What is the placental barrier? Transfer of antibiotics through the placental barrier.

From the very beginning of pregnancy and up to its end, it is formed and functions mother-placenta-fetus system. The most important component of this system is placenta, which is a complex body, in the formation of which derivatives take part trophoblast and embryoblast, and decidual tissue. The function of the placenta is primarily aimed at providing sufficient conditions for the physiological course of pregnancy and the normal development of the fetus. These functions include: respiratory, nutritional, excretory, protective, endocrine. All metabolic, hormonal, immune processes during pregnancy are provided through vascular system of mother and fetus. Despite the fact that the blood of the mother and fetus does not mix, as their separates the placental barrier, all the necessary nutrients and oxygen the fetus receives from the mother's blood. The main structural component of the placenta is hairy tree .

At normal development pregnancy there is a relationship between the growth of the fetus, its body weight and the size, thickness, weight of the placenta. Up to 16 weeks of pregnancy, the development of the placenta outstrips the growth rate of the fetus. In case of death embryo (fetus) inhibition of growth and development chorionic villus and progression of involution-dystrophic processes in the placenta. Having reached the required maturity at 38-40 weeks of pregnancy, the processes of formation of new vessels and villi in the placenta stop.

The mature placenta is a disc-shaped structure with a diameter of 15-20 cm and a thickness of 2.5-3.5 cm. Its mass reaches 500-600 g. Maternal surface of the placenta, which faces the wall of the uterus, has a rough surface formed by the structures of the basal part of the decidua. Fruit surface of the placenta, which faces the fetus, is covered amniotic membrane. Under it are visible vessels that go from the place of attachment of the umbilical cord to the edge of the placenta. The structure of the fetal part of the placenta is represented by numerous chorionic villi, which are combined into structural formations - cotyledons. Each cotyledon is formed by a stem villus with branches containing fetal vessels. The central part of the cotyledon forms a cavity, which is surrounded by many villi. In a mature placenta, there are 30 to 50 cotyledons. Cotyledon of the placenta is conditionally comparable to a tree, in which the supporting villi of the 1st order are its trunk, the villi of the 2nd and 3rd orders are large and small branches, the intermediate villi are small branches, and the terminal villi are leaves. Cotyledons are separated from each other by partitions (septa) emanating from the basal plate.

Intervillous space on the fetal side, it is formed by the chorionic plate and villi attached to it, and on the maternal side, it is limited by the basal plate, the decidua, and septa extending from it. Most of the placental villi are freely immersed in the intervillous space and bathed in mother's blood. There are also anchor villi, which are fixed to the basal decidua and provide attachment of the placenta to the wall of the uterus.

spiral arteries, which are the terminal branches of the uterine and ovarian arteries, nourishing the pregnant uterus, open into the intervillous space with 120-150 mouths, providing a constant flow of oxygen-rich maternal blood into the intervillous space. Due pressure difference, which is higher in the maternal arterial bed compared to the intervillous space, oxygenated blood, from the mouths of the spiral arteries goes through the center of the cotyledon to the villi, washes them, reaches the chorionic plate and by separating septa returns to the maternal circulation through the veins. In this case, the blood flow of the mother and fetus are separated from each other. Those. maternal and fetal blood does not mix between themselves.

Passage of blood gases, nutrients, metabolic products and other substances from maternal to fetal blood and vice versa is carried out at the moment of contact of the villi with the mother's blood across the placental barrier. It is formed by the outer epithelial layer of the villus, the stroma of the villus, and the wall of the blood capillary located inside each villus. Fetal blood flows through this capillary. Saturated in this way with oxygen, the blood of the fetus from the capillaries of the villi is collected into larger vessels, which are eventually combined into vein of the umbilical cord, according to which oxygenated blood flows to the fetus. Having given up oxygen and nutrients in the body of the fetus, blood, depleted in oxygen and rich in carbon dioxide, flows from the fetus through two arteries of the umbilical cord to the placenta, where these vessels divide radially according to the number of cotyledons. As a result of further branching of the vessels inside the cotyledons, the fetal blood again enters the capillaries of the villi and is again saturated with oxygen, and the cycle repeats. Due to the passage through the placental barrier of blood gases and nutrients, the respiratory, nutritional and excretory functions of the placenta are realized. In this case, oxygen enters the bloodstream of the fetus and carbon dioxide and other products of fetal metabolism are removed. At the same time, proteins, lipids, carbohydrates, microelements, vitamins, enzymes and much more are transported towards the fetus.

The placenta performs an important protective (barrier function) through the placental barrier, which has a selective permeability in two directions. In the normal course of pregnancy, the permeability of the placental barrier increases up to 32-34 weeks of pregnancy, after which it decreases in a certain way. However, unfortunately, a fairly large number of drugs, nicotine, alcohol, narcotic substances, pesticides, other toxic chemicals, as well as a number of pathogens penetrate the placental barrier relatively easily into the fetal circulation. infectious diseases which has an adverse effect on the fetus. In addition, under the influence of pathogenic factors, the barrier function of the placenta is even more disturbed.

The placenta is anatomically and functionally related to amnion (aqueous shell) that surrounds the fetus. The amnion is a thin membrane, which lines the surface of the placenta facing the fetus, passes to umbilical cord and merges with the skin of the fetus in the umbilical ring. Amnion is actively involved in the exchange amniotic fluid, in a number of metabolic processes, and also performs a protective function.

connects placenta and fetus umbilical cord, which is a cord-like formation. Umbilical cord contains two arteries and one vein. Two arteries in the umbilical cord carry oxygen-depleted blood from the fetus to the placenta. The vein of the umbilical cord carries oxygenated blood to the fetus. The vessels of the umbilical cord are surrounded by a gelatinous substance, which is called "Wharton's jelly". This substance provides the elasticity of the umbilical cord, protects the vessels and provides nutrition to the vascular wall. The umbilical cord may attach (most often) to the center of the placenta and less commonly to the side of the umbilical cord or to the membranes. The length of the umbilical cord during a full-term pregnancy is on average about 50 cm.

Placenta, fetal membranes and umbilical cord together form afterbirth, which is expelled from the uterus after the baby is born.

The placenta connects the fetus with the mother's body and consists of the fetal (villous chorion) and maternal (decidua) parts (Fig. 20-4 and 20-5). In the placenta, the chorionic villi containing the blood capillaries of the fetus are washed by the blood of the pregnant woman circulating in the intervillous space. The blood of the fetus and the blood of the pregnant woman are separated by the placental barrier - the trophoblast, the stroma of the villi and the endothelium of the fetal capillaries. The transfer of substances across the placental barrier is carried out by passive diffusion (oxygen, carbon dioxide, electrolytes, monosaccharides), active transport (iron, vitamin C) or facilitated diffusion mediated by carriers (glucose, Ig).

Rice. 20–5 . Decidual shell uterus And placenta. The uterine cavity is lined by the parietal part of the decidua. The decidua facing the villous chorion is part of the placenta.

Blood flow in the placenta

Umbilical cord, or umbilical cord (Fig. 20-3, 20-4) - a cord-like formation containing two umbilical arteries and one umbilical vein that carry blood from the fetus to the placenta and back. The umbilical arteries carry venous blood from the fetus to the chorionic villi in the placenta. Through the vein, arterial blood flows to the fetus, enriched with oxygen in the blood capillaries of the villi. The total volumetric blood flow through the umbilical cord is 125 ml/kg/min (500 ml/min).

Arterial blood pregnant it is injected directly into the intervillous space (lacunae, see Fig. 20-3 and 20-4) under pressure and shocks from about a hundred spiral arteries located perpendicular to the placenta. The lacunae of a fully formed placenta contain about 150 ml of washing villi of maternal blood, completely replaced 3-4 times per minute. From the intervillous space, venous blood flows through venous vessels located parallel to the placenta.

Placental barrier. The placental barrier (maternal blood  fetal blood) includes: syncytiotrophoblast  cytotrophoblast  trophoblast basement membrane  connective tissue of the villus  basement membrane in the wall of the villus capillaries  endothelium of the villus capillaries. It is through these structures that the exchange between the blood of the pregnant woman and the blood of the fetus takes place. It is these structures that implement the protective (including immune) function of the fetus.

Functions of the placenta

The placenta performs many functions, including the transport of nutrients and oxygen from the pregnant woman to the fetus, the removal of fetal waste products, the synthesis of proteins and hormones, and the immunological protection of the fetus.

Transport function

 Transfer oxygen And dioxide carbon occurs by passive diffusion.

 O 2 . The partial pressure of oxygen (Po 2 ) of the arterial blood of the spiral arterioles at pH 7.4 is 100 mm Hg with an oxygen saturation of Hb of 97.5%. At the same time, Po 2 blood in the venous part of the fetal capillaries is 23 mm Hg. at 60% saturation of Hb with oxygen. Although the Po 2 of maternal blood rapidly decreases to 30–35 mm Hg as a result of oxygen diffusion, even this difference of 10 mm Hg enough to provide an adequate supply of oxygen to the fetus. Additional factors contribute to the efficient diffusion of oxygen from mother to fetus.

 The fetal Hb has a greater affinity for oxygen than the definitive Hb of the pregnant woman (the HbF dissociation curve is shifted to the left). At the same Po2, fetal Hb binds 20–50% more oxygen than maternal Hb.

 The concentration of Hb in the blood of the fetus is higher (this increases the oxygen capacity) than in the blood of the mother. Thus, despite the fact that fetal oxygen saturation rarely exceeds 80%, fetal tissue hypoxia does not occur.

The pH of fetal blood is lower than the pH of adult whole blood. With an increase in the concentration of hydrogen ions, the affinity of oxygen for Hb decreases (the effect Bor a), so oxygen is more easily transferred from the mother's blood to the tissues of the fetus.

 CO 2 diffuses through the structures of the placental barrier in the direction of the concentration gradient (approximately 5 mm Hg) between the blood of the umbilical arteries (48 mm Hg) and the blood of lacunae (43 mm Hg). In addition, fetal Hb has a lower affinity for CO 2 than maternal definitive Hb.

 Urea, creatinine, steroid hormones, fatty acids, bilirubin. Their transfer occurs by simple diffusion, but the placenta is poorly permeable to bilirubin glucuronides formed in the liver.

 Glucose- facilitated diffusion.

 Amino acids And vitamins- active transport.

 Squirrels(e.g. transferrin, hormones, some Ig classes), peptides, lipoproteins receptor-mediated endocytosis.

 electrolytes- Na + , K + , Cl - , Ca 2+ , phosphate - cross the barrier by diffusion and active transport.

Immunological protection

 Maternal antibodies of the IgG class transported through the placental barrier provide passive immunity to the fetus.

