Anesthesia

The chief virtue of a purely physical interpretation of anesthesia lies in the fact that it fits all forms of anesthesia by whatever means produced. This no chemical hypothesis can do. The mechanism of anesthesia as here set forth is not to be expressed as the coagulation of protoplasm but as gelatinization, or thixotropic setting, for the latter two processes unlike the first are readily reversible. Identical results are obtained when anesthesia or the cessation of protoplasmic movement is accomplished by mechanical (88) or electrical shock. 

That a state of anesthesia should exist when protoplasm has been gelatinized is evident from the fact that with an increase in viscosity there must be a decrease in metabolic activity which reaches a minimum at maximum viscosity, or at reversible gelatinization of the protoplasm. Not only is metabolism, taken as a whole, slowed down by gelatinization of the protoplasm, but either the gelatinization or the anesthetic agent itself undoubtedly interferes with enzyme activity. 

For larger tumors, multiple tumors, and tumors in areas where it may be difficult to apply sufficient local anesthesia (e.g., periost involvement in the scalp), general anesthesia is recommended. This may be handled by short-acting anesthetic agents such as propofol combined with short-acting opioids [15]. As pulses should be administered within approximately a 20 min window, the anesthesia can be short and the pahent discharged on the same day [9]. 

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Anesthesia. Materials that have unquestionable anesthetic properties are chloral hydrate [302-17-0] paraldehyde, dimethoxymethane [109-87-5] and acetaldehyde diethyl acetal. In iadustrial exposures, however, any action as an anesthesia is overshadowed by effects as a primary irritant, which prevent voluntary inhalation of any significant quantities. The small quantities which can be tolerated by inhalation are usually metabolized so rapidly that no anesthetic symptoms occur. 

The narcotic potency and solubiUty in oHve oil of several metabohcaHy inert gases are Hsted in Table 10. The narcotic potency, ED q, is expressed as the partial pressure of the gas in breathing mixtures requited to produce a certain degree of anesthesia in 50% of the test animals. The solubiUties are expressed as Bunsen coefficients, the volume of atmospheric pressure gas dissolved by an equal volume of Hquid. The Hpid solubiHty of xenon is about the same as that of nitrous oxide, a commonly used light anesthetic, and its narcotic potency is also about the same. As an anesthetic, xenon has the virtues of reasonable potency, nonflammability, chemical inertness, and easy elimination by the body, but its scarcity and great cost preclude its wide use for this purpose (see Anesthetics). 

ED q, narcotic potency, is expressed as the partial pressure of a gas in breathing mixtures requited to produce a certain degree of anesthesia in 50% of the test animals. 

Biological Activities and Analogues. Somatostatin exerts some neurotropic actions, eg, as a tranquilizer and as a spontaneous motor activity depressor. It also lengthens barbiturate anesthesia time and induces sedation and hypothermia. These actions are consistent with the strong association between somatostatin and GABA in the primate cerebral cortex, 90—95% of somatostatin-positive ceHs also contain GABA (100). 

Gycloparaffins. Members of this class produce effects much like the paraffins, except that unsaturated cycloparaffins are more noxious than the saturated counterparts. Breathing high concentrations of cycloparaffin vapors can result in irritation and anesthesia. 

M. J. Halsey, R. A. Miller, and J. A. Sutton, Molecular Mechanisms in General Anesthesia, ChurchiU Livingston, Edinburgh, Scodand, 1974. 

Eupatin (69, R = H) and Eupatoretin (69, R = CH3), which are isolated from thistle perennials, show moderate cytotoxicity against human carcinoma of the nasopharynx (236). Baicaleia (70) salts exhibit antiallergic and antiinflammatory activity. 3,4,5-Trimethoxyphenoxyacetamides are hypotensives and diuretics and are useful for controlling arrhythmia duting anesthesia (237). 

The microdialysis sampling process which allows the monitoring of small molecules in circulation within an animal, is an example. An artificial capillary is placed in the tissue region of interest, and a sample is coUected via dialysis. In the case of a laboratory animal such as a rat, a probe is placed in the jugular vein under anesthesia. Elow rates ate of the order of 1 p.L/min. 

The onset of action is fast (within 60 seconds) for the intravenous anesthetic agents and somewhat slower for inhalation and local anesthetics. The induction time for inhalation agents is a function of the equiUbrium estabUshed between the alveolar concentration relative to the inspired concentration of the gas. Onset of anesthesia can be enhanced by increasing the inspired concentration to approximately twice the desired alveolar concentration, then reducing the concentration once induction is achieved (3). The onset of local anesthetic action is influenced by the site, route, dosage (volume and concentration), and pH at the injection site. 

