Medicine. Nursing

INHALATION ANESTHESIA is a type of general anesthesia provided by gaseous or volatile anesthetics entering the body through the respiratory tract.

Desired effects of anesthesia Sedation Amnesia Analgesia Immobility in response to painful stimulation Muscle relaxation

What is general anesthesia Amnesia (hypnotic component) Analgesia Akinesia (immobility) Autonomic reflex control (Snow, Guedel 1937, Eger 2006) Concept Perouansky, 2011: Amnesia Akinesia Hypnotic component Eger and Soner, 2006: Amnesia Immobility Eliminated sleep (example ketamine) and hemodynamic control (moderate tachycardia is tolerated normally, everything can be leveled out with vasoactive drugs)

The concept of multicomponent anesthesia Prosthetics of vital functions Monitoring Analgesia Hypnotic component Myorelaxation

Concept of general anesthesia—defining clinical goals Stansky and Shafer, 2005 Suppression of response to verbal stimuli Suppression of motor response to traumatic stimuli Suppression of hemodynamic response to tracheal intubation From this point of view, inhalational anesthetics are true anesthetics

General anesthesia - AI capabilities Switching off consciousness - level of the basal ganglia, cerebral cortex, disintegration of signals in the central nervous system Amnesia - effects on different areas Anesthesia - pain (WHO) = is an unpleasant sensory or emotional sensation associated with actual or potential tissue damage that can be describe at the time of occurrence of this damage. During surgery, the nociceptive pathways are activated, but there is no feeling of pain (the patient is unconscious). PAIN control is relevant after recovery from anesthesia Patient immobility - absence of a motor response to a painful stimulus - realized at the level of the spinal cord Absence of hemodynamic reactions

Inhalation anesthesia Advantages Disadvantages ØPainless induction of anesthesia ØGood controllability of the depth of anesthesia ØLow threat of maintaining consciousness during anesthesia ØPredictable rapid recovery from anesthesia ØPowerful general anesthetic activity of the drug ØFast awakening and the possibility of early activation of patients ØReduced use of opioids, muscle relaxants and faster restoration of gastrointestinal function ØRelatively slow induction ØProblems of the arousal stage ØThreat of developing airway obstruction ØHigh cost (when using traditional anesthesia with high gas flow) ØOperating room air pollution

The main advantage of using AIs is the ability to control them at all stages of anesthesia. AIs are indicated for induction (especially with predicted difficult intubation, in patients with obesity, concomitant pathology and a burdened allergic history, in pediatric practice) and maintenance of anesthesia during long-term operations as part of a general combined anesthesia. An absolute contraindication to the use of AI is the fact of malignant hyperthermia and a history of adverse (primarily allergic) reactions. A relative contraindication is short-term surgical interventions, when the AI is used in an open respiratory circuit with the patient breathing independently or in a semi-closed circuit with mechanical ventilation under conditions of high gas flow, which does not harm the patient, but significantly increases the cost of anesthesia.

HISTORICAL DATA - ETHER Diethyl ether was synthesized in the 8th century AD. e. Arab philosopher Jabir ibn Hayyam in Europe was obtained in the 13th (1275) century by the alchemist Raymond Lullius in 1523 - Paracelsus discovered its analgesic properties 1540 - again synthesized by Cordus and included in the European Pharmacopoeia William E. Clarke, medical student from Rochester (USA) in January 1842 was the first to use ether for anesthesia during surgery (tooth extraction). A few months later, on May 30, 1842, the surgeon Crawford Williamson Long (USA) used ether for the purpose of anesthesia when removing two small tumors on the neck of a patient who was afraid of pain, but this became known only in 1952. Morton, a dentist who received his diploma in 1844 on the advice of the chemist Jackson, used ether first in an experiment on a dog, then on himself, then in his practice from August 1 to September 30 A. E. Karelov, St. Petersburg MAPO 1846.

Historical dates for anesthesia October 16, 1846 William Morton - first public demonstration of general anesthesia with ether William Thomas Green Morton (1819 -1868)

History of inhalational anesthesia - chloroform Chloroform was first independently prepared in 1831 as a rubber solvent by Samuel Guthrie, then by Justus von Liebig and Eugène Soubeiran. The formula for chloroform was established by the French chemist Dumas. He also came up with the name “chloroform” in 1834, due to the property of this compound to form formic acid upon hydrolysis (Latin formica is translated as “ant”). In clinical practice, chloroform was first used as a general anesthetic by Holmes Coote in 1847, and it was introduced into widespread practice by obstetrician James Simpson, who used chloroform to reduce pain during childbirth. In Russia, the method of producing medical chloroform was proposed by the scientist Boris Zbarsky in 1916, when he lived in the Urals in the village of Vsevolodo-Vilva in the Perm region.

James Young Simpson (James Yuong Simpson, 1811–1870) On November 10, 1847, at a meeting of the Medico-Surgical Society of Edinburgh, J. Y. Simpson made a public announcement about his discovery of a new anesthetic - chloroform. At the same time, he was the first to successfully use chloroform to anesthetize childbirth (on November 21, 1847, the article “On a new anesthetic, more effective than sulfuric ether”) was published.

Nitrous oxide (N 2 O) was synthesized in 1772 by Joseph Priestley. Humphry Davy (1778 -1829) experimented with N 2 O on himself at Thomas Beddoe's Pneumatic Institute. In 1800, Sir Davy's essay was published, dedicated to his own feelings from the effects of N 2 O (laughing gas). In addition, he more than once expressed the idea of using N 2 O as analgesia during various surgical procedures (“... Nitrous oxide, apparently, along with other properties, has the ability to eliminate pain, it can be successfully used in surgical operations...." .. It was first used as an anesthetic by Gardner Colton and Horace Wells (for tooth extraction) in 1844, Edmond Andrews in 1868 used it in a mixture with oxygen (20%) after the first recorded death during anesthesia with pure nitrous oxide.

American dentist Horace Wells (1815 -1848) in 1844 accidentally happened to attend a demonstration of the effect of N 2 O inhalation, which was organized by Gardner Colton. Wells drew attention to the patient's absolute insensitivity to pain in the injured leg. In 1847, his book “The History of the Discovery of the Use of Nitrous Oxide, Ether and Other Liquids in Surgical Operations” was published.

Second generation of inhalational anesthetics In 1894 and 1923, there was a largely accidental introduction into practice of chloroethyl and ethylene. Cyclopropane was synthesized in 1929 and introduced into clinical practice in 1934. All inhalational anesthetics of that period were explosive with the exception of chloroform, had hepatotoxicity and cardiotoxicity, which limited their use in clinical practice

The era of fluorinated anesthetics Shortly after the Second World War, the production of halogenated anesthetics began. In 1954, fluroxene was synthesized, the first halogenated inhalational anesthetic. In 1956, halothane appeared. In 1960, methoxyflurane appeared. In 1963-1965, enflurane and isoflurane were synthesized. In 1992. the clinical use of desflurane began. In 1994, sevoflurane was introduced into clinical practice. Xenon was first used experimentally in the 50s of the 20th century, but is still not popular due to its extremely high cost.

History of the development of inhalation anesthesia 20 Anesthetics used in clinical practice (total) Sevoflurane Isoflurane 15 Halothane Ethyl vinyl ether Winetene 0 1830 Fluroxene Propyl methyl ether Isoproprenyl vinyl ether Trichlorethylene 5 Enflurane Methixiflurane 10 Cyclopropane Ethylene Chloroform Ethyl chloride Ester NO 2 18 50 Desflurane 1870 1890 1910 1930 1950 Year of “entry” into clinical practice 1970 1990

The most commonly used inhalational anesthetics today are Halothane Isoflurane Desflurane Sevoflurane Nitrous oxide Xenon

The action develops quickly and is easily reversible; it seems that it largely depends on the properties of the anesthetic itself and the low-energy intermolecular interactions and bonds it forms. AIs act on the synaptic membranes of neurons in the brain and spinal cord, predominantly affecting the phospholipid or protein components of the membranes.

Mechanism of action It is assumed that the mechanism of action of all inhalational anesthetics at the molecular level is approximately the same: anesthesia occurs due to the adhesion of anesthetic molecules to specific hydrophobic structures. By binding to these structures, anesthetic molecules expand the bilipid layer to a critical volume, after which the function of the membrane undergoes changes, which in turn leads to a decrease in the ability of neurons to induce and conduct impulses among themselves. Thus, anesthetics cause depression of excitation at both the presynaptic and postsynaptic levels.

According to the unitary hypothesis, the mechanism of action of all inhalational anesthetics at the molecular level is the same and is determined not by the type, but rather by the number of molecules of the substance at the site of action. The action of anesthetics is a physical process rather than interaction with specific receptors. A strong correlation with the potency of anesthetic agents has been noted for the oil/gas ratio (Meyer and Overton, 1899 -1901). This is supported by the observation that the potency of an anesthetic is directly dependent on its fat solubility (Meyer-Overton rule). Binding of the anesthetic to the membrane can significantly change its structure. Two theories (the fluidity theory and the lateral phase separation theory) explain the effect of the anesthetic by influencing the shape of the membrane, one theory by reducing conductivity. How changes in membrane structure cause general anesthesia can be explained by several mechanisms. For example, the destruction of ion channels leads to disruption of the permeability of the membrane to electrolytes. Conformational changes in hydrophobic membrane proteins may occur. Thus, regardless of the mechanism of action, depression of synaptic transmission develops.

The mechanism of action of inhalational anesthetics has not yet been studied and the internal mechanisms of general anesthesia through their action currently remain completely unknown. “Theories” = hypotheses: Coagulation, Kuhn, 1864 Lipoid, Meyer, Overton, 1899 -1901 Surface tension, Traube, 1913 Adsorption, Lowe, 1912 Critical volume Violations of redox processes in cells, hypoxic, Verworn, 1912 Aqueous microcrystals, Pauling, 1961 Membrane, Hober, 1907, Bernstein, 1912 Hodgkin, Katz, 1949 Parabiosis, Vvedensky, Ukhtomky, Reticular.

When halogen-containing AIs interact with GABA receptors, activation and potentiation of the effects of γ-aminobutyric acid occurs, and interaction with glycine receptors causes activation of their inhibitory effects. At the same time, there is inhibition of NMDA receptors, H-cholinergic receptors, inhibition of presynaptic Na+ channels and activation of K2R and K+ channels. It is assumed that gaseous anesthetics (nitrous oxide, xenon) block NMDA receptors and activate K2P channels, but do not interact with GABA receptors.

The effects of different anesthetics on ion channels are not identical. In 2008, S. A. Forman and V. A. Chin proposed dividing all general anesthetics into three classes: – class 1 (propofol, etomidate, barbiturates) are “pure” GABA sensitizers (GABA - γ-aminobutyric acid); – class 2 – active against ionotropic glutamate receptors (cyclopropane, nitrous oxide, xenon, ketamine); – Class 3 – halogen-containing drugs that are active against not only GABA, but also acetylcholine receptors in the center and periphery. Halogen-containing anesthetics are, strictly speaking, hypnotics with pronounced analgesic activity rather than true anesthetics.

At the macroscopic level, there is no single region of the brain where inhalational anesthetics exert their action. They affect the cerebral cortex, hippocampus, sphenoid nucleus of the medulla oblongata and other structures. They also suppress the transmission of impulses in the spinal cord, especially at the level of interneurons of the dorsal horns involved in pain reception. It is believed that the analgesic effect is caused by the action of the anesthetic primarily on the brain stem and spinal cord. One way or another, the higher centers that control consciousness are the first to be affected, and the vital centers (respiratory, vasomotor) are more resistant to the effects of the anesthetic. Thus, patients under general anesthesia are able to maintain spontaneous breathing, close to normal heart rate and blood pressure. From all of the above, it becomes clear that the “target” for inhalational anesthetic molecules is brain neurons.

The final (expected) effect of anesthetics depends on achieving their therapeutic (certain) concentration in the tissue of the central nervous system (anesthetic activity), and the speed of obtaining the effect depends on the speed of achieving this concentration. The anesthetic effect of inhalational anesthetics is realized at the level of the brain, and the analgesic effect is realized at the spinal level.

Functions of evaporators Ensuring the evaporation of inhalation agents Mixing steam with the carrier gas flow Controlling the composition of the gas mixture at the outlet, despite variables Delivering safe and accurate concentrations of inhalational anesthetics to the patient

Classification of evaporators ♦ Supply type In the first option, gas is drawn through the evaporator due to a decrease in pressure in the final section of the system; in the second, the gas fills the evaporator, being forced through it under high pressure. ♦ Nature of anesthetic Determines which anesthetic can be used in this vaporizer. ♦ Temperature Compensation Indicates whether the evaporator is temperature compensated. ♦ Flow stabilization It is important to determine the optimal gas flow rate for a given evaporator. ♦ Flow Resistance Determines how much force is required to force gas through the evaporator. In general, evaporators are most often classified by the type of gas supply and the presence of calibration (with and without calibration). Calibration is a term that is used to describe the accuracy of a procedure that occurs under certain conditions. Thus, evaporators can be calibrated to supply anesthetic concentrations with an error of ± 10% of the set values at a gas flow of 2 -10 l/min. Beyond these gas flow limits, the accuracy of the evaporator becomes less predictable.

Types of evaporators Direct-flow evaporators (drawover) – the carrier gas is “pulled” through the evaporator due to a decrease in pressure in the final section of the system (during the patient’s inhalation) Fill evaporators (plenum) – the carrier gas is “pushed” through the evaporator under pressure exceeding ambient.

