Characteristics of inhalational anesthetics. Inhalational anesthetics: main representatives, mechanism of action

The degree of protection of the body from surgical trauma currently continues to be a subject of debate. Inadequate anesthetic protection is fraught with serious complications, the preconditions for which are laid during surgery, but such complications can be prevented, including by rational anesthetic protection.

In turn, the anesthesia method is required to provide neurovegetative protection and analgesia that does not compromise the functions of organs and systems. Each method of pain relief has its pros and cons. Selecting patient protective equipment is often not an easy task. This is determined by the specifics of the surgical intervention, the characteristics of the patient, as well as the preferences of the anesthesiologist.

Encouraging results have been obtained with the use of inhalational anesthetics. Thus, by 2012, the share of anesthesia based on sevoflurane exceeded 70% of the number of general anesthesia in Russia compared to 2004, where this value was 21%.

This group combines: medical gases (nitrous oxide and xenon), halogen-containing drugs - first generation (halothane), second (enflurane and isoflurane), and third (sevoflurane and desflurane). The choice in favor of an inhalational anesthetic today is obvious, but also difficult. At the moment, inhalation anesthesia is experiencing a kind of “renaissance.”

Organotoxicity

Renaissance of inhalational anesthetics in modern practice is connected with the fact that entire generations of domestic anesthesiologists were brought up in the belief that the implementation combined anesthesia is possible only within the framework of total intravenous anesthesia, and halogen-containing drugs are a dead-end development path due to problems with organ toxicity.

Experts return to discuss this problem more than once, and most often this is due to the emergence of a new drug, or the discovery of new mechanisms for the implementation of this effect for already known and actively used drugs. This question, is by no means didactic in nature, because according to E.D. Kharasch, it is the answer that most often provides decisive influence at the choice of the anesthesiologist.

It is generally accepted that organ toxicity results from changes in cellular structure and/or function that occur following the onset of anesthetic administration. The higher the solubility of the anesthetic in the blood, the higher the likelihood of the formation of toxic metabolites.

The level of biotransformation reflects the measure of probable toxicity, which decreases in the following sequence: methoxyflurane (65%) > halothane (20%) > sevoflurane (3%) > enflurane (2.4%) > isoflurane (0.2%) > desflurane (0 .02%).

In relation to inhalational anesthetics, hepatotoxicity and nephrotoxicity are discussed. The problem of hepatotoxicity arose following the advent of halothane. Halothane is known to cause acute liver necrosis (ALN) or subclinical hepatotoxicity.

SNP is considered an autoimmune process initiated by the peroxidation of halothane to form trifluoroacetate. The latter is adsorbed by hepatocyte membranes and causes the formation of autoantibodies, which leads to SNP. Similar cases are rare, but their consequences are fatal.

Isoflurane, enflurane and desflurane also form trifluoroacetate during biodegradation, however, due to significantly lower biotransformation, the above drugs are less likely to cause SNP.

Hepatotoxicity is associated with anaerobic metabolism of halothane, activation of lipid peroxidation processes and inhibition of cytochrome P450 activity. The only one selective inhibitor cytochrome P450 – disulfiram. According to some data, its preventive administration inhibits the increase in the concentration of fluoride ion.

Sevoflurane occupies a special position among halogen-containing anesthetics. There are no descriptions in the literature of confirmed cases of the development of SNP after anesthesia with this drug. With regards to isoflurane, there is evidence of the effective maintenance of total hepatic blood flow and blood flow through the mesenteric vessels when used.

Regarding acute renal failure, direct nephrotoxicity has been proven only for methoxyflurane, which can cause polyuria resistant to vasopressin. The active agent is considered to be fluoride ion, formed during the process of biodegradation with a threshold concentration of 50-80 µmol/l.

As new halogenated anesthetics became available, this mechanism was transferred to them. All of them were tested for its content in the patients’ blood plasma and, which was: for enflurane 20-30 µmol/l, isoflurane 1.3-3.8 µmol/l, traces of desflurane.

Regarding sevoflurane, then this indicator exceeded 50 µmol/l, but, despite this, the level of nitrogenous wastes in the blood was within the normal range. There are two possible explanations for this. First, sevoflurane is slightly soluble in tissues and has limited availability for biotransformation. And second, its metabolism occurs in the liver, not in the kidneys.

Another substance with a nephrotoxic effect is formed by the interaction of sevoflurane with the lime adsorbent compound A. Its nephrotoxicity was first shown in rats. A likely common element of nephrotoxicity is biotransformation to reactive thiols via glutathione and beta-lyases.

But despite the presence of a potentially toxic metabolic pathway (involving beta-lyases) shared between rats and humans, there are important interspecies differences in the renal effects of Compound A. Rats develop severe kidney damage, whereas an increased incidence of clinically significant nephrotoxicity in humans has not been reported. reported. This is probably due to the low activity of renal beta-lyases in the human body.

However, according to other studies, in volunteers who were anesthetized with low-flow sevoflurane for 8 hours, the occurrence of transient disturbances kidney function.

Organoprotection

Preconditioning – beneficial changes in the myocardium caused by rapid adaptive processes in it during a short-term episode of severe ischemia/reperfusion, which protect the myocardium from ischemic changes until the next episode of ischemia/reperfusion.

