from the mandrake fruit. Bian Que (Chinese: 扁鹊, Wade–Giles: Pien Ch'iao, c. 300 BC) was a legendary Chinese internist and surgeon who reportedly used general anesthesia for surgical procedures. 

Throughout Europe, Asia, and the Americas a variety of Solanum species containing potent tropane alkaloids were used for anesthesia. In 13th-century Italy, Theodoric Borgognoni used similar mixtures along with opiates to induce unconsciousness, and treatment with the combined alkaloids proved a mainstay of anesthesia until the nineteenth century. Local anesthetics were used in Inca civilization where shamans chewed coca leaves and performed operations on the skull while spitting into the wounds they had inflicted to anesthetize. Cocaine was later isolated and became the first effective local anesthetic. It was first used in 1859 by Karl Koller, at the suggestion of Sigmund Freud, in eye surgery in 1884. German surgeon August Bier (1861–1949) was the first to use cocaine for intrathecal anesthesia in 1898. Romanian surgeon Nicolae Racoviceanu-Piteşti (1860–1942) was the first to use opioids for intrathecal analgesia; he presented his experience in Paris in 1901.

Early Arab writings mention anesthesia by inhalation. This idea was the basis of the "soporific sponge" ("sleep sponge"), introduced by the Salerno school of medicine in the late twelfth century and by Ugo Borgognoni (1180–1258) in the thirteenth century. The sponge was promoted and described by Ugo's son and fellow surgeon, Theodoric Borgognoni (1205–1298). In this anesthetic method, a sponge was soaked in a dissolved solution of opium, mandragora, hemlock juice, and other substances. The sponge was then dried and stored; just before surgery the sponge was moistened and then held under the patient's nose. When all went well, the fumes rendered the patient unconscious.

Sir Humphry Davy’s Researches chemical and philosophical: chiefly concerning nitrous oxide (1800), pages 556 and 557 (right), outlining potential anesthetic properties of nitrous oxide in relieving pain during surgery
 
The most famous anesthetic, ether, may have been synthesized as early as the 8th century, but it took many centuries for its anesthetic importance to be appreciated, even though the 16th century physician and polymath Paracelsus noted that chickens made to breathe it not only fell asleep but also felt no pain. By the early 19th century, ether was being used by humans, but only as a recreational drug.

Meanwhile, in 1772, English scientist Joseph Priestley discovered the gas nitrous oxide. Initially, people thought this gas to be lethal, even in small doses, like some other nitrogen oxides. However, in 1799, British chemist and inventor Humphry Davy decided to find out by experimenting on himself. To his astonishment he found that nitrous oxide made him laugh, so he nicknamed it "laughing gas". In 1800 Davy wrote about the potential anesthetic properties of nitrous oxide in relieving pain during surgery, but nobody at that time pursued the matter any further.

American physician Crawford W. Long noticed that his friends felt no pain when they injured themselves while staggering around under the influence of diethyl ether. He immediately thought of its potential in surgery. Conveniently, a participant in one of those "ether frolics", a student named James Venable, had two small tumors he wanted excised. But fearing the pain of surgery, Venable kept putting the operation off. Hence, Long suggested that he have his operation while under the influence of ether. Venable agreed, and on 30 March 1842 he underwent a painless operation. However, Long did not announce his discovery until 1849.

Contemporary re-enactment of Morton's 16 October 1846, ether operation; daguerrotype by Southworth & Hawes
 
Morton's ether inhaler

Horace Wells conducted the first public demonstration of the inhalational anesthetic at the Massachusetts General Hospital in Boston in 1845. However, the nitrous oxide was improperly administered and the patient cried out in pain. On 16 October 1846, Boston dentist William Thomas Green Morton gave a successful demonstration using diethyl ether to medical students at the same venue. Morton, who was unaware of Long's previous work, was invited to the Massachusetts General Hospital to demonstrate his new technique for painless surgery. After Morton had induced anesthesia, surgeon John Collins Warren removed a tumor from the neck of Edward Gilbert Abbott. This occurred in the surgical amphitheater now called the Ether Dome. The previously skeptical Warren was impressed and stated, "Gentlemen, this is no humbug." In a letter to Morton shortly thereafter, physician and writer Oliver Wendell Holmes, Sr. proposed naming the state produced "anesthesia", and the procedure an "anesthetic".

