Classification of inhalation anesthetics according to 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 anesthesia by inhaling ethyl ether vapors. Later, the properties of other inhalation agents were studied - chloroform appeared, and then halothane, which opened the era of halogen-containing inhalation anesthetics. It is noteworthy that all these drugs have now been superseded by more modern ones and are practically not used.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 inhalation of inhalation agents. The mechanisms of action of inhalation 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 to be performed.
Inhalation general anesthesia is based on the concept of MAC - the minimum alveolar concentration. MAC is a measure of the activity of an inhalation anesthetic, which is defined as its minimum alveolar concentration at the saturation stage, which is sufficient to prevent 50% of patients from responding to a standard surgical stimulus (skin incision). If we graphically depict the logarithmic dependence of MAC on the fat solubility of anesthetics, we get a straight line. This suggests that the strength of an inhalation anesthetic will directly depend on its fat solubility. In the 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 can serve as an indirect indicator of its concentration in the brain. However, for many inhalation anesthetics in a real clinical situation, the process of achieving saturation-equilibrium can take several hours. The solubility ratio "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 inhalation anesthetic is soluble in blood, the faster the alignment of PA, Pa and Pb occurs and, accordingly, the faster the state of anesthesia occurs and exits from it. However, the speed of onset of anesthesia is not yet the strength of the inhalation anesthetic itself, which is well demonstrated by the example of nitrous oxide - the speed of onset of anesthesia and exit from it is very fast, but as an anesthetic, nitrous oxide is very weak (its MAC is 105).
In terms of specific drugs, the currently most commonly used inhalational anesthetics are halothane, isoflurane, sevoflurane, desflurane, and nitrous oxide, with halothane increasingly being phased out of daily practice due to its hapatotoxicity. Let's analyze these substances in more detail.
Halothane- classical halogenated agent. A strong anesthetic with a very narrow therapeutic corridor (the difference between the working and toxic concentrations is very small). A classic preparation for induction into general anesthesia in children with airway obstruction, as it allows you to wake up the child with an increase in obstruction and a decrease in minute ventilation, plus, it has a rather pleasant smell and does not irritate the airways. Halothane is quite toxic - this concerns the possible occurrence of postoperative liver dysfunction, especially against the background of its other pathology.
Isoflurane- an isomer of enflurane, which has a vapor saturation pressure close to that of halothane. It has a strong ethereal odor, which makes it unsuitable for inhalation induction. Due to not entirely 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 that refute the latter statement. It reduces the metabolic needs of the brain and at 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 available due to the high price. Suitable for inhalation induction, as it has a rather pleasant smell and, when used correctly, causes an almost instantaneous shutdown of consciousness due to relatively low solubility in the blood. More cardiostable compared to halothane and isoflurane. With deep anesthesia, it causes muscle relaxation sufficient for tracheal intubation in children. During the metabolism of sevoflurane, fluoride is formed, which can, under certain conditions, exhibit nephrotoxicity.
Desflurane- is 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 a low solubility in blood (the “blood:gas” ratio is even lower than that of nitrous oxide), which leads to a rapid onset of anesthesia and exit from it. These properties make desflurane preferred for use in bariatric surgery and in patients with impaired fat metabolism.
ETHER (diethyl ether)
A very cheap non-halogenated anesthetic, the production cycle is simple, so it can be produced in any country. Morton in 1846 demonstrated the effects of ether 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. It has a strong characteristic odour.
Advantages: stimulates respiration and cardiac output, maintains blood pressure and induces 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 muscles of the abdominal wall. Safe drug.
Flaws: flammable in liquid state, slow onset of action, slow recovery, pronounced secretion (requires atropine). It irritates the bronchi, therefore, due to coughing, mask induction into anesthesia is difficult. Postoperative nausea and vomiting (PONV) is relatively rare in Africa, in contrast to European countries where patients vomit very frequently.
Indications: any general anesthesia, especially good for caesarean section (the fetus is not oppressed, the uterus contracts well). Small doses are life-saving in especially severe cases. Etheric necrosis is indicated in the absence of an oxygen supply.
Contraindications: there are no absolute contraindications for ether.
Active evacuation of vapors from the operating room should be ensured wherever possible to prevent contact between heavy, non-flammable ether vapors and an electrocoagulator or other electrical apparatus that could cause an explosion, and to prevent exposure of operating room personnel to exhaled anesthetic.
