Inhalational anesthetic

An inhalational anesthetic is a chemical compound possessing general anesthetic properties that is delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporiser and an anesthetic delivery system. Agents of significant contemporary clinical interest include volatile anesthetic agents such as isoflurane, sevoflurane and desflurane, as well as certain anesthetic gases such as nitrous oxide and xenon.

Although some of these are still used in clinical practice and in research, the following anaesthetic agents are primarily of historical interest in developed countries:

Volatile anaesthetic agents share the property of being liquid at room temperature, but evaporating easily for administration by inhalation. The volatile anesthetics used in the developed world today include: Desflurane, isoflurane and sevoflurane. Other agents widely used in the past include ether, chloroform, enflurane, halothane, methoxyflurane. All of these agents share the property of being quite hydrophobic (i.e., as liquids, they are not freely miscible with water, and as gases they dissolve in oils better than in water).

The ideal volatile anaesthetic agent offers smooth and reliable induction and maintenance of general anaesthesia with minimal effects on non-target organ systems. In addition it is odorless or pleasant to inhale; safe for all ages and in pregnancy; not metabolised; rapid in onset and offset; potent; safe for exposure to operating room staff; and has a long shelf life. It is also cheap to manufacture; easy to transport and store; easy to administer and monitor with standard operating room equipment; stable to light, plastics, metals, rubber and soda lime; and non-flammable and environmentally safe. None of the agents currently in use are ideal, although many have some of the desirable characteristics. For example, sevoflurane is pleasant to inhale and is rapid in onset and offset. It is also safe for all ages. However, it is expensive (approximately 3 to 5 times more expensive than isoflurane), and approximately half as potent as isoflurane.

Other gases or vapors which produce general anaesthesia by inhalation include nitrous oxide, carbon dioxide, cyclopropane, and xenon. These are stored in gas cylinders and administered using flowmeters, rather than vaporisers. Cyclopropane is explosive and is no longer used for safety reasons, although otherwise it was found to be an excellent anaesthetic. Xenon is odorless (odourless) and rapid in onset, but is expensive and requires specialized equipment to administer and monitor. Nitrous oxide, even at 80% concentration, does not quite produce surgical level anaesthesia in most people at standard atmospheric pressure, so it must be used as an adjunct anaesthetic, along with other agents.

Under hyperbaric conditions (pressures above normal atmospheric pressure), other gases such as nitrogen, and noble gases such as argon, krypton, and xenon become anaesthetics. When inhaled at high partial pressures (more than about 4 bar, encountered at depths below about 30 metres in scuba diving), nitrogen begins to act as an anaesthetic agent, causing nitrogen narcosis. However, the minimum alveolar concentration (MAC) for nitrogen is not achieved until pressures of about 20 to 30 atm (bar) are attained. Argon is slightly more than twice as anaesthetic as nitrogen per unit of partial pressure (see argox). Xenon however is a usable anaesthetic at 80% concentration and normal atmospheric pressure.

Endogenous analogs of inhaled anesthetics are compounds that the body produces and that have the properties and similar mode of action of inhaled anesthetics. Among the gases in the human body, carbon dioxide is among the most abundant and produces anesthesia from insects to humans. CO₂ anesthesia was first demonstrated to the king of France in the early 1800s by Henry Hill Hickman. Initially CO₂ was thought to work through anoxia, but in the early 1900, increased CO₂ in the lung showed a dramatic increase oxygenation of the brain disproving the anoxia argument. Prior to the development of modern anesthetics, CO₂ was used extensively by psychiatrists in a treatment called carbon dioxide inhalation therapy.

The full mechanism of action of volatile anaesthetic agents is unknown and has been the subject of intense debate. "Anesthetics have been used for 160 years, and how they work is one of the great mysteries of neuroscience," says anaesthesiologist James Sonner of the University of California, San Francisco. Anaesthesia research "has been for a long time a science of untestable hypotheses," notes Neil L. Harrison of Cornell University.