Anesthetic

An anesthetic (or anaesthetic) is a drug that causes "anesthesia": a reversible loss of sensation. Anesthetics contrast with analgesics (painkillers), which relieve pain without eliminating sensation. These drugs are generally administered to facilitate surgery, although they can be used for other medical purposes. A wide variety of drugs are used in modern anesthetic practice. Many are rarely used outside of anesthesia, although others are used commonly by all disciplines. Anesthetics are categorized into two classes:
*General anesthetics, which cause a reversible loss of consciousness.
*Local anesthetics, which cause a reversible loss of sensation for a limited region of the body while maintaining consciousness. 
Combinations of anesthetics are sometimes used for their synergistic and additive therapeutic effects. Adverse effects, however, may also be increased.
==Local anesthetics==
Each of the local anesthetics have the suffix "-caine" in their names (derived from "cocaine, which can also has properties as a local anesthetic, through the German Kokaine. The suffix "-ine" in chemistry refers to an alkaline compound).
*Procaine
*Amethocaine
*Lidocaine (also known as Lignocaine)
*Prilocaine
*Bupivacaine
*Levobupivacaine
*Ropivacaine
*Mepivacaine
*Dibucaine
Local anesthetics work by preventing transmission of nerve impulses without causing unconsciousness. They act by binding to fast sodium channels from within (in an open state). 
Local anesthetics are based on either ester or amide. Ester-based local anesthetics (e.g., procaine, amethocaine, cocaine, benzocaine, tetracaine) are generally unstable in solution and fast-acting, and allergic reactions are common. Amide-based local anesthetics (e.g., lidocaine, prilocaine, bupivacaine, levobupivacaine, ropivacaine, mepivacaine, dibucaine and etidocaine) are generally heat-stable, with a long shelf life (around 2 years). They have a slower onset and longer half-life than ester anesthetics, and are usually racemic mixtures (i.e. have an equal amount of mirror image molecules), with the exception of levobupivacaine (which is S(-) -bupivacaine) and ropivacaine (S(-)-ropivacaine). These agents are generally used within regional and epidural or spinal techniques, due to their longer duration of action, which provides adequate analgesia for surgery, labor, and symptomatic relief.
Only preservative-free local anesthetic agents may be injected into the spinal canal to affect the cerebrospinal fluid.
==General anesthetics==
General anesthetics come in two types - inhaled and injected. Inhaled agents also come in two types - those that exist naturally in gaseous form, and those which quickly evaporate into vapours.
===Inhaled agents===
*Desflurane
*Enflurane
*Halothane
*Isoflurane
*Methoxyflurane
*Nitrous oxide
*Sevoflurane
*Xenon (rarely used)
Volatile anaesthetic are specially formulated organic liquids that evaporate readily into vapors, and are given by inhalation for induction and/or maintenance of general anesthesia. Nitrous oxide and xenon are gases at room temperature rather than liquids, so they are not considered volatile agents. The ideal anesthetic vapor or gas should be non-flammable, non-explosive, and lipid-soluble. It should possess low blood gas solubility, have no end-organ (heart, liver, kidney) toxicity or side-effects, should not be metabolized, and should not be an irritant to the respiratory pathways of the patient. However, no anaesthetic agent currently in use meets all these requirements, nor can any anaesthetic agent be considered safe. There are inherent risks and drug interactions that are specific to each and every patient. The agents in widespread current use are isoflurane, desflurane, sevoflurane, and nitrous oxide. Nitrous oxide is a common adjuvant gas (i.e., used to affect how other anesthetic agents work on the patient), making it one of the most long-lived drugs still in current use. Because of its high potency, it cannot produce anesthesia on its own but is frequently combined with other agents. Halothane, an agent introduced in the 1950s, has been almost completely replaced in modern anesthesia practice by newer agents because of its shortcomings.