Anesthetics can initiate protective effects not only in the myocardium. Changing the balance of oxygen in the myocardium towards increasing its delivery and decreasing demand is considered an effective way to protect the heart from ischemia. Inhalational anesthetics have a positive effect on this process, but as research shows, the main mechanism for the implementation of the cardioprotective effect of inhalational anesthetics is not only this.

The ability to increase the heart's resistance to ischemia was first discovered in halothane, then in other inhalational anesthetics, and the mechanisms turned out to be similar to ischemic preconditioning (IPC), which gave rise to the right to define this phenomenon as anesthetic preconditioning (APC)

The mechanism of the effect in general outline clear: anesthetics cause a threshold increase active forms oxygen in the mitochondria, trigger a cascade of sequential reactions leading to the “blocking” of some mitochondrial channels. A mitochondria thus protected has a greater chance of surviving an ischemia/reperfusion episode. And then the rule comes into force - irreversible damage to the cell occurs when more than 40% of the mitochondria die.

Methodology and monitoring

Due to their pharmacokinetic and pharmacodynamic properties, inhalational anesthetics are used with a low gas flow, which reduces the cost of anesthesia. Besides, this method allows you to improve the microclimate in the breathing circuit by increasing the temperature and humidity of the inhaled gas mixture, thereby supporting the function of the bronchial epithelium.

equipment requirements

First, evaporators of liquid anesthetics must have a thermobarocompensation mechanism and ensure correct dosing in the gas flow range from 0.2 to 15 l/min.

Second, anesthesia based on low flows is possible only when using reversible breathing circuits: circulation and pendulum. Due to the design features, the circulating one is most suitable for anesthesia with reduced gas flow. The pendulum circuit is less convenient, since the adsorption processes of carbon dioxide (CO2) in such systems are less efficient.

Third, with a decrease in gas flow, the proportion of recirculating exhaled gas mixture with high content CO2. In this case, anesthesia machines must be equipped with adsorbers to remove CO2. The lime in the adsorber should be considered to have expired if the inhaled CO2 concentration exceeds 6-7 mmHg. A color indicator is added to the lime sorbent, the color of which changes from white to pink as the sorption capacity for CO2 is depleted.

And fourth, the breathing circuit must be sealed: the amount of permissible leakage should not exceed 100 ml/min. Insufficient tightness leads to the entry of atmospheric air into the circuit, and as a result, a violation of the ratio of the concentration of oxygen and inhalational anesthetic occurs.

The modern concept of inhalation anesthesia involves its combination with other methods of pain relief. There is now an understanding that the fascination with drug combinatorics is giving way to an approach using limited quantity drugs.

The most commonly used combination is: muscle relaxant - opiate - inhalational anesthetic. Studies have shown that during anesthetic management, general anesthesia enflurane or isoflurane, in combination with fentanyl, is much more effective than neuroleptanalgesia and ataralgesia, and the pharmacokinetics and framacodynamics of inhalational anesthetics ensure a quick and smooth introduction to anesthesia, guaranteed efficiency and a quick awakening.

However, it is worth noting that inhalational anesthetics for induction of anesthesia are used only in pediatric practice. Although, according to some authors, inhalation induction may be widespread in adults, this requires a fundamental change in existing stereotypes.

Thus, inhalation anesthesia is becoming increasingly popular, which is determined by its good controllability and relative safety. This is due to the possibility of quickly achieving the required concentration in the body and, if necessary, reducing it just as quickly, which ensures a shortening of induction and recovery periods, ease and accuracy of control over this process.

However, in Russia, as in most countries of the European Union, there are no recommendations on the use of the inhalation technique, so the choice of pain relief method remains with the anesthesiologist. This dictates the need for a differentiated approach to the choice of anesthetic approach, increasing the efficiency and safety of anesthesia, adapting it to the characteristics of surgery and reducing the number of complications both in the intra- and postoperative periods.

Shadus V.S., Dobronosova M.V., Grigoriev E.V.

Modern inhalational anesthetics are much less toxic than their predecessors, and at the same time more effective and manageable. In addition, the use of modern anesthesia and respiratory equipment can significantly reduce their intraoperative consumption.

Pharmacodynamics of liquid inhalational anesthetics

Central nervous system

At low concentrations, liquid inhalational anesthetics cause amnesia. As the dose increases, the depression of the central nervous system increases in direct proportion. They increase intracerebral blood flow and reduce the rate of brain metabolism.

The cardiovascular system

Inhalational anesthetics cause a dose-dependent inhibition of myocardial contractility and a decrease in total peripheral resistance due to peripheral vasodilation. All drugs, with the exception of isoflurane, do not cause tachycardia. In addition, all inhalational anesthetics increase the sensitivity of the myocardium to the action of arrhythmogenic agents (adrenaline, atropine, etc.), which should be taken into account when using them together.

Respiratory system

All inhalational anesthetics cause dose-dependent respiratory depression with a decrease in respiratory rate, an associated increase in respiratory volume, and an increase in the partial pressure of carbon dioxide in the artery. According to the degree of respiratory depression in equimolar concentrations, they are arranged in descending order: halothane - isoflurane - enflurane, thus, enflurane is the drug of choice for anesthesia with preserved spontaneous breathing.