 The body of a pregnant woman does not reject an immunologically alien fetus due to local inhibition of the woman's cellular immunity reactions and the absence of glycoproteins of the major histocompatibility complex (HLA) in chorion cells.

 Chorion synthesizes substances that inhibit the cellular immune response (an extract from syncytiotrophoblast inhibits in vitro reproduction of cells of the immune system of the pregnant woman).

 Trophoblast cells do not express HLA Ag, which provides protection of the fetoplacental complex from recognition by immunocompetent cells of the pregnant woman. That is why the areas of trophoblast split off from the placenta, getting into the lungs of a woman, are not rejected. At the same time, other types of cells in the villi of the placenta carry HLA Ag on their surface. The trophoblast also does not contain erythrocyte Ag systems AB0 and Rh.

Detoxification some LS.

Endocrine function. The placenta is an endocrine organ. The placenta synthesizes many hormones and other biologically active substances that are important for the normal course of pregnancy and fetal development (CHT, progesterone, chorionic somatomammotropin, fibroblast growth factor, transferrin, prolactin, relaxins, corticoliberin, estrogens and others; see Fig. 20– 6, as well as figures 20–12 in the book, see also tables 18–10).

 chorionic gonadotropin(CHT) maintains the continuous secretion of progesterone in the corpus luteum until the placenta begins to synthesize progesterone in an amount sufficient for the normal course of pregnancy. HCG activity increases rapidly, doubling every 2-3 days and reaching a peak on the 80th day (80,000-100,000 IU / L), then decreases to 10,000-20,000 IU / L and remains at this level until the end of pregnancy.

 Marker pregnancy. HCG is produced only by syncytiotrophoblast cells. HCG can be detected in the blood serum of a pregnant woman 8-9 days after fertilization. The amount of secreted HCG is directly related to the mass of the cytotrophoblast. In early pregnancy, this circumstance is used to diagnose normal and abnormal pregnancy. The content of HCG in the blood and urine of a pregnant woman can be determined by biological, immunological and radiological methods. Immunological (including radioimmunological) tests are more specific and sensitive than biological methods. With a decrease in the concentration of HCG by half compared to normal values, implantation disorders (for example, an ectopic pregnancy or an undeveloped uterine pregnancy) can be expected. An increase in the concentration of HCG above normal values ​​is often associated with multiple pregnancies or hydatidiform mole.

 Stimulation secretions progesterone yellow body. An important role of HCG is to prevent the regression of the corpus luteum, which usually occurs 12-14 days after ovulation. Significant structural homology between HCG and LH allows HCG to bind to luteocyte receptors for LH. This leads to the continuation of the work of the corpus luteum after the 14th day from the moment of ovulation, which ensures the progression of pregnancy. Starting from the 9th week, the synthesis of progesterone is carried out by the placenta, the mass of which by this time allows the formation of progesterone in an amount sufficient to prolong the pregnancy (Fig. 20–6).

 Stimulation synthesis testosterone cells Leidiga in a male fetus. By the end of the first trimester, HCG stimulates the fetal gonads to synthesize steroid hormones necessary for the differentiation of the internal and external genital organs.

 Synthesis and secretion of HCG maintains secreted cytotrophoblast gonadoliberin.

 Progesterone. In the first 6-8 weeks of pregnancy, the main source of progesterone is the corpus luteum (the content in the blood of a pregnant woman is 60 nmol / l). Starting from the second trimester of pregnancy, the placenta becomes the main source of progesterone (blood content 150 nmol / l). The corpus luteum continues to synthesize progesterone, but in the last trimester of pregnancy, the placenta produces 30-40 times more of it. The concentration of progesterone in the blood continues to increase until the end of pregnancy (blood content 500 nmol / l, about 10 times more than outside pregnancy), when the placenta synthesizes 250 mg of progesterone per day. To determine the content of progesterone, a radioimmune method is used, as well as the level of pregnandiol, a metabolite of progesterone, chromatographically.

 Progesterone promotes decidualization of the endometrium.

 Progesterone, inhibiting the synthesis of Pg and reducing sensitivity to oxytocin, inhibits the excitability of the myometrium before the onset of childbirth.

 Progesterone promotes the development of breast alveoli.

Rice. 20 –6 . Content hormones V plasma blood at pregnancy

 Estrogens. During pregnancy, the content of estrogens in the blood of a pregnant woman (estrone, estradiol, estriol) is significantly increased (Fig. 20-6) and exceeds the values ​​outside of pregnancy by about 30 times. Wherein estriol makes up 90% of all estrogens (1.3 nmol/l at the 7th week of pregnancy, 70 nmol/l by the end of pregnancy). By the end of pregnancy, urinary excretion of estriol reaches 25–30 mg/day. The synthesis of estriol occurs during the integration of the metabolic processes of the pregnant woman, placenta and fetus. Most of the estrogen is secreted by the placenta, but it does not synthesize these hormones. de novo, but only the aromatization of steroid hormones synthesized by the adrenal glands of the fetus. Estriol is an indicator of the normal functioning of the fetus and the normal functioning of the placenta. For diagnostic purposes, the content of estriol is determined in peripheral blood and daily urine. High concentrations of estrogen cause an increase in the muscle mass of the uterus, the size of the mammary gland, and the external genital organs.

 Relaxins- hormones from the insulin family - during pregnancy, they have a relaxing effect on the myometrium, before childbirth they lead to the expansion of the uterine os and an increase in the elasticity of the tissues of the pubic joint.

 Somatomammotropins 1 And 2 (placental lactogens) are formed in the placenta 3 weeks after fertilization and can be determined in the blood serum of a woman by radioimmunoassay from 6 weeks of pregnancy (35 ng/ml, 10,000 ng/ml at the end of pregnancy). The effects of somatomammotropins, like those of growth hormone, are mediated by somatomedins.

 Lipolysis. Stimulate lipolysis and increase plasma free fatty acids (energy reserve).

 carbohydrate exchange. Suppress glucose utilization and gluconeogenesis in pregnant women.

 insulinogenic action. They increase the content of insulin in the blood plasma, while reducing its effects on target cells.

 Dairy glands. They induce (like prolactin) the differentiation of secretory sections.

 Prolactin. During pregnancy, there are three potential sources of prolactin: the anterior pituitary of the mother and fetus, and the decidua of the uterus. In a non-pregnant woman, the content of prolactin in the blood is in the range of 8-25 ng / ml, during pregnancy it gradually increases to 100 ng / ml by the end of pregnancy. The main function of prolactin is to prepare the mammary glands for lactation.

 Releasing–hormones. In the placenta, all known hypothalamic releasing hormones and somatostatin are synthesized (see Tables 18–10).

As a result of the changes described above, the sensitivity of the body of a pregnant woman to pharmacological drugs changes. Of great importance for the rational use of pharmacological agents used to provide anesthesia to pregnant women are the features of the transplacental transition of a particular pharmacological agent.

It is known that the transplacental transition of various pharmacological substances is carried out with the help of diffusion, active transport and transport through the chorionic villi. The degree and rate of transfer of medicinal substances through the placenta depend on the total surface of the placental membrane and its thickness, the intensity of the uteroplacental circulation, the duration of pregnancy, the molecular weight of pharmacological substances, the ability of the drug to dissolve in lipids, association with proteins and a number of other points.

The paraplacental transition of pharmacological substances is not excluded. At the same time, the role of amniotic fluid is emphasized, which not only contributes to the excretion of metabolic products, but can also be involved in supplying the fetus with the necessary substrates, as well as in the metabolism of drugs used in pregnant women. Moreover, the paraplacental transfer of substances ends, as a rule, simultaneously with the rupture of the membranes.

For drugs used in obstetric anesthesiology, the concentration gradient in combination with the volume of placental blood flow is of no small importance; molecular weight of pharmacological substances. Substances with a molecular weight below 600 (gases, crystalloid solutions, etc.) pass through the placental barrier freely. The permeability of substances with a molecular weight of more than 600 is less pronounced. However, if placental permeability is impaired, substances with a mass of 40,000-80,000 and their metabolites can penetrate the placental barrier.

The degree of ionization of drug molecules is also important. Ionized substances cross the placenta to a lesser extent than non-ionized ones. The latter, especially easily soluble in lipids (ether, halothane, etc.), neurotropic, analgesic agents easily cross the placenta. Muscle relaxants, which are poorly soluble in fats and are high-molecular compounds, are largely retained by the placental barrier, some of them still enter the body of the fetus.

A significant role is played by the characteristics of the fetus associated with age, the functional state of the nervous, endocrine, enzymatic systems, as well as other factors that determine the reactivity of the fetus. Newborns have a slow metabolism. Equally important is the ability of pharmacological agents to bind to plasma proteins. Erythrocytes are also involved in the transfer of drugs, but their role is insignificant, since their surface is 200 times smaller than the surface of the protein. In newborns, plasma proteins have a lower ability to bind drugs compared to adult women. At the same time, the distribution of drugs in newborns, especially in small children, differs from adults due to immaturity and increased permeability of membranes, especially the blood-brain barrier. The distribution of drugs in newborns is also influenced by the volume of the extracellular space. So, in newborns, it is about 40% of body weight, in adults - 20%. In an immature fetus, the brain contains less myelin, which causes hypersensitivity nervous formations of the fetus to the effects of any pharmacological agents, including drugs and neurodepressants. In this regard, newborns often experience various negative side reactions to pharmacological drugs administered to the mother.

When using pharmacological agents in a pregnant woman, the concentration gradient must also be taken into account. It is known that the higher it is, the lower the molecular weight of the drug, the faster the equilibrium of the concentrations of this drug in the organisms of the mother and fetus will be achieved.

A decrease in the volume of circulating blood (bleeding, gestosis) with a simultaneous decrease in protein fractions also leads to the fact that pharmacological drugs circulate in higher concentrations and most of them are in a protein-free state, and therefore the drugs penetrate the fetus in higher concentrations. .

The nature of the contractile activity of the uterus also has a great influence on the penetration of pharmacological preparations. With vigorous labor, intrauterine pressure can reach fairly high numbers (70-80 mm Hg. Art.) With a simultaneous sharp increase in intra-amniotic pressure, exceeding the pressure in the arterial vessels of the uterus. Violent labor activity can cause a complete cessation of arterial blood flow into the intervillous space, thereby preventing the passage of pharmacological drugs through the placental barrier.