Scheme of a flow-through evaporator Low resistance to the flow of the gas mixture Gas passes through the evaporator only during inhalation, the flow is not constant and pulsating (up to 30 -60 l per minute during inhalation) There is no need for compressed gas supply

Plenum evaporators are designed for use with a constant flow of gas under pressure and have a high internal resistance. Modern models are specific for each anesthetic. Flow stabilized, operate with an accuracy of +20% at a flow of fresh gas mixture from 0.5 to 10 l/min

Vaporizer safety Special vaporizer markings Drug level indicator Proper vaporizer placement in the circuit: - Fill vaporizers are installed after the rotameters and in front of the oxygen - Flow vaporizers are installed in front of the bellows or bag Locking device to prevent multiple vaporizers from being activated at the same time Monitoring anesthetic concentration Potential hazards: Inverting the vaporizer Reverse connection Evaporator tip-over Incorrectly filling evaporator

Pharmacokinetics studies Ø Absorption Ø Distribution Ø Metabolism Ø Excretion Pharmacokinetics – studies the relationship between the dose of a drug, its concentration in tissues and duration of action.

Pharmacokinetics of inhalational anesthetics The depth of anesthesia is determined by the concentration of the anesthetic in the brain tissues The concentration of the anesthetic in the alveoli (FA) is related to the concentration of the anesthetic in the brain tissues The alveolar concentration of the anesthetic is influenced by factors related to: ▫ with the entry of the anesthetic into the alveoli ▫ with the elimination of the anesthetic from the alveoli

Basic physical parameters of inhalational anesthetics Volatility or “Saturated Vapor Pressure” Solubility Power

The drugs we call "inhalational anesthetics" are liquids at room temperature and atmospheric pressure. Liquids are composed of molecules that are in constant motion and have a common affinity. If the surface of a liquid comes into contact with air or another gas, some molecules break away from the surface. This process is evaporation, which increases with heating of the medium. Inhalational anesthetics are able to evaporate quickly and do not require heat to become vapor. If we pour an inhalational anesthetic into a container, for example, into a jar with a lid, over time the vapor generated from the liquid will accumulate in the free space of this jar. In this case, the steam molecules move and create a certain pressure. Some of the vapor molecules will interact with the surface of the liquid and become liquid again. Eventually, this process reaches an equilibrium in which equal numbers of molecules leave the liquid and return to it. "Vapour pressure" is the pressure created by the vapor molecules at the equilibrium point.

Saturated Vapor Pressure (SVP) Saturated vapor pressure (SVP) is defined as the pressure created by steam in equilibrium with the liquid phase. This pressure depends on the drug and its temperature. If the saturated vapor pressure (SVP) is equal to atmospheric pressure, the liquid boils. Thus, water at sea level at 100°C has a saturated vapor pressure (SVP) = 760 mm Hg. Art. (101.3 k. Pa).

Volatility This is a general term that is related to saturated vapor pressure (VVP) and latent heat of evaporation. The more volatile a drug is, the less energy is required to convert the liquid into vapor and the greater the pressure created by that vapor at a given temperature. This indicator depends on the nature of the temperature and on the drug. Thus, trichlorethylene is less volatile compared to ether.

The volatility or "Vapor Pressure" of DNP reflects the ability of the anesthetic to evaporate, or in other words, its volatility. All volatile anesthetics have different evaporation properties. What determines the intensity of evaporation of a particular anesthetic? . ? The pressure that the maximum number of evaporated molecules will exert on the walls of the vessel is called “saturated vapor pressure.” The number of molecules evaporated depends on the energy status of a given liquid, that is, on the energy status of its molecules. That is, the higher the energy status of the anesthetic, the higher its DNP is an important indicator because, using it, the maximum concentration of anesthetic vapor can be calculated.

For example, the DNP of isoflurane at room temperature is 238 mm. H.G. Therefore, in order to calculate the maximum concentration of its vapors, we make the following calculations: 238 mm. Hg / 760 mm. HG * 100 = 31%. That is, the maximum concentration of Isoflurane vapor at room temperature can reach 31%. Compared to isoflurane, the anesthetic methoxyflurane has a DNP of only 23 mm. HG and its maximum concentration at the same temperature reaches a maximum of 3%. The example shows that there are anesthetics characterized by high and low volatility. Highly volatile anesthetics are used only with the use of specially calibrated evaporators. The vapor pressure of anesthetic agents may change as the ambient temperature increases or decreases. First of all, this dependence is relevant for anesthetics with high volatility.

Examples: Take the lid off a paint can and you will smell it. At first the smell is quite strong, since the steam is concentrated in the jar. This steam is in equilibrium with the paint, so it can be called saturated. The can has been closed for an extended period of time and the vapor pressure (SVP) represents the point at which equal amounts of paint molecules become vapor or return to the liquid phase (paint). Very soon after you remove the lid, the smell disappears. The vapor diffused into the atmosphere, and since the paint has low volatility, only very small amounts are released into the atmosphere. If you leave the paint container open, the paint will remain thick until it evaporates completely. When the lid is removed, the smell of gasoline, which is more volatile, continues to persist, since a large number of molecules evaporate from its surface. Within a short period of time, there is no gasoline left in the container; it completely turns into steam and enters the atmosphere. If the container was filled with gasoline, when you open it on a hotter day you will hear a characteristic whistle, but on a cold day it will, on the contrary, suck in air. Saturated vapor pressure (SVP) is higher on warm days and lower on cold days, as it depends on temperature.

Latent heat of evaporation Latent heat of evaporation is defined as the amount of energy required to convert 1 g of liquid into vapor without changing temperature. The more volatile a liquid is, the less energy is required. The latent heat of vaporization is expressed in k. J/g or k. J/mol, based on the fact that different drugs have different molecular weights. In the absence of an external source of energy, it can be taken from the liquid itself. This causes the liquid to cool (use of thermal energy).

Solubility A gas dissolves in a liquid. At the beginning of dissolution, gas molecules actively move into the solution and back. As more and more gas molecules mix with liquid molecules, a state of equilibrium gradually sets in, where there is no longer an intense transition of molecules from one phase to another. The partial pressure of the gas at equilibrium in both phases will be the same.

The speed of onset of the expected effect of an inhalational anesthetic depends on the degree of its solubility in the blood. Anesthetics with high solubility are absorbed in large quantities by the blood, which does not allow reaching a sufficient level of alveolar partial pressure for a long time. The degree of solubility of an inhalational anesthetic is characterized by the blood/Oswald gas solubility coefficient (λ is the ratio of anesthetic concentrations in two phases at equilibrium). It shows how many parts of the anesthetic must be in 1 ml of blood from the amount of anesthetic that is in 1 ml of the anesthetic-respiratory mixture in the alveolar space so that the partial pressure of this anesthetic is equal and identical in both the blood and the alveoli.

Vapors and gases with different solubilities create different partial pressures in the solution. The lower the solubility of a gas, the greater the partial pressure it is able to create in solution compared to a highly soluble gas under the same conditions. An anesthetic with low solubility will create a greater partial pressure in the solution than one with high solubility. The partial pressure of the anesthetic is the main factor determining its effect on the brain.

the solubility coefficient of sevoflurane is 0.65 (0.630.69), i.e., this means that at the same partial pressure, 1 ml of blood contains 0.65 of the amount of sevoflurane that is in 1 ml of alveolar gas, i.e. The blood capacity of sevoflurane is 65% of the gas capacity. for halothane, the blood/gas distribution coefficient is 2.4 (240% of the gas capacity) - to achieve equilibrium, 4 times more halothane must be dissolved in the blood than sevoflurane.

BLOOD / GAS Xenon Desflurane Nitrous oxide Sevoflurane Isoflurane Enflurane Halothane Methoxyflurane Trichlorethylene Ether – 0. 14 – 0. 42 – 0. 47 – 0. 59 – 1. 4 – 1. 9 – 2. 35 – 2. 4 – 9. 0 – 12, 0 Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 59

There are 12 bubbles/ml of sevoflurane dissolved in the blood. Sevoflurane gas contains 20 bubbles/ml. No diffusion when the partial pressures are equal solubility coefficient blood/sevoflurane gas = 0.65

Blood - 50 bubbles/ml Gas - 20 bubbles/ml No diffusion when partial pressures are equal solubility coefficient blood/halothane gas = 2.5

The solubility coefficient determines the possibility of using an inhalational anesthetic. Induction - is it possible to carry out mask induction? Maintenance - How quickly will the depth of anesthesia change in response to changes in vaporizer concentration? Awakening – How long will it take for the patient to wake up after the anesthetic is stopped?

Potency of the volatile anesthetic The ideal volatile anesthetic allows anesthesia to be achieved using high concentrations of oxygen (and low concentrations of volatile anesthetic). The minimum alveolar concentration (MAC) is a measure of the potency of volatile anesthetics. MAK is identical to ED 50 in pharmacology. MAC is determined by measuring the concentration of anesthetic directly in the exhaled gas mixture in young and healthy animals subjected to inhalation anesthesia without any premedication. The MAC essentially reflects the concentration of the anesthetic in the brain, because upon the onset of anesthesia there will be an equilibrium between the partial pressure of the anesthetic in the alveolar gas and in the brain tissue.

MAC MINIMUM ALVEOLAR CONCENTRATION MAC is a measure of the activity (equipotency) of an inhalational anesthetic and is defined as the minimum alveolar concentration in the steady-state phase that is sufficient to prevent a reaction in 50% of patients at sea level to a standard surgical stimulus (skin incision). (1 atm = 760 mm Hg = 101 k. Ra). Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 65

MAC concept - dose-response approach for AIs Facilitates comparisons between drugs Helps in studies of the mechanism of action Characterizes drug interactions

Why MAC? 1. Alveolar concentration can be measured 2. In a state close to equilibrium, partial pressures in the alveoli and brain are approximately the same 3. High cerebral blood flow leads to rapid equalization of partial pressures 4. MAC does not change depending on different painful stimuli 5. Individual variability extremely low 6. Gender, height, weight and duration of anesthesia do NOT affect MAC 7. MACs of different anesthetics are summed up

By comparing the concentration of different anesthetics required to achieve MAC, we can tell which one is stronger. For example: MAC. for isoflurane 1.3%, and for sevoflurane 2.25%. That is, different concentrations of anesthetics are required to achieve MAC. Therefore, drugs with low MAC values are powerful anesthetics. A high MAC value indicates that the drug has a less pronounced anesthetic effect. Potent anesthetics include halothane, sevoflurane, isoflurane, and methoxyflurane. Nitrous oxide and desflurane are weak anesthetics.

FACTORS INCREASING MAC Children under 3 years of age Hyperthermia Hyperthyroidism Catecholamines and sympathomimetics Chronic alcohol abuse (induction of the P 450 system of the liver) Overdose of amphetamines Hypernatremia Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 69

FACTORS THAT REDUCE MAC Neonatal period Old age Pregnancy Hypotension, decreased CO Hypothermia Hypothyroidism Alpha 2 agonists Sedatives Acute alcohol intoxication (depression - competitive - P 450 systems) Chronic abuse of amphetamines Inhalation anesthesia // Lithium A. E. Karelov, St. Petersburg MAPO 7 0

FACTORS THAT REDUCE MAC Pregnancy Hypoxemia (less than 40 torr) Hypercapnia (more than 95 torr) Anemia Hypotension Hypercalcemia Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 71

FACTORS NOT AFFECTING MAC Hyperthyroidism Hypothyroidism Gender Duration of exposure Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 72

MAC 1, 3 MAC is an effective dose for 95% of subjects. 0.3 -0.4 MAC – MAC of awakening. MACs of different anesthetics add up: 0.5 MAC N 2 O (53%) + 0.5 MAC halothane (0.37%) cause CNS depression comparable to the effect of 1 MAC enflurane (1.7%). Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 73

MAC AND FAT/GAS RATIO Methoxyflurane Trichlorethylene Halothane Isoflurane Enflurane Ether Sevoflurane Desflurane Xenon Nitrous oxide – 0.16 // … – 0.17 // 960 – 0.77 // 220 – 1.15 // 97 – 1.68 / / 98 – 1.9 // 65 – 2.0 // … – 6.5 // 18.7 – 71 // … – 105 // 1.4 Measure of fat solubility Fat solubility correlates with anesthetic power Higher fat solubility – higher power of the anesthetic Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 74

The anesthetic effect depends on achieving a certain partial pressure of the anesthetic in the brain, which in turn directly depends on the partial pressure of the anesthetic in the alveoli. Abstractly, this relationship can be thought of as a hydraulic system: pressure created at one end of the system is transmitted through the fluid to the opposite end. The alveoli and brain tissue are “opposite ends of the system,” and the fluid is blood. Accordingly, the faster the partial pressure in the alveoli increases, the faster the partial pressure of the anesthetic in the brain increases, which means the faster induction of anesthesia will occur. The actual concentration of anesthetic in the alveoli, circulating blood and brain is important only because it is involved in achieving the anesthetic partial pressure.

The most important requirement in establishing and maintaining anesthesia is the delivery of the appropriate amount of anesthetic to the patient's brain (or other organ or tissue). Intravenous anesthesia is characterized by direct entry of the drug into the bloodstream, which delivers it to the site of action. When inhalational anesthetics are used, they must first pass the pulmonary barrier to enter the bloodstream. Thus, the basic pharmacokinetic model for an inhalational anesthetic must be complemented by two additional sectors (breathing circuit and alveoli), realistically representing the anatomical space. Because of these two additional sectors, inhalational anesthesia is somewhat more difficult to administer than intravenous anesthesia. However, it is the ability to regulate the degree of intake and leaching of an inhalational anesthetic through the lungs from the blood that is the only and main element in controlling this type of anesthesia.