Morton at first attempted to hide the actual nature of his anesthetic substance, referring to it as Letheon. He received a US patent for his substance, but news of the successful anesthetic spread quickly by late 1846. Respected surgeons in Europe including Liston, Dieffenbach, Pirogov, and Syme quickly undertook numerous operations with ether. An American-born physician, Boott, encouraged London dentist James Robinson to perform a dental procedure on a Miss Lonsdale. This was the first case of an operator-anesthetist. On the same day, 19 December 1846, in Dumfries Royal Infirmary, Scotland, a Dr. Scott used ether for a surgical procedure. The first use of anesthesia in the Southern Hemisphere took place in Launceston, Tasmania, that same year. Drawbacks with ether such as excessive vomiting and its explosive flammability led to its replacement in England with chloroform

Discovered in 1831 by an American physician Samuel Guthrie (1782–1848), and independently a few months later by Frenchman Eugène Soubeiran (1797–1859) and Justus von Liebig (1803–73) in Germany, chloroform was named and chemically characterised in 1834 by Jean-Baptiste Dumas (1800–84). In 1842, Dr Robert Mortimer Glover in London discovered the anaesthetic qualities of chloroform on laboratory animals. In 1847, Scottish obstetrician James Young Simpson was the first to demonstrate the anesthetic properties of chloroform on humans and helped to popularise the drug for use in medicine. Its use spread quickly and gained royal approval in 1853 when John Snow gave it to Queen Victoria during the birth of Prince Leopold. During the birth itself, chloroform met all the Queen’s expectations; she stated it was “delightful beyond measure”. Unfortunately, though free of ether's flammability and consequent explosion hazard, chloroform is not as safe pharmacologically, especially when administered by an untrained practitioner (medical students, nurses, and occasionally members of the public were often pressed into giving anesthetics at this time). This led to many deaths from the use of chloroform that (with hindsight) might have been preventable. The first fatality directly attributed to chloroform anesthesia was recorded on 28 January 1848 after the death of Hannah Greener.

John Snow of London published articles from May 1848 onwards "On Narcotism by the Inhalation of Vapours" in the London Medical Gazette. Snow also involved himself in the production of equipment needed for the administration of inhalational anesthetics, the forerunner of today's anesthesia machines.

The first comprehensive medical textbook on the subject, Anesthesia, was authored in 1914 by anesthesiologist Dr. James Tayloe Gwathmey and the chemist Dr. Charles Baskerville. This book served as the standard reference for the specialty for decades and included details on the history of anesthesia as well as the physiology and techniques of inhalation, rectal, intravenous, and spinal anesthesia.

Of these first famous anesthetics, only nitrous oxide is still widely used today, with chloroform and ether having been replaced by safer but sometimes more expensive general anesthetics, and cocaine by more effective local anesthetics with less abuse potential.

Society and culture

Almost all healthcare providers use anesthetic drugs to some degree, but most health professions have their own field of specialists in the field including medicine, nursing and dentistry. 

Doctors specializing in anaesthesiology, including perioperative care, development of an anesthetic plan, and the administration of anesthetics are known in the US as anesthesiologists and in the UK, Canada, Australia, and NZ as anaesthetists or anaesthesiologists. All anesthetics in the UK, Australia, New Zealand, Hong Kong and Japan are administered by doctors. Nurse anesthetists also administer anesthesia in 109 nations. In the US, 35% of anesthetics are provided by physicians in solo practice, about 55% are provided by anesthesia care teams (ACTs) with anesthesiologists medically directing anesthesiologist assistants or certified registered nurse anesthetists (CRNAs), and about 10% are provided by CRNAs in solo practice. There can also be anesthesiologist assistants (US) or physicians' assistants (anaesthesia) (UK) who assist with anesthesia.

Special populations

There are many circumstances when anesthesia needs to be altered for special circumstances due to the procedure (such as in cardiac surgery, cardiothoracic anesthesiology or neurosurgery), the patient (such as in pediatric anesthesia, geriatric, bariatric or obstetrical anesthesia) or special circumstances (such as in trauma, prehospital care, robotic surgery or extreme environments).

Cryonics (updated)

From Wikipedia, the free encyclopedia

Technicians prepare a body for cryopreservation in 1985.
 
Cryonics (from Greek κρύος kryos meaning 'cold') is the low-temperature freezing (usually at −196 °C) of a human corpse, with the hope that resuscitation may be possible in the future. It is regarded with skepticism within the mainstream scientific community and has been characterized as quackery.