It is known that with the introduction of the mother of pharmacological preparations of multidirectional action, about 1/2-2/3 of the blood from the placenta passes through the fetal liver. There, inactivation of most of the drugs used by the pregnant woman occurs. As a result, the concentration of certain pharmacological agents in the fetal liver is ten times higher than their concentration in the brain and other tissues of the fetus. Moreover, the blood leaving through the portal system is diluted with blood coming from the intestinal vessels and before entering through the left atrium and then to the brain, the concentration of the drug is significantly reduced. In addition, about 50% of the blood from the total cardiac output returns to the placenta, without getting to the tissues of the fetus due to shunting through the duct. Thus, the tissues of the fetus receive only about half of the drug that enters its blood through the placental barrier.

The above data must be taken into account in the anesthesia of childbirth, as well as in the conduct of anesthesia during operative delivery. Currently, the main way to prevent and relieve pain is the use of drugs. The term "painkillers" is used to denote substances that relieve pain sensitivity. The classification of painkillers can be represented as follows.

I. Opioid (narcotic) analgesics:

A) opioid receptor agonists (morphine, sufentanil);

B) agonists-antagonists and partial agonists of opioid receptors (buprenorphine, butorphanol, nalbuphine, pentosacin).

Opiates are substances extracted from opium. Their pharmacological action is due to interaction with opioid receptors in the central nervous system and peripheral tissues. Opioid receptor agonists have a pronounced analgesic property. Under the influence of these drugs, the pain perception threshold increases, weakening the emotional and behavioral reactions to pain. Their analgesic effect is due to the influence on the interneuronal transmission of (pain) impulses at the permitted levels of the central nervous system. There is another concept, according to which the analgesic effect is due to peripheral receptors.

Agonists - antagonists and partial agonists of opioid receptors differ from substances from the agonist group in the following ways. With an increase in their doses, the analgesic effect and respiratory depression increase to a certain limit, and then the narcogenic potential is much less, i.e., this group of substances is safer than morphine and similar drugs, but in some cases it may be inferior to them in effectiveness.

Pentazocine at a dose of 30-60 mg causes analgesia corresponding to the effect of morphine at a dose of 10 mg (average therapeutic dose). Increasing the dose of more than 30 mg usually does not lead to respiratory depression, but dysphoria and other psychomimetic effects may appear. At the same time, unlike morphine, pentazocine can cause an increase in blood pressure and tachycardia. In this regard, this drug should be used with caution in cardiovascular pathology.

Nalbufin is similar in pharmacodynamics to pentazocine.

Buprenorphine binds strongly to opioid receptors, its action is longer than that of morphine (about 6 hours). Analgesic doses are an order of magnitude smaller (0.3-0.6 mg).

Butorphanol is closer to morphine in terms of efficiency, speed of onset of effect, duration of action (4-6 hours), but is used in smaller doses (2 mg); negative property is an increase in blood pressure.

II. Non-opioid drugs of central action with analgesic activity.

These include:

1. Clonidine and guanfacine. Clonidine has a fairly pronounced analgesic property. Its feature is the ability to prevent adverse hemodynamic disturbances in case of pain, without causing drug dependence and without adversely affecting respiratory function. At the same time, the analgesic effect may be accompanied by hypotension, which is less pronounced with epidural administration of clonidine. Guanfacine differs from the latter in greater receptor activity and is close to clonidine in all its properties.

2. Sodium channel blockers (membrane stabilizing agents). These include carbamazepine, difenin. These drugs, by blocking the sodium channels of neutron membranes in the nuclei of the trigeminal nerve, reduce the activity of the generator of pathologically enhanced excitation. As a result, in the membranes of the afferent fibers of the trigeminal nerve, the impulse that forms pain syndrome. These drugs also have antiepileptic properties.

3. Inhibitors of neuronal reuptake of monoamines (serotonin, norepinephrine) amitriptyline, imizin. The analgesic properties of tricyclic antidepressants were discovered in the early 1960s. The analgesic effect is associated with inhibition of neuronal reuptake of monoamines in the corresponding brain synapses. As a result, segmental and supraspinal mechanisms of control of pain impulses are enhanced.

4. Antagonists of excitatory amino acids (ketamine, dextromethorphan, memantine). Ketamine, a non-competitive NMDA receptor antagonist, has a pronounced analgesic property. In situations of acute pain, the analgesic effect of ketamine when injected into a vein usually develops within 10 minutes and lasts 2-3 hours. Ketamine causes an increase in blood pressure and an increase in heart rate with an increase in its minute volume. Common side effects are hallucinations and other mental disturbances. More promising drugs from the group of excitatory amino acid antagonists are memantine and dextrometrophane, which do not have such side effects as ketamine.

5. Nitrous oxide. The analgesic effect of nitrous oxide, corresponding to 10 mg of morphine, appears when the gas is inhaled at a concentration of 30-50%. The low lipophilicity of the compound determines the rapid onset of action and its equally rapid disappearance after the cessation of inhalation. Consideration should be given to the inhibitory effect of nitrous oxide on bone marrow function during prolonged inhalation due to inhibition of methionine synthase. Nitrous oxide inhalations in analgesic concentrations should be limited to 6 hours.

6. Blockers of histamine H1 receptors (diphenhydramine). Histamine plays an important role in peripheral nociceptive mechanisms, but the role of CNS histaminergic neurons in pain perception and control is unclear. Histamine H1 receptor blockers are quite effective for pain of moderate intensity after surgical operations, in childbirth.

7. GABA-B-mimetics (baclofen) are chemically similar to gamma-aminobutyric acid. The main pharmacological effect of baclofen is antispastic: by inhibiting spinal reflexes, it reduces muscle tension. In terms of effectiveness, it is inferior to sodium channel blockers.

8. L-type calcium channel blockers (verapamil, nimodipine) and N-type channel blockers SNX-III. Calcium ions are involved in the regulation of pain sensitivity at different stages of nociceptive signaling. At the same time, calcium channels of the membranes are blocked, which leads to a decrease in the current of calcium ions to the endings of the primary afferents in the spinal cord and, accordingly, to inhibition of the release of mediators.

9. Inhibitors of cyclooxygenase (COX) mainly in the central nervous system - non-narcotic analgesics. The latter include salicylates, pyrazolone derivatives (amidopyrine, analgin, etc.) and paraminophenol (phenacetin, paracetamol). Non-narcotic analgesics are inferior to opioid ones in terms of the severity of their analgesic effect; they are less effective for intense pain. Their analgesic effect is manifested mainly in moderate pain associated with inflammatory processes. Non-narcotic analgesics do not cause euphoria, drug dependence, do not depress breathing.

Non-narcotic analgesics have analgesic and antipyretic effects. These effects of non-narcotic analgesics are associated with the fact that they inhibit the activity of COX, under the influence of which prostaglandins are formed in tissues from unsaturated fatty acids, which are involved in the processes of pain, inflammation and fever. Acting on pain nerve endings, prostaglandins increase their sensitivity to bradykinin, a peptide that is formed in tissues during inflammation simultaneously with prostaglandins and is a stimulator of pain endings. By inhibiting the synthesis of prostaglandins, non-narcotic analgesics reduce the sensitivity of nerve endings to bradykinin. They can be successfully used for the purpose of pain relief in childbirth.

At the present stage of development of anesthesiology in obstetrics, preparations of various groups have become widespread. Let us dwell on the drugs most widely used in practice.

Propanidide (sombrevin, epantol) - when administered intravenously, it partially binds to plasma proteins, quickly decomposes into inactive metabolites, after 25 minutes. after administration, it is not detected in the blood, it is excreted through the lungs, with urine and feces. The narcotic effect occurs 20-40 days after the administration of sombrevin. The surgical stage of anesthesia lasts 3-5 minutes. Propanidide causes a more pronounced hypnotic effect than analgesic. After 10-20 seconds after the start of intravenous administration, consciousness is lost, breathing quickens and deepens. Arterial pressure decreases, pulse rate increases by 20-40 per minute. After the phase of increased bioelectrical activity, a stage of displaced waves occurs with a predominance of high-amplitude delta and theta rhythms, and later there are signs of an increasing depression in the bioelectrical activity of the brain. Cardiac output, peripheral vascular resistance and systemic arterial pressure decrease, cardiac output increases. Sombrevin crosses the placental barrier, but decomposes into inactive metabolites after 15 minutes. There is evidence that the drug can lead to respiratory depression, acidosis in the fetus, cause histamine-like reactions in the mother.

Ketamine hydrochloride (calypsol, ketalar) - half-life is about 2 hours. After intravenous administration, the narcotic effect occurs after 30 seconds and lasts 5-10 minutes, after intramuscular injection - after 3-5 minutes and lasts 12-15 minutes. Possessing a strong analgesic effect, it does not relax skeletal muscles and does not inhibit reflexes from the respiratory tract. In pregnant women, it increases the tone of the uterus. With its introduction, laryngeal and pharyngeal reflexes are preserved, there is a tendency to increase blood pressure by 20-25% of the initial level, an increase in heart rate by 20-30%. According to the literature, ketamine is able to stimulate the adrenal cortex, causing ACTH- and GHB-like effects. When using ketamine, there is no negative effect on gas exchange, oxygen consumption by the brain decreases in conditions of massive blood loss. The drug penetrates the placental barrier and in doses of more than 1.2 mg / kg of the mother's weight causes inhibition of the vital functions of the fetal body.

There is evidence that sombrevin and ketalar also affect the body's immunological system. Thus, with the introduction of sombrevin, the number of T- and B-lymphocytes decreases by 15 and 4%, respectively, while with the introduction of ketalar, they increase (by 10 and 6%, respectively), which indicates a lower risk of using ketalar in patients with allergic diseases, with blood loss and with insufficiency of the immune system. This is important, since during pregnancy there is a shift in the immune system of the mother's body, which consists in a decrease in cellular and humoral immunity. In addition, a number of immunological systems are directly related to perinatal damage to the fetal central nervous system.

Barbiturates (thiopental sodium, hexenal). After intravenous administration, 65-70% of the dose of barbiturates binds to plasma proteins, and the remaining free fraction acts as a narcotic. The narcotic action of barbiturates is based on inhibition of the cerebral cortex and blockade of synapses (inhibition of the synthesis of acetylcholine and other mediators) of the ascending part of the activating system of the brain stem, an increase in the excitability threshold of nerve cells due to a decrease in the permeability of the membrane potential, and an extension of the refractoriness period of cells. They practically do not affect the contractile activity of the uterus, reduce cardiac output, which is due to the suppression of sympathetic-adrenal activity, a direct effect on the myocardium.

The analgesic phase of anesthesia is usually not pronounced, and after 30-60 seconds, loss of consciousness occurs; there is no excitation, there is an increase in pharyngeal, laryngeal and eye reflexes.

Barbiturates - weak acids, having a low molecular weight, penetrate the placental barrier, and the degree of fetal depression is directly proportional to the concentration of anesthetic in the mother's blood. Barbiturates reduce the level of bilirubin in newborns and are successfully used in hypoxic conditions of the body in general anesthesiology.