Diagram of anesthesia-respiratory apparatus Breathing circuit Evaporator CO 2 adsorber Fan Control unit + monitor

Barriers between the anesthesia machine and the brain Lungs Fresh gas flow Arterial blood Dead space Breathing circuit Brain Venous blood Fi Solubility FA Fa Alveolar blood flow Solubility and absorption Volatility (DNP) Power (MAC) Pharmacological effects SI

FACTORS AFFECTING PHARMACOKINETICS Factors affecting the fractional concentration in the inhaled mixture (FI). Factors influencing fractional alveolar concentration (FA). Factors influencing fractional concentration in arterial blood (Fa).

Fi – fractional concentration of anesthetic in the inhaled mixture v Flow of fresh gas v Volume of the breathing circuit – hoses of the MRI machine – 3 m v Absorbing capacity of surfaces in contact with the mixture - rubber tubes absorb ˃ plastic and silicone → delay induction and recovery. The greater the fresh gas flow, the smaller the volume of the breathing circuit and the lower the absorption, the more accurately the concentration of anesthetic in the inhaled mixture corresponds to the concentration set on the evaporator

FA – fractional alveolar concentration of anesthetic Ventilation. The effect of concentration. Second gas effect. Effect of increased influx. Intensity of blood absorption.

Factors affecting the delivery of anesthetic to the alveoli Ventilation ▫ As alveolar ventilation increases, the delivery of anesthetic to the alveoli increases ▫ Respiratory depression slows the increase in alveolar concentration

N.B. Concentration Increasing the fractional concentration of anesthetic in the inhaled mixture not only increases the fractional alveolar concentration, but also rapidly increases the FA/Fi concentration effect. If, against the background of a high concentration of nitrous oxide, another inhalational anesthetic is administered, the entry of both anesthetics into the pulmonary bloodstream will increase (due to the same mechanism). The influence of the concentration of one gas on the concentration of another is called the second gas effect.

Factors influencing the elimination of anesthetic from the alveoli Solubility of the anesthetic in the blood Alveolar blood flow Difference between the partial pressure of the anesthetic in the alveolar gas and venous blood

Receipt of anesthetic from the alveoli into the blood If the anesthetic does not enter the blood from the alveoli, then its fractional alveolar concentration (FA) will quickly become equal to the fractional concentration in the inhaled mixture (Fi). Since during induction the anesthetic is always absorbed to some extent by the blood of the pulmonary vessels, the fractional alveolar concentration of the anesthetic is always lower than its fractional concentration in the inhaled mixture (FA/Fi

Solubility is high (K = blood/gas) - FA - P partial in the alveoli and in the blood grows slowly!!! Diffusion into the blood Lungs (FA) Active/dissolved tissue fractions Solubility is low (K = blood/gas) - FA - P partial in the alveoli and in the blood grow quickly!!! Diffusion into the blood Tissue saturation Required gas concentration in the inhaled mixture Induction time

Factors influencing the elimination of anesthetic from the alveoli Alveolar blood flow ▫ In the absence of pulmonary or intracardiac shunting, blood is equal to cardiac output ▫ As cardiac output increases, the rate of anesthetic entry from the alveoli into the bloodstream increases, the rise in FA decreases, so induction lasts longer ▫ Low cardiac output, on the contrary, increases risk of overdose of anesthetics, since in this case FA increases much more quickly ▫ This effect is especially pronounced with anesthetics with high solubility and a negative effect on cardiac output

Factors influencing the elimination of anesthetic from the alveoli Difference between the partial pressure of the anesthetic in the alveolar gas and venous blood ▫ Depends on the uptake of the anesthetic into tissues ▫ Determined by the solubility of the anesthetic in the tissues (blood/tissue partition coefficient) and tissue blood flow ▫ Depends on the difference between the partial pressure in the arterial blood and those in the tissue. Depending on the blood flow and solubility of anesthetics, all tissues can be divided into 4 groups: well-vascularized tissues, muscles, fat, weakly vascularized tissues

The difference between the partial pressure of the anesthetic in the alveolar gas and the partial pressure in the venous blood - this gradient depends on the uptake of the anesthetic by various tissues. If the anesthetic is absolutely not absorbed by the tissues, then the venous and alveolar partial pressures will be equal, so that a new portion of the anesthetic will not flow from the alveoli into the blood. The transfer of anesthetics from the blood to tissues depends on three factors: the solubility of the anesthetic in the tissue (blood/tissue partition coefficient), tissue blood flow, the difference between the partial pressure in the arterial blood and that in the tissue. Characteristics Proportion of body weight, % Proportion of cardiac output, % Perfusion, ml/min/100 g Relative solubility Time to reach equilibrium 10 50 20 Poorly vascularized tissues 20 75 19 6 O 75 3 3 O 1 1 20 O 3 -10 min 1 -4 hours 5 days Good Muscle vascularized tissue Fat O

The brain, heart, liver, kidneys and endocrine organs constitute a group of well-vascularized tissues, and it is here that a significant amount of the anesthetic first arrives. The small volume and moderate solubility of anesthetics significantly limit the capacity of tissues of this group, so that a state of equilibrium quickly occurs in them (arterial and tissue partial pressures become equal). Blood flow in the muscle tissue group (muscle and skin) is less and consumption of the anesthetic is slower. In addition, the volume of the muscle tissue group and, accordingly, their capacity is much larger, so it may take several hours to achieve equilibrium. The blood flow in the adipose tissue group is almost equal to the blood flow in the muscle group, but the extremely high solubility of anesthetics in adipose tissue results in such a high total capacity (Total Capacity = Tissue/Blood Solubility X Tissue Volume) that it takes several days to reach equilibrium. In the group of weakly vascularized tissues (bones, ligaments, teeth, hair, cartilage), blood flow is very low and anesthetic consumption is negligible.

The rise and fall of alveolar partial pressure precede similar changes in partial pressure in other tissues. Fa reaches Fi more quickly with nitrous oxide (an anesthetic with low blood solubility) than with methoxyflurane (an anesthetic with high blood solubility).

Factors influencing the fractional concentration of an anesthetic in arterial blood (Fa) Violation of ventilation-perfusion relationships Normally, the partial pressure of an anesthetic in the alveoli and in arterial blood after reaching equilibrium becomes the same. Violation of the ventilation-perfusion relationship leads to the appearance of a significant alveolo-arterial gradient: the partial pressure of the anesthetic in the alveoli increases (especially when using highly soluble anesthetics), in the arterial blood it decreases (especially when using low-soluble anesthetics).

The anesthetic content in the brain quickly equalizes with arterial blood. Time constant (2-4 min) is the blood/brain distribution coefficient divided by cerebral blood flow. Blood/brain partition coefficients differ little among AIs. After one time constant, the partial pressure in the brain is 63% of the partial blood pressure.

Time Constant The brain requires about 3 time constants to reach equilibrium with arterial blood. Time constant for N2O/desflurane = 2 min. Time constant for halothane/ISO/SEVO = 3 -4 min.

For all inhalational anesthetics, equilibrium between brain tissue and arterial blood is achieved in approximately 10 minutes

Arterial blood has the same partial pressure with the alveoli PP inhaled = 2 A Equilibrium is complete on both sides of the alveolar-capillary membrane PP alveolar = A = PP

Fet. IA = key quantity Currently measuring Fet. At steady state, we have a good way to determine the concentration in the brain, despite all the difficulties of pharmacokinetics. When equilibrium is achieved: End tidal = alveolar = arterial = brain

Summary (1) (Fi): (2) (FA): 1 - fresh gas flow 2 - gas absorption circuit 3 - breathing circuit volume Gas supply: 1 - concentration 2 - MOAlv. Vent Gas removal: 1 - solubility in blood (3) (Fa): V/Q disturbances 2 - alveolar blood flow 3 - gas consumption by tissues

FA is the balance between the entry and exit of AI from the alveoli. Increased entry of AI into the alveoli: High % on the evaporator + MOD + fresh mixture flow. Venous pressure AI (PA) = 4 mm Hg FI = 16 mm Hg FA = 8 mm Hg FA / FI = 8/16 = 0. 5 Blood pressure agent (PV) agent = 8 mm Hg Increased excretion of AI from the alveoli into the blood: Low P in the vein, high solubility, high CO

High solubility = slow rise FA N 2 O, low blood / gas Halothane, high blood / gas

The entry of AI from the alveoli into the blood is “absorption” FI = 16 mm Hg FA = 8 mm Hg Venous (PA) agent = 4 mm Hg Arterial (PV) agent = 8 mm Hg

The flow of gas from the alveoli (“absorption”) is proportional to the blood/gas coefficient Input Inhaled “FI” PP = 16 mm Hg Alveoli “FA” PP = 8 mm Hg Output (“uptake”) is low Sevoflurane b/g = 0. 7 Blood and tissues PP = 6 mm Hg

The flow of gas from the alveoli (“absorption”) is proportional to the blood/gas coefficient Input Inhaled “FI” PP = 16 mm Hg Alveoli “FA” PP = 4 mm Hg Output (“uptake”) is large Halothane b/g = 2. 5 Blood and tissues PP = 2 mm Hg

Delay time between turning on the evaporator and the accumulation of AI in the brain 4% sevoflurane Closed system (“hoses”) PP= 30 mm Hg PP = 24 mm Hg evaporator At sea level Inhaled AI “FI” PP = 16 mm Hg Alveoli “FA” PP = 8 mm Hg Arterial blood PP = 8 mm Hg brain PP = 5 mm Hg

When venous blood pressure = alveolar, absorption stops and FA / FI = 1.0 FI = 16 mm Hg FA = 16 mm Hg Venous (PA) agent = 16 mm Hg FA / FI = 16/16 = 1.0 Arterial ( PV) agent = 16 mm Hg

Awakening depends on: - removal of the exhaled mixture, - high fresh gas flow, - small volume of the breathing circuit, - insignificant absorption of the anesthetic in the breathing circuit and anesthesia machine, - low solubility of the anesthetic, - high alveolar ventilation

Advantages of modern inhalation anesthesia ØPowerful general anesthetic activity of the drug. Ø Good handling. Ø Quick awakening and the possibility of early activation of patients. Ø Reduced use of opioids, muscle relaxants and faster recovery of gastrointestinal function.

“Inhalation anesthesia is most indicated for long-term and traumatic operations, while for relatively low-traumatic and short-term interventions, the advantages and disadvantages of inhalation and intravenous techniques are mutually compensated” (Likhvantsev V.V., 2000).

Conditions for the use of inhalational anesthetics: the presence of anesthesia-respiratory equipment intended for the use of inhalational anesthetics, the presence of appropriate evaporators (“each volatile anesthetic has its own evaporator”), full monitoring of the gas composition of the respiratory mixture and the functional systems of the body, removal of waste gases outside the operating room.

The main advantage of using AIs is the ability to control them at all stages of anesthesia, which ensures, first of all, the safety of the patient during surgery, since their effect on the body can be quickly stopped.

minor gynecological operations with severe concomitant pathology (circulatory system, respiratory system); short-term interventions in obese patients

short-term diagnostic studies (MRI, CT, colonoscopy, etc.) New Drugs: Alternatives and Adjuncts to Bupivacaine in Paediatric Regional Anaesthesia Per-Arne Lönnqvist, Stockhom, Sweden - SGKA-APAMeeting 2004

with limited possibility of using non-inhalational anesthetics - allergic reactions - bronchial asthma - difficulties in providing vascular access, etc.

in pediatrics - providing vascular access, - induction of anesthesia, - conducting short-term studies Rapid Sequence Induction in Pediatric Anaesthesia Peter Stoddart, Bristol, United Kingdom - SGKAAPA-Meeting 2004

An absolute contraindication to the use of AI is the fact of malignant hyperthermia and a history of adverse (primarily allergic) reactions. A relative contraindication is short-term surgical interventions, when the AI is used in an open respiratory circuit with the patient breathing independently or in a semi-closed circuit with mechanical ventilation under conditions of high gas flow, which does not harm the patient, but significantly increases the cost of anesthesia.

“An ideal inhalation anesthetic” Properties Physico-chemical stability - should not be destroyed under the influence of light and heat inertness - should not enter into chemical reactions with metal, rubber and soda lime no preservatives should not be flammable or explosive should have a pleasant odor should not accumulate in atmosphere have a high oil/gas distribution coefficient (i.e., be fat-soluble), correspondingly low MAC have a low blood/gas distribution coefficient (i.e., low solubility in liquid) do not metabolize - do not have active metabolites and are excreted unchanged be non-toxic Clinical have analgesic, antiemetic, anticonvulsant effects no respiratory depression bronchodilator properties no negative effect on the cardiovascular system no decrease in coronary, renal and hepatic blood flow no effect on cerebral blood flow and intracranial pressure no trigger of malignant hyperthermia no epileptogenic properties Economic relative cheapness accessibility for the healthcare system acceptability in terms of cost-effectiveness and cost-utility economic feasibility of use for the healthcare system cost savings of the healthcare budget

Each of the inhalational anesthetics has its own so-called anesthetic activity or “potency”. It is defined by the concept of “minimum alveolar concentration” or MAC. It is equal to the concentration of anesthetic in the alveolar space, which in 50% of patients prevents a reflex motor reaction to a painful stimulus (skin incision). MAC is an average value, which is calculated for people aged 30-55 years and expressed as a percentage of 1 atm, reflects the partial pressure of the anesthetic in the brain and allows you to compare the “power” of different anesthetics. The higher the MAC, the lower the anesthetic activity of the drug MAC awakening – 1/3 MAC 1, 3 MAC – 100% absence of movement in patients 1, 7 MAC – MAC BAR (hemodynamically significant MAC)

MAC – partial pressure, not concentration Yes - MAC is expressed as a %, but this implies a % of atmospheric pressure at sea level

Is it possible to survive with 21% oxygen in the air? Not if you are on top of Everest!!! Also, MAC reflects partial pressure and not concentration.