They also have bronchodilator activity (halothane > enflurane > isoflurane), which can be used in the appropriate situation.

Liver

Inhalational anesthetics tend to reduce organ blood flow in the liver. This inhibition is especially pronounced during anesthesia with halothane, less so with enflurane, and is practically absent when using isoflurane. The development of hepatitis has been described as a rare complication of halothane anesthesia, which served as the basis for limiting the use of the drug.

urinary system

Inhalational anesthetics reduce renal blood flow in two ways: by reducing system pressure and an increase in total peripheral resistance in the kidneys.

Pharmacodynamics of gaseous inhalational anesthetics

Nitrous oxide (N 2 O) is a colorless gas with a sweetish odor. Has weak analgesic properties. Causes myocardial depression. In healthy patients, this effect is neutralized by activation of the sympathoadrenal system. Prolonged exposure can lead to agranulocytosis, myeloblastic anemia. With professional contact, the development of polyneuropathy is possible.

Xenon (Xe)- a monatomic gas without color or taste. Chemically indifferent, does not undergo biotransformation in the body. Does not irritate the respiratory tract. It is excreted unchanged through the lungs. It has a more powerful narcotic potential compared to nitrous oxide. Does not affect the conductivity and contractility of the myocardium. Indicated for patients with a compromised cardiovascular system. Flaw- high price.

DEVICE OF THE ANESTHESIA MACHINE

During inhalation anesthesia, an anesthetic is introduced into the patient's body using anesthesia machine, consisting of three main blocks:

Gas mixture formation block, or the gas supply system provides the output of a certain gas mixture. IN normal conditions gas for anesthesia machines in a hospital comes from a central gas supply system called a gas distribution system. The system lines are routed to the operating room. Cylinders attached to the anesthesia machine can store gas for emergency supply. Oxygen, air and nitrous oxide supplies are standard. The gas mixture formation unit is necessarily equipped with a reducer to reduce gas pressure. In the central distribution, the pressure is usually 1.5 atm, in the cylinder - 150 atm. To submit

liquid anesthetic there is an evaporator. Patient ventilation system includes a breathing circuit (more on that below), an absorber, a respirator and a dosimeter. Dosimeters are used to regulate and measure the flow of gaseous

general anesthetics, entering the breathing circuit, which is important with modern methods of low-flow anesthesia.

Exhaust gas removal system

collects excess gases from the patient circuit and gas mixture forming device and removes these gases outside the hospital. Thus, the exposure of personnel working in the operating room to inhalational anesthetics is reduced.

The main difference between anesthesia equipment is the design of the breathing circuit. The breathing circuit includes corrugated hoses, breathing valves, a breathing bag, an adsorber, a mask, and an endotracheal or tracheostomy tube. Currently, the International Commission for Standardization (ISO) proposes to be guided by the following classification of breathing circuits.

Depending on the design features

highlight:

circuits with carbon dioxide absorber (fully reversible circuits),

partially reversible circuits (Mapleson circuits),

non-reversible contours. Reversin is a circuit where the gas-narcotic mixture is partially or completely returned to the system for re-inhalation. Reversion can be constructed as a pendulum (one hose with an adsorber) or circular (different hoses). Depending on the functional features.

Breathing circuits can be divided into: open, half-open, half-closed and closed inhalation and exhalation are carried out from the atmosphere and into the atmosphere. During inhalation, the air flow captures anesthetic vapors that enter the Airways. Currently, this method is used extremely rarely, although it has its advantages: simplicity, minimal breathing resistance, and the absence of a dead space effect. Disadvantages: inability to accurately dose general inhalation anesthetic and perform mechanical ventilation, insufficient oxygenation, contamination of the operating room with anesthetic vapors.

Breathing circuits can be divided into: semi-open circuit the gas-narcotic mixture enters the respiratory tract from cylinders, passing through dosimeters and evaporators, and exhalation is carried out into the atmosphere. Advantages: precise dosing of anesthetic, possibility of mechanical ventilation. Disadvantages: excessive loss of heat and moisture, relatively large dead space, wasteful use of general inhalational anesthetics.

Breathing circuits can be divided into: semi-closed circuit inhalation is carried out from the apparatus, and part of the exhaled mixture is released into the atmosphere. At closed circuit inhalation is carried out from the device and the entire exhaled mixture is returned to the device. Advantages: saving of anesthetics and oxygen, minor losses of heat and moisture, low breathing resistance, less pollution of the operating room atmosphere. Disadvantages: the possibility of anesthetic overdose and hypercapnia, the need to control the inhaled and exhaled concentrations of anesthetics, monitoring the gases of the inhaled and exhaled mixture, the problem of disinfecting the anesthesia machine, the need to use an adsorber - a device for absorbing excess carbon dioxide. Soda lime is used as a chemical carbon dioxide absorber.

Open and semi-open circuits are classified as non-reversible. Closed and semi-closed - to reversible.

TYPES OF INHALATION NARCOSIS

Inhalation anesthesia can be performed simple mask, hardware-mask, endotracheal, endobronchial and tracheostomy methods.