The membrane enzyme luciferase, responsible for light emission in fireflies, is sensitive to anesthetics (20,21), and the concentrations of inhalational agents which inhibit luciferase are the same as those which cause general anesthesia. Studies of various classes of inhalational agents and luciferase demonstrated that above a certain chain length in a homologous series, a point is reached where higher members are not anesthetic. The same cut-off effect in efficacy is observed in anesthesia (22). This effect is not explainable by Hpid theory. 

The agent should be odorless, nonflammable at concentrations which are likely to be used in the operating room, and stable both on storage and to soda lime, which is used as the CO2 absorber in the anesthetic circuit. Induction of, and recovery from, anesthesia should be rapid, and minimal side effects... 

Historical Inhalation Agents. Diethyl ether produces excellent surgical anesthesia, but it is flammable (see Ethers). Chloroform is a nonflammable, sweet smelling, colorless Hquid which provides analgesia at nonanesthetic doses and can provide potent anesthesia at 1% (see Chlorocarbons AND CHLOROHYDROCARBONs). However, a metabohte causes hepatic cell necrosis. Tdlene, a nonflammable colorless Hquid, has a slower onset and recovery and a higher toxicity and chemical reactivity than desirable. Cyclopropane is a colorless gas which has rapid induction (2 —3 min) and recovery characteristics and analgesia is obtained in the range of 3—5% with adequate skeletal muscle relaxation (see Hydrocarbons). The use of cyclopropane has ceased, however, because of its flammabiHty and marked predisposition to cause arrhythmias. 

Nitrous Oxide. Nitrous oxide, described by Priesdy in 1772, was first used to reHeve severe dental pain in the latter part of the 18th century. Sometime in the mid-1800s N2O was successfully used as an anesthetic, and its widespread usage coincided with the development of anesthesia machines. Nitrous oxide is a nonflammable, colorless, odorless, and tasteless gas that can exist as a Hquid under pressure at room temperature. It is normally stored in cylinders. However, it supports combustion. 

Because of fluoride ion associated renal impairment, the duration of anesthesia using methoxyflurane must be limited (51,52). 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

Sevoflurane. Sevoflurane, l,l,l,3,3,3-hexafluoro-2-propyl fluromethyl ether [28523-86-6] is nonpungent, suggesting use in induction of anesthesia. The blood/gas partition coefficient is less than other marketed products (Table 1) yet similar to nitrous oxide, suggesting fast onset and recovery. In animal studies, recovery was faster for sevoflurane than for isoflurane, enflurane, or halothane (76). Sevoflurane is stable to light, oxygen, and metals (28). However, the agent does degrade in soda lime (77). 

Methohexital [18652-93-2] (Brevital), C 4H gN202, (2) is a barbiturate iv anesthetic iaduction agent that has a slightly faster onset than thiopentone and less accumulation. The recovery from anesthesia is also slightly faster and better. However, iaduction is associated with an iacreased iacidence of excitatory phenomena. Methohexital also causes respiratory and cardiovascular depression and is unstable ia solution, necessitating reconstitution before use (99). 

Local anesthetics produce anesthesia by blocking nerve impulse conduction in sensory, as well as motor nerve, fibers. Nerve impulses are initiated by membrane depolarization, effected by the opening of a sodium ion channel and an influx of sodium ions. Local anesthetics act by inhibiting the channel s opening they bind to a receptor located in the channel s interior. The degree of blockage on an isolated nerve depends not only on the amount of dmg, but also on the rate of nerve stimulation (153—156). 

Specific Local Anesthetic Agents. Clinically used local anesthetics and the methods of appHcation are summarized in Table 5. Procaine hydrochloride [51-05-8] (Novocain), introduced in 1905, is a relatively weak anesthetic having along onset and short duration of action. Its primary use is in infiltration anesthesia and differential spinal blocks. The low potency and low systemic toxicity result from rapid hydrolysis. The 4-arninobenzoic acid... 

Chloroprocaine hydrochloride [3858-89-7] is characterized by low potency, rapid onset, short duration of action, and low systemic toxicity. It is indicated for infiltration anesthesia at 1—2% and for extradural anesthesia at 2—3% when short surgical procedures are performed under regional anesthesia. Chloroprocaine may be mixed with long duration agents such as bupivacaine (22, R = n-Q [) to afford a more rapid onset and shorter duration of action than bupivacaine alone. 

Tetracaine (20, X = H, R = R = is primarily used in spinal anesthesia providing a slow onset, high potency, and a long duration of... 

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