MAC At sea level the atmospheric pressure is 760 mm Hg. % MAC = 2.2%, and the partial pressure will be: 2. 2% X 760 = 16. 7 mm Hg At altitude, the pressure is lower and will be 600 mm Hg, and MAC% of sevoran will be = 2. 8%, and the pressure remains unchanged (16.7 / 600 = 2.8%)

Question: What is the %MAC of sevoran at a depth of 33 feet underwater? Answer: 1. 1%, since barometric pressure is 2 atmospheres or 1520 mmHg. And since the partial pressure of sevoran is constant, then: 16. 7 mm Hg / 1520 mm Hg = 1. 1%

MAC value of inhalational anesthetics in a patient aged 30-60 years at atmospheric pressure Anesthetic MAC, % Halothane 0.75 Isoflurane 1.15 Sevoflurane 1.85 Desflurane 6.6 Nitrous oxide 105

Properties of an ideal inhalation anesthetic Sufficient strength Low solubility in blood and tissues Resistance to physical and metabolic degradation, no damaging effect on organs and tissues of the body No predisposition to the development of seizures No irritant effect on the respiratory tract No or minimal effect on the cardiovascular system Environmental safety (no influence on the ozone layer of the earth) Acceptable cost

Solubility of the anesthetic in the blood A low blood/gas distribution coefficient indicates a low affinity of the anesthetic for the blood, which is the desired effect, as it ensures a rapid change in the depth of anesthesia and rapid awakening of the patient after the end of anesthesia Partition coefficient of inhalational anesthetics in the blood at 37°C Anesthetic Desflurane Blood gas 0.45 Nitrous oxide Sevoflurane Isoflurane Halothane 0.47 0.65 1.4 2.5

Distribution coefficient of inhalational anesthetics in tissues at 37°C Anesthetic Brain/blood Muscle/blood Fat/blood Nitrous oxide 1, 1 1, 2 2, 3 Desflurane 1, 3 2, 0 27 Isoflurane 1, 6 2, 9 45 Sevoflurane 1 , 7 3, 1 48 Halothane 1, 9 3, 4 51

Resistance to degradation When assessing the metabolism of inhaled anesthetics, the most important aspects are: ▫ The proportion of the drug that undergoes biotransformation in the body ▫ The safety of the metabolites formed during biotransformation for the body

Resistance to degradation Halothane, Isoflurane and Desflurane undergo biotransformation in the body with the formation of trifluoroacetate, which can cause liver damage. Sevoflurane has an extrahepatic mechanism of biotransformation, its metabolic rate ranges from 1 to 5%, which is slightly higher than that of isoflurane and desflurane, but significantly lower than at halothane

Resistance to metabolic degradation and potential hepatotoxic effect of some inhalational anesthetics Anesthetic Halothane Metabolism, % Incidence of liver damage 15 -20 1: 35000 Isoflurane 0.2 1: 1000000 Desflurane 0.02 1: 10000000 Sevoflurane 3.3 -

Resistance to degradation Nitrous oxide is practically not metabolized in the body, but it causes tissue damage by inhibiting the activity of vitamin B 12-dependent enzymes, which include methionine synthetase, which is involved in DNA synthesis. Tissue damage is associated with bone marrow depression (megaloblastic anemia), as well as damage to the nervous system (peripheral neuropathy and funicular myelosis) These effects are rare and presumably occur only in patients with vitamin B12 deficiency and long-term use of nitrous oxide

Resistance to degradation Sevoflurane is not hepatotoxic Approximately 5% of sevoflurane is metabolized in the body to form fluoride ions and hexafluoroisopropanol Fluoride ion has potential nephrotoxicity at plasma concentrations exceeding 50 μmol/L Studies assessing the metabolism of sevoflurane in children have demonstrated that maximum fluoride levels vary between 10 -23 µmol/l and decreases rapidly upon completion of anesthesia. There were no cases of nephrotoxicity in children after anesthesia with sevoflurane.

Protective effect of inhaled anesthetics Clinical studies of the use of propofol, sevoflurane and desflurane as anesthetics in patients with coronary artery disease undergoing coronary artery bypass surgery showed that the percentage of patients with elevated postoperative troponin I levels, reflecting damage to myocardial cells, was significantly higher in the propofol group compared with groups sevoflurane and desflurane

Properties of an ideal inhalation anesthetic Sufficient strength Low solubility in blood and tissues Resistance to physical and metabolic degradation, no damaging effect on organs and tissues of the body No predisposition to the development of seizures No irritant effect on the respiratory tract No or minimal effect on the cardiovascular system Environmental safety ( no impact on the ozone layer of the earth) Acceptable cost

Predisposition to the development of seizures Halothane, isoflurane, desflurane and nitrous oxide do not cause seizures. Cases of epileptiform activity on the EEG and seizure-like movements during sevoflurane anesthesia are described in the medical literature, however, these changes were short-lived and resolved spontaneously without any clinical manifestations in the postoperative period. In a number cases at the stage of awakening in children there is increased arousal and psychomotor activity ▫ May be associated with a rapid restoration of consciousness against the background of insufficient analgesia

Irritant effect on the respiratory tract Halothane and Sevoflurane do not cause irritation of the respiratory tract The threshold for the development of respiratory tract irritation is 6% when using desflurane and 1.8% when using isoflurane Desflurane is contraindicated for use as induction through a mask in children due to the high percentage of side effects effects: laryngospasm, cough, breath holding, desaturation Due to the absence of an irritating odor and low risk of respiratory tract irritation, sevoflurane is the most commonly used inhalational anesthetic used for induction of anesthesia

Effect of inhalational anesthetics on hemodynamics With a rapid increase in the concentration of desflurane and isoflurane, tachycardia and an increase in blood pressure are observed, which is more pronounced with desflurane compared to isoflurane, however, when these anesthetics are used to maintain anesthesia, there are no large differences in the hemodynamic effects. Sevoflurane reduces cardiac output, but to a much lesser extent. than halothane, and also reduces systemic vascular resistance. A rapid increase in the concentration of sevoflurane (0.5 MAC, 1.5 MAC) causes a moderate decrease in heart rate and blood pressure. Sevoflurane to a much lesser extent sensitizes the myocardium to endogenous catecholamines, the serum concentration of adrenaline, at which disturbances are observed heart rate, sevoflurane is 2 times higher than halothane and comparable to isoflurane

Choice of anesthetic: nitrous oxide Low power limits its use, is used as a carrier gas for other more powerful inhalational anesthetics Odorless (allows for easier perception of other inhalational anesthetics) Has a low solubility coefficient, which ensures rapid induction and rapid recovery from anesthesia Causes increased cardiodepressive effects halothane, isoflurane Increases pressure in the pulmonary artery system Has a high diffusion capacity, increases the volume of cavities filled with gas, therefore it is not used for intestinal obstruction, pneumothorax, operations with artificial circulation During the period of recovery from anesthesia, it reduces the alveolar oxygen concentration, therefore within 5 -10 minutes after the anesthetic is turned off, high concentrations of oxygen must be used

Choice of anesthetic: halothane Halothane has some characteristics of an ideal inhalational anesthetic (sufficient potency, lack of irritation to the respiratory tract) However, high solubility in blood and tissues, pronounced cardiodepressive effects and the risk of hepatotoxicity (1: 350001: 60000) have led to its displacement from clinical practice modern inhalational anesthetics

Choice of anesthetic: isoflurane Not recommended for induction of anesthesia ▫ Has an irritating effect on the respiratory tract (cough, laryngospasm, apnea) ▫ With a sharp increase in concentration has a pronounced effect on hemodynamics (tachycardia, hypertension) Has potential hepatotoxicity (1: 1,000,000) Has a relatively high solubility in blood and tissues (higher than sevoflurane and desflurane) Has minimal impact on the Earth's ozone layer Cheaper drug compared to sevoflurane and desflurane Most common inhalational anesthetic

Choice of anesthetic: desflurane Not recommended for induction of anesthesia ▫ Has an irritating effect on the respiratory tract (cough, laryngospasm, apnea) ▫ With a sharp increase in concentration, it has a pronounced effect on hemodynamics (tachycardia hypertension) Has the lowest solubility in organs and tissues compared to isoflurane and sevoflurane Does not have hepatotoxicity Has a cardioprotective effect Environmentally friendly Has a relatively high cost, comparable to sevoflurane

Choice of anesthetic: sevoflurane Does not cause irritation of the respiratory tract Does not have a pronounced effect on hemodynamics Less soluble in blood and tissues than halothane and isoflurane Does not have hepatotoxicity Has a cardioprotective effect Metabolic products have potential nephrotoxicity (no reliable cases of nephrotoxicity have been noted after the use of sevoflurane) Environmentally safe Increases epileptiform activity on the EEG In some cases, it can cause the development of postoperative agitation Drug of choice for inhalation induction The most common inhalational anesthetic in pediatric practice

There are three phases of the first degree of anesthesia according to Artusio (1954): initial - pain sensitivity is preserved, the patient is contactable, memories are preserved; medium – pain sensitivity is dulled, slight stunning, memories of the operation may be retained, they are characterized by inaccuracy and confusion; deep - loss of pain sensitivity, half-asleep state, reaction to tactile irritation or loud sound is present, but it is weak.

Excitation stage When performing general anesthesia with ether, loss of consciousness at the end of the analgesia phase is accompanied by pronounced speech and motor excitation. Having reached this stage of ether anesthesia, the patient begins to make erratic movements, utter incoherent speeches, and sing. A long stage of excitement, about 5 minutes, is one of the features of ether anesthesia, which forced us to abandon its use. The excitation phase of modern drugs for general anesthesia is weak or absent. In addition, the anesthesiologist can use them in combination with other drugs to eliminate negative effects. In patients suffering from alcoholism and drug addiction, it can be quite difficult to exclude the stage of excitation, since biochemical changes in the brain tissue contribute to its manifestation.

Stage of surgical anesthesia It is characterized by complete loss of consciousness and pain sensitivity and weakening of reflexes and their gradual inhibition. Depending on the degree of decrease in muscle tone, loss of reflexes and the ability to spontaneous breathing, four levels of surgical anesthesia are distinguished: Level 1 - level of movement of the eyeballs - against the background of restful sleep, muscle tone and laryngeal-pharyngeal reflexes are still preserved. Breathing is smooth, pulse is slightly increased, blood pressure is at the initial level. The eyeballs make slow circular movements, the pupils are evenly constricted, they react quickly to light, the corneal reflex is preserved. Superficial reflexes (skin) disappear. Level 2 – level of the corneal reflex. The eyeballs are fixed, the corneal reflex disappears, the pupils are constricted, and their reaction to light is preserved. The laryngeal and pharyngeal reflexes are absent, muscle tone is significantly reduced, breathing is even, slow, pulse and blood pressure are at the initial level, the mucous membranes are moist, the skin is pink.

Level 3 – level of pupil dilation. The first signs of an overdose appear - the pupil dilates due to paralysis of the smooth muscles of the iris, the reaction to light is sharply weakened, and dryness of the cornea appears. The skin is pale, muscle tone sharply decreases (only sphincter tone is preserved). Costal breathing gradually weakens, diaphragmatic breathing predominates, inhalation is somewhat shorter than exhalation, pulse quickens, blood pressure decreases. Level 4 – level of diaphragmatic breathing – a sign of overdose and a harbinger of death. It is characterized by a sharp dilation of the pupils, their lack of reaction to light, a dull, dry cornea, complete paralysis of the respiratory intercostal muscles; Only diaphragmatic breathing is preserved - shallow, arrhythmic. The skin is pale with a cyanotic tint, the pulse is threadlike and rapid, blood pressure is not determined, sphincter paralysis occurs. The fourth stage - AGONAL STAGE - paralysis of the respiratory and vasomotor centers, manifested by cessation of breathing and cardiac activity.

Awakening stage - recovery from anesthesia After the cessation of the flow of general anesthesia into the blood, awakening begins. The duration of recovery from the state of anesthesia depends on the rate of inactivation and elimination of the narcotic substance. For broadcasting, this time is about 10 -15 minutes. Awakening after general anesthesia with propofol or sevoflurane occurs almost instantly.