Mask general anesthesia in an open manner using simple masks(Esmarch, Vancouver, Schimmelbusch) is rarely used, despite its simplicity, since it makes it impossible to accurately dose the anesthetic, use gaseous agents, and it is difficult to prevent the development of hypoxemia, hypercapnia and complications due to aspiration of saliva, mucus, and vomit into the respiratory tract. In addition, the operating room is sharply contaminated with general inhalational anesthetics with all the ensuing consequences (inadequacy of the anesthesiological and surgical teams, damage to the gene pool of the medical staff).

Hardware method of mask general anesthesia allows you to dose an inhalational anesthetic, use oxygen, gaseous general inhalational anesthetics, a chemical carbon dioxide absorber, use various breathing circuits, reduce moisture and heat transfer, provide auxiliary and artificial ventilation lungs. However, with this method it is necessary to constantly ensure the patency of the airways and the tightness of the oronasal mask; it is difficult to prevent aspiration of gastric contents into the respiratory tract. Mask general anesthesia is indicated for low-traumatic operations that do not require muscle relaxation and mechanical ventilation, for anatomical and topographical abnormalities oral cavity and respiratory tracts that complicate tracheal intubation, if it is necessary to perform operations or manipulations in primitive conditions.

Endotracheal method of general anesthesia is currently the mainstay in most areas of surgery.

The inhalational anesthetic enters the respiratory tract through an endotracheal tube inserted into the lumen of the trachea.

The main stages of intubation anesthesia are:

Introductory anesthesia. Achieved by administering drugs for intravenous anesthesia for rapid deep sleep and reducing the dose of inhalational anesthetic.

Administration of muscle relaxants.

All muscle relaxants are divided into two large groups depending on their mechanism of action.

Mechanism of action non-depolarizing (antidepolarizing) muscle relaxants is associated with competition between the latter and acetylcholine for specific receptors (therefore they are also called competitive). As a result, the sensitivity of the postsynaptic membrane to the effects of acetylcholine sharply decreases. As a result of the action of competitive relaxants on the neuromuscular synapse, its postsynaptic membrane, which is in a state of polarization, loses the ability to enter a state of depolarization, and, accordingly, the muscle fiber loses the ability to contract. That is why these drugs are called non-depolarizing.

Termination of neuromuscular blockade caused by antidepolarizing blockers can be facilitated by the use of anticholinesterase drugs (neostigmine, proserine): the normal process of biodegradation of ACh is disrupted, its concentration in the synapse increases sharply, and as a result it competitively displaces the relaxant from its connection with the receptor. It should be remembered, however, that the duration of action of angiocholinesterase drugs is limited, and if the end of their action occurs before the destruction and elimination of the muscle relaxant, the neuromuscular block may re-develop, a situation known to clinicians as recurarization.

Myoparalytic effect depolarizing muscle relaxants is due to the fact that they act on the postsynaptic membrane like acetylcholine, causing its depolarization and stimulation of the muscle fiber. However, due to the fact that they are not immediately removed from the receptor and block the access of acetylcholine to the receptors, the sensitivity of the end plate to acetylcholine is sharply reduced.

In addition to the above classification, Savarese J. (1970) proposed that all muscle relaxants be divided depending on the duration of the neuromuscular block they cause: ultra-short action - less than 5 - 7 minutes, short action - less than 20 minutes, medium duration - less than 40 minutes and long acting– more than 40 minutes (Table 3).

Before tracheal intubation, ultra-short and short-acting muscle relaxants are administered.