Sodium hydroxybutyrate (sodium salt of gamma-hydroxybutyric acid GHB) is similar in action to gamma-aminobutyric acid, a mediator of inhibition of the central nervous system. It is well absorbed, within 4 hours only 10% of the drug is released, the rest is utilized as an exchange substrate, 98% is excreted through the lungs in the form of carbon dioxide. The mechanism of action of GHB is closely related to carbohydrate metabolism. Being a precursor of gamma-aminobutyric acid, it contributes to the emergence of inhibitory processes in the brain tissue. Thanks to the intervention in metabolic processes, it protects the body from the harmful effects of oxygen deficiency. With the introduction of GHB, there is a decrease in the rate of cerebral blood flow by 11%. The drug greatly potentiates the action of other analgesics and drugs.

Narcotic action of GHB of cortical origin. Anesthesia occurs only with deep anesthesia, which is accompanied by vegetative shifts in the form of hypotension, bradycardia, respiratory depression and severe muscle relaxation while maintaining eye reflexes. It has a pronounced hypothermic effect without complications characteristic of hypothermia (disorders heart rate). Does not violate energy exchange, processes of phosphorylation of respiration, brain and other tissues.

GHB penetrates the placental barrier, is widely used in obstetrics in the treatment of fatigue in childbirth, for pain relief.

Droperidol due to its high water solubility is well and rapidly absorbed. Plasma proteins bind about 90% of the drug. The maximum plasma concentration is determined 2-6 hours after oral administration and 10-60 minutes after intramuscular injection and remains high for about 3 days. Droperidol changes little in the body, is metabolized mainly in the liver, 15% of the drug is excreted in the bile. The release of droperidol is slow: for 5 days only 40% of a single dose is excreted by the kidneys. During natural childbirth, droperidol is practically not detected in the blood of a newborn, during caesarean section, the concentration of droperidol in the blood is 3 10-6-6 10-6 mg / ml, and in the blood of a newborn 5 10-7 - 8 10-7 mg / ml, not causes fetal depression. With the introduction of droperidol, blood oxygen saturation decreases, the minute volume of breathing increases by 1%, and the activity of neuropeptides increases.

It has an antiemetic effect, lowers body temperature, is a pronounced anticonvulsant agent. Possessing an adrenolytic effect, it improves peripheral circulation, eliminating vascular spasms. Potentiates the effect of narcotic analgesics, especially fentanyl.

Sibazone (Relanium, Seduxen, Diazepam) when taken orally is absorbed in an amount of about 75%, the maximum plasma level is observed after 1-1.5 hours. Plasma proteins bind about 98% of sibazon.

The half-life in the blood plasma of a woman is 1-3 days, in newborns - 31 hours. The mechanism of action is associated with an increase in the activity of endogenous gamma-aminobutyric acid. The sedative and anticonvulsant effects usually last long in pregnant women, since the elimination period is somewhat longer than in non-pregnant women. In the blood of the fetus, the highest concentration is created 5 minutes after intravenous administration. In the blood of the umbilical cord of a newborn, the concentration of sibazon is equal to that in the venous blood of the mother when administered at a dose exceeding 10 mg or more. At the same time, the concentration of the drug in the brain is low. At the same time, the occurrence of apnea in newborns, hypotension, hypothermia, and sometimes signs of neurological depression are not uncommon. With prolonged use of sibazon, respiratory depression in newborns and the transition of respiratory acidosis to metabolic is possible. This is due to a fairly high level in the blood of the child, both the drug itself and its active metabolite N-desmethyldiazepam. Sibazon is able to accelerate the opening of the cervix, contributing to the removal anxiety state in a number of women in childbirth.

Promedol is easily absorbed by any route of administration. The maximum plasma concentration is determined after 1-2 hours. After intravenous administration, plasma concentration decreases within 1-2 hours. About 40% of promedol binds to plasma proteins, where it is mostly neutralized. In the body, it is hydrolyzed to meperidic and normeperedic acids, followed by conjugation. A small amount is excreted by the kidneys unchanged.

The mechanism of action of promedol is based on interaction with opiate receptors. It has an analgesic, sedative effect, depresses the respiratory center. After parenteral administration, the analgesic effect occurs after 10 minutes and lasts 2-4 hours. In addition to analgesic, it has an antispasmodic effect, contributing to the opening of the cervix. Easily penetrates through the placenta. 2 minutes after intravenous and somewhat later after intramuscular administration in the blood of the umbilical cord, a concentration approximately equal to that in the mother's blood plasma is observed. However, there may be significant fluctuations in individual fetuses depending on their prenatal state. The maximum concentration of promedol and its toxic metabolite, norpethidine, in the blood plasma of a newborn is observed 2-3 hours after its administration to the mother. The elimination half-life of Promedol from the body of a newborn is 22.7 ± 3.2 hours, in the mother 2.53 ± 0.6 hours.

Promedol is generally safe for both mother and child. However, in some cases, the drug can cause depression in the newborn due to the fact that it has an overwhelming effect on the processes of glycolysis and the respiratory center.

Fentanyl is an opioid receptor agonist and is 200-400 times more effective than morphine in analgesic activity. The short duration of the effect of fentanyl is due to the rapid metabolism of the compound, as well as its redistribution in the body. Biotransformation of fentanyl occurs mainly in the liver. Excreted by the kidneys and through gastrointestinal tract predominantly in the form of metabolites and partially unchanged. Penetrating through the placental barrier, it can cause narcotic depression in the fetus.

Pentazocine - belongs to the group of agonist-antagonists of opioid receptors and at a dose of 30-50 mg. causes analgesia corresponding to the effect of morphine at a dose of 10 mg. Moreover, an increase in the dose of more than 30 mg does not entail respiratory depression, however, this increases the incidence of dysphoria and other psychomimetic effects. Pentazocine can cause an increase in blood pressure, tachycardia (not recommended in women with cardiovascular disease with high hypertension).

Diprivan (propofol) is a new intravenous anesthetic of ultrashort action. In 1993, it was registered by the Pharmaceutical Committee of the Ministry of Health of the Russian Federation and approved for clinical use in our country. Practical experience in the use of propofol has been accumulated abroad (more than 40 million anesthesias have been performed) for both short and long-term surgical interventions in almost all areas of medicine.

Diprivan quickly induces sleep, maintains unconsciousness throughout the infusion of the drug with a rapid recovery of consciousness after stopping its administration, interacts well with narcotic analgesics and neuroleptics, and has less side effects compared to other intravenous anesthetics. However, a number of publications also point to possible undesirable manifestations of diprivan during anesthesia, including the deterioration of some parameters of central hemodynamics, although data on this issue are extremely contradictory.

In foreign literature, all drugs administered intravenously during anesthesia have one common term - “intravenous anesthetics”. In the strict sense of this term, Diprivan is not an anesthetic, since it does not have any pronounced analgesic properties, but is only able to increase the threshold of pain sensitivity, as, for example, most ataractics and tranquilizers. Therefore, from the point of view of pharmacology, Diprivan is not an anesthetic, but a hypnotic.

A very valuable quality of Diprivan is the ability to cause good muscle relaxation. The muscle relaxant effect of Diprivan really exists. This is confirmed by a significant number of publications, some of which report the possibility of tracheal intubation without the use of muscle relaxants. It should be noted that the drug has a good ability to suppress laryngeal-pharyngeal reflexes. This circumstance also explains the fact that foreign anesthesiologists consider propofol to be an ideal means for introducing a laryngeal mask - a modern means of maintaining airway patency, both in conditions of spontaneous breathing and with mechanical ventilation. Another side of the muscle relaxant action of Diprivan is also known - the ability to reduce muscle hypertonicity and even convulsive syndrome.

All undesirable effects of Diprivan can be divided into 2 groups:

1) complications that occurred during or after anesthesia,

2) complications that may occur as a result of the use of Diprivan in intensive care.

After anesthesia, agitation, severe asthenia, intracranial hypertension, drowsiness, trembling, hallucinations, neurological disorders. Allergic reactions after the use of the drug are rare.

Nitrous oxide is one of the components of general anesthesia for caesarean section. The drug is insoluble in lipids, it dissolves in blood plasma up to 23 vol.%. Very quickly (2-3 minutes) is absorbed and excreted by the lungs unchanged. 5-10 minutes after the start of inhalation, tissue saturation with anesthetic reaches a maximum. For 5-6 minutes it is completely removed from the blood.

A relatively weak anesthetic with a high degree of safety, mixed with oxygen at a concentration of 50 vol.%, causes analgesia without loss of consciousness and changes in reflex excitability. At a concentration of 50-70 vol.% causes euphoria, laughter, confusion. It affects only the central nervous system, does not depress respiration, the cardiovascular system, does not adversely affect the liver, kidneys, metabolism, and contractile activity of the uterus. It quickly crosses the placenta, after 2-19 minutes the concentration of nitrous oxide in the blood of the vein of the umbilical cord is 80%, with longer inhalation - 90% of the level in the mother's blood. Prolonged inhalation of nitrous oxide is sometimes accompanied by the birth of a child with a low Apgar score, which is considered as a consequence of increased release of catecholamines by nitrous oxide in the mother's body and uterine vasoconstriction in response to inhalation. There is evidence that nitrous oxide is able to protect the brain from ischemic damage, although to a lesser extent compared to isoflurane, halothane and improves uteroplacental circulation and cerebral oxygenation.

M-cholinolytics (atropine, metacin) practically do not penetrate the central nervous system and are only capable of eliminating spasm of smooth muscles. As a rule, they are used as an adjunct to sedation to relieve the side effects of the anesthetics used. Penetrate through the placental barrier, do not adversely affect the condition of the fetus and newborn.

Relaxants (ditilin, listenone, myorelaxin, etc.) are slowly and incompletely absorbed in the digestive tract. Do not cross the placenta. They have muscarine and nicotine-like effects. They cause persistent depolarization of subsynaptic membranes in myoneural synapses, disrupting the transmission of trigger impulses from the axons of somatic nerves to muscle fibers, resulting in their relaxation. They do not violate the functions of the liver and kidneys, do not affect the coagulation and anticoagulation systems of the blood. These relaxants do not affect the condition of the newborn, but in some newborns with impaired feto-placental permeability, some authors note a low Apgar score.

The positive and negative aspects of the pharmacological agents used in obstetric anesthesiology listed in this chapter do not occur in all women in labor and fetuses. The frequency of possible manifestations of each of these drugs depends on many circumstances and, above all, on the state of health of the woman herself, the presence or absence of disorders of the fetoplacental complex, obstetric pathology and other factors. As can be seen from the presented data, all drugs mainly penetrate the placental barrier, affecting not only the condition of the mother, but also the condition of the fetus and newborn.