Malignant hyperthermia A disease that occurs during general anesthesia or immediately after it, characterized by hypercatabolism of skeletal muscles, manifested by increased oxygen consumption, accumulation of lactate, increased production of CO 2 and heat First described in 1929 (Ombredan syndrome) The development of MH is provoked by ▫ Inhalation anesthetics ▫ Succinylcholine

Malignant hyperthermia A hereditary disease that is transmitted in an autosomal dominant manner. The average incidence is 1 in 60,000 general anesthesia cases using succinylcholine and 1 in 200,000 without its use. Signs of MH can occur both during anesthesia with the use of trigger agents, and after several hours after its completion Any patient can develop MH, even if the previous general anesthesia was uneventful

Pathogenesis The triggering mechanism for the development of MH is inhalational anesthetics (halothane, isoflurane, sevoflurane) alone or in combination with succinylcholine. Trigger substances release calcium reserves from the sarcoplasmic reticulum, causing contracture of skeletal muscles and glycogenolysis, increasing cellular metabolism, which results in increased oxygen consumption, excess heat production, lactate accumulation Affected patients develop acidosis, hypercapnia, hypoxemia, tachycardia, rhabdomyolysis with subsequent increases in serum creatine phosphokinase (CPK) as well as potassium ions with a risk of developing cardiac arrhythmia or cardiac arrest and myoglobinuria with a risk of developing renal failure

Malignant hyperthermia, early signs In most cases, signs of MH occur in the operating room, although they may appear during the first postoperative hours ▫ Unexplained tachycardia, rhythm disturbances (ventricular extrasystoles, ventricular bigemia) ▫ Hypercapnia, increased RR if the patient is spontaneously breathing ▫ Spasm of the masticatory muscles (impossibility to open the mouth), generalized muscle rigidity ▫ Skin marbling, sweating, cyanosis ▫ A sharp increase in temperature ▫ The anesthesia machine canister becomes hot ▫ Acidosis (respiratory and metabolic)

Laboratory diagnosis of MH Changes in CBS: ▫ Low p. H ▫ Low p. O 2 ▫ High p. CO 2 ▫ Low bicarbonate ▫ Large base deficiency Other laboratory signs ▫ Hyperkalemia ▫ Hypercalcemia ▫ Hyperlactatemia ▫ Myoglobinuria (dark urine color) ▫ Increased CPK levels Caffeine-halothane contractile test is the gold standard for diagnosing susceptibility to MH

Diagnosis of predisposition to MH Caffeine test Test with halothane The muscle fiber is placed in a caffeine solution with a concentration of 2 mmol/l Normally, its rupture occurs when a force of 0.2 g is applied to the muscle fiber. With a predisposition to MH, rupture occurs with a force of > 0.3 g The muscle fiber is placed in a container with a physiological solution, through which a mixture of oxygen and carbon dioxide and halothane is passed. The fiber is stimulated by an electrical discharge every 10 seconds. Normally, it will not change the force of contraction when applying a force of > 0.5 g for the entire time that halothane is present in the gas mixture. When the concentration of halothane in the environment surrounding the muscle fiber decreases by 3%, the breaking point of the fiber drops from > 0.7 to > 0.5 G

What to do if chewing muscle rigidity develops Conservative approach Stop anesthesia Obtain a muscle biopsy for laboratory testing Postpone anesthesia to a later date Liberal approach Switch to non-trigger anesthetic drugs Close monitoring of O 2 and CO 2 Treatment with dantrolene

Differential diagnosis for rigidity of masticatory muscles Myotonic syndrome Dysfunction of the temporomandibular joint Insufficient administration of succinylcholine

Neuroleptic malignant syndrome Symptoms are similar to malignant hyperthermia ▫ Fever ▫ Rhabdomyolysis ▫ Tachycardia ▫ Hypertension ▫ Agitation ▫ Muscular rigidity

Neuroleptic malignant syndrome The attack occurs after long-term use of: ▫ Phenothiazines ▫ Haloperidol ▫ Abrupt withdrawal of drugs for the treatment of Parkinson's disease Possibly provoked by depletion of dopamine The condition is not inherited Succinylcholine is not a trigger Treatment with dantrolene is effective If the syndrome develops during anesthesia, treatment is carried out according to the protocol for the treatment of malignant hyperthermia

Treatment of malignant hyperthermia Mortality in the fulminant form without the use of dantrolene is 60 - 80% The use of dantrolene and rational symptomatic therapy has reduced mortality in developed countries to 20% or lower

Diseases associated with MH ▫ King-Denborough syndrome ▫ Central core disease ▫ Duschenne muscular dystrophy ▫ Fukuyama muscular dystrophy ▫ Myotonia congenita ▫ Schwartz-Jampel syndrome High risk of suspicion for the development of MH Trigger agents should be avoided

First steps 1. 2. 3. Call for help Warn the surgeon about the problem (abort the operation) Follow the treatment protocol

Treatment protocol 1. Stop administration of trigger drugs (inhalational anesthetics, succinylcholine) Hyperventilation (MOV 2-3 times higher than normal) with 100% oxygen at high flow (10 l/min or more), disconnect the evaporator 2. ▫ change the circulation system and adsorbent not necessary (waste of time) 3. Switch to the use of non-trigger anesthetic drugs (TBA) 4. Administration of dantrolene at a dose of 2.5 mg/kg (repeat if no effect, total dose up to 10 mg/kg) 5. Cool the patient ▫ ▫ Ice on the head, neck, axillary areas, groin area Stop cooling at body temperature

Monitoring Continue routine monitoring (ECG, Sat, Et. CO 2, indirect BP) Measure core temperature (esophageal or rectal temperature sensor) Place large bore peripheral catheters Discuss placement of CVC, arterial line and urinary catheter Electrolyte and blood gas analysis blood (liver, kidney enzymes, coagulogram, myoglobin)

Further treatment Correction of metabolic acidosis at p. H

Dantrolene The drug was introduced into clinical practice in 1974. A muscle relaxant with non-curare-like action. Reduces the permeability of calcium channels of the sarcoplasmic reticulum. Reduces the release of calcium into the cytoplasm. Prevents the occurrence of muscle contracture. Limits cellular metabolism. Nonspecific antipyretic.

Dantrolene The dosage form for intravenous administration appeared in 1979. Bottle 20 mg + 3 g mannitol + Na. OH Onset of action after 6 -20 minutes Effective plasma concentration lasts 5 -6 hours Metabolized in the liver, excreted by the kidneys Shelf life 3 years, ready solution - 6 hours

Side effects Muscle weakness up to the need for prolonged mechanical ventilation Reduces myocardial contractility and cardiac index Antiarrhythmic effect (extends the refractory period) Dizziness Headache Nausea and vomiting Severe drowsiness Thrombophlebitis

Therapy in the PICU Observation for at least 24 hours. Administration of dantrolene at a dose of 1 mg/kg every 6 hours for 24-48 hours. ▫ For the treatment of an adult patient, up to 50 ampoules of dantrolene may be required Monitoring core temperature, gases, blood electrolytes, CPK , myoglobin in blood and urine and coagulogram parameters

Cleaning the anesthesia machine Replacement of evaporators Replacement of all parts of the device circuit Replacement of the absorber with a new one Replacement of anesthesia masks Ventilation of the device with pure oxygen with a flow of 10 l/min for 10 minutes.

Anesthesia in patients predisposed to MH Adequate monitoring: ▫ Pulse oximeter ▫ Capnograph ▫ Invasive blood pressure ▫ CVP ▫ Core temperature monitoring

Anesthesia in patients with a predisposition to MH Dantrolene 2.5 mg/kg IV 1.5 hours before anesthesia (currently recognized as unfounded) General anesthesia ▫ Barbiturates, nitrous oxide, opioids, benzodiazepines, propofol ▫ Use of non-depolarizing muscle relaxants Regional anesthesia Local anesthesia accompanied by drug sedation Postoperative observation for 4-6 hours.

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Halothane(Halothane). Synonyms: Ftorotan(Phthorothanum), Narcotan(Narcotan).

pharmachologic effect: has a strong, fast-passing narcotic effect, does not cause excitement or tension in the patient during anesthesia. Switching off consciousness occurs 1-2 minutes after applying fluorotane at a concentration of 1:200 (0.5 vol.%) with oxygen, the surgical stage occurs after 3-5 minutes; awakening - 35 minutes after stopping the supply of fluorotane.

Indications: is the means of choice for many surgical interventions, varying in volume and trauma. For short-term interventions that do not require muscle relaxation, superficial anesthesia is acceptable.

Mode of application: anesthesia with fluorotane can be carried out along any circuit, but it is better to use a semi-closed one. The fluorotane evaporator is always installed outside the circulation circle. Inhalation mononarcosis while maintaining spontaneous breathing is carried out in the following mode: the introductory phase begins when 1:40-1:33 (2.5-3 vol.%) fluorotane is administered for 34 minutes, maintenance of anesthesia is possible when 1:100-1 is administered: 66 (1 - 1.5 vol.%) preparation with oxygen or a mixture consisting of 50% oxygen and 50% nitrous oxide.

Side effect: possible depression of the function of the cardiovascular system, hepatotoxic effect (if liver function is impaired), sensitization of the heart to catecholamines, increased bleeding in the surgical area, chills, pain.

: During anesthesia, adrenaline, norepinephrine, aminophylline, and aminazine should not be used. The use of an azetotropic mixture consisting of fluorothane and ether (2:1), with an oxygen concentration of at least 50%, makes it possible to reduce the amount of fluorothane used. Contraindications: hyperthyroidism, cardiac arrhythmia, hypotension, organic liver damage.

Release form: dark bottles of 50 and 250 ml. Storage conditions: in a dry, cool place, protected from light. List B.

Nitrous oxide(Nitrogenium oxydulatum). Synonym: Oxydum nitrosum.

pharmachologic effect: when inhaled pure gas causes a narcotic state and asphyxia. After inhalation ceases, it is excreted completely unchanged through the respiratory tract. Has weak narcotic activity. To more completely relax the muscles, muscle relaxants are needed, which not only enhances the relaxation of the mouse, but also improves the course of anesthesia.

Indications: used for operations in the maxillofacial area and in the oral cavity.

Mode of application: prescribed in a mixture with oxygen using devices for gas anesthesia; during anesthesia, the content of nitrous oxide in the mixture is reduced from 80 to 40%.

To obtain the required level of anesthesia, it is combined with other narcotic drugs - cyclopropane, fluorotane, barbiturates, and is also used for neuroleptanalgesia.

Side effect: Possible nausea and vomiting after anesthesia.

see Droperidol, Hexenal, Methoxyflurane, Cyclopropane.

Contraindications: caution is required when prescribing to persons with severe hypoxia and impaired diffusion of gases in the lungs.

Release form: metal cylinders according to Yul under pressure in a liquefied state.

Storage conditions: In a separate room at room temperature, away from heat sources.

Isoflurane(Isoflurane). Synonym: Foran(Forane).

Pharmachologic effect: has a rapid immersion in and recovery from anesthesia, a rapid weakening of pharyngeal and laryngeal reflexes. During anesthesia, blood pressure decreases in proportion to its depth. Heart rate does not change. Anesthesia levels are easily changed. Muscle relaxation is sufficient for operations. Surgical anesthesia occurs in 7-10 minutes at a concentration of 1.5-3 vol.%.

Indications: means for inhalation anesthesia.

Mode of application: The concentration of anesthetic produced by a Foran-calibrated vaporizer must be maintained very carefully. The value of the minimum concentration depends on age: for 20-year-old patients - 1.28% in oxygen, for 40-year-olds - 1.15%, for 60-year-olds - 1.05%; newborns - 1.6%, children under 12 months - 1.8%. The initial recommended concentration is 0.5%. It is recommended to maintain anesthesia at a level of 1-2.5% in a mixture with oxygen or oxygen and nitrous oxide.

Side effect: in case of overdose - severe arterial hypotension, heart rhythm disturbances, changes in the blood (leukocytosis).

Contraindications: hypersensitivity to the drug. Use with caution in patients with increased intracranial pressure.

Interaction with other drugs: enhances the effect of muscle relaxants, especially with simultaneous use of nitrous oxide.

Release form: liquid for anesthesia in bottles.

Storage conditions: at a temperature of +15°-30° C for 5 years.

Methoxyflurane(Methoxyfluranum). Synonyms: Ingalan(1phalanum), Pentran(Pentran).

pharmachologic effect: superior to ether and chloroform in narcotic activity. Inhalation of 1:200-1:125 (0.5-0.8 vol.%) of the drug leads to pronounced analgesia.

Anesthesia occurs slowly (10 minutes), the stage of excitation is pronounced. Awakening after stopping the supply of methoxyflurane - up to 60 minutes. Anesthesia depression persists for 2-3 hours.

Indications: used for sanitation of the oral cavity under anesthesia, preparation of teeth for permanent denture structures in people with hypersensitivity.

Mode of application: for induction of anesthesia, it is rarely used in its pure form (the patient falls asleep only after 8-10 minutes). Analgesia with Pentran is possible using a special evaporation system such as “Tringal”. The technique is simple, safe and has virtually no contraindications when using subnarcotic doses of the drug (up to 0.8 vol.%).

Side effect: when using the drug in the post-anesthesia period, headache, postoperative depression, depression of renal function with the development of polyuria, and cardiac sensitization to catecholamines are possible.

Interaction with other drugs: Not used with adrenaline and norepinephrine. A combination of 1:200-1:100 (0.5-1.0 vol.%) methoxyflurane with nitrous oxide and oxygen l:I, as well as barbiturates and muscle relaxants is used for prolonged operations.

Contraindications: Use caution if you have kidney or liver disease.

release form: 100 ml dark glass bottles.

Storage conditions: in tightly closed bottles in a cool place. List B.

Trichlorethylene(Trichloraethylenum). Synonyms: Narkogen(Narcogen), Trichlorene(Trichlorene), Trilene(Trilen).

pharmachologic effect: is a powerful narcotic with a rapid onset of effect, the effect of the drug ends 2-3 minutes after stopping the supply.

Small concentrations already in the first stage of anesthesia provide strong analgesia. Does not cause an increase in the secretion of the salivary and bronchial glands, does not affect blood circulation.

Mode of application: used for anesthesia in a semi-open system using special anesthesia devices with a calibrated evaporator (“Tritek”) without an absorber in a concentration of 1:167-1:83 (0.6-1.2 vol.%). For short-term anesthesia, analgesia during minor operations and painful manipulations, it is used in a concentration of 1:333-1:167 (0.3-0.6 vol.%) in a mixture with oxygen or air or with a mixture containing 50% nitrous oxide and 50 % oxygen. Cannot be used in a closed or semi-closed system due to possible ignition of decomposition products in the absorber.

