Saving Pains

The History and Chemistry Behind General Anesthetic Identification

At the dawn of the 20^th century, there existed only three primary general anesthetics that surgeons used to produce anesthesia: chloroform (CHCl₃), ethyl ether (CH₃CH₂OCH₂CH₃), and nitrous oxide (N₂O). With the advent of improved technology and the drive to replace older, more dangerous anesthetics with those that would remain effective yet safe to the patient, a variety of new compounds are used by today's anesthesiologists. While there is a risk with any anesthetic administered, the compounds in use today have greatly reduced this risk as compared to even 20 years ago. The role of an anesthesiologist has been developed since the first days of anesthesia when a surgeon or apprentice, without any sort of training, would administer the medicine. Nowadays, anesthesiologists are certified in the field of anesthesiology after rigorous schooling, and the necessity of their presence in the operating room is unquestioned.

General anesthetics are like any other chemical in that they each have a unique structure and distinguishing chemical properties. For example, they each have unique IR, ¹H-NMR, ¹³C-NMR and MS spectra. As many of the currently used anesthetics are small molecules, highly halogenated and very volatile, mass spectrometry is a useful diagnostic tool for this general class of compounds. Indeed, mass spectrometers are used to routinely monitor operating room conditions to ensure proper levels of the anesthetic to the patient versus to the doctors and nurses performing the operation.

Dr. Crawford Long Discovers The Usefulness of Ether

Ether, known as "sweet vitriol" until 1730, was discovered in 1275 by a Spanish chemist named Raymundus Lullius. While ethyl ether was first created in a laboratory in 1540 by a German scientist named Valerius Cordus, it wasn't until 1841 that the anesthetic property of ether was put to work. After witnessing "ether frolics", public gatherings of those who would take ether for amusement, and noting the lack of pain felt by those getting injured at these events,

Long's Classic: Ethyl Ether

Dr. Crawford W. Long returned from schooling in Pennsylvania to his hometown of Jefferson, Georgia. While it is believed Dr. Long used ether for minor operations in 1841, the first recorded use of ether as an anesthetic occurred on March 30, 1842, when Long used applied it in the removal of two tumors from the neck of James M. Venable. Venable felt no pain from the procedure and paid two dollars for the tumor extraction.

Four years later, on September 30, 1846, Dr. William Morton, a former dental partner of Dr. Horace Wells, who had advocated the use of nitrous oxide as an anesthetic, administered ether to remove a tooth of a patient in Boston. In October of the same year, Morton gave a public demonstration of ether's anesthetic property at Massachusetts General Hospital. With the procedure occurring with great success, Morton was later wrongly credited as the discoverer of ether's surgical use. The year following the successful demonstration, Sir James Young Simpson, a future pioneer in anesthesiology, introduced ether for use as an anesthetic for childbirth. Ether wouldn't suit him for such purposes for very long.

In the present, ethyl ether, a volatile, colorless, and very odiferous compound, is often used as a solvent for certain oils, rubber, and other fatty compounds. In its purest form, ether is a component in the preparation of Grignard reagents. Ether is also utilized along with other anesthetics to produce a state known as "balanced anesthesia"; this combination is used due to the slow rate at which ether causes unconsciousness in patients. If administered at high concentrations, respiratory arrest can occur. More minor symptoms from ether exposure include dizziness, nasal irritation, and the drying of skin. The molecular formula of ethyl ether is (CH₃CH₂)O.

Simpson Finds Ether Unsuitable For Anesthetic Purposes

Sir James Young Simpson, a Scottish physician, was no stranger to anesthesiology. In 1847, he brought ether into the realm of obstetrics but found that its odor and the large amount needed to induce unconsciousness made it impractical as an anesthetic. He therefore began a quest to find a better anesthetic, one which would cost less, would require a smaller dosage to induce unconsciousness, and would not exhibit a distinct odor. In October, 1847, a chemist named David Waldie suggested that Simpson might try chloroform as an anesthetic.

Civil War Surgeon's Choice: Chloroform

Waldie was prepared to make a sample of chloroform for Simpson's evaluation purposes, but due to a fire in his own laboratory he could not do so. Simpson obtained chloroform elsewhere, and once discovered as an anesthetic, gave Waldie little credit for the original idea.

Chloroform, which had been discovered in 1831 and 1832 independently by three scientists - Samuel Guthrie, Justus von Liebig, and Eugene Soubeiran - had originally been used as a treatment for asthma. When Waldie suggested the possible anesthetic properties of chloroform to Simpson, it was only one of several chemicals already suggested to the obstetrician. In a practice of the time, Simpson invited friends to his house to try out the different chemicals on themselves. On November 4, 1847, Simpson and Drs. Matthew Duncan and George Keith, inhaled the vapors of chloroform and subsequently became unconscious. Eleven days later, a public demonstration was held at the Royal Infirmery of Edinburgh at which time chloroform's property as an anesthetic was again proven successfully. It eventually displaced ether as the anesthetic of choice throughout much of the world. Chloroform did many of the things Simpson had wanted: it's odor wasn't persistent, a lesser amount could be used to cause unconsciousness, it was cheaper, and its effects on the body occurred more rapidly than ether. Due to it's lower volatility, cost, and the amount needed for dosage, chloroform was the choice anesthetic of surgeons in the American Civil War; over a million pounds of the chemical was used in this conflict.

Today, chloroform is seldom used as an anesthetic. It has been found that its effects on the body can be serious, resulting in damage to both the liver and the kidneys. Chloroform is found in today's environment and is formed through many avenues, including exhaust from automobiles, chlorination of water at a sewage treatment plant, and chlorination of drinking water. Minor effects of chloroform exposure include dizziness, headaches, and fatigue. Chloroform is utilized today in the manufacturing of pesticides and dyes, as well as for obtaining penicillin. Chloroform is a clear, colorless, and nonflammable liquid and has a molecular formula of CHCl₃.

The Newer Generation of Anesthetics

In the spirit of Sir James Young Simpson, the search for the better general anesthetic continues today. An ideal anesthetic would cause unconsciousness quickly, would display no side effects, and would require no "maintenance" by an anesthesiologist.

A Modern Anesthetic: Halothane

Unfortunately, such a perfect chemical does not yet exist. There have been many improvements since the days of ethyl ether and chloroform usage. Today, many anesthetics are given intravenously so that they are absorped more quickly and the effects on the body occur rapidly. Two new inhalation anesthetics introduced in the 1990s that are used frequently are desflurane and sevoflurane.

Through the 1930s and 1940s, cyclopropane, trichloroethylene, and ethylene were among the general anesthetics used. In 1951, halothane, also known as fluothane, was synthesized. Five years later, it was introduced into the realm of medicine for use as an anesthetic. A nonflammable, volatile liquid, halothane is a potent anesthetic, and unfortunately, has a much higher price tag than chloroform and ethyl ether. Halothane has no nauseating odor, such as ether, but has been shown to affect the cardiovascular and reproductive systems in humans. Though halothane is still in usage, the common choice of inhalation anesthetics of today include nitrous oxide, desflurane, isoflurane, and sevoflurane.