Practical recommendations: before giving a large concentration of anesthetic, it is better to intubate the patient. After the introduction 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 needs of the patient, after 5 minutes, the dose can be reduced to 6-8%. Please note that vaporizer performance may vary. Patients at high risk, particularly septic or shock patients, may require only 2%. Turn off the vaporizer until the end of the operation to prevent prolonged recovery from anesthesia. Over time, you will learn to wake up patients so that they themselves leave the operating table. If you have to anaesthetize a strong and young man for an inguinal hernia, save yourself and do better spinal anesthesia.
In most cases where ether anesthesia is beneficial (laparotomy, caesarean section), diathermy is not required. Where diathermy is required (pediatric surgery), it is better to use halothane.
Nitrous oxide
Physical Properties: nitrous oxide (N 2 O, "laughing gas") - the only inorganic compound used in clinical practice inhalation anesthetics. 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 circulation. Although in vitro the anesthetic causes myocardial depression, in practice blood pressure, cardiac output and heart rate do not change or increase slightly due to an increase in the concentration of catecholamines. Myocardial depression may be of clinical importance in coronary artery disease and hypovolemia: the resulting arterial hypotension increases the risk of myocardial ischemia. Nitrous oxide causes pulmonary artery constriction, which increases pulmonary vascular resistance (PVR) and leads to increased right atrial pressure. Despite the vasoconstriction of the skin, the total peripheral vascular resistance (OPVR) 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 CNS stimulation and possibly activation of pulmonary stretch receptors. The overall effect is a slight change in the 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 carotid bodies, is significantly inhibited when nitrous oxide is used, even at low concentrations.
B. Central nervous system. Nitrous oxide increases cerebral blood flow, causing some increase in intracranial pressure. Nitrous oxide also increases the oxygen consumption of the brain (CMRO 2). Nitrous oxide at a concentration below 1 MAC provides adequate pain relief in dentistry and when performing minor surgical interventions.
D. Neuromuscular conduction. Unlike other inhalation anesthetics, nitrous oxide does not cause noticeable muscle relaxation. Conversely, at high concentrations (when used in hyperbaric chambers), it causes skeletal muscle rigidity.
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 blood flow to the liver, but to a lesser extent than other inhalational 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 vomiting center in the medulla oblongata. In contrast, studies by other scientists have found no link between nitrous oxide and vomiting.
Biotransformation and toxicity
During awakening, almost all nitrous oxide is removed through the lungs. A small amount diffuses through the skin. Less than 0.01% of the anesthetic that enters the body undergoes biotransformation, which occurs in the gastrointestinal tract and consists in the restoration of the substance under the action 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. Prolonged exposure to anesthetic concentrations of nitrous oxide causes bone marrow depression (megaloblastic anemia) and even neurological deficits (peripheral neuropathy and funicular myelosis). To avoid a teratogenic effect, nitrous oxide is not used in pregnant women. Nitrous oxide weakens the body's immunological resistance to infections by inhibiting chemotaxis and the mobility of polymorphonuclear leukocytes.
Contraindications
Although nitrous oxide is considered slightly soluble compared to other inhalational anesthetics, its blood solubility 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 intracavitary pressure. Conditions in which it is dangerous to use nitrous oxide include air embolism, pneumothorax, acute intestinal obstruction, pneumocephalus (after closure of the dura after neurosurgery or after pneumoencephalography), air pulmonary cysts, intraocular air bubbles and plastic surgery on the eardrum. Nitrous oxide can diffuse into the cuff of the endotracheal tube, causing compression and ischemia of the tracheal mucosa. Since 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 the prototypical pediatric inhalation anesthetic; its use has declined since the introduction of isoflurane and sevoflurane. Enflurane is rarely used in children.
Inhalation anesthetics can induce apnea and hypoxia in preterm infants and neonates and are therefore not commonly used in this setting. With general anestezin, endotracheal intubation and controlled mechanical ventilation are always necessary. Older children during short operations, if possible, breathe spontaneously through a mask or through a tube inserted into the larynx without controlled ventilation. With a decrease in the expiratory volume of the lungs and increased work of the respiratory muscles, it is always necessary to increase the oxygen tension in the inhaled air.
Action on the cardiovascular system. Inhalation anesthetics reduce cardiac output and cause peripheral vasodilation, and therefore often lead to hypotension, especially in patients with hypovolemia. The hypotensive effect is more pronounced in newborns than in older children and adults. Inhalation anesthetics also partially suppress the response of baroreceptors and heart rate. One MAC of halothane reduces cardiac output by approximately 25%. The ejection fraction is also reduced by about 25%. With one MAC of halothane, heart rate often increases; however, an increase in the concentration of the anesthetic can cause bradycardia, and severe bradycardia during anesthesia indicates an overdose of the anesthetic. Halothane and related inhalation agents increase the sensitivity of the heart to catecholamines, which can lead to arrhythmias. In addition, inhalation anesthetics reduce the pulmonary vasomotor response to hypoxia in the pulmonary circulation, which contributes to the development of hypoxemia during anesthesia.