Side effect: in case of overdose (concentration over 1:66-1.5 vol.%), severe respiratory depression develops with cardiac arrhythmia.

Interaction with other drugs: Due to the sensitization of the myocardium by trichlorethylene to catecholamines, it cannot be used together with adrenaline and norepinephrine.

Contraindications: Caution is required for liver and kidney diseases, heart rhythm disturbances, lung diseases, anemia.

Release form: ampoules of 1, 2, 6 and 7 ml, bottles of 25, 50, 100, 250. 300 ml, aluminum containers.

Storage conditions: in a dry, cool place. List B.

Chloroethyl(Aethylii chloridum). Synonyms: Ethyl chloride(Aethylis chloridum). Ethyl chloride.

Pharmachologic effect: chloroethyl has a small therapeutic range, so it is not currently used as an inhalation anesthetic. It is used for short-term superficial anesthesia of the skin due to rapid evaporation, which leads to severe cooling of the skin, vasospasm and decreased sensitivity.

Indications: prescribed for the treatment of erysipelas (cryotherapy), neuralgia, neuromyositis, diseases of the temporomandibular joint; for small superficial operations (skin incisions), for painful dressings in the postoperative period, for the treatment of burns, for soft tissue bruises, insect bites.

Mode of application: applied externally by irrigating the skin of the desired area of the maxillofacial area. The rubber cap is removed from the side capillary of the ampoule, the ampoule is warmed in the palm of your hand and the released stream is directed to the surface of the skin from a distance of 25-30 cm. After frost appears on the skin, the tissues become dense and insensitive. For medicinal purposes, the procedure is carried out once a day for 7-10 days.

Side effect: with strong cooling, tissue damage and skin hyperemia are possible.

Contraindications: violation of the integrity of the skin, vascular diseases.

Release form: ampoules of 30 ml.

Storage conditions: in a cool place. List B.

Cyclopropane(Cyclopropanum). Synonym: Cyclopropane.

Pharmachologic effect: has a strong narcotic effect. At a concentration of 1:25 (4 vol.%) causes analgesia, 1:16.7 (6 vol.%) - turns off consciousness, 1:12.5-1:10 (8-10 vol.%) - causes anesthesia ( Stage III), 1:5-1:3.3 (20-30 vol.%) - deep anesthesia. It is not destroyed in the body and is quickly (10 minutes after stopping inhalation) eliminated from the body. Does not affect the functions of the liver and kidneys.

Indications: prescribed for short-term operations of the maxillofacial area in hospitals and clinics, for patients with lung diseases, liver diseases and diabetes.

Mode of application: for introductory and main anesthesia in a mixture with oxygen in a closed and semi-closed system using devices with dosimeters. To maintain anesthesia, use 1.6-1:5.5 (15-18 vol.%) cyclopropane. In the Shane-Ashman mixture: after introductory intravenous anesthesia with sodium thiopental, a mixture of gases is administered (nitrous oxide - 1 part, oxygen - 2 parts, cyclopropane - 0.4 parts).

Side effect: causes a slight slowdown in the pulse, an increase in the secretion of the salivary and bronchial glands. In case of an overdose, respiratory arrest and cardiac depression, headache, vomiting, and intestinal paresis are possible. Diuresis decreases. Possible arrhythmias, increased sensitivity of the myocardium to adrenaline, increased blood pressure (increased bleeding).

Interaction with other drugs: should not be used simultaneously with adrenaline, norepinephrine.

Release form: steel cylinders of 1 or 2 liters of liquid preparation under pressure.

Storage conditions: away from sources of fire in a cool place.

Eiflurane(Enflurant). Synonym: Etran(Ethrane).

Pharmachologic effect: an inhaled concentration of enflurane from 2% to 4.5% provides surgical anesthesia within 7-10 minutes. The blood pressure level during anesthesia is inversely proportional to the drug concentration. Heart rate does not change.

Indications: a means for inhalation anesthesia in combination with oxygen or with a mixture of oxygen + nitrous oxide.

Mode of application: for anesthesia, evaporators specially calibrated for enflurane are used. Premedication is selected individually. Anesthesia can be induced using enflurane with oxygen alone or in combination with an oxygen + nitrous oxide mixture, while to prevent agitation, a hypnotic dose of a short-acting barbiturate must be administered to induce unconsciousness, followed by the enflurane mixture. The surgical level of anesthesia can be maintained at 0.5-3%.

Side effect: overexcitation of the central nervous system during hyperventilation, increase and decrease in blood pressure.

Contraindications: hypersensitivity to the drug.

Interaction with other drugs: enhances the effect of muscle relaxants.

Release form: liquid for inhalation anesthesia in amber bottles of 150 and 250 ml.

Storage conditions: Shelf life is 5 years at a temperature of 15-30° C.

Ether for anesthesia(Aether pro narcosi). Synonyms: Diethyl Ether, Ether Anaesthesicus.

pharmachologic effect: is an inhalational general anesthetic, a volatile liquid with a boiling point of +34-36°C. The resorptive effect of ether when used in inhalation is to disrupt the synaptic transmission of excitation to the central nervous system. The mechanism of action is associated with the stabilization of electrically excitable areas of neuronal membranes, blockade of the entry of sodium ions inside the cell and disruption of the generation of action potentials. Analgesia and loss of consciousness are observed at concentrations of ether in the inhaled mixture of 1.50-1:25 (2-4 vol.%); superficial anesthesia is provided with a concentration of 1:20-12.5 (58 vol.%), deep 1:10-1:8.3 (10-12 vol.%).

During the stage of surgical anesthesia, it relaxes skeletal muscles well. The narcotic latitude (range between narcotic and toxic concentrations in the blood) for ether is 50-150 mg/100 ml. Ether anesthesia develops slowly over 12-20 minutes, and is also characterized by a long elimination period - awakening is observed 20-40 minutes after stopping the supply of ether. Post-drug depression is possible for several hours. When applied topically, the ether has a drying, irritating, and moderate antimicrobial effect.

Indications: used during general anesthesia in a hospital setting during plastic surgery, operations for neoplasms of the maxillofacial area, as well as for maintaining anesthesia.

The wound surface of dentin and enamel is degreased and dried with ether before filling, fixing locking fasteners, inlays, crowns, the surface of dentures adjacent to the abutment teeth, as well as root canals before filling them, fixing artificial stumps with a pin or pin teeth.

Method of application: in surgical practice it can be used in an open, semi-open and closed system. Combined anesthesia with fluorotane and nitrous oxide is possible.

Side effect: irritates the mucous membrane of the upper respiratory tract, at the beginning of anesthesia it can cause reflex changes in breathing, up to its stop, bronchospasm, vomiting, cardiac arrhythmias. Increases the release of catecholamines into the blood. Has a toxic effect on the functions of parenchymal organs (liver, kidneys). After anesthesia using ether, bronchopneumonia may develop. Interaction with other drugs: as mentioned above, combinations with fluorotane and nitrous oxide are possible. For induction of anesthesia, it is possible to use barbiturates (hexenal, thiopental). Side effects of ether are prevented by administering anticholinergics (atropine, metacin). It should be remembered that ether vapors are explosive.

Contraindications: severe diseases of the cardiovascular system with cardiac decompensation, acute respiratory diseases, severe liver and kidney diseases, as well as acidosis and diabetes mellitus.

Release form: bottles of 100 and 150 ml.

Storage conditions: in a place protected from light. List B.

If the seal of the bottle is broken under the influence of light and air, the formation of toxic substances (peroxides, aldehydes, ketones) is possible. For anesthesia, ether is used only from bottles opened immediately before the operation.

Dentist's Guide to Medicines
Edited by Honored Scientist of the Russian Federation, Academician of the Russian Academy of Medical Sciences, Professor Yu. D. Ignatov

8. M-anticholinergic drugs.

9. Ganglion blocking agents.

11. Adrenergic agonists.

14. Means for general anesthesia. Definition. Determinants of depth, rate of development and recovery from anesthesia. Requirements for an ideal narcotic drug.

15. Means for inhalation anesthesia.

16. Means for non-inhalation anesthesia.

17. Ethyl alcohol. Acute and chronic poisoning. Treatment.

18. Sedative-hypnotics. Acute poisoning and measures of assistance.

19. General ideas about the problem of pain and pain relief. Drugs used for neuropathic pain syndromes.

20. Narcotic analgesics. Acute and chronic poisoning. Principles and remedies.

21. Non-narcotic analgesics and antipyretics.

22. Antiepileptic drugs.

23. Drugs effective for status epilepticus and other convulsive syndromes.

24. Antiparkinsonian drugs and drugs for the treatment of spasticity.

32. Means for preventing and relieving bronchospasm.

33. Expectorants and mucolytics.

34. Antitussives.

35. Drugs used for pulmonary edema.

36. Drugs used for heart failure (general characteristics) Non-glycoside cardiotonic drugs.

37. Cardiac glycosides. Intoxication with cardiac glycosides. Help measures.

38. Antiarrhythmic drugs.

39. Antianginal drugs.

40. Basic principles of drug therapy for myocardial infarction.

41. Antihypertensive sympathoplegic and vasorelaxants.

I. Drugs affecting appetite

II. Remedies for decreased gastric secretion

I. Sulfonylurea derivatives

70. Antimicrobial agents. General characteristics. Basic terms and concepts in the field of chemotherapy of infections.

71. Antiseptics and disinfectants. General characteristics. Their difference from chemotherapeutic agents.

72. Antiseptics – metal compounds, halogen-containing substances. Oxidizing agents. Dyes.

73. Antiseptics of the aliphatic, aromatic and nitrofuran series. Detergents. Acids and alkalis. Polyguanidines.

74. Basic principles of chemotherapy. Principles of classification of antibiotics.

75. Penicillins.

76. Cephalosporins.

77. Carbapenems and monobactams

78. Macrolides and azalides.

79. Tetracyclines and amphenicols.

80. Aminoglycosides.

81. Antibiotics of the lincosamide group. Fusidic acid. Oxazolidinones.

82. Antibiotics, glycopeptides and polypeptides.

83. Side effects of antibiotics.

84. Combined antibiotic therapy. Rational combinations.

85. Sulfonamide drugs.

86. Derivatives of nitrofuran, hydroxyquinoline, quinolone, fluoroquinolone, nitroimidazole.

87. Anti-tuberculosis drugs.

88. Antispirochetal and antiviral agents.

89. Antimalarial and antiamoebic drugs.

90. Medicines used for giardiasis, trichomoniasis, toxoplasmosis, leishmaniasis, pneumocystosis.

91. Antifungal agents.

I. Drugs used in the treatment of diseases caused by pathogenic fungi

II. Drugs used in the treatment of diseases caused by opportunistic fungi (for example, candidiasis)

92. Anthelmintics.

93. Anti-blastoma drugs.

94. Remedies used for scabies and pediculosis.

15. Means for inhalation anesthesia.

basic means for inhalation anesthesia.

a) liquid drugs for inhalation anesthesia: halothane (fluorothane), enflurane, isoflurane, diethyl ether(non-halogenated anesthetic)

b) gas anesthetics: nitrous oxide.

Requirements for anesthesia.

rapid induction of anesthesia without arousal stage

ensuring sufficient depth of anesthesia for the necessary manipulations

good control over the depth of anesthesia

quick recovery from anesthesia without aftereffects

sufficient narcotic breadth (the range between the concentration of the anesthetic that causes anesthesia and its minimum toxic concentration, which depresses the vital centers of the medulla oblongata)

no or minimal side effects

ease of technical use

fire safety of drugs

reasonable cost

The mechanism of the analgesic effect of anesthesia.

General mechanism: change in the physicochemical properties of membrane lipids and the permeability of ion channels → decreased influx of Na + ions into the cell while maintaining the output of K + ions, increased permeability for Cl - ions, cessation of the flow of Ca 2+ ions into the cell → hyperpolarization of cell membranes → decreased excitability of postsynaptic structures and impaired release of neurotransmitters from presynaptic structures.

Anesthetic agent

Mechanism of action

Nitrous oxide, ketamine

Blockade of NMDA receptors (glutamine) coupled to Ca 2+ channels on the neuron membrane →

a) cessation of Ca 2+ current through the presynaptic membrane → disruption of transmitter exocytosis,

b) cessation of Ca 2+ current through the postsynaptic membrane - disruption of the generation of long-term excitatory potentials

1) Blockade of H n -cholinergic receptors associated with Na + channels → disruption of Na + current into the cell → cessation of generation of spike APs

2) Activation of GABA A receptors associated with Cl - - channels → entry of Cl - into the cell → hyperpolarization of the postsynaptic membrane → decrease in neuron excitability

3) Activation of glycine receptors associated with Cl - channels → entry of Cl - into the cell → hyperpolarization of the presynaptic membrane (transmitter release decreases) and postsynaptic membrane (neuron excitability decreases).

4) Disrupts the processes of interaction between proteins responsible for the release of transmitters from the vesicles of the presynaptic terminal.

Advantages of halothane anesthesia.

high narcotic activity (5 times stronger than ether and 140 times more active than nitrous oxide)

rapid onset of anesthesia (3-5 min) with a very short stage of excitation, pronounced analgesia and muscle relaxation

easily absorbed in the respiratory tract without causing irritation of mucous membranes

inhibits the secretion of glands of the respiratory tract, relaxes the respiratory muscles of the bronchi (the drug of choice for patients with bronchial asthma), facilitating mechanical ventilation

does not cause gas exchange disturbances

does not cause acidosis

does not affect kidney function

quickly excreted from the lungs (up to 85% unchanged)

Halothane anesthesia is easily manageable

large narcotic latitude

fire safe

decomposes slowly in air

Advantages of ether anesthesia.

pronounced narcotic activity

anesthesia when using ether is relatively safe and easy to manage

pronounced muscle relaxation of skeletal muscles

does not increase myocardial sensitivity to adrenaline and norepinephrine

sufficient narcotic breadth

relatively low toxicity

Advantages of anesthesia induced by nitrous oxide.

does not cause side effects during the operation

does not have irritating properties

does not have a negative effect on parenchymal organs

causes anesthesia without preliminary stimulation and side effects

fire safe (non-flammable)

excreted almost invariably through the respiratory tract

quick recovery from anesthesia without aftereffects

Interaction between adrenaline and halothane.

