Anesthetic Agents

ANESTHETIC AGENTS, Anaesthetica (from the Greek a- negative particle, aisthesis- sensation), substances that suppress sensitivity. Usually this refers to substances capable of preventing the sensation of pain during surgical or other medical intervention, in contrast to analgetica. A strict boundary cannot be drawn between both groups. A. s. depending on whether they cause loss of sensitivity throughout the body or only at the site of application, are divided into A. s. of general and local action. A. agents of general action cause loss of sensitivity as a result of their effect on the central nervous system, to which they are carried by the blood, depending on the method of their administration. Particular interest is attached to the introduction of volatile A. agents through the lungs in the form of vapor or gas, which are usually inhaled in mixture with air. Such A. agents are called inhalational. Their main representatives are chloroform, ether, ethyl bromide, and nitrous oxide. Anesthesia occurs when the saturation of the central nervous system with A. substances reaches a certain limit, e.g., for chloroform about 0.04% in the blood, this limit being reached the faster the higher the concentration of A. s. in the inhaled air and the greater the amount of the latter passing per minute through the lungs. At the end of the anesthesia, when the patient breathes pure air, the A. substance is also excreted through the lungs, and as it is excreted from the blood, the central nervous system is freed from the A. substance. Regarding the action of A. s. of the fatty series, to which all the most important A. s. of general action belong, several theories exist. According to the theory of Overton and Meyer, the main moment determining the action of these substances is their ability to pass from the blood into the central nervous system, which in turn depends on how well a given A. substance is soluble in fats (resp. in the lipoids of the central nervous system) than in water (resp. in the blood), i.e., on the so-called coefficient of distribution -5555" The narcotic action changes from substance to substance more or less parallel to the change in the mentioned coefficient of distribution. Traube's theory places the strength of action of the substances under consideration in dependence on their lowering of surface tension, which according to the Gibbs-Thomson law must cause their accumulation at the boundary of the disperse and dispersion phase, i.e., in this case on the surface of cells bathed by blood in which the A. substance is dissolved. Both theories, however, in Likhachev's opinion, do not contradict each other. Traube's theory explains the reason for the accumulation of substances on the surface of cells, while Overton and Meyer's theory explains the reason for their penetration into the cells. The very essence of the action is explained by colloid theories, assuming that substances, penetrating into cells, disrupt the specific permeability of their shells necessary for the correctness of their life functions; therefore, when this permeability is disrupted, cells cease to function normally - anesthesia occurs. During anesthesia, the action of anesthetic agents on various parts of the central nervous system occurs in a certain order, namely: first the brain is affected, then the spinal cord, and finally the medulla oblongata, which probably depends on the different functional stability of these parts. Externally this is manifested by the following symptoms: first there is depression of consciousness and sensitivity, then follows a period of excitement with loss of consciousness, after which reflexes are lost and muscle tone disappears. At this time the so-called period of tolerance occurs, when the operation is begun. Finally, the last period, dangerous to life, is characterized by considerable weakening of respiration and fall of blood pressure, which depends on the depression of the medulla oblongata and heart centers. When evaluating various A. s., the following properties must be taken into consideration. 1. The strength of the narcotic action. 2. General toxicity (and here too, as in other cases, therapeutic value is determined by the ratio between the strength of therapeutic, in this case narcotic, action and toxicity). The more favorable this ratio, the longer the interval between paralysis of the spinal cord and dangerous phenomena from the medulla oblongata, i.e., the longer the operative period. In view of the brevity of the mentioned period during anesthesia, ethyl bromide is not used for long operations. In evaluating toxicity, special attention must be paid to the toxic action on the heart and vasomotor center and the possibility of causing death before the onset of complete anesthesia with careless use of the A. substance (this is most frequently observed with chloroform - in status thymico-lymphaticus and in cases of particularly pronounced excitement). 