Volatile anaesthetic

The volatile anaesthetics are a class of general anaesthetic drugs. They share the property of being liquid at room temperature, but evaporating easily for administration by inhalation (some experts make a distinction between volatile and gas anesthetics on this basis, but both are treated in this article, since they probably do not differ in mechanism of action). All of these agents share the property of being quite hydrophobic (i.e., as liquids, they are not freely miscible with in water, and as gases they dissolve in oils better than in water).

Ideal properties of volatile anesthetics
The ideal volatile anaesthetic agent offers smooth and reliable induction and maintenance of general anaesthesia with minimal effects on other organ systems. In addition it is odourless or pleasant to inhale; safe for all ages and in pregnancy; not metabolised; rapid in onset and offset; potent; and safe for exposure to operating room staff. It is also cheap to manufacture; easy to transport and store, with a long shelf life; easy to administer and monitor with existing equipment; stable to light, plastics, metals, rubber and soda lime; non-flammable and environmentally safe.

None of the agents currently in use is 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.

Administration
Anaesthetists administer these agents using an anaesthetic vaporiser attached to an anaesthetic machine.

Agents
Agents stored as liquids and administered by vaporizer include:


 * diethyl ether - pungent smelling and extremely flammable; still used in the Third World
 * chloroform - now abandoned for clinical use
 * trichloroethylene - now abandoned for clinical use
 * halothane  - sweet smelling, slow onset and offset, potent, risk of hepatitis with repeated use
 * methoxyflurane - analgesic, slow onset and offset, still used by paramedics as an emergency analgesic in trauma cases, but abandoned for hospital use as it is metabolised to toxic fluoride ions
 * enflurane - pungent smelling, lowers seizure threshold, relatively slow onset and offset
 * isoflurane - pungent smelling
 * sevoflurane - sweet smelling and quite rapid onset and offset, expensive
 * desflurane - pungent smelling but very rapid onset and offset, not very potent, expensive, requires special vaporiser

Agents which are stored as gases under pressure
Other gases or vapours which produce general anaesthesia by inhalation include nitrous oxide, cyclopropane and xenon. These are stored in 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 anesthetic. Xenon is odourless and extremely rapid in onset, but is extremely expensive and requires specialised equipment to administer and monitor. Nitrous oxide, even at 80% concentration, does not quite produce surgical level anesthesia in most persons, so it must be used as an adjunct anesthetic, along with other agents.

Hyperbaric anesthesia
Under hyperbaric conditions, other gasses such as krypton, argon, and nitrogen become anesthetics, although 1 to 1.5 MAC concentrations would not be achieved for nitrogen until pressures of about 20 to 30 atm (bar). Argon is slightly more than twice as anesthetic as nitrogen per unit of partial pressure (see argox).

Neurological Theories of Action
The full mechanism of action of volatile anesthetic 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 anesthesiologist James Sonner of the University of California, San Francisco“. Anesthesia research "has been for a long time a science of untestable hypotheses," notes Neil L. Harrison of Cornell University.

"Most of the injectable anesthetics appear to act on a single molecular target," says Sonner. "It looks like inhaled anesthetics act on multiple molecular targets. That makes it a more difficult problem to pick apart."

The possibility of anesthesia by the inert gas argon in particular (even at 10 to 15 bar) suggests that the mechanism of action of volatile anesthetics is an effect best described by physical chemistry, and not a chemical bonding action. However, the agent may bind to a receptor with a weak interaction. A physical interaction such as swelling of nerve cell membranes from gas solution in the lipid bilayer may be operative. Notably, the gases hydrogen, helium, and neon have not been found to have anesthetic properties at any pressure. Helium at high pressures produces nervous irritation ("anti-anesthesia"), suggesting that the anesthetic mechanism(s) may be operated in reverse by this gas (i.e., nerve membrane compression).