Inhalation anesthetics reduce the supply of oxygen. In the perioperative period, catabolism increases and the need for oxygen increases. Therefore, a sharp discrepancy between the need for oxygen and its provision is possible. A reflection of this imbalance may be metabolic acidosis. Due to the suppressive effect 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 vasodilation of the brain, but halothane is more active than sevoflurane or isoflurane. Therefore, in children with elevated ICP, impaired cerebral perfusion or head trauma, and in neonates at risk of intraventricular hemorrhage, halothane and other inhaled agents should be used with extreme caution. Although inhalational anesthetics reduce the oxygen consumption of the brain, they can disproportionately reduce blood circulation and thus impair the oxygen supply to the brain.
There is no "ideal" inhalation anesthetic, but certain requirements apply to any of the inhalation anesthetics. An "ideal" drug should have a number of properties listed below.
/. Low cost. The drug should be cheap and easy to manufacture.
Physical 2. Chemical stability. The drug should have a long shelf life and be
impact properties over a wide temperature range, it should not react with metals, rubber or
plastics. It must retain certain properties under ultraviolet irradiation and does not require the addition of stabilizers.
Non-flammable/non-explosive. Vapors must not ignite or sustain combustion at clinically used concentrations and when mixed with other gases such as oxygen.
The drug should 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 the environment. The drug should not destroy ozone or cause other changes in the environment, even in minimal concentrations.
/. Pleasant for inhalation, does not irritate the respiratory tract and does not increase secretion.
Biological properties
The low blood/gas solubility ratio ensures rapid induction and recovery from anesthesia.
The high exposure force 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.
Non-toxic even with chronic exposure to low 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 the function of the myocardium and respiration and are metabolized and biotransformed to a greater or lesser extent.
Halothane
Halothane is relatively cheap, but it is chemically unstable and breaks down when exposed to light. It is stored in dark bottles with the addition of 0.01% thymol as a stabilizer. Of the three halogenated preparations, halothane has the highest blood gas solubility and therefore the slowest onset of action; despite this, halothane is most often used for inhalation induction of anesthesia, as it has the least irritating effect on the respiratory tract. Halothane is metabolized by 20% (see "Effect of anesthesia on the liver"). Characteristics of halothane: MAC - 0.75; solubility coefficient blood / gas at a temperature of 37 "C - 2.5; boiling point 50 "C; vapor 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 that. It causes paroxysmal epileptiform activity on the EEG at a concentration of more than 3%. 2% anesthetic undergoes biotransformation, with the formation of a nephrotoxic metabolite and an increase in the concentration of fluorine 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 very expensive. It irritates the respiratory tract and can cause coughing, increased secretion, especially in patients without premedication. Of the three halogen-containing anesthetics, this is the most potent vasodilator: at 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; vapor saturation pressure at a temperature of 20 "C - 250 mm Hg.
The above advantages and disadvantages of the three most well-known halogenated 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, their properties and advantages have been evaluated.
Sevoflurane
It is methylisopropyl ether halogenated with fluorine ions. It is not flammable at clinically used concentrations. It does not appear to have any major side effects on the cardiovascular system and respiratory system. The main theoretical advantage is the very low blood/gas solubility ratio (0.6), which allows it to be used for rapid inhalation induction, especially in children. The main disadvantage, which may limit its widespread use, is the instability upon contact with soda lime.
Desflurane (1-163)
This is a methylethyl halogenated ether, the 163rd in a series of synthesized halogenated anesthetics. Its structure is similar to isoflurane, but does not contain chloride ions. Animal studies show that desflurane is biologically stable and non-toxic. Preliminary use of the drug in clinical practice showed that it is pleasant to inhale and does not irritate the respiratory tract. Desflurane has an exceptionally low blood/gas solubility ratio 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 issues and further evaluate the use of desflurane in clinical practice.
additional literature
Heijke S., Smith G. Quest for the ideal inhalational anaesthetic agent.- British Journal of
Anaesthesia, 1990; 64:3-5. JonesP.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). Effect of anesthesia on the liver (p. 298). Nitrous oxide (p. 323).