Cryonics procedures can only begin after clinical death, and cryonics "patients" are legally dead. Cryonics procedures ideally begin within minutes of death, and use cryoprotectants to prevent ice formation during cryopreservation. It is unlikely that a corpse could be reanimated after undergoing vitrification, which causes damage to the brain including its neural networks. The first corpse to be frozen was that of Dr. James Bedford in 1967. As of 2014, about 250 bodies were cryopreserved in the United States, and 1,500 people had made arrangements for cryopreservation after their legal death.

Concept

Cryonic proponents go further than the mainstream consensus in asserting that the brain does not have to be continuously active to survive or retain memory. Cryonics controversially asserts that a human survives even within an inactive brain that has been badly damaged, provided that original encoding of memory and personality can, in theory, be adequately inferred and reconstituted from structure that remains. Cryonicists argue that as long as brain structure remains intact, there is no fundamental barrier, given our current understanding of physical law, to recovering its information content. The cryonics' argument that death does not occur as long as brain structure remains intact and theoretically repairable has received some mainstream medical discussion in the context of the ethical concept of brain death and organ donation.

Cryonics uses temperatures below −130 °C, called cryopreservation, in an attempt to preserve enough brain information to permit future revival of the cryopreserved person. Cryopreservation may be accomplished by freezing, freezing with cryoprotectant to reduce ice damage, or by vitrification to avoid ice damage. Even using the best methods, cryopreservation of whole bodies or brains is very damaging and irreversible with current technology. 

Cryonics requires future technology to repair or regenerate tissue that is diseased, damaged, or missing. Brain repairs in particular will require analysis at the molecular level. This far-future technology is usually assumed to be nanomedicine based on molecular nanotechnology. Biological repair methods or mind uploading have also been proposed.

Practice

Costs can include payment for medical personnel to be on call for death, vitrification, transportation in dry ice to a preservation facility, and payment into a trust fund intended to cover indefinite storage in liquid nitrogen and future revival costs. As of 2011, U.S. cryopreservation costs can range from $28,000 to $200,000, and are often financed via life insurance. KrioRus, which stores bodies communally in large dewars, charges $12,000 to $36,000 for the procedure. Some patients opt to have only their brain cryopreserved, rather than their whole body.

As of 2014, about 250 people have been cryogenically preserved in the U.S., and around 1,500 more have signed up to be preserved. As of 2016, four facilities exist in the world to retain cryopreserved bodies: three in the U.S. and one in Russia.

Obstacles to success

Preservation injury

Long-term preservation of biological tissue can be achieved by cooling to temperatures below −130 °C. Immersion in liquid nitrogen at a temperature of −196 °C (77 kelvins and −320.8 °F) is often used for convenience. Low temperature preservation of tissue is called cryopreservation. Contrary to popular belief, water that freezes during cryopreservation is usually water outside cells, not water inside cells. Cells don't burst during freezing, but instead become dehydrated and compressed between ice crystals that surround them. Intracellular ice formation only occurs if the rate of freezing is faster than the rate of osmotic loss of water to the extracellular space.

Without cryoprotectants, cell shrinkage and high salt concentrations during freezing usually prevent frozen cells from functioning again after thawing. In tissues and organs, ice crystals can also disrupt connections between cells that are necessary for organs to function. The difficulties of recovering large animals and their individual organs from a frozen state have been long known. Attempts to recover frozen mammals by simply rewarming them were abandoned by 1957. At present, only cells, tissues, and some small organs can be reversibly cryopreserved.

When used at high concentrations, cryoprotectants can stop ice formation completely. Cooling and solidification without crystal formation is called vitrification. The first cryoprotectant solutions able to vitrify at very slow cooling rates while still being compatible with whole organ survival were developed in the late 1990s by cryobiologists Gregory Fahy and Brian Wowk for the purpose of banking transplantable organs. This has allowed animal brains to be vitrified, warmed back up, and examined for ice damage using light and electron microscopy. No ice crystal damage was found; remaining cellular damage was due to dehydration and toxicity of the cryoprotectant solutions. Large vitrified organs tend to develop fractures during cooling, a problem worsened by the large tissue masses and very low temperatures of cryonics.