3. The degree of exciting action at the beginning of anesthesia, since considerable excitement is very undesirable (one of the reasons for the limited use of ethyl chloride). 4. The irritating properties of the vapors of A. substances. This factor determines in some cases (e.g., with ether) the limit of maximum allowable concentration of vapors during anesthesia. 5. The consequences from the use of A. substances, where both general toxic properties (e.g., chloroform can cause fatty degeneration of the heart and parenchymatous organs) and local irritating properties (ether in narcotic concentration can cause pneumonia) play a role. 6. Finally, the speed of absorption of A. s. by the organism, as well as the speed of excretion is important. Here rapid excretion makes it difficult to maintain anesthesia at the proper depth, but on the other hand it is advantageous, since in threatening phenomena depending on the perception of too large an amount of A. s., the organism quickly gets rid of this excess (ethyl chloride and nitrous oxide).-Of non-volatile A. s. of general action, practical use has been made from among A. s. of the fatty series hedonal (methyl-isopropyl-carbinol-urethane) and more recently - avertin* (tribromoethyl alcohol), and from among alkaloids-scopolamine. The mentioned substances are introduced for the purpose of anesthesia per os (hedonal), in enemas (avertin and hedonal), under the skin (scopolamine) or into the blood (hedonal). These substances are excreted partly by the kidneys in unchanged form, and partly are broken down in the organism. Thus, their elimination from the organism occurs much more slowly than from volatile A. s. excreted by the lungs. On the other hand, non-volatile A. s. are introduced at once in relatively large quantities, i.e., in their use anesthesia is by no means to such an extent in the hands of the anesthetist as is the case with the use of volatile A. agents. Nevertheless, with anesthesia by some of these substances, quite satisfactory results have been obtained. In the use of A. s., combinations of substances are also used, i.e., mixed anesthesia. For example, a mixture of ACE (alcohol 1 part, ether 2 parts, chloroform 3 parts) is used, which, however, has no special advantages over pure ether or chloroform. In scopolamine anesthesia, as a rule, in addition to scopolamine, morphine is injected. Hedonal anesthesia is usually enhanced by inhaling small amounts of chloroform. A. s. of local action cause loss of sensitivity as a result of their effect on the endings or fibers of sensory nerves. This effect can be chemical (physicochemical) and physical, direct and indirect. The most characteristic physicochemical effect is manifested in the cocaine group. Substances of this group possess specific organotropy to sensory nerve endings and fibers. The effect is also enhanced indirectly due to the constricting action of cocaine on blood vessels, by virtue of which the substance, on the one hand, is longer retained at the site of introduction, and on the other, due to slower penetration into the general circulation, can be used in larger quantities. The constriction of vessels and the resulting decrease in blood flow affects the nutrition of nerves and their endings and thereby further contributes to their depression. Thus, the vasoconstrictive action of cocaine plays an essential role in its anesthetic action, which is especially enhanced when adrenalin is introduced simultaneously. The absence of this action in eucaine B, stovaine and other substitutes for cocaine significantly reduces their therapeutic value. The local action of cocaine is also enhanced when it is introduced in hypotonic NaCl solution, due to the resulting impregnation of the nerves with fluid. A number of A. s. of local action, which are liquids with low boiling points (e.g., ether, ethyl chloride, etc.), lower sensitivity, mainly due to the cooling of nerves and their endings caused by the withdrawal of heat from tissues by evaporation. To this is added the direct action of the substances on the nerves, which is facilitated by the easy diffusion of the substances through tissues and the constriction of vessels by cold. In the use of local A. s., depending on the depth of location of the area of effect, an attempt is made to influence, mainly, either the nerve endings (terminal anesthesia) or the nerve fibers and trunks (conduction anesthesia).

The first occurs when mucous membranes are lubricated with a solution of anesthetic agents, the second - when anesthetic solutions are injected into nerve trunks or surrounding tissues. The same goal is pursued by lumbar and sacral anesthesia methods (see Local Anesthesia).