In theory, any inhaled anesthetic agent can be used for induction of general anesthesia. However, most of the halogenated anesthetics are irritating to the airway, perhaps leading to coughing, laryngospasm and overall difficult inductions. For this reason, the most frequently used agent for inhalational induction is sevoflurane. All of the volatile agents can be used alone or in combination with other medications to maintain anesthesia (nitrous oxide is not potent enough to be used as a sole agent).
Volatile agents are frequently compared in terms of potency, which is inversely proportional to the minimum alveolar concentration (i.e., the concentration of an anesthetic in the lungs that will prevent movement in 50% of patients). Potency is directly related to lipid (fat) solubility. However, certain pharmacokinetic properties of volatile agents have become another point of comparison. Most important of those properties is known as the blood/gas partition coefficient. This concept refers to the relative solubility of a given agent in blood. Those agents with a lower blood solubility (i.e., a lower blood–gas partition coefficient; e.g., desflurane) give the anesthesia provider greater rapidity in titrating the depth of anesthesia, and permit a more rapid emergence from the anesthetic state upon discontinuing their administration. In fact, newer volatile agents (e.g., sevoflurane, desflurane) have been popular not due to their potency, but due to their versatility for a faster emergence from anesthesia, thanks to their lower blood–gas partition coefficient.
===Intravenous agents (non-opioid)===
While there are many drugs that can be used intravenously to produce anesthesia or sedation, the most common are:
*Barbiturates
**Amobarbital (trade name: Amytal)
**Methohexital (trade name: Brevital)
**Thiamylal (trade name: Surital)
**Sodium thiopental (trade name: Pentothal, referred to as thiopentone in the UK)
*Benzodiazepines
**Diazepam
**Lorazepam
**Midazolam
*Etomidate
*Ketamine
*Propofol
The two barbiturates mentioned above, thiopental and methohexital, are ultra-short-acting, and are used to induce and maintain anesthesia. However, though they produce unconsciousness, they provide no pain relief and must be used with other agents. Benzodiazepines can be used for sedation before or after surgery and can be used to induce and maintain general anesthesia. When benzodiazepines are used to induce general anesthesia, midazolam is preferred. Benzodiazepines are also used for sedation during procedures that do not require general anesthesia. Like barbiturates, benzodiazepines have no pain-relieving properties. Propofol is one of the most commonly used intravenous drugs employed to induce and maintain general anesthesia. It can also be used for sedation during procedures or in the ICU. Like the other agents mentioned above, it renders patients unconscious without producing pain relief. Because of its favorable physiological effects, etomidate has been primarily used in sick patients. Ketamine is infrequently used in anesthesia because of the unpleasant experiences that sometimes occur on emergence from anesthesia, which include vivid dreaming, extracorporeal experiences, and illusions. However, like etomidate it is frequently used in emergency settings and with sick patients because it produces fewer adverse physiological effects. Unlike the intravenous anesthetic drugs previously mentioned, ketamine produces profound pain relief, even in doses lower than those that induce general anesthesia. Also unlike the other anesthetic agents in this section, patients who receive ketamine alone appear to be in a cataleptic state, unlike other states of anesthesia that resemble normal sleep. Ketamine-anesthetized patients have profound analgesia but keep their eyes open and maintain many reflexes.
===Neonatal and infant neurotoxicity concerns===
Concerns have been raised as to the safety of general anesthetics, in particular ketamine and isoflurane in neonates and young children due to significant neurodegeneration. The risk of neurodegeneration is increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam. This has led to the FDA and other bodies to take steps to investigate these concerns. These concerns have arisen from animal studies involving rats and non-human primates. Research has found that anesthetics which enhance GABA or block NMDA can precipitate neuronal cell death in these animals. The developing central nervous system is most vulnerable to these potential neurotoxic effects during the last trimester of pregnancy and shortly after birth. Melatonin, a free oxygen radical scavenger and indirect antioxidant is known to reduce the toxicity of a range of drugs has been found in a rat study to reduce the neurotoxicity of anesthetic agents to the early developing brain. Recent research in animals has found that all sedatives and anesthetics cause extensive neurodegeneration in the developing brain. There is also some evidence in humans that surgery and exposure to anesthetics in the early developmental stages causes persisting learning deficits.