3.4. Anesthesia of physiological and complicated childbirth

At present, non-pharmacological and medical methods(scheme 3).

Non-pharmacological methods of labor pain relief

The purpose of psychoprophylactic preparation of a pregnant woman for childbirth is to remove the psychogenic component of labor pain, eliminate the idea of ​​its inevitability, the oppressive feeling of fear and contribute to the creation of a new idea of ​​childbirth as a favorable physiological process in which pain is not necessary. Impact on the cerebral cortex in the process of psychoprophylactic preparation helps to reduce pain. Women in labor who have undergone psychoprophylactic preparation for childbirth require a smaller dose of medications for labor pain relief. The method was proposed in our country by I.Z. Velnovsky and K.I. Platonov in 1940.

An important psychological point is the presence of a husband or another person close to the woman in labor during childbirth, if there is mutual consent to this. It is useful for a pregnant woman to get acquainted in advance with the doctor and midwife who will conduct the birth.

The method of psychoprophylactic preparation requires painstaking, long-term individual preparation of a pregnant woman for childbirth, taking into account the knowledge acquired by the woman in labor during childbirth (selective muscle relaxation, breathing regulation).

In practical healthcare, the choice of the method of anesthesia for childbirth is often stereotyped and decided during childbirth. However, during childbirth it is difficult to determine the psycho-emotional state of the woman in labor in order to choose an adequate method of pain relief. Among non-drug methods, methods that reduce pain stimuli deserve attention. These include freedom of movement of the woman in labor, counter-pressure on the nerve endings, and abdominal decompression. Of these methods, the first two can be successfully used.

Considerable attention is given to methods that activate peripheral receptors. Among these methods, attention should be paid to hydrotherapy (warm baths), acupuncture and acupressure, transcutaneous electrical nerve stimulation, etc.

Under the influence warm baths temperature and tactile receptors of the skin are activated, which inhibits the transmission of impulses to the cortex. The centers of the brain (thalamus and cortex) send inhibitory impulses to the dorsal column and inhibit the transmission of pain signals. Hydrotherapy reduces pain, provides relaxation, reduces physiological tension and pressure on the abdominal muscles, allows the uterus to contract more efficiently, improves oxygenation.

The disadvantages of the method of childbirth under water include the difficulties of providing asepsis, monitoring the nature of the contractile activity of the uterus and the fetus, the moment of discharge of amniotic fluid, etc.

Touching and massage during childbirth is widely practiced in a number of countries. Various types of massage stimulate skin receptors, increase the neural activity of many myelin fibers. These stimuli are transmitted more quickly than pain stimuli. The action of "bombing" the central nervous system reduces pain.

Many clinics use acupuncture and acupressure to relieve childbirth. Acupuncture blocks the sensory and emotional components of pain, but the mechanism of action is not well understood. Effective for pain relief in the first stage of labor is the following acupuncture recipe on the anterior abdominal wall (VCH-guan-yuan), in the area of ​​the hand (GI4-xe-ry), in the upper third of the leg (E36-zu-san-li) in the lower third of the leg (RP6 - san-yin-jiao).

In the second stage of labor, the use of biologically active points in the sacrum (V31 and V34-ba lyao) is effective.

Acupressure is essentially "acupuncture without needles" that achieves an analgesic effect.

Acupuncture and acupressure help relieve pain during labor, normalize labor and do not adversely affect the fetus. This method limits the motor activity of the woman in labor and requires careful monitoring, and therefore the session is limited in time.

Transcutaneous electrical nerve stimulation (TENS) has been successfully used to anesthetize childbirth. For this purpose, the domestic apparatus "Delta-101" is used, this is a single-channel electrical stimulator that generates asymmetric bipolar impulses. Pulse repetition rate 30-120 Hz, current strength 10-60 mA, pulse duration 0.5-0.8 ms. To achieve the greatest effect, 2 Delta-101 devices are used simultaneously. Two pairs of lead electrodes in the form of plates with an area of ​​20 cm2, treated with electrically conductive paste, are fixed with an adhesive plaster in the zone of maximum pain on the skin of the anterior abdominal wall (trigger zones of the uterus) and behind paravertably in the zone of segmental innervation TX-LII.

With this technique, the afferent fibers are “bombarded” and the gates are “closed” for pain. It is believed that this leads to an increase in the level of endorphins in the cerebrospinal fluid. According to our data, the analgesic effect is achieved in 80.6% of women.

TENS does not adversely affect the contractile function of the uterus, the cardiac activity of the fetus, the condition of the newborn.

There is a positive experience with the use of a water block for the purpose of labor pain relief. To do this, 0.1 ml of sterile water is injected intradermally at four points in the region of the edge of the sacrum, or near it, there is a decrease in pain within 2 hours. The mechanism of action is the same as during transcutaneous electrical stimulation.

In 1955, O. Heyns proposed the use of abdominal decompression for labor pain relief. According to the author, with this technique, placental blood flow and fetal oxygenation increase, labor pain decreases. The method is not devoid of global action and complications, and therefore has not received distribution.

The role of hypnosis in labor pain relief has long been proven. But an indispensable condition is a good command of this technique.

Effective for relieving pain in childbirth is focusing and diverting the attention of women in labor: and for this purpose they use music, television and other factors.

Music promotes distraction, relaxation, rhythmic breathing, requires a smaller dose of medication. According to Goldstein (1980), it promotes the production of endophyrin and thus reduces pain.

In foreign literature, there is experience in audio analgesia, i.e., the use of noises (“the noise of the sea”, “the noise of an incident wave”) for labor pain relief. A woman in labor during a contraction increases the strength of the sound, which serves as a distraction.

Non-drug methods require time, effort in teaching techniques (specialist), their effectiveness is unpredictable to a greater extent due to the complexity of the pain system and the characteristics of the human body. In case of insufficiency of anesthesia, an appointment is required medications but at a lower dose.

Medical methods of labor pain relief

The use of drugs for the treatment of pain and anxiety in parturient women involves the use of anesthetics and analgesics, both narcotic and non-narcotic, and their combination with sedatives and neuroleptics. Recently, the arsenal of means for labor pain relief has grown significantly. It includes sedatives, numerous derivatives of the phenothiazine series, benzodiazepines, antispasmodics, and the latest analgesics of various structures.

One of the most commonly used analgesics is promedol. 20 mg of the drug is administered intramuscularly, the duration of its action is 1.5-2 hours. After its administration, monotony of the fetal heart rate may appear, labor activity is preserved. However, in doses greater than 40 mg, promedol depresses respiration and causes severe drug dependence. In addition, it can cause a state of stupor, nausea, vomiting, causes atony of smooth muscles, and constipation. The described side effects are inherent in almost all potent analgesics, with the exception of pentazocine (Lexir, Fortral).

The drug is effective for labor pain relief and is safe for the fetus and newborn. 30 mg of pentazocine produces the same degree of analgesia as 10 mg of morphine or 100 mg of promedol. It is also known that pentazocine has a stimulating effect on hemodynamics and respiration, and hysterographic data indicate its labor-stimulating effect. The drug, however, does not have any pronounced sedative effect. It is considered to be non-narcotic, incapable of causing addiction.

Tramal (50-100 mg intramuscularly) is currently successfully used to anesthetize spontaneous labor, which does not adversely affect the course of labor and the condition of the newborn. Sometimes there is depression in the newborn and vomiting in the pregnant woman.

Moradol at a dose of 0.025-0.03 mg/kg of body weight is an effective means of labor pain relief. The analgesic effect, as with the above drugs, occurs after 15-20 minutes; the duration of its action is on average 2 hours. Moradol does not adversely affect the fetal circulatory function and the contractile activity of the uterus.

The method of neuroleptanalgesia, which provides a kind of mental rest, satisfactory analgesia, accompanied by stabilization of hemodynamic parameters and the absence of a significant effect on the nature of labor and a negative effect on the condition of the fetus and newborn, has become quite widespread for labor pain relief.

Fentanyl is administered intramuscularly at a dose of 0.5-1.0 ml of a 0.005% solution. The greatest effect is achieved when it is combined with droperidol 2.5-5.0 mg (1-2 ml). If necessary, a second dose is administered after 3-4 hours. Neuroleptanalgesia should not be used if patients have severe hypertension of the pulmonary circulation, increased tone bronchioles, ventilation failure. You should be prepared for the possibility of developing drug-induced depression in the newborn. In this regard, an attempt was made to use the so-called "pure antagonist" naloxone in childbirth in order to eliminate the depressive effect of narcotic analgesics on the respiratory function of newborns.

Another common method of labor pain relief is the method of ataralgesia - the combined use of analgesics with 5-10 mg of sibazon, seduxen, etc. Since benzodiazepine derivatives are among the safest tranquilizers, their combination with analgesics is especially indicated for severe fear, anxiety and mental stress of the woman in labor.

The combination of dipidolor with seduxen favorably affects the course of labor, shortens the total duration of labor and the period of cervical dilatation.

Schematically, the sequence of actions during anesthesia during childbirth can be represented as follows:

At the beginning of labor activity (latent phase of labor, cervical dilatation by 3-4 cm with relatively painless contractions to relieve tension, fear), the use of tranquilizers (trioxazine 0.3-0.6 g, elenium 0.01-0.015 g, seduxen 0.01 g, etc.);

With the development of regular painful contractions, combined or independent use of inhaled or non-inhaled analgesics in combination with sedatives or antispasmodics is indicated. Easily suggestible women in labor may use acupuncture, therapeutic electroanalgesia, transcutaneous electrical nerve stimulation;

With the ineffectiveness of these methods of labor pain relief or in the presence of extragenital pathology, preeclampsia, discoordinated labor activity, it is advisable to use prolonged epidural (epidural) anesthesia.

IN practical activities frequently used combination

Painkillers, sedatives and antispasmodics. The following prescriptions can be recommended:

1) promedol 20-40 mg + no-shpa 40 mg,

2) promedol 20-40 mg + seduxen 10 mg + papaverine 20-40 mg,

3) moradol 1-2 mg + seduxen 10 mg + no-shpa 40 mg,

4) tramal 100 mg + diphenhydramine 20 mg + no-shpa 40 mg with a frigid cervix - metacin 1 ml 0.1%.

After the introduction of these combinations of drugs, monotony of the fetal heart rate is observed (according to ECG), pain is observed in 30-60% of women in labor. Attempts to achieve complete pain relief by significantly increasing the doses of analgesics or reducing the intervals between injections is fraught with the risk of developing weakness of labor, increased blood loss during childbirth, and narcotic depression of the fetus.

