Anesthetics. History and Methods of Application

An anesthetic is a drug that causes total loss of sensory perception and thus enables complex surgical procedures to be carried out painlessly. The first surgical uses of ether and chloroform as inhalation anesthetics began in the 1840s, but they were administered crudely by holding a sponge or cloth saturated with the drug over the patient’s nose and mouth.

By 1910, mixtures of nitrous oxide with ether had begun to replace chloroform, though anesthetic ether and chloroform are still manufactured. Other compounds were soon introduced; and as surgeons demanded deeper, more controlled levels of anesthesia, the professional anesthetist became an essential member of every surgical team.

There are many factors to be considered in choosing a suitable anesthetic agent for each patient. The ideal anesthetic should allow rapid induction followed by ease of control and the possibility of rapid reversal. It should give good muscle relaxation, have few toxic or adverse effects, and be stable in soda lime, used in anesthesia equipment to absorb expired carbon dioxide.

Inhalation anesthetics are administered in mixtures with oxygen alone or with a 30/70 mixture of nitrous oxide and oxygen. They are also often combined with drugs that relax muscles and block neuromuscular impulse transmission, making surgical operations easier. Artificial respiration may be required to maintain proper levels of oxygen and carbon dioxide in the blood as deep anesthesia can bring the patient close to death.

Most modern inhalation anesthetics are synthetic halogen-substituted hydrocarbons or ethers. Fluorine, the most common halogen substitute, decreases flammability and boiling point and increases the stability of the molecule. It also reduces fluctuations in heart rate. Fluroxene, introduced in 1960, gives rapid onset and recovery and is stable in soda lime; however, it is unstable in light and readily metabolized in the body.

It was replaced in 1962 by methoxyflurane and in 1963 by enflurane. Methoxyflurane is the most potent of the inhaled anesthetics, but like fluroxene it is metabolized. Because fluoride ions cause renal damage, the duration of methoxyflurane anesthesia must be limited. Enflurane is the least potent of the inhaled anesthetics. Later inhalation anesthetics include Sevoflurane, launched in Japan in 1989, and Desflurane. Both are less subject to metabolism in the body, but Sevoflurane is unstable in soda lime.

Modern research has been concentrated on the discovery of safer anesthetic agents, and new compounds steadily replace older, less satisfactory ones. However, all halogen-substituted anesthetics tend to trigger hypermetabolic reactions accompanied by rapid temperature rise, increased oxygen use, and carbon dioxide production.

In addition to inhalation techniques, anesthesia may also be produced by intravenous injection. There are two types of injection anesthetics, those used only to induce anesthesia and those used both to induce and maintain anesthesia. Since the ideal injection agent is yet to be discovered, a ‘‘balanced’’ anesthesia is frequently employed with one drug injected for rapid induction followed by an inhalation agent to maintain anesthesia.

French surgeon Pierre Cyrpien Ore; first attempted to produce anesthesia by intravenous injection of chloral hydrate in 1874. Improved safety was achieved with hedonal (methylpropylur- ethane) in 1899, and this was followed during the early 1900s by the intravenous injection of diluted chloroform and ether, as well as hedonal.

Toward the end of World War I, barbiturates manufactured by the Swiss firm Hofmann-La Roche were introduced. In the 1920s chemical research revealed a large number of barbiturates, including thiopental sodium (Pentothal) and hexobarbitone, which is said to have been used in up to 10 million cases by the end of World War II. Pentothal is still widely used, but another group of drugs, the benzodiazepines, including diazepam (Valium) and chlordia-zepoxide hydrochloride (Librium), were introduced in the early 1960s as muscle relaxants and tranquilizers. Several other drugs in this range are used in neurosurgery and cardiovascular surgery.

Among the opiates, morphine is the most common and most potent drug. It is used in high doses as an anesthetic, despite its propensity to cause nausea and vomiting, respiratory and cardiovascular depression, and hypotension (lowered blood pressure). Fentanyl citrate, a synthetic opioid 50 to 100 times more potent than morphine, was introduced in the 1960s. It is used in cardiac surgery in very large doses to produce profound analgesia and suppress cardiovascular reflexes. Since the 1980s other synthetic opioids have been approved for clinical use.

An important difference between inhalation and injection anesthetics is that the former exert physical effects on the respiratory system, whereas the latter function by combining chemically with receptor molecules in the cells. There are two kinds of receptors, the GABA (g-aminobutyric acid) receptor and the opiate receptor. As the injected anesthetic is chemically bound to its receptor, removal from the system is slow and other drugs (antagonists) are required to reverse the anesthetic effects.

A third type, local anesthetics, produces loss of sensation in limited areas without loss of consciousness. They are usually administered by subcutaneous injection around sensory nerve endings to block the passage of nervous impulses. Some local anesthetics also block the motor nerves enabling operations to be carried out while the patient remains conscious.

The choice of local anesthetic depends on the type and length of the dental or surgical procedure for which it is to be used. The ideal local anesthetic should have rapid onset and long duration, and it should be useful in situations requiring differential blockage of sensory and motor nerve fibers. Obstetric and postoperative pain relief requires a powerful sensory block accompanied by minimal motor block, whereas limb surgery requires both sensory and motor block.

A special form of regional nerve block may be caused by injecting a local anesthetic into the spinal cord, either into the space between the membranes that surround the cord (epidural anesthesia) or into the cerebrospinal fluid (spinal anesthesia). In these cases the anesthetic can be adjusted to block conduction in nerves entering and leaving the cord at the desired level.

New compounds are constantly being investigated for anesthetic properties, though the anesthetist now has a wide range of choice. It seems likely that future advances in anesthesia will depend upon developments in the computerization of monitoring and control of the patient’s physiological status in response to these agents rather than on the discovery of new anesthetic compounds.