Classification of inhalational anesthetics by physicochemical properties. Inhalation anesthesia - advantages and disadvantages
If we turn to the history of anesthesiology, it becomes clear that this specialty began precisely with the use of inhalation anesthesia - the famous operation of W. Morton, in which he demonstrated the possibility of performing anesthesia by inhaling ethyl ether vapor. Subsequently, the properties of other inhalation agents were studied - chloroform appeared, and then halothane, which ushered in the era of halogen-containing inhalational anesthetics. It is noteworthy that all these drugs have now been replaced by more modern ones and are practically not used.
Inhalation anesthesia is a type of general anesthesia in which the state of anesthesia is achieved by inhaling inhalation agents. The mechanisms of action of inhalational anesthetics, even today, are not fully understood and are being actively studied. A number of effective and safe drugs have been developed that allow this type of anesthesia.
Inhalational general anesthesia is based on the concept of MAC - minimum alveolar concentration. MAC is a measure of the activity of an inhalational anesthetic, which is defined as its minimum alveolar concentration at saturation stage, which is sufficient to prevent the reaction of 50% of patients to a standard surgical stimulus (skin incision). If you graphically depict the logarithmic dependence of MAC on the fat solubility of anesthetics, you will get a straight line. This suggests that the strength of an inhalational anesthetic will directly depend on its fat solubility. In a state of saturation, the partial pressure of the anesthetic in the alveolus (PA) is in equilibrium with the partial pressure in the blood (Pa) and, accordingly, in the brain (Pb). Thus, RA may serve as an indirect indicator of its concentration in the brain. However, for many inhalational anesthetics in a real clinical situation, the process of achieving saturation-equilibrium can take several hours. The solubility coefficient “blood: gas” is a very important indicator for each anesthetic, as it reflects the rate of equalization of all three partial pressures and, accordingly, the onset of anesthesia. The less soluble the inhalational anesthetic is in the blood, the faster the leveling of PA, Pa and Pb occurs and, accordingly, the faster the state of anesthesia and recovery from it. However, the speed of onset of anesthesia is not yet the strength of the inhalational anesthetic itself, which is well demonstrated by the example with nitrous oxide - the speed of onset of anesthesia and recovery from it is very fast, but as an anesthetic, nitrous oxide is very weak (its MAC is 105).
In terms of specific drugs, the most commonly used inhalational anesthetics today are halothane, isoflurane, sevoflurane, desflurane and nitrous oxide, with halothane increasingly being phased out of routine practice due to its hapatotoxicity. Let's look at these substances in more detail.
Halothane- a classic halogen-containing agent. A strong anesthetic with a very narrow therapeutic corridor (the difference between the working and toxic concentrations is very small). A classic drug for inducing general anesthesia in children with airway obstruction, as it allows you to wake up the child when obstruction increases and minute ventilation decreases, plus, it has a fairly pleasant odor and does not irritate the airways. Halothane is quite toxic - this concerns the possible occurrence of postoperative liver dysfunction, especially against the background of other liver pathologies.
Isoflurane is an isomer of enflurane, which has a vapor saturation pressure close to halothane. It has a strong ethereal odor, which makes it unsuitable for inhalation induction. Due to the poorly studied effects on coronary blood flow, it is not recommended for use in patients with coronary artery disease, as well as in cardiac surgery, although there are publications refuting the latter statement. Reduces the metabolic needs of the brain and in a dose of 2 MAC or more can be used for the purpose of cerebroprotection during neurosurgical interventions.
Sevoflurane- a relatively new anesthetic, which a few years ago was less accessible due to its high price. Suitable for inhalation induction, as it has a fairly pleasant odor and, when used correctly, causes almost instantaneous loss of consciousness due to its relatively low solubility in the blood. More cardiostable compared to halothane and isoflurane. During deep anesthesia, it causes muscle relaxation sufficient for tracheal intubation in children. The metabolism of sevoflurane produces fluoride, which can be nephrotoxic under certain conditions.
Desflurane- similar in structure to isoflurane, but has completely different physical properties. Already at room temperature in high altitude conditions it boils, which requires the use of a special evaporator. It has low solubility in the blood (the blood:gas ratio is even lower than that of nitrous oxide), which causes a rapid onset and recovery from anesthesia. These properties make desflurane preferable for use in bariatric surgery and in patients with lipid disorders.
ETHER (diethyl ether)
A very cheap non-halogenated anesthetic, the production cycle is simple, so it can be produced in any country. Morton demonstrated the effects of ether in 1846 and since then this drug has been considered the “first anesthetic.”
Physical properties: low boiling point (35C), high DNP at 20C (425 mm Hg), blood/gas ratio 12 (high), MAC 1.92% (low power). Cost from $10/l. Ether vapors are extremely volatile and non-flammable. Explosive when mixed with oxygen. Has a strong characteristic odor.