Epidural analgesia

The desire to achieve a full-fledged analgesic effect in labor pain relief with minimal impact on the body of the mother and newborn has contributed to the emergence of interest in the use of epidural analgesia for labor pain relief, since its pronounced analgesic and antispasmodic effect is combined with the absence of a depressant effect on the functions of the respiratory system, heart, liver, kidneys.

The method of epidural analgesia in childbirth has been studied quite fully. There is a large amount of information about the positive effect of epidural analgesia on the birth act, the absence of a negative effect on the fetus and newborn. The beneficial effect of epidural analgesia during pregnancy and childbirth complicated by preeclampsia is important. The positive role of epidural analgesia in anesthesia of childbirth in the breech presentation of the fetus has been established.

Epidural analgesia has a positive effect on the course of preterm labor, reducing the period of cervical dilatation and lengthening the period of expulsion, which contributes to a smoother advancement of the fetal head. At the same time, the muscles of the perineum relax and the pressure on the head decreases.

It has been established that in parturient women who underwent labor pain relief with narcotic analgesics, children are born with neuroreflex activity significantly worse than in mothers who received epidural analgesia during childbirth.

At the same time, the latter may cause a decrease in uterine activity due to a decrease in aortocaval compression. There was also an increase in the duration of labor and a decrease in uterine activity in the second stage of labor, which contributes to an increase in the number of surgical deliveries. It is also known about the negative hemodynamic effect of epidural analgesia during childbirth associated with the development of peripheral vasodilation, which in turn leads to a decrease in venous return, the occurrence of the Bainbridge reflex and bradycardia. In addition to the described possible negative effects of epidural analgesia, such as hypotension of the bladder, hyperthermia have also been noted.

For epidural analgesia, both local anesthetics and narcotic and non-narcotic analgesics, as well as sibazon and ketamine are currently used.

Epidural analgesia provides long-term and highly effective pain relief from the onset of labor until the birth of the child, but can lead to serious complications if careful monitoring and special preventive actions are not carried out. The negative attitude towards this method is due to the fact that some doctors do not have the technique or the necessary knowledge to use it. Properly performed epidural analgesia with sufficient coverage of all segments can reduce pressure on the perineum and protect it from ruptures. For the mother, the most attractive aspect of epidural analgesia is that she remains conscious, can actively participate in the birth process and communicate immediately with her baby.

If necessary, a caesarean section is performed during childbirth, it can be performed under the same epidural anesthesia without additional anesthesia. The same applies to manual examination of the uterus after childbirth, stitching up perineal injuries.

During analgesia in childbirth, the anesthetic is injected into the epidural space, followed by blockade of the subdural nerves in the segments with TX-LI.

Of the large group of local anesthetics in pregnant women, lidocaine is most widely used, since bupivakin has a pronounced cardiotoxic effect, and novocaine has a neurotoxic effect. Lidocaine easily crosses the placental barrier, the addition of adrenaline to the anesthetic solution significantly reduces the concentration of anesthetic in the fetal blood.

Lidocaine is metabolized in the liver, the rate of its detoxification depends on the hepatic blood flow, the function of hepatocytes and the degree of affinity of the drug for blood proteins. These factors can explain why prolonged infusions of the drug in pregnant women with preeclampsia, when liver function is impaired, the drug often accumulates, which subsequently manifests itself as neuro- and cardiotoxicity in relation to the mother and fetus.

When performing epidural analgesia, trust relationship an anesthesiologist with the patient, including a soothing conversation, as well as an examination of the lumbar region. The essence of the procedure should be explained to the pregnant woman in terms accessible to her and her consent should be obtained.

Preliminary preparation of monitoring equipment, taking into account all possible complications, is mandatory. For this purpose, a peripheral or central vein should be catheterized in order to introduce 500-1000 ml of crystalloid solutions before the onset of regional blockade. In women who are in labor, the infusion solution should contain glucose, which should not be administered with the onset of the second stage of labor.

The puncture of the epidural and subdural spaces can be performed with the woman in the lateral or sitting position. The position on the left side avoids the syndrome of aortocaval compression and postural reactions after the introduction of the test dose. Many anesthesiologists use the sitting position for puncture, since this position makes it easier to identify the midline of the back, which is often difficult due to swelling. subcutaneous tissue lumbar region and sacrum. Another advantage of performing the puncture in the sitting position is the easier flow of CSF. This is especially useful when using small diameter needles.

The back is treated with an antiseptic solution, the excess of which is removed. The puncture site is covered with sterile linen. For puncture, the space between L3-L4, or between L2-L3 along the midline of the back can be used.

After local infiltration anesthesia, the skin is pierced with a thick needle to facilitate subsequent insertion of the epidural needle. The epidural needle is slowly advanced into the interspinous ligament. A 5 ml syringe is attached to it, in which there is an air bubble. Slightly pressing on the piston to feel the resistance, slowly advance the needle. When the latter passes the yellow ligament, the resistance increases. After the needle passes through the yellow ligament, a sharp loss of resistance will be felt - the needle has entered the epidural space.

After the needle enters the epidural space, the syringe should be disconnected and there should be no discharge of blood or cerebrospinal fluid from it. In epidural analgesia, the resistance loss test is most useful in locating the needle lumen.

Other methods common in general surgical practice (“drop suction”, etc.) are less suitable for pregnant women in the third trimester, since women have a significant increase in pressure in the epidural space, which often becomes positive.

This is due to an increase in intra-abdominal pressure and compression of the main veins. Therefore, when introducing a solution, some effort is often required; and sometimes even a reverse current is noted, which in general surgical practice is usually regarded as an incorrect identification of the epidural space.

As a result of the influence of these factors in pregnant women, the risk of getting the anesthetic into the subdural space or into the lumen of the vessel increases. In the first case, a total spinal block occurs, which is evidenced by deep arterial hypotension, bradycardia, loss of consciousness and protective reflexes, dilated pupils and respiratory arrest. This complication occurs when the dose of local anesthetic intended for epidural analgesia is inadvertently administered, i.e. too large.

The manifestation of cardio- and neurotoxicity of local anesthetics is more often observed with intravascular ingestion of injected solutions: convulsions, arterial hypotension, arrhythmias, up to ventricular fibrillation occur.

Before inserting the epidural catheter, 3 ml of local anesthetic must be injected. This small volume of fluid pushes the dura away from the catheter. Then you should advance the catheter about 3 cm behind the needle and remove the latter. The catheter in this case remains in place. The catheter should not be advanced more than 3 cm, so as not to increase the risk of a monolateral block. It is contraindicated to change the position of the catheter at the time of removing the needle, as the latter can damage the catheter.

The distribution of local anesthetic solutions in the subarachnoid space is influenced by many different factors. In our opinion, the following factors are of greatest clinical importance.

An increase in intra-abdominal pressure almost always leads to a greater spread of the local anesthetic solution during subdural anesthesia. This is due to the expansion of the venous plexuses, due to which the volume of the subarachnoid space decreases, especially in aortocaval compression syndrome. Most often, this can be observed with multiple pregnancies, polyhydramnios, large fetuses, etc.

Anatomical changes in the spinal column. Scoliosis does not significantly affect the course of subdural anesthesia. Kyphosis at full term may alter the distribution of the local anesthetic solution. At non-pregnant women in the supine position Bottom part The S-curve of the spine is aligned, facilitating cranial distribution of the solution. In pregnant women in the third trimester, this bend may, on the contrary, increase, and then most of the injected solution accumulates below the injection site.

CSF pressure and volume. CSF is produced by the venous plexus of the lateral ventricles at a rate of about 0.35 ml/min (500 ml per day) and absorbed by the venous system of the meninges. CSF circulation in the subarachnoid space is very slow, so it does not have a significant effect on the distribution of local anesthetic solutions. The volume of cerebrospinal fluid is about 150 ml, half of this amount is in the cranial cavity. The remaining 75 ml fills the subarachnoid space of the spinal cord, and in this volume the solution of local anesthetics during subdural anesthesia can be distributed. Clinical practice shows that usually anesthetics are distributed in a much smaller volume. In full-term pregnancy, the volume of cerebrospinal fluid in the thoracic and lumbar regions decreases due to an increase in intra-abdominal pressure and increased venous volume in the epidural space. Due to this, both in the epidural and subdural spaces, the local anesthetic solution spreads much more widely, and therefore, with the same amount of local anesthetic solution injected as in non-pregnant women, the area of ​​anesthesia distribution may be much larger than desired.

In full-term pregnancy, CSF pressure is normal. Sharp and sudden, but short-term rises in CSF pressure that occur during contractions and attempts do not change the distribution of local anesthetic solutions in the subarachnoid space.

The nature of solutions of local anesthetics is the main factor determining their distribution in the subarachnoid space. The most important are the four main indicators: specific gravity, relative density local anesthetic solution in relation to the cerebrospinal fluid, the volume of the solution and the concentration of the anesthetic in the solution. Hypertonic solutions are preferred because the use of hypotonic lidocaine solutions shortens the duration of anesthesia, making it unsuitable for many operations. Successful implementation of subdural anesthesia with hypotonic solutions is possible only if very powerful local anesthetics are used.

Anxiety, fear, emotional characteristics of the patient may require additional administration of sedatives. Sometimes these funds are used to eliminate the "effect of the presence of the patient." We believe that sedatives should not be used before the baby is born. If, after the extraction of the fetus, it persists or such a need arises, then one should not strive for deep inhibition with sedatives in order to improve the quality of pain relief. Much more effective is the additional introduction of solutions of local anesthetics into a catheter installed in the epidural space.

For almost a decade and a half, obstetric practice has been using combined subdural-epidural anesthesia and analgesia. The epidural space is punctured with a conventional epidural needle, through which a needle is then inserted to puncture the subdural space. After removal of the subdural needle, the epidural space is catheterized. The main application of the method is the intraspinal administration of narcotic analgesics for effective pain relief of contractions, followed by the use of continuous infusion epidural analgesia from the end of the first stage of labor.

Epidural analgesia in the first stage of labor

Continuous epidural infusion analgesia (PEIA) is a rational and fairly simple method that provides long-term and safe labor pain relief.

After we have made sure that the epidural blockade is performed correctly, 0.5% lidocaine solution should be constantly infused into the epidural space at an initial rate of 10 ml/hour. Subsequently, the feed rate is adjusted depending on the response of the woman in labor.

The method is indicated for pain relief of contractions for 1.5-2 hours or more. It provides a number of advantages that cannot be achieved by fractional administration of anesthetics. When the drug is given in fractional, bolus doses, it is difficult to completely eliminate pain mothers who appear with increased contractions. When using PEIA, the need for local anesthetics is reduced by one third, due to which the development of a motor block is practically eliminated. This high analgesic effect, combined with a reduction in the amount of anesthetic, is associated with the phenomenon of preemptive analgesia.

