Anaesthetic vapours

The minimum alveolar concentration of an anaesthetic vapour at equilibrium is the concentration required to prevent movement to a standardized surgical stimulus in 50% of unpremedicated subjects studied at sea level... 

The best anaesthetic vapour was found to be a 1 2 3 mixture of alcohol, chloroform, and ether, known as ACE. Despite being widely used, it was always known that ACE presented a risk, and yet it was the anaesthetic of choice for more than 100 years. Ether caused serious fires and explosions in operating theatres and while the risk of this was small - about one serious incident every 100,000 operations - it was alarming when it happened. Chloroform was not a fire risk but it could be deadly to some patients, killing them within minutes in certain tragic cases, and seriously damaging the liver of others. (Nitrous oxide was less risky, and continues to be used even today, but it does not produce deep anaesthesia.)... 

ANAESTHETIC VAPOURS fSEDA-32, 243 SEDA-33, 257 SEDA-34, 195 SEDA-35, 217] ... 

LPG is considered to be non-toxic witli no chronic effects, but the vapour is slightly anaesthetic. In sufficiently high concentrations, resulting in oxygen deficiency, it will result in physical asphyxiation. The gases are colourless and odourless but an odorant or stenching agent (e.g. methyl mercaptan or dimethyl sulphide) is normally added to facilitate detection by smell down to approximately 0.4% by volume in air, i.e. one-fifth of the lower flammable limit. The odorant is not added for specific applications, e.g. cosmetic aerosol propellant. 

Examples of preservatives are phenylmercuric nitrate or acetate (0.002% w/v), chlorhexidine acetate (0.01 % w/v), thiomersal (0.01 % w/v) and benzalkorrium chloride (0.01 % w/v). Chlorocresol is too toxic to the comeal epithehum, but 8-hydroxyquinoline and thiomersal may be used in specific instances. The principal considerahon in relation to antimicrobial properties is the activity of the bactericide against Pseudomonas aeruginosa, a major source of serious nosocomial eye infections. Although benzal-konium chloride is probably the most active of the recommended preservatives, it cannot always be used because of its incompatibility with many compounds commonly used to treat eye diseases, nor should it be used to preserve eye-drops containing anaesthetics. Since benzalkonium chloride reacts with natural mbber, silicone or butyl rabber teats should be substituted. Since silicone mbber is permeable to water vapour, products should not be stored for more than 3 months after manufacture. As with all mbber components, the mbber teat should be pre-equilibrated with the preservative prior to... 

Propane has a characteristic natural gas odour and is basically insoluble in water. It is a simple asphyxiant but at high concentrations has an anaesthetic effect. The TLV is 2500 ppm. It is usually shipped in low-pressure cylinders as liquefied gas under its own vapour pressure of ca 109 psig at 21°C. Its pressure/temperature profile is given in Figure 9.7. 

Inhalation (IH) The administration of volatile gases and vapours, followed by drug absorption in the lungs or nasal mucosa. Examples include general anaesthetics like nitrous oxide, nicotine from the tar droplets in tobacco smoke, cannabinoids from cannabis leaf smoke and various opiates from burning opium resin. 

All inhaled anaesthetic drugs must be soluble in blood and brain in order to pass across the alveolar-capillary membrane and the blood-brain barrier. The term used to quantify solubility is partition coefficient. For anaesthetic purposes this is defined as the ratio of the concentration of dissolved gas/vapour in the blood to the concentration in the alveoli at... 

The rate at which the alveolar concentration of a vapour or gas approaches the inspired concentration is directly proportional to its inspired concentration. This is sometimes referred to as the concentration effect. It states that the higher the inspired anaesthetic concentration, the more rapid the rise in alveolar concentration and hence the more quickly equilibrium is attained between tensions in the alveoli and the brain. In practice, it is necessary to strike a balance to avoid irritation of the airway, or other unwanted phenomena, due to excessively high inspired concentrations of vapour. 

In theory, induction should be rapid, but in practice the inspired vapour concentration must be increased slowly to avoid airway irritation. MAC is 1.15% in 100% oxygen and 0.56% in 30% oxygen, making it less potent than halothane (0.75% and 0.29% at these oxygen concentrations). Isoflurane is the most potent of all the currently available anaesthetic ethers. Recovery from isoflurane anaesthesia is rapid and clear and the drug is suitable for use in day surgery. Cardiovascular system... 