Halothane activates the allosteric center of myocardial β-adrenergic receptors and increases their sensitivity to catecholamines. Administration of adrenaline or norepinephrine against the background of halothane to increase blood pressure can lead to the development of ventricular fibrillation, therefore, if it is necessary to maintain blood pressure during halothane anesthesia, phenylephrine or methoxamine should be used.

Interaction between adrenaline and ethyl ether.

Does not increase the sensitivity of the myocardium to the arrhythmogenic effect of catecholamines.

Disadvantages of halothane anesthesia.

bradycardia (as a result of increased vagal tone)

hypotensive effect (as a result of inhibition of the vasomotor center and direct myotropic effect on blood vessels)

arrhythmogenic effect (as a result of a direct effect on the myocardium and its sensitization to catecholamines)

hepatotoxic effect (as a result of the formation of a number of toxic metabolites, therefore re-use no earlier than 6 months after the first inhalation)

increased bleeding (as a result of suppression of the sympathetic ganglia and dilatation of peripheral vessels)

pain after anesthesia, chills (as a result of rapid recovery from anesthesia)

increases blood flow to the vessels of the brain and increases intracranial pressure (cannot be used during operations in persons with TBI)

inhibits the contractile activity of the myocardium (as a result of disruption of the process of calcium ions entering the myocardium)

depresses the respiratory center and can cause respiratory arrest

Disadvantages of ether anesthesia.

ether vapors are highly flammable and form explosive mixtures with oxygen, nitrous oxide, etc.

causes irritation of the mucous membranes of the respiratory tract  reflex change in breathing and laryngospasm, significant increase in salivation and secretion of the bronchial glands, bronchopneumonia

a sharp increase in blood pressure, tachycardia, hyperglycemia (as a result of an increase in the content of adrenaline and norepinephrine, especially during periods of excitement)

vomiting and respiratory depression in the postoperative period

prolonged stage of excitement

slow onset of anesthesia and slow recovery from it

convulsions are observed (rarely and mainly in children)

depression of liver and kidney function

development of acidosis

development of jaundice

Disadvantages of nitrous oxide anesthesia.

low narcotic activity (can only be used for induction of anesthesia in combination with other NS and to provide superficial anesthesia)

nausea and vomiting in the postoperative period

neutropenia, anemia (as a result of oxidation of the cobalt atom in the composition of cyanocobalamin)

diffusion hypoxia after cessation of nitrous oxide inhalation (nitrous oxide, poorly soluble in the blood, begins to be intensively released from the blood into the alveoli and displaces oxygen from them)

flatulence, headache, pain and congestion in the ears

Halothane (fluorothane), isoflurane, sevoflurane, dinitrogen, nitric oxide (nitrous oxide).

PHTOROTHANUM (Phthorothanum). 1, 1, 1-Trifluoro-2-chloro-2-bromoethane.

Synonyms: Anestan, Fluctan, Fluothne, Ftorotan, Halan, Halothane, Halothanum, Narcotan, Rhodialotan, Somnothane.

Ftorotan does not burn or ignite. Its vapors, when mixed with oxygen and nitrous oxide in the ratios used for anesthesia, are explosion-proof, which is a valuable property when used in a modern operating room.

Fluorotane slowly decomposes under the influence of light, so it is stored in orange glass bottles; thymol (O, O1%) is added for stabilization.

Ftorotan is a powerful narcotic, which allows it to be used independently (with oxygen or air) to achieve the surgical stage of anesthesia or as a component of combined anesthesia in combination with other narcotics, mainly with nitrous oxide.

Pharmacokinetically, fluorotane is easily absorbed from the respiratory tract and rapidly excreted unchanged by the lungs; Only a small part of fluorotane is metabolized in the body. The drug has a rapid narcotic effect, stopping soon after the end of inhalation.

When using fluorotane, consciousness usually turns off 1-2 minutes after the start of inhaling its vapors. After 3-5 minutes, the surgical stage of anesthesia begins. 3 - 5 minutes after stopping the supply of fluorotane, patients begin to awaken. Anesthesia depression completely disappears 5 - 10 minutes after short-term and 30 - 40 minutes after long-term anesthesia. Excitement is rare and weakly expressed.

Ftorotan vapors do not cause irritation of mucous membranes. There are no significant changes in gas exchange during anesthesia with fluorotane; blood pressure usually decreases, which is partly due to the inhibitory effect of the drug on the sympathetic ganglia and the expansion of peripheral vessels. The tone of the vagus nerve remains high, which creates conditions for bradycardia. To some extent, fluorotane has a depressing effect on the myocardium. In addition, fluorotane increases the sensitivity of the myocardium to catecholamines: the administration of adrenaline and norepinephrine during anesthesia can cause ventricular fibrillation.

Ftorotan does not affect kidney function; in some cases, liver function disorders with the appearance of jaundice are possible.

Under fluorotane anesthesia, various surgical interventions can be performed, including on the abdominal and thoracic cavities, in children and the elderly. Non-flammability makes it possible to use it when using electrical and X-ray equipment during surgery.

Ftorotan is convenient for use during operations on the organs of the chest cavity, since it does not cause irritation of the mucous membranes of the respiratory tract, inhibits secretion, relaxes the respiratory muscles, which facilitates artificial ventilation. Fluorothane anesthesia can be used in patients with bronchial asthma. The use of fluorotan is especially indicated in cases where it is necessary to avoid agitation and tension of the patient (neurosurgery, ophthalmic surgery, etc.).

Fluorothane is part of the so-called azeotron mixture, consisting of two volume parts of fluorothane and one volume part of ether. This mixture has a stronger narcotic effect than ether, and less strong than fluorotane. Anesthesia occurs more slowly than with fluorotane, but faster than with ether.

During anesthesia with fluorotane, the supply of its vapor should be accurately and smoothly adjusted. It is necessary to take into account the rapid change of stages of anesthesia. Therefore, fluorotane anesthesia is carried out using special evaporators located outside the circulation system. The oxygen concentration in the inhaled mixture must be at least 50%. For short-term operations, fluorotan is sometimes also used with a regular anesthesia mask.

To avoid side effects associated with stimulation of the vagus nerve (bradycardia, arrhythmia), the patient is administered atropine or metacin before anesthesia. For premedication, it is preferable to use promedol rather than morphine, which stimulates the centers of the vagus nerve less.

If it is necessary to enhance muscle relaxation, it is preferable to prescribe relaxants of a depolarizing type of action (ditilin); when using drugs of a non-depolarizing (competitive) type, the dose of the latter is reduced compared to the usual one.

During anesthesia with fluorotane, due to inhibition of the sympathetic ganglia and dilation of peripheral vessels, increased bleeding is possible, which requires careful hemostasis and, if necessary, compensation for blood loss.

Due to the rapid awakening after cessation of anesthesia, patients may feel pain, so early use of analgesics is necessary. Sometimes chills are observed in the postoperative period (due to vasodilation and heat loss during surgery). In these cases, patients need to be warmed with heating pads. Nausea and vomiting usually do not occur, but the possibility of their occurrence should be considered in connection with the administration of analgesics (morphine).

Anesthesia with fluorotane should not be used in case of pheochromocytoma and in other cases when the level of adrenaline in the blood is increased, with severe hyperthyroidism. It should be used with caution in patients with cardiac arrhythmias, hypotension, and organic liver damage. During gynecological operations, it should be taken into account that fluorotane can cause a decrease in the tone of the uterine muscles and increased bleeding. The use of fluorotan in obstetrics and gynecology practice should be limited only to those cases where relaxation of the uterus is indicated. Under the influence of fluorotane, the sensitivity of the uterus to drugs that cause its contraction (ergot alkaloids, oxytocin) decreases.

During anesthesia with fluorotane, adrenaline and norepinephrine should not be used to avoid arrhythmias.

It should be taken into account that persons working with fluorotane may develop allergic reactions.

NITROGEN OXIDE (Nitrogenium oxidulatum).

Synonyms: Dinitrogen oxide, Nitrous oxide, Oxydum nitrosum, Protoxide d'Azote, Stickoxydal.

Small concentrations of nitrous oxide cause a feeling of intoxication (hence the name<веселящий газ>) and slight drowsiness. When pure gas is inhaled, a narcotic state and asphyxia quickly develop. When mixed with oxygen, when dosed correctly, it causes anesthesia without preliminary stimulation or side effects. Nitrous oxide has weak narcotic activity, and therefore it must be used in high concentrations. In most cases, combined anesthesia is used, in which nitrous oxide is combined with other, more powerful anesthetics and muscle relaxants.

Nitrous oxide does not cause respiratory irritation. In the body it remains almost unchanged and does not bind to hemoglobin; is in a dissolved state in plasma. After cessation of inhalation, it is excreted (completely after 10 - 15 minutes) through the respiratory tract unchanged.

Anesthesia using nitrous oxide is used in surgical practice, operative gynecology, surgical dentistry, and also for pain relief during childbirth.<Лечебный аналгетический наркоз>(B.V. Petrovsky, S.N. Efuni) using a mixture of nitrous oxide and oxygen is sometimes used in the postoperative period to prevent traumatic shock, as well as to relieve pain attacks in acute coronary insufficiency, myocardial infarction, acute pancreatitis and other pathological conditions accompanied by pain that cannot be relieved by conventional means.

To more completely relax the muscles, muscle relaxants are used, which not only enhances muscle relaxation, but also improves the course of anesthesia.

After stopping the supply of nitrous oxide, oxygen should be continued for 4 to 5 minutes to avoid hypoxia.

Nitrous oxide should be used with caution in cases of severe hypoxia and impaired diffusion of gases in the lungs.

To relieve labor pain, they use the method of intermittent autoanalgesia using a mixture of nitrous oxide (40 - 75%) and oxygen using special anesthesia machines. The woman in labor begins to inhale the mixture when signs of contraction appear and ends inhalation at the height of the contraction or towards its end.

To reduce emotional arousal, prevent nausea and vomiting and potentiate the effect of nitrous oxide, premedication with intramuscular injection of a 0.5% solution of diazepam (seduxen, sibazon) is possible.

Therapeutic anesthesia with nitrous oxide (for angina pectoris and myocardial infarction) is contraindicated in severe diseases of the nervous system, chronic alcoholism, and alcohol intoxication (excitement and hallucinations are possible).

Drugs for inhalation anesthesia pharmacology

Inhalation agents are widely used in pediatric anesthesiology. The occurrence of anesthesia when using them depends on the value of the partial volumetric content of the anesthetic agent in the inhaled mixture: the higher it is, the sooner anesthesia occurs, and vice versa. The speed of onset of anesthesia and its depth depend to a certain extent on the solubility of substances in lipids: the larger they are, the faster anesthesia develops.

In young children, inhalation agents should be used very carefully. They, especially in the first months of life, have more tissue hemoperfusion than older children and adults. Therefore, in young children, a substance administered by inhalation is more likely to enter the brain and, within a few seconds, can cause profound depression of its function, even to the point of paralysis.

Comparative characteristics of drugs for inhalation anesthesia

Ether for anesthesia (ethyl or diethyl ether) is a colorless, volatile, flammable liquid with a boiling point of +34-35 ° C, forming explosive mixtures with oxygen, air, and nitrous oxide.

The positive properties of diethyl ether are its great therapeutic (narcotic) breadth and ease of control of the depth of anesthesia.

The negative properties of diethyl ether include: explosiveness, pungent odor, slow development of anesthesia with a long second stage. Introductory or basic anesthesia allows you to avoid the second stage. A strong irritant effect on the receptors of the mucous membranes leads to the occurrence of reflex complications during this period: bradycardia, respiratory arrest, vomiting, laryngospasm, etc. Cooling of the lung tissue as a result of evaporation of ether from its surface and the development of infection in the abundantly secreted mucus contribute to the occurrence of pneumonia and bronchopneumonia in postoperative period. The risk of these complications is especially great in young children. Sometimes in children whose anesthesia was induced by ether, a decrease in the content of albumin and γ-globulins in the blood is noted.

The ester increases the release of catecholamines from the adrenal medulla and presynaptic endings of sympathetic fibers. This may result in hyperglycemia (undesirable in children with diabetes), relaxation of the lower esophageal sphincter, which facilitates regurgitation (passive flow of stomach contents into the esophagus) and aspiration.

Ether should not be used in dehydrated children (especially under the age of 1 year), since after the end of anesthesia they may experience dangerous hyperthermia and convulsions, often (in 25%) ending in death.

All this limits the use of ether in children under 3 years of age. At older ages, it is still sometimes used.