Against the background of reliable analgesia, the mother remains quite active, the likelihood of various complications decreases. With a constant level of analgesia, tachyphylaxis occurs less frequently, which is usually observed with repeated injections of the drug. The state of hemodynamics is more stable, which is achieved by a uniform sympathetic blockade, which, with fractional injections of the drug, changes with each subsequent injection. Cardio- and neurotoxic reactions are minimized because anesthetics are administered at a very slow rate.

In the event that the catheter migrates into the vessel, this will be manifested by the resumption of the pain syndrome, and sometimes this complication is manifested by convulsions, severe arterial hypotension or arrhythmia.

Migration of the catheter into the subarachnoid space during epidural analgesia in childbirth is extremely rare. But even if this happened, then under the conditions of PEIA, a life-threatening total spinal block will not occur, since the complication will manifest itself as a gradually increasing motor blockade of the lower extremities.

The greater safety of the method does not relieve the doctor of the obligation to ensure reliable monitoring during childbirth and does not at all provide him with the opportunity to leave the woman in labor alone during even the calmest course of the anesthesia process.

The metering device must be tagged with an indication that the drugs are administered epidurally, and the rate of administration must be accurately marked.

Delivery room personnel may confuse epidural lines with those for intravenous infusion. This is especially dangerous in settings where dosing devices are also used for oxytocin infusion.

When performing PEIA, it must be remembered that large volumes of low concentration solutions are distributed to a greater number of segments (dermatomes) than small volumes of concentrated solutions. For example: 0.5% lidocaine solution at an infusion rate of 44 ml/hour covers 16 dermatomes (220 mg), if 1% lidocaine solution is used at half the rate (22 ml/hour), then the same 220 mg only covers 10 dermatomes.

Understanding the mechanism of pain in the first stage of labor, one should, of course, prefer solutions of low concentration. Although high concentrations of anesthetic provide a stronger block, it is best to start with solutions of low concentration, and if the depth of analgesia is insufficient, the doctor can at any time deepen the block by applying a solution of a higher concentration.

In most cases, if the level of analgesia is not deep enough, you can simply slightly increase the infusion rate, after making sure that the catheter has not migrated into the lumen of the vessel.

At the onset of the second stage of labor, analgesia must be continued, since the cessation of infusion in this period causes very severe pain.

Epidural analgesia in the second stage of labor

For pain relief in the second stage of labor, continuation of PEIA that was started in the first stage of labor is ideal. If it was not used, it is necessary to carry out the same measures as at the beginning of epidural analgesia for the first stage of labor. However, preventive bolus intravenous fluid should be increased to 1000-1500 ml, due to an increase in the dose of local anesthetic for pain relief of the second stage of labor and, accordingly, a greater risk of arterial hypotension.

First, the same 3-4 ml is injected. local anesthetic solution as a test dose. If after 5 minutes there are no signs of intravascular and subdural injection of the drug, then 10-15 ml is administered. solution, and the rate of administration should not exceed 5 ml for 30 s.

Blood pressure should be measured every 2 minutes during the first 15 minutes after injection. Subsequently, blood pressure is monitored every 5 minutes until the onset of blockade of sensitivity and stabilization of hemodynamics.

If epidural analgesia is used only from the moment regular contractions are established, then it is preferable to start it when the cervix is ​​more than 5 cm open. This avoids the negative effect of epidural analgesia on the birth process.

If PEIA continues in the second stage of labor, started in the first period, then the concentration of the solution must be increased to 1.5-2%. Abrupt cessation of PEIA in the second stage of labor often results in very severe pain. As a physiological reaction to the pain syndrome, which is described above, anxiety, fear, fright, and sometimes even anger arise.

The advantages of continuing PEIA in the second stage of labor are a weak motor block and the ability to subsequently control attempts. The duration of the second stage of labor in this case, as a rule, does not change. Continuous injection of anesthetic into the epidural space eliminates the abrupt change in hemodynamics that can occur with fractional administration of the drug. Adequate perineal anesthesia is often required during and immediately after the birth of the baby. In most women, it persists for 15-20 minutes after stopping the infusion of lidocaine. If anesthesia of the perineum is insufficient, then 10-15 ml of a 1.5% lidocaine solution is additionally injected in a jet.

Complications of PEIA in childbirth

The most likely complications can be systematized as follows.

1. Insufficient blockade of pain sensitivity: the most main danger This complication is the disappointment of the woman in labor in the method and in the anesthesia team. Unfortunately, even in the most experienced hands, this complication occurs in 5-10% of cases. The most common cause of inadequate blockade is an overly advanced catheter or spinal disorders that restrict the spread of the anesthetic. If the catheter is advanced no further than 3-4 cm beyond the needle lumen, this complication is less common. Most often, the advancement of the catheter is difficult when it is not in the epidural space. Forcible advancement of the catheter is unacceptable, as this may cause damage to the sharp edges of the needle or migration into the lumen of the vessel. The best way out in this situation is to repeat the puncture and the entire procedure in another intervertebral space.

2. The occurrence of a unilateral block is usually a consequence of the fact that the catheter is located laterally. Less commonly, this indicates anatomical abnormalities in the epidural space. In this case, the woman in labor must be turned on the side on which there is no effect, the catheter is pulled up by 1-2 cm. In this position, the woman in labor is given the next dose. If this does not help, it is necessary to repeat the puncture.

3. Maternal hypotension is the most common side effect of a successful epidural block. Since, with a decrease in blood pressure, the possibilities of autoregulation of the uteroplacental blood flow are sufficiently preserved, one should not panic if this complication occurs. However, the preservation of normal placental blood flow during arterial hypotension due to compensatory mechanisms can easily be disturbed, especially in pregnant women with preeclampsia, diabetes and uteroplacental insufficiency. For this reason, continuous monitoring of the fetus in the delivery room is necessary to assess how it responds to maternal hypotension. To correct hypotension caused by epidural blockade, it is usually sufficient to increase the rate of intravenous infusion.

4. Intravascular ingestion of an anesthetic can manifest itself as a slow development of toxic effects. Timely noticed, this complication quickly passes when the catheter is where it needs to be - in the epidural space.

5. Accidental puncture of the dura with a subdural catheter may occur with small-diameter sharp needles when the usual resistance loss landmarks are reduced and the needle can easily pass through the dura. Approximately half of these patients develop post-puncture pain syndrome, including headache. The frequency of this complication, even in experienced hands, is 0.5-1%. Epidural analgesia sometimes contributes to the occurrence of hyperthermia in childbirth. This effect is associated with sympathetic blockade and disruption of normal thermoregulation, and is not too dangerous.

Absolute contraindications to epidural analgesia in childbirth are:

1) lack of qualified anesthesia personnel and equipment for round-the-clock monitoring, both during childbirth and in the postpartum period;

2) infectious inflammation at the puncture site, as well as septicemia;

3) coagulopathy, confirmed by laboratory or expected due to the nature of the existing pathology;

4) anatomical anomalies: splitting of the vertebral arches or myelomeningocele, pronounced kyphoscoliosis (caudal access is possible), congenital malformations of the vascular system of the spine.

Relative contraindications:

1) anatomical or technical difficulties in performing a puncture or catheterization of the epidural space (obesity, curvature of the spine),

2) lack of consciousness or insanity of the patient;

3) uncorrected hypovolemia;

4) neurological diseases, for example, multiple sclerosis;

5) heart disease in the absence of full hemodynamic monitoring.

Spinal methods of analgesia with narcotic analgesics

Epidural analgesia with concentrated solutions of local anesthetics can sometimes prolong the duration of the first and second stages of labor, and then there is a need for the use of oxytocin or for operative delivery. These shortcomings have stimulated clinicians to search for other pharmacological agents capable of inducing a sufficient level of analgesia when administered epidurally or subdurally.

For the first time, data that the subarachnoid administration of narcotic analgesics causes analgesia in humans appeared in the late 70s. In the 1980s, the use of opioids for epidural and subdural anesthesia began to spread in obstetric anesthesiology. Both methods provide good analgesia when using low doses of drugs and give less dangerous side effects compared to autoanalgesia with intravenous administration of narcotic analgesics.

The requirements for the use of narcotic analgesics in the epidural and subdural route of administration are very simple: long-term analgesia should be provided with a small dose of the drug and be accompanied by minimal resorptive effects.

Small doses of epidural or subdural narcotic drugs can provide adequate analgesia in the parturient woman with minimal side effects on both the mother and the newborn. With intravenous or intramuscular use of large doses of narcotic analgesics, these effects are always significantly greater.

The standard technique for epidural analgesia in labor involves the administration of a bolus dose of local anesthetics followed by a continuous infusion. The first reports of satisfactory analgesia in labor with epidural morphine instead of local anesthetics caused disbelief. Subsequent studies have shown that the use of low doses of morphine in epidural anesthesia (2.0-5.0 mg) does not provide satisfactory pain relief during contractions. Morphine in doses of 7-8 mg causes prolonged analgesia, which can last up to 24 hours. The main disadvantage is the slow development of analgesia (from 30 to 90 minutes) and severe side effects. Most parturient women note insufficient analgesia, accompanied by nausea, vomiting and pruritus. It is also very important that the fetus is at risk of exposure to high doses of morphine, which crosses the placental barrier well.

The use of fentanyl (150-200 mcg) for epidural analgesia has made it possible to achieve more significant success. Long-term infusions into the epidural space of low doses of fentanyl (2.5 μg/hour) provide effective postoperative analgesia in general surgical patients, which can also be used in parturients. Epidural administration of 50-200 μg of fentanyl causes a rapid (after 5-10 minutes) onset of analgesia, but, unfortunately, the effect does not last long (1-2 hours). Rapid and prolonged pain relief with minimal side effects can be achieved with a combination of low doses of morphine and fentanyl. Such analgesia occurs a few minutes after the administration of the drugs and lasts 4-5 hours. Usually this is enough for childbirth. Due to the sharp reduction in doses of drugs administered in such a combination, the side effects and complications of each of them are minimized. The combination of epidural administration of narcotic analgesics and local anesthetics gave an excellent result. The addition of fentanyl (50-150 mcg) improves the quality of analgesia compared to using only a local anesthetic. Newborn Apgar scores, umbilical cord blood gases, and neurologic status remain normal.

Of particular interest is the use of narcotic analgesics such as agonist-antagonists. For example, stadol (butarphanol) is an opioid K-receptor agonist and an M-receptor antagonist. Therefore, it has not only analgesic properties, but also has a sedative and antitussive effect, increases blood pressure, etc. Epidural use of stadol together with local anesthetics during contractions can reduce the side effects of both drugs, but at the same time provide full and prolonged anesthesia without blockade of motor nerves.