There is no “ideal” inhalational anesthetic, but certain requirements are imposed on any of the inhalational anesthetics. An “ideal” drug should have a number of properties listed below.
/. Low cost. The drug should be cheap and easy to produce.
Physical 2. Chemical stability. The drug must have a long shelf life and be
properties strong over a wide temperature range, it should not react with metals, rubber or
plastics. It must retain certain properties when ultraviolet irradiation and do not require added stabilizers.
Non-flammable/non-explosive. Vapors should not ignite or sustain combustion at clinically used concentrations and when mixed with other gases, such as oxygen.
The drug must evaporate at room temperature and atmospheric pressure with a certain pattern.
The adsorbent should not react (with the drug) accompanied by the release of toxic products.
Safety for environment. The drug should not destroy ozone or cause other environmental changes even in minimal concentrations.
/. Pleasant to inhale, does not irritate the respiratory tract and does not cause increased secretion.
Biological properties
The low blood/gas solubility ratio ensures rapid induction of anesthesia and recovery from it.
The high potency allows the use of low concentrations in combination with high oxygen concentrations.
Minimum side effect on other organs and systems, such as the central nervous system, liver, kidneys, respiratory and cardiovascular systems.
Does not undergo biotransformation and is excreted unchanged; does not react with other drugs.
It is non-toxic even with chronic exposure to small doses, which is very important for operating room personnel.
None of the existing volatile anesthetics meets all these requirements. Halothane, enflurane and isoflurane destroy ozone in the atmosphere. All of them inhibit myocardial and respiratory function and undergo metabolism and biotransformation to a greater or lesser extent.
Halothane
Halothane is relatively cheap, but it is chemically unstable and degrades when exposed to light. It is stored in dark bottles with 0.01% thymol added as a stabilizer. Of the three halogen-containing drugs, halothane has the highest gas solubility in the blood and, therefore, the slowest onset of action; but despite this, halothane is most often used for inhalational induction of anesthesia, since it has the least irritating effect on the respiratory tract. Halothane is metabolized by 20% (see "Effect of anesthesia on the liver"). Halothane characteristics: MAC - 0.75; solubility coefficient blood/gas at a temperature of 37 "C - 2.5; boiling point 50 "C; steam saturation pressure at 20 "C - 243 mm Hg.
Enflurane
The MAC of enflurane is 2 times greater than that of halothane, so its potency is half as strong. It causes paroxysmal epileptiform activity on the EEG at a concentration of more than 3%. 2% of the anesthetic undergoes biotransformation, resulting in the formation of a nephrotoxic metabolite and an increase in the concentration of fluoride in the serum. Characteristics of enflurane: MAC - 1.68; solubility coefficient blood/gas at a temperature of 37 "C 1.9; boiling point 56" C; steam saturation pressure at 20 °C - 175 mm Hg. Isoflurane
Isoflurane is very expensive means. It irritates the respiratory tract and can cause coughing and increased secretion, especially in patients without premedication. Of the three halogen-containing anesthetics, it is the most powerful vasodilator: in high concentrations it can cause coronary steal syndrome in patients with concomitant coronary pathology. Characteristics of isoflurane: MAC - 1.15; solubility coefficient blood/gas at a temperature of 37 "C - 1.4; boiling point 49" C; steam saturation pressure at a temperature of 20 "C - 250 mm Hg.
The above advantages and disadvantages of the three most well-known halogen-containing anesthetics contributed to further research and the search for similar compounds for clinical trial their anesthetic effect in humans. IN last years Two new drugs of this group were synthesized and their properties and advantages were assessed.
Sevoflurane
This is methyl isopropyl ether, halogenated with fluorine ions. It is non-flammable at clinically used concentrations. He doesn't seem to have a serious problem side effects on SSS and respiratory system. The main theoretical advantage is the very low blood/gas solubility coefficient (0.6), which allows it to be used for rapid inhalation induction, especially in children. The main disadvantage that may limit its widespread use is instability when in contact with soda lime.
Desflurane (1-163)
This is a halogenated methyl ethyl ether, the 163rd in a series of synthesized halogenated anesthetics. Its structure is similar to isoflurane, but does not contain chlorine ions. Experiments with animals show that desflurane is biologically stable and non-toxic. Preliminary use of the drug in clinical practice has shown that it is pleasant to inhale and does not irritate the respiratory tract. Desflurane has an exceptionally low blood/gas solubility coefficient and can therefore also be used for rapid inhalation induction. The main disadvantages of the drug are high cost and high pressure steam saturation, which does not allow its use with traditional evaporators. Research is ongoing to overcome these problems and further evaluate the use of des-flurane in clinical practice.
additional literature
Heijke S., Smith G. Quest for the ideal inhalational anaesthetic agent.- British Journal of
Anaesthesia, 1990; 64: 3-5. Jones P.M., Cashman J.N., Mant T.G.K. Clinical impressions and cardiorespiratory effects of a new fluorinated inhalation anaesthetic, desflurane (1-163), in volunteers.- British Journal of Anaesthesia, 1990; 64: 11-15. Related Topics
Intravenous anesthetics (p. 274). The effect of anesthesia on the liver (p. 298). Nitrous oxide (p. 323).

Long-term inhalation anesthesia made it possible to study the pharmacokinetics of inhalational anesthetics

Most effective inhalational anesthetics do not have a pronounced irritating effect and are not flammable. These include nitrous oxide and fluorinated hydrocarbons, such as halothane (fluorothane) and related compounds enflurane and isoflurane. However, ether, despite its irritating properties and explosiveness, is cheap and relatively safe; when working with it, the participation of a qualified anesthesiologist is not required; because of this, in some countries it continues to be used to this day.

Inhalational anesthetic nitrous oxide

Nitrous oxide (used since 1844). When used correctly, it is a safe anesthetic; when used incorrectly, anoxia develops due to insufficient oxygenation. With prolonged use (for several hours) in a patient, for example in intensive care units (after heart surgery), function depression may occur. bone marrow with a transition to megaloblastic hematopoiesis due to inhibition of the coenzyme vitamin B12, necessary for normal folate metabolism. Nitrous oxide has an analgesic effect, but is relatively ineffective as an anesthetic, so when used in isolation it cannot maintain anesthesia during surgery. Because of this, it is usually used with other analgesics or inhalational anesthetics such as halothane (fluorothane). Nitrous oxide is used only for very short-term operations, such as in dentistry. Induction and recovery from anesthesia occurs quickly. Nitrous oxide is not explosive, but it can catch fire. It diffuses into all cavities of the body that contain air and causes an increase in pressure, sometimes dangerous, for example with pneumothorax.