The use of vitrification rather than freezing for cryonics was anticipated in 1986, when K. Eric Drexler proposed a technique called fixation and vitrification, anticipating reversal by molecular nanotechnology. In 2016, Robert L. McIntyre and Gregory Fahy at the cryobiology research company 21st Century Medicine, Inc. won the Small Animal Brain Preservation Prize of the Brain Preservation Foundation by demonstrating to the satisfaction of neuroscientist judges that a particular implementation of fixation and vitrification called aldehyde-stabilized cryopreservation could preserve a rabbit brain in "near perfect" condition at −135 °C, with the cell membranes, synapses, and intracellular structures intact in electron micrographs. Brain Preservation Foundation President, Ken Hayworth, said, "This result directly answers a main skeptical and scientific criticism against cryonics—that it does not provably preserve the delicate synaptic circuitry of the brain.” However the price paid for perfect preservation as seen by microscopy was tying up all protein molecules with chemical crosslinks, completely eliminating biological viability. Actual cryonics organizations use vitrification without a chemical fixation step, sacrificing some structural preservation quality for less damage at the molecular level. Some scientists, like Joao Pedro Magalhaes, have questioned whether using a deadly chemical for fixation eliminates the possibility of biological revival, making chemical fixation unsuitable for cryonics.

While preservation of both structure and function has been possible for brain slices using vitrification, this goal remains elusive for whole brains. In absence of a revived brain, or brain simulation from somehow scanning a preserved brain, the adequacy of present vitrification technology (with or without fixation) for preserving the anatomical and molecular basis of long-term memory as required by cryonics is still unproven. 

Outside the cryonics community, many scientists have a blanket skepticism toward existing preservation methods. Cryobiologist Dayong Gao states that "we simply don't know if (subjects have) been damaged to the point where they've 'died' during vitrification because the subjects are now inside liquid nitrogen canisters." Biochemist Ken Storey argues (based on experience with organ transplants), that "even if you only wanted to preserve the brain, it has dozens of different areas, which would need to be cryopreserved using different protocols."

Revival

Those who believe that revival may someday be possible generally look toward advanced bioengineering, molecular nanotechnology, or nanomedicine as key technologies. Revival would require repairing damage from lack of oxygen, cryoprotectant toxicity, thermal stress (fracturing), freezing in tissues that do not successfully vitrify, and reversing the cause of death. In many cases extensive tissue regeneration would be necessary.

According to Cryonics Institute president Ben Best, cryonics revival may be similar to a last in, first out process. People cryopreserved in the future, with better technology, may require less advanced technology to be revived because they will have been cryopreserved with better technology that caused less damage to tissue. In this view, preservation methods would get progressively better until eventually they are demonstrably reversible, after which medicine would begin to reach back and revive people cryopreserved by more primitive methods.

Legal issues

Historically, a person had little control regarding how their body was treated after death as religion had jurisdiction over the disposal of the body. However, secular courts began to exercise jurisdiction over the body and use discretion in carrying out of the wishes of the deceased person. Most countries legally treat preserved individuals as deceased persons because of laws that forbid vitrifying someone who is medically alive. In France, cryonics is not considered a legal mode of body disposal; only burial, cremation, and formal donation to science are allowed. However, bodies may legally be shipped to other countries for cryonic freezing. As of 2015, the Canadian province of British Columbia prohibits the sale of arrangements for body preservation based on cryonics. In Russia, cryonics falls outside both the medical industry and the funeral services industry, making it easier in Russia than in the U.S. to get hospitals and morgues to release cryonics candidates.

In London in 2016, the English High Court ruled in favor of a mother's right to seek cryopreservation of her terminally ill 14-year-old daughter, as the girl wanted, contrary to the father's wishes. The decision was made on the basis that the case represented a conventional dispute over the disposal of the girl's body, although the judge urged ministers to seek "proper regulation" for the future of cryonic preservation following concerns raised by the hospital about the competence and professionalism of the team that conducted the preservation procedures. In Alcor Life Extension Foundation v. Richardson, the Iowa Court of Appeals ordered for the disinterment of Richardson, who was buried against his wishes for cryopreservation.

A detailed legal examination by Jochen Taupitz concludes that cryonic storage is legal in Germany for an indefinite period of time.

Ethics

In 2009, writing in Bioethics, David Shaw examines the ethical status of cryonics. The arguments against it include changing the concept of death, the expense of preservation and revival, lack of scientific advancement to permit revival, temptation to use premature euthanasia, and failure due to catastrophe. Arguments in favor of cryonics include the potential benefit to society, the prospect of immortality, and the benefits associated with avoiding death. Shaw explores the expense and the potential payoff, and applies an adapted version of Pascal's Wager to the question.