===Intravenous opioid analgesic agents===
While opioids can produce unconsciousness, they do so unreliably and with significant side effects. So, while they are rarely used to induce anesthesia, they are frequently used along with other agents such as intravenous non-opioid anesthetics or inhalational anesthetics. Furthermore, they are used to relieve pain of patients before, during, or after surgery. The following opioids have short onset and duration of action and are frequently used during general anesthesia:
*Alfentanil
*Fentanyl
*Remifentanil
*Sufentanil (Not available in the UK)
The following agents have longer onset and duration of action and are frequently used for post-operative pain relief:
*Buprenorphine
*Butorphanol
*Heroin (diacetyl morphine), (not available in U.S.)
*Hydromorphone
*Levorphanol
*Meperidine, also called pethidine in the UK, New Zealand, Australia and other countries
*Methadone
*Morphine
*Nalbuphine
*Oxycodone, (not available intravenously in U.S.)
*Oxymorphone
*Pentazocine
===Key side effects===
Although it's much safer in the modern era, no session under general anesthesia is perfectly safe and precautions generally have to be taken in order to ensure the safety of the patient.
The main concern is that most general anesthetics cause nausea (which is not a concern for local anesthetics, which rarely cause nausea). When a patient is unconscious, they are still capable of vomiting and, as they are generally laying on their back, vomit can block the windpipe and the anesthetic mask. The primary precaution is to ensure that the patient has not eaten or drunk anything for a period of several hours before surgery. However, the nausea effect can easily continue in post-operative situations and, as a rule, patients have to be monitored during recovery as well. 
The vital signs of a patient must also be carefully monitored as certain anesthetics can lead to bradycardia and depressed breathing. Patients are often put on pure oxygen as a precaution. 
Anesthetic levels must be monitored continuously as well, particularly for the more fast-acting, short-lasting anesthetics. Although these have the advantage of easing recovery (patients regain consciousness shortly after they are discontinued), they pose a small risk the patient will start to regain consciousness during the procedure.
==Muscle relaxants==
Muscle relaxants don't render patients unconscious or relieve pain. Instead, they're sometimes used after a patient is rendered unconscious (induction of anesthesia) to facilitate intubation or surgery by paralyzing skeletal muscle.
*Depolarizing muscle relaxants
**Succinylcholine (also known as suxamethonium in the UK, New Zealand, Australia and other countries, "Celokurin" or "celo" for short in Europe)
**Decamethonium
*Non-depolarizing muscle relaxants
**Short acting
***Mivacurium
***Rapacuronium
**Intermediate acting
***Atracurium
***Cisatracurium
***Rocuronium
***Vecuronium
**Long acting
***Alcuronium
***Doxacurium
***Gallamine
***Metocurine
***Pancuronium
***Pipecuronium
***Tubocurarine
===Adverse effects===
*Depolarizing Muscle Relaxants i.e. Suxamethonium
**Hyperkalemia – A small rise of 0.5 mmol/l occurs normally, this is of little consequence unless potassium is already raised such as in renal failure
**Hyperkalemia – Exaggerated potassium release in burn patients (occurs from 24 hours after injury, lasting for up to 2 years), neuromuscular disease and paralyzed (quadriplegic, paraplegic) patients. The mechanism is reported to be through upregulation of acetylcholine receptors in those patient populations with increased efflux of potassium from inside muscle cells. May cause life-threatening arrhythmia
**Muscle aches, commoner in young muscular patients who mobilize soon after surgery
**Bradycardia, especially if repeat doses are given
**Malignant hyperthermia, a potentially life-threatening condition in susceptible patients
**Suxamethonium Apnea, a rare genetic condition leading to prolonged duration of neuromuscular blockade, this can range from 20 minutes to a number of hours. Not dangerous as long as it is recognized and the patient remains intubated and sedated, there is the potential for awareness if this does not occur.