Nitrous oxide mixed with oxygen in a 50% concentration is used in obstetric practice for the purpose of analgesia, for painful dressings, pain in the postoperative period, as well as for myocardial infarction and injuries. It is technically easier to produce mixtures of gases in one cylinder (entonox) than in devices with a mixer for mixing gases before being supplied from different cylinders. However, when cooled to -8 C, the gases dilute and practically separate, resulting in a high concentration of oxygen initially, but the pain is not relieved. A dangerously low concentration of oxygen is then introduced. Avoid cooling cylinders containing a mixture of gases. To do this, it is recommended to keep them in horizontal position, heat in warm water and turn three times before use (to mix the gases) or leave at room temperature (10 C or higher) for 2 hours.

Inhalational anesthetic – halothane

Halothane (fluorothane, used since 1956). This is an extremely convenient anesthetic that has a pronounced effect against a background of mild irritation, minor coughing and breath holding. Induction and recovery from anesthesia occur quickly. Halothane is non-flammable, but it has four significant disadvantages: it causes a decrease in blood pressure, depresses breathing, and causes bradycardia and arrhythmias. It increases the sensitivity of the myocardium to the action of adrenaline and norepinephrine. In addition, the anesthetic is expensive, but despite all this, it occupies a major place in anesthesiology.

Halothane (fluorothane) may cause, especially when reuse, acute injury hepatocytes: halothane hepatitis. The mechanism of its development has not been established. It is believed that hepatitis is caused by idiosyncrasies and peculiarities of drug metabolism in the body or immune reaction with the production of antibodies directed at certain components of liver cells that are changed under the influence of the anesthetic or its metabolites and become antigenic in relation to their own body. The problem remains unresolved. Halothane hepatitis is very rare (less than one case in 10,000; the incidence may be even lower if precautions are taken). In addition, it is difficult to establish a connection between hepatitis and halothane use, since jaundice may be due to other reasons, such as pre-existing pathological process or viral infection.

Currently, they try not to re-use halothane for 2 months (ideally 4-6 months) after its use. In this case, the patient’s reaction to the previous use of an anesthetic should be analyzed. Halothane should not be re-prescribed if the patient experienced febrile state(especially unexplained fever lasting more than 5 days), minimal signs of liver damage or jaundice. Additional risk factors include belonging to female, obesity, middle age, hypoxia and induction of liver enzymes.

Kinetics. Halothane is a liquid with a boiling point at 50 C. About 70% of it is eliminated through the lungs within 24 hours and about 10% is metabolized in the liver by inducing hepatic metabolizing enzymatic systems. In anesthesiologists working with halothane, the metabolizing function of the liver may also be partially induced.

Inhalation anesthetic enflurane

Enflurane (used since 1966) is similar to halothane, but is less active and safer when used with epinephrine. It is metabolized less than halothane and may not cause unwanted hepatotoxicity. Sometimes it causes seizures.

Inhalational anesthetic isoflurane

Isoflurane (used since 1982) is an isomer of enflurane, and is less fat soluble than halothane and enflurane, providing rapid induction of anesthesia. Isoflurane is metabolized slightly (10 and 100 times less than enflurane and halothane, respectively), so its hepatotoxicity (both for the patient and for those working with him medical workers) is low. It inhibits function less than similar drugs of cardio-vascular system, but can dilate blood vessels, which has a beneficial effect when a hypotensive effect is needed. It probably increases the sensitivity of the heart to the action of catecholamines less than chemically similar drugs. Isoflurane can be used in obstetric practice for analgesia. Its use is limited due to its high cost.

Inhalational anesthetic ethyl ether

Ethyl ether (used since 1842) is relatively low-toxic and has been recognized as a safe anesthetic when used by doctors who do not have special training in anesthesiology. Breathing is stopped at a lower concentration in the blood than that required to stop the heart, so an irreversible toxic reaction is easier to avoid than with other anesthetics. It is easier to provide artificial respiration than to restore heart function after it has stopped.

The ether is characterized by two significant drawbacks that reduce its clinical value. In air, its vapors can ignite, and when mixed with oxygen they are explosive; the introduction of anesthesia is slow and subjectively unpleasant for the patient. Induction of anesthesia can be accelerated by adding a small amount of halothane or by stimulating respiration with carbon dioxide. The specific odor and irritating effect of ether on the central nervous system cause cough, laryngospasm and increased secretion of the mucous membranes. In addition, it has a vasodilating effect, which at the 3rd level of phase III anesthesia can be so pronounced that it is accompanied by a sharp drop in blood pressure. Ether increases capillary bleeding.

During anesthesia, the sympathetic nervous system is activated, which neutralizes the effect of ether on hemodynamics. If the tone sympathetic system does not increase, collapse may develop, for example in patients taking beta-blockers. Hyperglycemia during ether anesthesia is primarily a result of the release of epinephrine.

With prolonged and deep anesthesia, recovery from it occurs slowly, and vomiting occurs, mainly due to the ingestion of saliva containing ether. Despite these disadvantages, the great practical advantage of the ether anesthesia method with the same qualifications of an anesthesiologist should once again be emphasized. Due to the technical simplicity of the method, mortality is lower than from complications associated with the use of more complex methods anesthesia.