Advantages: stimulates respiration and cardiac output, maintains blood pressure and causes bronchodilation. This is due to the sympathomimetic effect associated with the release of adrenaline. It is a good anesthetic due to its pronounced analgesic effect. Does not relax the uterus like halothane, but provides good relaxation of the abdominal wall muscles. Safe drug.
Flaws: flammable in a liquid state, slow onset of action, slow recovery, pronounced secretion (requires atropine). It irritates the bronchi, so coughing makes mask induction of anesthesia difficult. Postoperative nausea and vomiting (PONV) is relatively rare in Africa, in contrast to European countries, where vomiting in patients is very common.
Indications: any general anesthesia, especially good for caesarean section (the fetus is not depressed, the uterus contracts well). Small doses are life-saving in especially severe cases. Etheric nacrosis is indicated in the absence of oxygen supply.
Contraindications: There are no absolute contraindications for ether.
It is necessary, if possible, to actively remove vapors from the operating room to prevent contact between heavy non-flammable ether vapors and the electrocoagulator or other electrical devices, which can cause an explosion, and to prevent contact of operating room personnel with exhaled anesthetic.
Practical recommendations: Before giving a large concentration of anesthetic, it is better to intubate the patient. After the administration of atropine, thiopental, suxamethonium and intubation of the patient, artificial ventilation of the lungs is performed with 15-20% ether, and then, according to the patient’s needs, after 5 minutes the dose can be reduced to 6-8%. Please note that evaporator performance may vary. High-risk patients, particularly those with septic or shock conditions, may only require 2%. Turn off the vaporizer until the end of surgery to prevent prolonged recovery from anesthesia. Over time, you will learn to wake patients so that they leave the operating table on their own. If you are going to undergo anesthesia on a strong and young person for an inguinal hernia, take care of yourself and have a better spinal anesthesia.
In most cases where ether anesthesia is beneficial (laparotomy, cesarean section), diathermy is not required. Where diathermy is mandatory (pediatric surgery), it is better to use halothane.
Nitrous oxide
Physical properties: nitrous oxide (N 2 O, “laughing gas”) is the only inorganic compound of inhalational anesthetics used in clinical practice. Nitrous oxide is colorless, virtually odorless, does not ignite or explode, but supports combustion like oxygen.
Effect on the body
A. Cardiovascular system. Nitrous oxide stimulates the sympathetic nervous system, which explains its effect on blood circulation. Although the anesthetic causes myocardial depression in vitro, in practice blood pressure, cardiac output and heart rate are unchanged or slightly increased due to increased concentrations of catecholamines. Myocardial depression may have clinical significance in coronary artery disease and hypovolemia: the resulting arterial hypotension increases the risk of developing myocardial ischemia. Nitrous oxide causes constriction of the pulmonary artery, which increases pulmonary vascular resistance (PVR) and leads to increased right atrial pressure. Despite the narrowing of skin vessels, total peripheral vascular resistance (TPVR) changes slightly. Since nitrous oxide increases the concentration of endogenous catecholamines, its use increases the risk of arrhythmias.
B. Respiratory system. Nitrous oxide increases respiratory rate (i.e., causes tachypnea) and decreases tidal volume as a result of stimulation of the central nervous system and possibly activation of pulmonary stretch receptors. The overall effect is a slight change in minute volume of respiration and PaCO 2 at rest. Hypoxic drive, i.e., an increase in ventilation in response to arterial hypoxemia, mediated by peripheral chemoreceptors in the carotid bodies, is significantly inhibited by the use of nitrous oxide, even at low concentrations.
B. Central nervous system. Nitrous oxide increases cerebral blood flow, causing a slight increase in intracranial pressure. Nitrous oxide also increases brain oxygen consumption (CMRO 2). Nitrous oxide in a concentration of less than 1 MAC provides adequate pain relief in dentistry and during minor surgical procedures.
D. Neuromuscular conduction. Unlike other inhalational anesthetics, nitrous oxide does not cause noticeable muscle relaxation. On the contrary, in high concentrations (when used in hyperbaric chambers) it causes rigidity of skeletal muscles.
D. Kidneys. Nitrous oxide reduces renal blood flow due to increased renal vascular resistance. This reduces the glomerular filtration rate and diuresis.
E. Liver. Nitrous oxide reduces hepatic blood flow, but to a lesser extent than other inhaled anesthetics.
G. Gastrointestinal tract. Some studies have shown that nitrous oxide causes nausea and vomiting in the postoperative period as a result of activation of the chemoreceptor trigger zone and the vomiting center in the medulla oblongata. In contrast, studies by other scientists have found no connection between nitrous oxide and vomiting.