**Anaphylaxis
*Non-depolarizing Muscle Relaxants
**Histamine release e.g. Atracurium & Mivacurium
**Anaphylaxis
Another potentially disturbing complication where neuromuscular blockade is employed is 'anesthesia awareness'. In this situation, patients paralyzed may awaken during their anesthesia, due to an inappropriate decrease in the level of drugs providing sedation and/or pain relief. If this fact is missed by the anesthesia provider, the patient may be aware of his surroundings, but be incapable of moving or communicating that fact. Neurological monitors are increasingly available that may help decrease the incidence of awareness. Most of these monitors use proprietary algorithms monitoring brain activity via evoked potentials. Despite the widespread marketing of these devices many case reports exist in which awareness under anesthesia has occurred despite apparently adequate anesthesia as measured by the neurologic monitor.
==Intravenous reversal agents==
*Flumazenil, reverses the effects of benzodiazepines
*Naloxone, reverses the effects of opioids
*Neostigmine, helps reverse the effects of non-depolarizing muscle relaxants
*Sugammadex, new agent that is designed to bind Rocuronium therefore terminating its action
==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 in lower Mesopotamia as early as 3400 B.C.E..
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 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, mandrake, 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.
The most famous anesthetic, diethyl 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. Davy wrote about the potential anesthetic properties of nitrous oxide, 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 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. 
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 October 16, 1846, Boston dentist William T. G. 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 Robert Liston, Johann Friedrich Dieffenbach, Nikolay Ivanovich Pirogov, and James 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). Its anaesthetic properties were noted early in 1847 by Marie-Jean-Pierre Flourens (1794–1867). The use of chloroform in anesthesia is linked to James Young Simpson, who, in a wide-ranging study of organic compounds, found chloroform's efficacy on 4 November 1847. Its use spread quickly and gained royal approval in 1853 when John Snow gave it to Queen Victoria during the birth of Prince Leopold. 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.
Initially, surgery performed under anesthesia often resulted in the death of the patient due to secondary infection. Surgical acquired infections were common as surgeons had poor hygiene practices and no care was taken to sterilize the operating theatre. Even minor surgery could be fatal. Robert Lister, a British surgeon, developed techniques to prevent surgical infections that are still largely in use today such as the sterile field, hand-washing, gloves, surgical wear, face masks and sterile operating rooms.
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.
==On the series==
Anesthetics are commonly used on the series for many reasons:
*During surgery
*To induce a coma or continuous unconsciousness
*Less appropriately, to pull pranks on hospital personnel
Here are some of the many instances:
*In Distractions, Adam is put into an induced coma due to the pain of his burns. He is monitored by a primary anesthesiologist. 
*In Sleeping Dogs Lie, House anesthetizes Hannah just before she's about to confess to her girlfriend (and liver donor) that she's about to leave her.
*In Meaning, Richard McNeil suffers a throat spasm despite the use of a topical anesthetic used on his throat prior to an endoscopy.
*In Lines in the Sand, House manages to get Adam Kelvey to accept the face mask for the anesthetic by breathing some in himself.
*In Babies & Bathwater, Edward Vogler calls off Naomi Randolph's surgery just as she's put under anesthesia.
*In Dying Changes Everything, Chase refuses to perform surgery on Lou because she's too weak to be put under a general anesthetic. Kutner improvises and approaches the suspected ganglioma from the inside instead.
*In Painless, House uses a local anesthetic in the neck to isolate Jeff's brain from the rest of his body. The procedure considerably reduces his chronic pain, but doesn't eliminate it.
*In Big Baby, they want to perform another surgery on Sarah, but they can't until the anesthesia from her previous surgery has completely cleared her system.
Anesthetic at Wikipedia - This page uses content from Wikipedia under the Creative Commons license
Anesthesia at Wikipedia - This page uses content from Wikipedia under the Creative Commons license
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