In 2016, Charles Tandy wrote in favor of cryonics, arguing that honoring someone's last wishes is seen as a benevolent duty in American and many other cultures.

History

Cryopreservation was applied to human cells beginning in 1954 with frozen sperm, which was thawed and used to inseminate three women. Eight years later, the freezing of humans was first scientifically proposed by Michigan professor Robert Ettinger. In April 1966, the first human body was frozen, though it had been embalmed for two months. It was placed in liquid nitrogen and stored at just above freezing. The middle-aged woman from Los Angeles, whose name is unknown, was soon thawed out and buried by relatives.

The first body to be frozen with the hope of future revival was James Bedford's, a few hours after his cancer-caused death in 1967. He is the only cryonics patient frozen before 1974 still preserved today. Cryonics gained a poor reputation in the U.S. in the late 1970s after the Cryonics Society of California ran out of money to maintain cryopreservation of existing patients. Robert Nelson, a former TV repairman with no scientific background (who had processed Bedford's freezing before turning the body over to relatives), was sued for allowing nine bodies to decompose.

In 2018, a Y-Combinator startup called Nectome was recognized for developing a method of preserving brains with chemicals rather than by freezing. The method is fatal, performed as euthanasia under general anethesia, but the hope is that future technology would allow the brain to be physically scanned into a computer simulation, neuron by neuron.

Demographics

According to The New York Times, cryonicists are predominantly nonreligious white males, outnumbering women by about three to one. According to The Guardian, as of 2008, while most cryonicists used to be young, male and "geeky" recent demographics have shifted slightly towards whole families.

In 2015 Du Hong, a 61-year-old female writer of children's literature, became the first known Chinese national to be cryopreserved.

Reception

Scientists have expressed skepticism about cryonics in media sources, however the number of peer-reviewed papers on cryonics is limited because its speculative aspects place it outside of the focus of most academic fields. While most neuroscientists agree that all the subtleties of a human mind are contained in its anatomical structure, few neuroscientists will comment directly upon the topic of cryonics due to its speculative nature. Individuals who intend to be frozen are often "looked at as a bunch of kooks", despite many of them being scientists and doctors.

William T. Jarvis has written that "Cryonics might be a suitable subject for scientific research, but marketing an unproven method to the public is quackery".

According to cryonicist Aschwin de Wolf and others, cryonics can often produce intense hostility from spouses who are not cryonicists. James Hughes, the executive director of the pro-life-extension Institute for Ethics and Emerging Technologies, chooses not to personally sign up for cryonics, calling it a worthy experiment but stating laconically that "I value my relationship with my wife."

Cryobiologist Dayong Gao states that "People can always have hope that things will change in the future, but there is no scientific foundation supporting cryonics at this time." Alcor disagrees, stating that "There are no known credible technical arguments that lead one to conclude that cryonics, carried out under good conditions today, would not work." As well, while it is universally agreed that "personal identity" is uninterrupted when brain activity temporarily ceases during incidents of accidental drowning (where people have been restored to normal functioning after being completely submerged in cold water for up to 66 minutes), some people express concern that a centuries-long cryopreservation might interrupt their conception of personal identity, such that the revived person would "not be you".

Many people assert there would be no point in being revived in the far future if their friends and families are dead.

In fiction

Suspended animation is a popular subject in science fiction and fantasy settings, appearing in comic books, films, literature, and television. A survey in Germany found that about half of the respondents were familiar with cryonics, and about half of those familiar with cryonics had learned of the subject from films or television. Some commonly known examples of cryonics being used in popular culture include Demolition Man (film), Vanilla Sky, Fallout 4, Futurama, Passengers, Nip/Tuck and "The Neutral Zone" (Star Trek: The Next Generation).

Notable people

Cryopreserved

Among the cryopreserved are L. Stephen Coles (in 2014), Hal Finney (in 2014), and Ted Williams.

Associated with cryonics

The urban legend suggesting Walt Disney was cryopreserved is false; he was cremated and interred at Forest Lawn Memorial Park Cemetery. Robert A. Heinlein, who wrote enthusiastically of the concept in The Door into Summer (serialized in 1956), was cremated and had his ashes distributed over the Pacific Ocean. Timothy Leary was a long-time cryonics advocate and signed up with a major cryonics provider, but he changed his mind shortly before his death, and was not cryopreserved.

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