Biotransformation and toxicity
During awakening, almost all nitrous oxide is eliminated through the lungs. A small amount diffuses through the skin. Less than 0.01% of the anesthetic entering the body undergoes biotransformation, which occurs in the gastrointestinal tract and consists of the restoration of the substance under the influence of anaerobic bacteria.
By irreversibly oxidizing the cobalt atom in vitamin B12, nitrous oxide inhibits the activity of B-dependent enzymes. These enzymes include methionine synthetase, which is necessary for the formation of myelin, and thymidylate synthetase, which is involved in DNA synthesis. Long-term exposure to anesthetic concentrations of nitrous oxide causes bone marrow depression (megaloblastic anemia) and even neurological deficits (peripheral neuropathy and funicular myelosis). To avoid the teratogenic effect, nitrous oxide is not used in pregnant women. Nitrous oxide weakens the body's immunological resistance to infections by inhibiting the chemotaxis and mobility of polymorphonuclear leukocytes.
Contraindications
Although nitrous oxide is considered slightly soluble compared to other inhalational anesthetics, its solubility in the blood is 35 times higher than that of nitrogen. Thus, nitrous oxide diffuses into air-containing cavities faster than nitrogen enters the bloodstream. If the walls of the air-containing cavity are rigid, then it is not the volume that increases, but the intracavity pressure. Conditions in which it is dangerous to use nitrous oxide include air embolism, pneumothorax, acute intestinal obstruction, pneumocephalus (after suturing the dura mater at the end of neurosurgery or after pneumoencephalography), pulmonary air cysts, intraocular air bubbles and plastic surgery on the eardrum. Nitrous oxide may diffuse into the endotracheal tube cuff, causing compression and ischemia of the tracheal mucosa. Because nitrous oxide increases PVR, its use is contraindicated in pulmonary hypertension. Obviously, the use of nitrous oxide is limited when it is necessary to create a high fractional concentration of oxygen in the inhaled mixture.
, sevoflurane and desflurane. Halothane is a prototypical pediatric inhalational anesthetic; its use has decreased since the introduction of isoflurane and sevoflurane. Enflurane is rarely used in children.
Inhalational anesthetics can induce apnea and hypoxia in premature infants and newborns and are not often used in this setting. With general anesthesia, endotracheal intubation and controlled ventilation are always necessary. During short operations, older children, if possible, breathe spontaneously through a mask or through a tube inserted into the larynx without controlled ventilation. With a decrease in the volume of exhalation of the lungs and increased work of the respiratory muscles, it is always necessary to increase the oxygen tension in the inhaled air.
Effect on the cardiovascular system. Inhalational anesthetics reduce cardiac output and cause peripheral vasodilation and therefore often lead to hypotension, especially in hypovolemic patients. The hypotensive effect is more pronounced in newborns than in older children and adults. Inhalational anesthetics also partially suppress the baroreceptor response and heart rate. One MAC of halothane reduces cardiac output by approximately 25%. The ejection fraction is also reduced by approximately 25%. With one MAC of halothane, heart rate often increases; however, increased anesthetic concentrations may cause bradycardia, and significant bradycardia during anesthesia indicates anesthetic overdose. Halothane and related inhalation agents increase the sensitivity of the heart to catecholamines, which can lead to arrhythmias. In addition, inhalational anesthetics reduce the pulmonary vasomotor response to hypoxia in the pulmonary circulation, which contributes to the development of hypoxemia during anesthesia.
Inhalational anesthetics reduce oxygen supply. In the perioperative period, catabolism increases and the need for oxygen increases. Therefore, there may be a sharp discrepancy between the need for oxygen and its provision. A reflection of this imbalance may be metabolic acidosis. Due to their suppressive effects on the cardiovascular system, the use of inhalational anesthetics in preterm and newborn infants is limited, but they are widely used for induction and maintenance of anesthesia in older children.
All inhalational anesthetics cause cerebral vasodilation, but halothane is more potent than sevoflurane or isoflurane. Therefore, halothane and other inhaled agents should be used with extreme caution in children with elevated ICP, impaired cerebral perfusion or head trauma, and in neonates at risk for intraventricular hemorrhage. Although inhalational anesthetics reduce oxygen consumption by the brain, they can disproportionately reduce blood circulation and thereby impair the oxygen supply to the brain.
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 under ultraviolet irradiation and not require the addition of 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.
Safe for the 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.
Minimal side effects 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 concentrations greater 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; vapor saturation pressure at 20 °C - 175 mm Hg. Isoflurane
Isoflurane is a very expensive drug. 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 testing of their anesthetic effect in humans. In recent years, two new drugs of this group have been synthesized, and their properties and advantages have been evaluated.
Sevoflurane
This is methyl isopropyl ether, halogenated with fluorine ions. It is non-flammable at clinically used concentrations. It does not appear to have any serious side effects on the cardiovascular system or the 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 its high cost and high vapor saturation pressure, 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.
Further reading
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).