Means for inhalation anesthesia advantages and disadvantages

Ftorotan (halothane, fluotane, narcotan) is a colorless liquid with a sweet and pungent taste, its boiling point is +49-51 ° C. It does not burn or explode. Ftorotan is characterized by high solubility in lipids, so it is quickly absorbed from the respiratory tract and anesthesia occurs very quickly, especially in young children. It is quickly eliminated from the body unchanged by the respiratory tract. However, approximately a quarter of the fluorotane that enters the body undergoes biotransformation in the liver. A metabolite, fluoroethanol, is formed from it, which binds firmly to the components of cell membranes, nucleic acids of various tissues - liver, kidneys, fetal tissues, germ cells. This metabolite lingers in the body for about a week. With a single exposure to the body, there are usually no serious consequences, although cases of toxic hepatitis have been reported. When at least traces of fluorotane enter the human body again (from employees of anesthesiology departments), this metabolite accumulates in the body. There is information about the occurrence of mutagenic, carcinogenic and teratogenic effects of ftorotane in connection with this.

Ftorotan has N-cholinolytic and α-adrenolytic properties, but does not reduce and even increases the activity of B-adrenergic receptors. As a result, peripheral vascular resistance and blood pressure decrease, which is facilitated by the depression of myocardial function it causes (as a result of inhibition of glucose utilization). This is used to reduce blood loss during surgery. However, in young children, especially those who are dehydrated, it can cause a sudden drop in blood pressure.

Ftorotan relaxes the smooth muscles of the bronchi, which is sometimes used to eliminate intractable asthmatic conditions in children.

Against the background of hypoxia and acidosis, when the release of catecholamines from the adrenal glands increases, fluorotane can contribute to the occurrence of cardiac arrhythmias in children.

Ftorotan relaxes skeletal muscles (the result of an anticholinergic effect), which, on the one hand, facilitates operations, and, on the other hand, due to the weakness of the respiratory muscles, it reduces the volume of ventilation of the lungs, often not exceeding the volume of the “dead” space of the respiratory tract. Therefore, during fluorotane anesthesia, as a rule, the trachea is intubated and the child is transferred to controlled or assisted breathing.

Fluorothane is used with the help of special evaporators, both independently and in the form of a so-called azeotropic mixture (2 parts by volume of fluorothane and 1 volume part of ether). It is rational to combine it with nitrous oxide, which makes it possible to reduce both its concentration in the inhaled mixture from 1.5 to 1-0.5 vol.%, and the risk of undesirable effects.

Fluorotane is contraindicated in children with liver diseases and in the presence of severe cardiovascular pathology.

Flammable inhalation anesthetic

Cyclopropane is a colorless flammable gas with a characteristic odor and pungent taste (under a pressure of 5 atm and a temperature of + 20°C it turns into a liquid state). It dissolves poorly in water and well in fats and lipids. Therefore, cyclopropane is quickly absorbed from the respiratory tract, anesthesia occurs within 2-3 minutes, without the stage of excitation. It has a sufficient range of narcotic effects.

Cyclopropane is considered a flammable inhalation anesthetic. Cyclopropane is used using special equipment and with extreme caution due to the extreme flammability and explosiveness of its combinations with oxygen, air and nitrous oxide. It does not irritate lung tissue, is exhaled unchanged, and with the correct dosage has little effect on the function of the cardiovascular system, but increases the sensitivity of the myocardium to adrenaline. In addition, it increases the release of catecholamines from the adrenal glands. Therefore, when using it, cardiac arrhythmias often occur. Due to the rather pronounced cholinomimetic effect of cyclopropane (manifested in bradycardia, increased secretion of saliva, mucus in the bronchi), atropine is usually used for premedication.

Cyclopropane is considered the drug of choice for traumatic shock and blood loss. It is used for introductory and basic anesthesia, preferably in combination with nitrous oxide or ether. Liver diseases and diabetes are not contraindications to its use.

Classification of drugs for inhalation anesthesia

Nitrous oxide (N20) is a colorless gas, heavier than air (at a pressure of 40 atm it condenses into a colorless liquid). It is not flammable, but supports combustion and therefore forms explosive mixtures with ether and cyclopropane.

Nitrous oxide is widely used in anesthesia in adults and children. To induce anesthesia, a mixture of 80% nitrous oxide with 20% oxygen is created. Anesthesia occurs quickly (the high concentration of nitrous oxide in the inhaled gas mixture is important), but it is shallow, the skeletal muscles are not relaxed enough, and the surgeon’s manipulations cause a reaction to pain. Therefore, nitrous oxide is combined with muscle relaxants or other anesthetics (fluorotane, cyclopropane). In lower concentrations (50%) in the inhaled gas mixture, nitrous oxide is used as an analgesic (for reduction of dislocations, painful short-term procedures, incisions of phlegmons, etc.).

In small concentrations, nitrous oxide causes a feeling of intoxication, which is why it is called laughing gas.

Nitrous oxide has low toxicity, but when the oxygen content in the gas mixture is less than 20%, the patient experiences hypoxia (signs of which may include rigidity of skeletal muscles, dilated pupils, convulsions, drop in blood pressure), severe forms of which lead to the death of the cerebral cortex. Therefore, only an experienced anesthesiologist who knows how to use the appropriate equipment (NAPP-2) can use nitrous oxide.

Nitrous oxide is 37 times more soluble in blood plasma than nitrogen, and is capable of displacing it from gas mixtures, thereby increasing their volume. As a result, the volume of gases in the intestines, in the cavities of the inner ear (protrusion of the eardrum), in the maxillary (maxillary) and other cavities of the skull associated with the respiratory tract may increase. At the end of inhalation of the drug, nitrous oxide displaces nitrogen from the alveoli, almost completely filling their volume. This interferes with gas exchange and leads to severe hypoxia. To prevent it, after stopping inhaling nitrous oxide, it is necessary to give the patient 3-5 minutes to breathe 100% oxygen.

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State budgetary educational institution

Higher professional education

"Bashkir State Medical University" of the Ministry of Health of the Russian Federation

Medical College

I APPROVED

Deputy director for sustainable development

T.Z. Galeyshina

"___"___________ 20____

METHODOLOGICAL DEVELOPMENT of a lecture on the topic: “Drugs affecting the central nervous system

Discipline "Pharmacology"

Specialty 02/34/01. Nursing

Semester: I

Number of hours 2 hours

Ufa 20____

Topic: “Drugs affecting the central nervous system

(general anesthetics, hypnotics, analgesics)"

based on the work program of the academic discipline “Pharmacology”

approved "_____"_______20____

Reviewers for the presented lecture:

Approved at a meeting of the educational and methodological council of the college on “______”________20____.

1. Topic: “Drugs affecting the central nervous system

(general anesthetics, hypnotics, analgesics)"

2. Course: 1st semester: I

3. Duration: combined lesson 2 hours

4. Audience population – students

5. Educational goal: to consolidate and test knowledge on the topic: “Drugs affecting the efferent nervous system (adrenergic drugs)”, to acquire knowledge on a new topic: “Drugs affecting the central nervous system

(general anesthetics, hypnotics, analgesics)"

6. Illustrative material and equipment (multimedia projector, laptop, presentation, test tasks, information block).

7. The student must know:

· Means for inhalation anesthesia (ether for anesthesia, fluorotane, nitrous oxide).

· History of the discovery of anesthesia. Stages of anesthesia. Features of the action of individual drugs. Application. Complication of anesthesia.

· Drugs for non-inhalation anesthesia (sodium thiopental, propanide, sodium hydroxybutyrate, ketamine). Difference between non-inhalation anesthetics and inhalation drugs. Routes of administration, activity, duration of action of individual drugs. Application in medical practice. Possible complications.

· Ethanol (ethyl alcohol) Effect on the central nervous system. Effect on the functions of the digestive tract. Effect on skin, mucous membranes. Antimicrobial properties. Indications for use.

· Sleeping pills

Barbiturates (phenobarbital, etaminal - sodium, nitrazepam);

Benzadiazepines (temazepam, triazolam, oxazolam, lorazepam)

Cyclopyrrolones (zopiclone)

Phenothiazines (diprazine, promethazine)

· Hypnotics, principle of action. Effect on sleep structure. Application. Side effects. Possibility of developing drug dependence.

· Analgesics:

Narcotic analgesics – opium preparations (morphine hydrochloride omnopon, codeine). Synthetic narcotic analgesics (promedol, fentanyl, pentosacin, tramadol) their pharmacological effects, indications for use, side effects.

Non-narcotic analgesics, non-steroidal anti-inflammatory drugs (metamizole sodium (analgin), amidopyrine, acetylsalicylic acid). Mechanism of analgesic action. Anti-inflammatory and antipyretic properties. Application. Side effects.

Competencies being developed: studying the topic contributes to the formation

OK 1. Understand the essence and social significance of your future profession, show sustained interest in it.

OK 7. Take responsibility for the work of team members (subordinates) and for the results of completing tasks.

OK 8. Independently determine the tasks of professional and personal development, engage in self-education, consciously plan and carry out advanced training.

PC 2.1. Present information in a form understandable to the patient, explain to him the essence of the interventions.

PC 2.2. Carry out therapeutic and diagnostic interventions, interacting with participants in the treatment process.

PC 2.3. Cooperate with interacting organizations and services.

PC 2.4. Use medications in accordance with

with the rules for their use.

PC 2.6. Maintain approved medical records.

CHRONOCARD OF A COMBINED LESSON on the topic: “Drugs acting on the central nervous system (general anesthetics, hypnotics, analgesics)”

No.	Contents and structure of the lesson	Time (min.)	Teacher's activities	Student activity	Methodological justification
1.	Organizing time		-greeting students -checking the audience’s readiness for the lesson -marking those who are absent	-greeting from the teacher -report from the duty officer about absent students	-implementation of a psychological attitude towards educational activities, instilling organization, discipline, and a business approach; -activating the attention of students
2.	Determining the objectives of the lesson		- finalizing the lesson plan	-think through the stages of educational activities	-creating a holistic idea of the lesson -concentrating attention on the work ahead -creating interest and understanding the motivation for learning activities.
3.	Monitoring and correction of knowledge on the previous topic: “Drugs acting on efferent innervation (adrenergic drugs)”		- frontal survey - CMM solution for current monitoring	- answer questions on the previous topic - demonstrate the level of independent preparation for the lesson - collectively correct gaps in knowledge	- determination of the level of students’ independent preparation for the lesson, completeness of homework completion - correction of gaps in knowledge - development of self- and mutual control
4.	Motivation of the topic		-emphasizes the relevance of the topic	- write down the topic in a notebook	-formation of cognitive interests, concentration on the topic being studied
5.	Lecture-conversation with elements of interactivity		-provides awareness of the formation of knowledge on the topic	taking notes on a topic in a notebook	-formation of knowledge on the topic “Drugs affecting the blood system”
6.	Summing up the lesson, consolidating the material		-reflects the main issues of the topic; -with the help of students, analyzes the achievement of lesson goals;	- determine the level of mastery of the material and achievement of lesson goals	-development of analytical activity -formation of self-control and mutual control
7.	Homework, assignment for independent work		- suggests writing down your homework: prepare the topic “Drugs acting on the central nervous system (general anesthetics, hypnotics, analgesics)” for the next theoretical lesson.	- write down homework	-stimulating students’ cognitive activity and interest in mastering educational material

All medicinal substances acting on the central nervous system can be divided into two groups:

1. oppressive functions of the central nervous system (anesthetics, hypnotics, anticonvulsants, narcotic analgesics, some psychotropic drugs (neuroleptics, tranquilizers, sedatives);

2. exciting functions of the central nervous system (analeptics, psychostimulants, general tonics, nootropics).

Anesthetics

Anesthesia is a reversible depression of the central nervous system, which is accompanied by loss of consciousness, absence of all types of sensitivity, inhibition of spinal reflexes and relaxation of skeletal muscles while maintaining the function of the respiratory and vasomotor centers.

The official date of the discovery of anesthesia is considered to be 1846, when the American dentist William Morton used ether to anesthetize a tooth extraction operation.

In the action of ethyl ether, they release 4 stages:

I - stage of analgesia is characterized by a decrease in pain sensitivity and gradual depression of consciousness. RR, pulse and blood pressure were not changed.

II - stage of excitation, the cause of which is the switching off of the inhibitory influences of the cerebral cortex on the subcortical centers. A “subcortical riot” occurs. Consciousness is lost, speech and motor excitation develops. Breathing is irregular, tachycardia is noted, blood pressure is elevated, pupils are dilated, cough and gag reflexes are strengthened, and vomiting may occur. Spinal reflexes and muscle tone are increased.

III - stage of surgical anesthesia. Characterized by suppression of the function of the cerebral cortex, subcortical centers and spinal cord. The vital centers of the medulla oblongata - respiratory and vasomotor - continue to function. Breathing normalizes, blood pressure stabilizes, muscle tone decreases, reflexes are inhibited. The pupils are constricted.

There are 4 levels at this stage:

III 1 - superficial anesthesia;

III 2 - light anesthesia;

III 3 - deep anesthesia;

III 4 - ultra-deep anesthesia.

IV - recovery stage. Occurs when the drug is stopped. Gradually, the functions of the central nervous system are restored in the reverse order of their appearance. With an overdose of anesthesia, an agonal stage develops due to inhibition of the respiratory and vasomotor centers.

Requirements for anesthesia:

rapid onset of anesthesia without pronounced agitation

sufficient depth of anesthesia to allow the operation to be performed under optimal conditions

good control over the depth of anesthesia

quick and without consequences recovery from anesthesia

sufficient narcotic breadth - the range between the concentration of a substance that causes the stage of deep surgical anesthesia and the minimum toxic concentration that causes respiratory arrest due to depression of the respiratory center

do not cause tissue irritation at the injection site

· minimal side effects

· must not be explosive.

Means for inhalation anesthesia

Volatile liquids

Diethyl ether, Halothane (Ftorothan), enflurane (Ethran), isoflurane (Foran), sevoflurane.

Gaseous substances

Nitrous oxide

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