Liquid ether has a boiling point of 35 C, so it is not always suitable in hot climates, and since it is heavier than air, a layer of it can accumulate near the surface of the operating room floor, which can easily ignite. At open method it is important to take precautions to avoid irritating active substance did not come into contact with skin or eyes. Convulsions rarely complicate ether anesthesia. They are believed to be caused by several factors and are more common in children. Conditions conducive to their development include deep anesthesia, sepsis, atropine premedication, fever, overheating and carbon dioxide retention in the body. Seizures are dangerous and should be avoided. Treatment involves cooling the patient, intravenous administration diazepam (Sibazon) or barbiturates as anticonvulsants. After using the latter, oxygen and artificial respiration, since after a convulsive attack breathing is suppressed, and medicines aggravate this condition.

Ether decomposes to form toxic aldehydes and peroxides, especially if it is not protected from light and heat. Its decomposition is slowed by the addition of carbon dioxide and copper. If possible, avoid using the drug after long-term storage.

Inhalational anesthetic ethyl chloride

Ethyl chloride (chloroethyl) has been used since 1844. It is so strong remedy, which is dangerous even when used for induction of anesthesia. It is flammable and explosive substance with a boiling point of about 12 C, therefore at room temperature it can only be stored under pressure in a liquefied state. High degree volatility allows it to be used for local anesthesia; for this purpose it is applied to the skin, and, evaporating, as a result of cooling, it paralyzes the sensitive nerve endings(cryoanalgesia). Chlorofluoromethanes can be used for the same purpose.

Inhalation anesthetic chloroform

Chloroform (used since 1847) was the only non-explosive powerful anesthetic before its introduction into clinical practice in 1934 trichlorethylene. However, at present it is not used, since it depresses cardiac activity, has severe hepatotoxicity, and also due to the emergence of more advanced drugs.

Inhalation anesthetic cyclopropane(used since 1929) is a strong anesthetic, which is a flammable gas that does not have irritating properties. It is preferable to halothane if rapid induction of anesthesia is required and hypotension must be avoided. Cyclopropane increases the sensitivity of the myocardium to adrenaline and, along with the retention of carbon dioxide, which it causes due to respiratory depression, creates conditions for the development of arrhythmias. It causes laryngospasm. When the intake of cyclopropane into the body is stopped, it can sharply decrease arterial pressure, which is called “cyclopropane shock”. It is explained by a rapid decrease in the concentration of carbon dioxide in the blood.

Inhalational anesthetic trichlorethylene(used since 1934) is similar to chloroform, but less toxic. It is rarely used for anesthesia in surgical practice, since it has a weak anesthetic effect, but causes tachycardia and arrhythmia. However, it is an effective analgesic and is used in obstetric practice in the form of special dosages. dosage forms, which eliminates its overdose when used by the woman herself. Trichlorethylene should not be used through systems that absorb carbon dioxide as it forms when in contact with alkali. toxic substances, capable of damaging cranial nerves, especially V pair. It is unstable in air and light. At concentrations used in anesthesiology, trichlorethylene is non-flammable and non-irritating.

How dangerous are inhalational anesthetics for personnel?

Air pollution in operating rooms with inhalational anesthetics is unsafe for the body of personnel working in them. An anesthesiologist accumulates such an amount of halothane in the body within 3-4 hours that it is not completely eliminated even by the next morning. Epidemiological studies have brought attention to the issue of increased detection of teratogenicity, miscarriages, hepatitis and cancer in operating room workers. Obviously, a miscarriage is indeed real danger, for example, when working with nitrous oxide. Pregnant operating room employees should not be in areas contaminated with anesthetics.

The risk of air pollution is reduced with use closed systems inhalations and systems that remove waste gases, improving ventilation, which contributes to some purification of the operating room atmosphere; There are also filters that adsorb volatile substances, with the exception of nitrous oxide. One way to solve the problem is to increase the use of local or intravenous anesthesia without the use of inhalational anesthetics. Long-term inhalational anesthesia made it possible to study the pharmacokinetics of inhalational anesthetics.

Since the first public experiment using general anesthesia It was a long time since inhalational anesthetics were used in 1846. Two centuries ago, agents such as carbon monoxide (“laughing gas”), ether, halothane and chloroform were used as anesthetics. Since then, anesthesiology has made great progress: drugs that are safer and have a minimum number of side effects have been gradually improved and developed.

Due to high toxicity and flammability, drugs such as chloroform and ether are practically no longer used. Their place is reliably taken by new ones (plus nitrous oxide) inhalation agents: halothane, isoflurane, sevorane, methoxyflurane, desflurane and enflurane.

Inhalation anesthesia is often used for children who cannot always withstand intravenous administration. For adults, the mask method is usually used to maintain the analgesic effect with the main intravenous, although it is inhalation drugs give faster results due to the fact that when they enter the pulmonary vessels, these drugs are quickly distributed into the blood and are eliminated just as quickly.

Inhalation anesthetic drugs, brief description

Sevoran (based on the substance sevoflurane) is an ether for general anesthesia containing fluoride.

Pharmacology: sevoran is an inhaled anesthetic with general anesthetic action, produced in the form of a liquid. The drug has a slightly higher solubility in the blood than, for example, desflurane, and is slightly inferior in potency to enflurane. Ideally used for administering anesthesia. Sevoran is colorless and has no pungent odor; its effect is full force occurs in 2 minutes or less from the start of serving, which is very fast. Recovery from sevorane anesthesia occurs almost immediately due to its rapid removal from the lungs, which is why postoperative pain relief is usually required.