Desflurane is a fluorinated methyl ethyl ether identical to isoflurane except for the substitution of a chlorine by a fluorine atom (Figure 3.2). It is the least soluble of all the volatile anaesthetics with a similar blood/gas solubility to nitrous oxide (0.42). It is non-flammable under all clinical conditions. The vapour pressure of desflurane approaches 1 atm at 23°C making controlled administration impossible with a conventional vaporiser. A desflurane vaporiser is an electronically controlled pressurised device that delivers an accurately metered dose of vaporised desflurane into a stream of fresh gases passing through it. The MAC of desflurane (6.5% in adults) is the highest of any modern fluorinated agent but in common with these the value decreases in the elderly and in other circumstances (see below). 

The ethers are also an homologous series. We will only use the common compound simply called ether as a further example. It is really diethyl ether or ethoxy ethane, C2H5 O C2H5. Ether was one of the earliest inhaled anaesthetics and it has a sweet sickly smell. Diethyl ether has a low boiling point (no hydrogen bonding unlike ethanol) and is easily evaporated at room temperatures. If you leave the bottle open it will soon evaporate into a heavy vapour which is extremely flammable. Never use ether near flames or sparks because fire and explosions are possible. 

A series of compounds, but usually the word ether refers to only one member of the homologous series, diethyl ether or ethoxy ethane C2H5OC2H5. It is a heavy vapour with anaesthetic properties and was one of the earliest materials used to induce unconsciousness in patients. Better anaesthetics have been developed that are less harmful and easier to use. 

The vinyl chloride used to make PVC is a gas at room temperature and is therefore kept under pressure during the process of polymerization. The pressure chambers used have to be cleaned out periodically and during the early years of manufacture workers would enter the chambers to clean them after periods of use. Inside the chambers levels of vinyl chloride were high, enough at times for the workers who, presumably, were unprotected to be overcome by the fumes. Vinyl chloride is like an anaesthetic (attempts were made to use it as such in the 1940s), and hence breathing the vapour causes the victim to lose consciousness. 

Gases of interest are nitrous oxide and the inhalation vapours (or volatile halogenated anaesthetics) such as halothane (CF3CHBrCl), isoflurane (CHF2OCHCICF3) and enflurane (CHCIFCF2OCHF2). In this section electrochemical studies on nitrous oxide, halothane and isoflurane will be discussed. 

It is a basal anaesthetic agent of choice which is administered through rectum in the form of its solution. The main advantage of such an anaesthesia being its pleasant induction amalgamated with lack of irritating vapours. 

More recent examples of the construction of energy-temperature diagrams for drug polymorphs include those published by Schmidt and co-workers for two local anaesthetics, hydroxyprocaine hydrochloride (HPCHC, Figure 9, 11) and salicaine hydrochloride (SLCHC, Figure 9,12) [49,50]. Comprehensive solid-state analysis of these compounds included HSM, DSC, TG, FUR and Raman spectroscopy, SSNMR, PXRD, single crystal XRD and vapour pressure sorption analysis. 

The general anaesthetics appear to be the only pharmacological group (applied in the vapour phase) in which molecules of widely different structure have been correlated by Ferguson s principle. As they function by accumulating in essential parts of the nerve cells and disorganising their metabolism, such a mechanism depends on physical nature rather than on chemical structure. 

Use Its main use is as a solvent especially in the degreasing of metals. It has also been used as an anaesthetic. Figure 17.1 shows a single compartment vapour type plant used for cleaning by solvents. 

Acute Trichloroethylene is a powerful anaesthetic and can be dangerous in confined spaces. Early features include headache, dizziness, and lack of concentration and eventually unconsciousness. Its vapour may cause irritation of the eye and the skin can be blistered by the liquid. 

The simplest method to transfer molecules as neutrals into the gas phase is by thermal heating. Here, a temperature-controlled oven is located either before or after the nozzle in the pre-expansion region. This method has been used for a limited number of small biomolecules including some nucleobases [12—15], amino acids [1-5], anaesthetics [16-23] and several neurotransmitters [24-26]. However, this method often requires very high temperatures to achieve significant vapour pressures, resulting in impractical experimental conditions and unacceptable high levels of thermal decomposition. 

---