Inhalational anaesthetic agents

Spray Inhalation - Vaporization of Volatile Anaesthetic Agents and Medication... 

The phenomenon by which the speed of onset of inhalational anaesthetic agents is increased when they are administered with N20 as a carrier gas. 

Shulman, M., and M.S. Sadove. 1967. 1,1,1,2-Tetrafluoroethane An inhalation anaesthetic agent of intermediate potency. Anesth. Analg. 46(5) 629-633. 

Desflurane has the lowest blood/gas partition coefficient of any inhaled anaesthetic agent and thus gives particularly rapid onset and offset of effect. As it undergoes negligible metabolism (0.03%), any release of free inorganic fluoride is minimised this characteristic favours its use for prolonged anaesthesia. Desflurane is extremely volatile and caimot be administered with conventional vaporisers. It has a very pimgent odour and causes airway irritation to an extent that limits its rate of induction of anaesthesia. 

Halothane has the highest blood/gas partition coefficient of the volatile anaesthetic agents and recovery from halothane anaesthesia is comparatively slow. It is pleasant to breathe and is second choice to sevoflurane for inhalational induction of anaesthesia. Halothane reduces cardiac output more than any of the other volatile anaesthetics. It sensitises the heart to the arrhythmic effects of catecholamines and hypercapnia arrhythmias are common, in particular atrioventricular dissociation, nodal rhythm and ventricular extrasystoles. Halothane can trigger malignant hyperthermia in those who are genetically predisposed (see p. 363). 

Westrin P. Intravenous and inhalational anaesthetic agents. Bailliere s Clin Anaesthesiol 1996 10 687-715. 

Doxapram (respiratory stimulant that activates peripheral aortic and carotid body chemoreceptors) behaves as a physiological antagonist when used to reverse central respiratory depression caused by barbiturates or inhalational anaesthetic agents. 

There have been many attempts to produce a unified theory detailing the mechanism of action of inhalation anaesthetics but no single theory has been accepted. Early theories on the mechanism of action of inhalation anaesthetics can by summarised by means of the Meyer-Overton theory, which indicated that the potency of anaesthetic action was related to the lipophilicity of an anaesthetic compound. The Meyer-Overton theory suggested that lipids within the brain could be dissolved by anaesthetic agents, thereby interfering with brain cell activity, leading to anaesthesia. 

Inhalation general anaesthetics, such as halothane, stimulate CICR in a way similar to that of caffeine. Administration of these agents to patients with MH mutations in RyRl gene will cause the MH episodes. 

While ionophore-stimulated 5-LO product release from neutrophils is often used as an indication of 5-LO inhibition, one must interpret these results cautiously. For example, halothane, an inhalation anaesthetic which may cause membrane perturbation [26], and colchicine, a microtubule disrupter [27], both were active, but presumably not because of 5-LO inhibition. A23187 is assumed to stimulate 5-LO by raising the intracellular calcium level, but this agent causes many other effects which may or may not be related to 5-LO activation, including changes in membrane potential, protein phosphorylation, phospholipid turnover, cyclic nucleotide levels, and DNA and protein synthesis [28]. Also, the effects of some putative 5-LO inhibitors on product release from neutrophils has been shown to vary with the stimulant used [29]. 

Intravenous anaesthetics are mainly used for rapid induction of anaesthesia, which is then maintained by an inhalational agent. They also serve to reduce the amount of maintenance anaesthetics. 

Figure 3.1 Graph showing the ratio between inspired (FJ) and alveolar (FA) end-tidal concentrations of the agents shown. The least soluble agents approach equilibrium (FA/FI=1) the most rapidly. Also, since both inhalation and intravenous anaesthetic drugs tend to reduce cardiac output, they facilitate the uptake of volatile agents. It follows that any inhaled anaesthetic drug must be given with great caution to patients in shocked states, e.g. hypovolaemia, arrhythmias, myocardial infarction.

An increase in alveolar ventilation will cause an increase in the alveolar concentration of inhaled agent when semi-closed or open breathing circuits are employed. The effect is most noticeable with a highly soluble anaesthetic, such as diethyl ether. With modern, relatively insoluble agents, such as isoflurane and desflurane, the effects of changes in alveolar ventilation are less pronounced. 

In order to compare the anaesthetic, haemo-dynamic, and other effects of these agents, it is necessary to have a measure of potency so that equivalent doses of the agents may be administered. Eger in 1974 coined the term minimum aiveolar ventilation (MAC) to describe the potency of inhaled anaesthetics. MAC is defined as ... 

Membranes Inhalation anaesthetics (diethylether, chloroform, and their more modem replacements). The mode of action of these was enshrouded in mystery for a long time, but accumulating evidence now supports direct interaction with several ion channels. Nevertheless, there is a remarkably close correlation between the ability of these agents to partition into lipid membranes, as measured by their oil-water partition coefficients, and their narcotic activity so, in a sense, cell membranes may be considered the targets of these agents. 

Disadvantages. Ketamine produces no muscular relaxation. It increases intracranial and intraocular pressure. Hallucinations can occur during recovery (the emergence reaction), but they are minimised if ketamine is used solely as an induction agent and followed by a conventional inhalational anaesthetic. Their incidence is reduced by administration of a benzodiazepine both as a premedication and after the procedure. 

GENERAL ANAESTHETICS are either inhaled or injected agents and produce insensibility, mostly to alleviate pain during surgical procedures (e.g. halothane, thiopentone sodium). 

Basal anaesthetics are agents which induce a state of unconsciousness but the depth of unconsciousness is not enough for surgical procedures. They are often used to induce basal anaesthesia before the administration of inhalation anaesthetics. They are also used for repeated short procedures in children like the changing of painful dressings. Basal anaesthetics offer three cardinal merit points, namely devoid of mental distress, pleasant induction and lesser respiratory irritation. They are often administered through the rectum. Few deserve mention. 

Knockdown agents are a special form of incapacitating agent which rapidly produces an anaesthetic-Uke state following inhalation. There is one substantiated case of such agents being used in the civil setting, namely the 2002 Moscow Theatre incident, where the Russian special forces claimed they used a powerful opiate compound (a fentanyl). Fatalities occurred from respiratory failure and arrest (see Chap. 10). 

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