Sevoran is not flammable, not explosive, and does not contain any additives or chemical stabilizers.

The impact of sevoran on systems and organs is considered insignificant for the reason that side effects, if they occur, are weak and insignificant:

• promotion intracranial pressure and cerebral blood flow is insignificant, unable to provoke seizures;
• blood flow in the kidneys is slightly reduced;
• suppression of myocardial function and a slight decrease in pressure;
• liver function and blood flow remain at normal levels;
• nausea, vomiting;
• change in pressure in one direction or another (increase/decrease);
• increased cough;
• chills;
• excitement, dizziness;
• may cause some respiratory depression, which can be corrected with competent actions of the anesthesiologist.

Contraindications:

• predisposition to malignant hyperthermia;
• hypovolemia.

Sevoran should be used with caution to administer anesthesia during neurosurgical operations in patients with ICH (intracranial hypertension), and other surgical interventions in cases of renal dysfunction, during lactation. In some cases, these diseases and conditions may act as contraindications. During pregnancy, no harm from anesthesia with sevoran was detected for the mother and fetus.

Other inhaled drugs also have their pros, cons and principles of use.

Halothane. The degree of distribution of this drug in the blood and tissues is quite high, so the onset of sleep occurs slowly, and the longer the anesthesia lasts, the longer it will take to recover from it. Strong drug, suitable for both induction and maintenance of anesthesia. Often used in children when it is impossible to install an intravenous catheter. Due to the advent of safer anesthetics, I use halothane less and less, despite its low cost.

Side effects include a decrease in blood pressure, bradycardia, impaired skin, renal and cerebral blood flow, as well as abdominal blood flow, arrhythmia, and very rarely, instantaneous cirrhosis of the liver.

Isoflurane. The drug is one of the latest developments. It is distributed quickly through the blood, the onset of anesthesia (in just under 10 minutes) and awakening also take minimal time.

Side effects are mainly dose-dependent: decreased blood pressure, pulmonary ventilation, hepatic blood flow, diuresis (with increased concentration urine).

Enflurane. The rate of distribution of the drug in the blood is average, respectively, anesthesia and awakening also take time (10 minutes or a little less). Due to the fact that over time, drugs appeared that had significantly fewer side effects, enflurane faded into the background.

Side effects: breathing quickens, becomes shallow, reduces blood pressure, sometimes can increase intracranial pressure, and also cause convulsions, impairs blood flow gastrointestinal tract, kidneys and liver, relaxes the uterus (therefore not used in obstetrics).

Desflurane. Low degree of distribution in the blood, loss of consciousness occurs very quickly, just like awakening (5-7 minutes). Desflurane is used mainly as maintenance anesthesia for basic intravenous anesthesia.

Side effects: leads to drooling, shallow rapid breathing (it can stop), decreased blood pressure for the entire duration of inhalation, cough, bronchospasm (therefore induction of anesthesia not used), may increase ICP. There is no negative effect on the liver and kidneys.

Nitrous oxide. Pharmacology: the anesthetic dissolves very poorly in the blood, therefore, anesthesia occurs quickly. After its supply is stopped, diffuse hypoxia occurs, and to stop it, pure oxygen is introduced for some time. Has good analgesic properties. Contraindications: air cavities in the body (emboli, air cavities in pneumothorax, air bubbles in eyeball and etc.).

Side effects from the drug: nitrous oxide can significantly increase ICP (to a lesser extent when combined with non-inhalational anesthetics), increase the resulting pulmonary hypertension, increase the tone of the veins of the systemic and pulmonary circulation.

Xenon. An inert gas whose anesthetic properties were discovered in 1951. It is difficult to produce, as it must be released from the air, and the very small amount of gas in the air explains the high cost of the drug. But at the same time, the xenon method of pain relief is ideal, suitable even for particularly critical cases. Due to this, it is suitable for pediatric, general, emergency, obstetric and neurosurgery, as well as for therapeutic purposes during painful attacks and especially painful manipulations, in emergency medicine as prehospital care at severe pain or seizures.

It dissolves in the blood extremely poorly, which guarantees the rapid onset and end of anesthesia.

No contraindications have been found, but there are limitations:

• interventions on the heart, bronchi and trachea for pneumothorax;
• ability to fill air cavities (like nitrous oxide): emboli, cysts, etc.
• diffusion hypoxia with the mask method (not with the endotracheal method); to avoid problems, auxiliary ventilation is carried out in the first minutes.

Pharmacology of xenon:

• environmentally friendly, colorless and odorless, safe;
• does not enter into chemical reactions;
• the action and end of the action of the anesthetic occurs in a matter of minutes;
• not a narcotic drug;
• Spontaneous breathing is maintained;
• has an anesthetic, analgesic and muscle relaxant effect;
• stable hemodynamics and gas exchange;
• general anesthesia occurs when inhaling 65-70% of a mixture of xenon and oxygen, analgesia - at 30-40%.

It is possible to use the xenon method independently, but many drugs can also be combined well with it: non-narcotic and narcotic analgesics, tranquilizers, and intravenous sedatives.