Anesthesia is the loss of sensation of painful stimuli either with or without loss of consciousness. Anesthetic agents produce a state of anesthesia. Anesthetics can be broken down into two basic categories: general anesthetics (those that cause loss of consciousness), and local or regional anesthetics ( those that do not cause a loss of consciousness but rather "deaden" or "numb" the area).
The history of general anesthesia begins in ancient times with the inhalation of opium and other plant alkaloids. In the recent past dentists were instrumental in the introduction of diethyl ether and nitrousoxide. In 1846 William T. G. Morton (1819-1868), a Boston dentist, gave his famous demonstration of ether in the "ether dome" of the Massachusetts General Hospital. Morton was late for the procedure, and as he ran into the operating theater the surgeon, Doctor Warren, remarked, "Well, sir, your patient is ready." There surrounded by a somewhat hostile and silent audience Morton quietly worked. When the patient was unconscious and anesthetized Morton announced, "Doctor Warren, your patient is ready." The operation was begun, strong men surrounded the table prepared to restrain the patient, but they were not needed. When the procedure was completed Warren turned to the astonished audience and made the famous statement, "Gentlemen, this is no humbug." The age of general anesthesia had begun.
After 1846, ether was widely used in the United States. In 1847, chloroform was introduced by the Scottish obstetrician, James Simpson (1811- 1870). Although it became popular in England chloroform was never so in the United States due to its severe hepatotoxicity (damaging to the liver) and cardiovascular depressant effects. In 1929,chemists discovered cyclopropane. It became the most popular anesthetic for the next 30 years, however it was an explosive gas, and as more electrical devices came into use in the operating room the search for a new agent was intensely pursued. British chemists discovered halothane, a nonflammable anesthetic agent. In 1956, it was introduced into clinical practice and was a great success. Since that time most of the inhalation anesthetics which are halogenated hydrocarbons and ethers are modeled after halothane.
Unfortunately, in the late 1800s and early 1900s, to get adequate muscle relaxation for a sugical procedure, dangerously deep levels of anesthetic were needed. But in the 1940s chemists found that curare, a poison used by bow hunters in South America, acted by paralyzing certain muscle tissue. Curare began to be used as a muscle relaxant in surgery and allowed a much safer depth of anesthetic by inhalation.
Finally, intravenous compounds completed the spectrum of general anesthetic agents. In 1935, Lundy, introduced thiopental, a rapidly acting barbiturate for intravenous use. Short acting opioids have also been found effective. Today's anesthesia then consists of rapid inductions with a short acting barbiturate (or in young children inhaling halothane which, acts very rapidly due to their small body mass) and/or short acting intravenous opioids, enhanced by muscle relaxation provided by curare like drugs. Variation of this technique are common, but the basic pattern is fairly standard.
Local anesthetics act by blocking the transmission of electrical impulses through the axons of pain receptive nerve fibers. The first such drug was cocaine which grows in the Andean mountains between 3,000 and 9,000 ft. Used by the natives for centuries for its stimulatory effects to enhance hard work at altitude, it was first isolated by Albert Nieman(1834-1861) in 1860. When he tasted the newly isolated compound he noted a numbness of his tongue. William Halstead (1852-1922), a surgeon at the Johns Hopkins Hospital in Baltimore, demonstrated cocaine's local anesthetic use when injected. All the local anesthetics of 1999 stem from these early observations.
General anesthetics come from many types of chemical compounds. Figure 1 shows the structures of characteristic compounds from each major class. Nitrous oxide is discussed under its own section in this volume. Diethyl ether (commonly known as "ether") is the parent compound of the class of organic compounds known as ethers. At roomtemperature and standard pressure ethers are colorless, neutral liquids with pleasant odors. Ethers are easily soluble in organic liquids. Diethyl ether has a boiling point of 62.5oF(35o): therefore it can be inhaled, It can be bottled or in the case of medical uses contained in small cans with small cylindrical nozzles which can be capped. Diethyl ether is flammable and in the presence of an electric spark will ignite.
Chloroform (trichloromethane) is a clear, colorless, nonflammable, heavy, liquid. Its specific gravity is 1.476 at 68oF(20oC). The vapor which is approximately four times as dense as air will sink to the floor in an open operating room. Chlorform has a low solubility in water but is readily dissolved into animal fats and other organic solvents. It may be decomposed to toxic compounds when exposed to heat, flame, light, or oxygen. Halothane (2-bromo-2-chloro-1,1,1-triflouro-ethane) is a synthetic anesthetic liquid which is vaporized for inhalation as a general anesthetic. It has an asymmetric carbonatom and therefore has levo and dextro isomers but is supplied as a racemic mixture for anesthetic use.
Fentanyl (N-(1-phenethyl-4-piperidyl) propionanilide) is a commonly used synthetic opium alkaloid. It is very soluble in intravenous fluids and is rapid in onset and short-- acting in duration, making it an ideal "use as you go" narcotic anesthetic. By balancing its effects and side - effects against other agents being used a more effective and safer state of anesthesia may be obtained.
The chemistry of local anesthetics is more straightforward; all are either esters or amides. They have in common a general configuration of an organic ring, an intermediate chain, and an amine portion of their molecules (Figure 2a) . The aromatic end is lipophilic and binds to fatty tissue, whereas the hydrophilic end binds to water. Chemical alterations of either end of the molecule will also alter its water-fat (water - lipid) coefficient, its protein binding, and its activity as an anesthetic agent. In a biological system degradation of the molecule occurs at the intermediate bond level and accounts for differences in allergic reactions and metabolism. Commonly used amino esters are procaine, (Novocaine), and cocaine,and commonly used amino amides are lidocaine (Xylocaine) and bupivicaine (Marcaine). In general, allergic reactions to amino esters are much more common than amino amides
In order to demonstrate the clinical use of anesthetic agents, a typical surgical procedure, using all the classes of anesthetics in use in 1999, will be described. Closure of a cleft lip (incomplete formation of the lip, or "harelip") in an infant is such a procedure. The child is brought to the operating room, usually in the arms of its parents. Then while the infant is being rocked and held, a mask with flowing halothane is held very near the face. Within a few minutes the baby is unconscious, the parents leave the room, and continuing to use inhaled halothane an intravenous line is inserted. Through this line succinylcholine (a curare- type drug, but very short acting) is given. A tube is then placed through the mouth into the trachea and connected to a ventilator. With the airway thus controlled nitrous oxide, halothane, and oxygen are given in proper concentrations. Fentanyl or thiopental may be given intravenously if a deeper level of anesthesia is required during some parts of the procedure.
The surgeon then prepares the operative site for lip closure by cleansing the area, drawing proposed incision lines, and then injecting lidocaine (Xylocaine) with epinepherine to locally anesthetize the tissue which allows the anesthesiologist to lighten the level of general anesthesia. The procedure is performed, then the infant is placed on 100% oxygen until awakening, the tube is then removed, further oxygen is supplied by mask, and the child is taken to the recovery room. This scenario describes the usual case although many variations are used according to the needs of the patient and the training of the anesthesiologist.
One must admit that anesthetics have greatly improved since the days of the use of "strong men" to hold a reluctant and frightened patient down in order to achieve surgical intervention.
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