The only side effect observed with this is somnolence, which increases with dose, but does not require any treatment. Angar fetal assessment, umbilical cord blood gases, and neurologic tests remain normal. Thus, stodol-type agonists-antagonists can be used together with local anesthetics and their effect is comparable to the effects of morphine or promedol.

The first drug that began the use of narcotic analgesics for subdural analgesia of contractions was the same morphine. Women in labor did not feel pain, but "felt" contractions and, therefore, the blockade with narcotic analgesics was not as absolute as the blockade with local anesthetics. This may be recommended for those women who need pain relief while actively participating in childbirth. Although subdural analgesia with morphine gives good results in the first stage of labor, it is completely ineffective in the second. But to achieve pain relief in the first period, only 0.5 mg of morphine is enough.

Since the drug is injected directly into the cerebrospinal fluid, morphine provides sufficiently effective analgesia at much lower doses than with epidural administration. High concentrations in the cerebrospinal fluid during subdural analgesia can be achieved with the introduction of even 0.25 mg of morphine. The exact dosage has not yet been determined, but subdural doses in the range of 0.5-1.5 mg of morphine are, in our opinion, optimal.

Although subdural analgesia with morphine provides adequate pain relief during contractions, the method is not without its drawbacks.

Firstly, this use of the drug does not provide the controllability and flexibility that epidural analgesia with local anesthetics in the form (PEIA) gives us. If surgery is required during childbirth, such as the application of obstetrical forceps or an episiotomy, the addition of local anesthetics is required. Subdural analgesia with narcotic analgesics provides analgesia for visceral pain, i.e., only in the first stage of labor.

Secondly, the onset of analgesia occurs only after 45-60 minutes, therefore, the doctor must do subdural analgesia with morphine before the cervix has dilated by 3-4 cm and the contractions are relatively painless. The use of subdural anesthesia and analgesia with large doses of morphine may be accompanied by nausea, vomiting, urinary retention, discomfort and respiratory depression. It develops as a result of a general resorptive action.

The course of labor and the degree of cervical dilatation practically do not change with epidural or subdural analgesia with morphine (1-2 mg). However, epidural anesthesia with fentanyl or stadol combined with local anesthetic solutions can significantly shorten the first stage of labor.

The use of narcotic analgesics for subdural analgesia may find its place in cases where the cardiovascular and neuromuscular effects of local anesthetics are undesirable or even dangerous. For women in labor with concomitant cardiac pathology, the likelihood of complications increases at times of a sharp increase or decrease in total vascular resistance. This can be avoided if narcotic analgesics are used for epidural or subdural analgesia, while excluding the introduction of local anesthetics. The use of subdural analgesia with morphine may be useful in pregnant women with hypertension. For patients with aortic stenosis, Fallot's tetrad, Eisenmenger's syndrome, coarctation of the aorta, subdural analgesia with the use of narcotic analgesics is the method of choice for labor pain relief.

Effective analgesia, which is carried out with small doses of narcotic analgesics, eliminates not only the pain stress factors of the mother, but also reduces the risk of complications in the fetus. Narcotic analgesics pass through the placenta very quickly, which is another factor limiting their dose. Fentanyl (75 μg) injected into the epidural space crosses the placental barrier, but this does not show signs of drug-induced depression in the newborn.

The most dangerous side effect of this method is respiratory depression. Clinical experience suggests that the period of greatest risk of developing this complication is between 4 and 8 hours after the start of epidural analgesia, when the drug is distributed by the cerebrospinal fluid to the centers of respiratory regulation.

Within 2 hours, drugs should not be administered orally, intramuscularly, intravenously, or subcutaneously, unless prescribed by an anesthesiologist. It is necessary to carry out respiratory monitoring (respiratory rate, pulse oximetry), and in its absence, check the respiratory rate every 30 minutes for the first 12 hours, then every hour until 24 hours have elapsed from the moment the narcotic analgesic was administered. Keep the catheter in the vein with a heparin closure. Near the patient there should be tools, devices and medicines necessary for respiratory resuscitation (intubation kit with a laryngoscope, etc., naloxone in ampoules, etc.).

As a complication, nausea, vomiting, itching and urinary retention can occur. To treat these complications, you can use:

1) naloxone 0.25 ml (0.1 mg) every 15 minutes. in / in three times,

2) if there is no effect within 45 minutes, continuous intravenous administration of naloxone 0.2 mg/hour in a 0.4% solution should be started. If the situation does not improve within 60 minutes, increase the rate of administration to 0.4 mg/hour.

With the resumption of pain, the question of additional anesthesia is decided only by the anesthesiologist.

3) Cerucal 10 mg IV every 2 hours to eliminate nausea.

The most common side effect of epidural or subdural analgesia with narcotic analgesics is pruritus. The mechanism of pruritus is not fully understood, but it does not appear to be related to histamine release. Itching is dose-dependent and increases with an increase in the concentration of narcotic analgesic in the cerebrospinal fluid. Most often it appears with the use of morphine, less often with the use of fentanyl or promedol. Pyritramide (dipidolor) can be used for epidural anesthesia. Intravenous administration of naloxone (0.1-0.2 mg) is very effective in eliminating this side effect.

Urinary retention is a very annoying side effect, but in most women this problem is easily solved by catheterization of the bladder.

Thus, epidural and subdural analgesia with narcotic analgesics in obstetrics has proven itself very well. However, it should be remembered that these methods, which have many advantages, can be used with a good understanding of the essence of the method, the clinical pharmacology of the drugs used, and the clinical physiology of the functional changes that occur in the body. Adequate continuous monitoring of the condition of women in labor is necessary, especially when the doctor is still mastering this method. In the hands of an experienced specialist, any method looks like a beneficial miracle, no matter what dangers lurk in the essence of the method. But the best method can be discredited by inept and illiterate followers.

Rice. 2. Dependence of the use of labor pain relief methods on the intensity of pain and the degree of cervical dilatation.

Based on the above information, we propose the following scheme for the use of anesthesia methods in childbirth (Fig. 2).

Anesthesia for violations of the contractile function of the uterus

At present, the problem of contractile activity of the uterus is the most relevant in modern obstetrics, because a significant part of the pathological conditions that occur during pregnancy and childbirth are associated with a violation of the motor function of the uterus. Previous studies indicate the undoubted role of neurohumoral regulation functional state uterus. The leading role in this process is played by the hypothalamus and structures of the limbic complex, primarily the amygdala nuclei and cortical formations in the temporal lobes of the cerebral hemispheres. The placenta, ovaries and other endocrine glands also have a regulatory effect on the motor function of the uterus. The uterus, as an effector, plays a certain role in the nature of labor activity and, in a feedback manner, influences other competent systems. The role of the central corrective link belongs to the amygdala complex and the hypothalamus, which provide the female sexual functions.

The act of childbirth proceeds in the presence of a formed generic dominant, which unites both higher nerve centers and executive organs into a single dynamic system. A special role in the contractile activity of the uterus is assigned to chemoreceptors, which include cholinergic and adrenoreceptors. Recently, a close relationship has been found between the hormonal activity of the fetus and the placenta, which gives reason to talk about the so-called feto-placental unit or feto-placental system, which plays an important role in regulating the contractile activity of the uterus.

Most authors point to the role of estrogens, which enhance the synthesis of proteins of the actomyosin complex, enhance energy metabolism, increase the activity of enzymatic reactions, and ripen the cervix.

Since the onset of labor activity, the contractile function of the uterus is closely related to the intensity of tissue metabolism of the myometrium, the level of energy metabolism. In the dynamics of childbirth, metabolic processes reach the highest level, which is associated with a significant expenditure of energy. The proportion of anaerobic glycolysis, metabolic acidosis increases.

Except enzyme systems, hormones, mediators, biologically active compounds take part in the regulation of labor activity.

In addition to the regulation of labor activity, all of these factors are involved in the regulation of blood circulation, change the permeability of cell membranes, the hemostasis system, etc.

Violation at one of these stages, of course, leads to a violation of labor activity. Under the influence of labor, especially of a protracted nature, there are persistent changes in many metabolic processes that lead to a rapid depletion of the body's energy resources.

In addition, the weakness of labor activity leads to a violation of the neuropsychic state of a woman, an increase in the frequency of surgical interventions, the frequency of asphyxia of the fetus and newborn. Perinatal mortality increases sharply, ranging from 10.3 to 37.5%. Maternal mortality in this pathology is 0.7-2.8%.

Hypertensive disorders of the contractile activity of the uterus are less common than hypotonic. The essence of this pathology, according to I.S. Sidorova (1997), is to change the functional balance of the autonomic nervous system with the dominance of the influence of the parasympathetic part, hyperproduction of acetylcholine, which causes contraction of the circular muscles of the uterus. Often there is a lack of synchrony of contractions and relaxations of various parts of the uterus. Of particular risk in this pathology are such formidable complications as placental abruption, uterine rupture, bleeding due to combined abnormalities of the contractile activity of the uterus and a violation of the hemostasis system.

The following forms of uterine dysfunction are distinguished: pathological preliminary period, discoordination of labor, rapid labor, segmental dystocia, uterine tetanus. A pathological preliminary period is observed in women with endocrine disorders, obesity, autonomic neuroses, neurocirculatory vascular dystonia, in the presence of fear of childbirth, in pregnant women with aggravated obstetric history, complicated by the course of this pregnancy, in nulliparous women, etc.

The pathological preliminary period is a kind of protective reaction of the pregnant woman's body, aimed at the development of contractions, in the absence of sufficient readiness for childbirth, and, above all, the uterus. This reaction is realized through an increase in the contractile activity of the uterus, usually discoordinated, aimed at maturation of the cervix and its opening.

The pathological preliminary period is characterized by painful irregular contractions, pain in the lower abdomen, in the sacrum and lower back, lasting more than 6 hours, sometimes several days, disrupting the daily rhythm of sleep and wakefulness, causing woman fatigue and signs of fetal suffering. The main etiological moments leading to the development of clinical manifestations of the pathological preliminary period are functional changes in the central nervous system, which has been proven by encephalographic studies. Autonomic and endocrine disorders also testify to this.

It should be borne in mind that with a long preliminary period, energy consumption increases, which leads to a rapid depletion of energy resources and the development of weakness of tribal forces. If this is accompanied by prenatal rupture of amniotic fluid against the background of an "immature" cervix, it is necessary to assume the presence of deeper violations of the neuroendocrine and myogenic regulation of the contractile activity of the uterus.

Treatment of the pathological preliminary period should begin with central regulation by introducing sibazon, seduxen, diazepam intramuscularly at a dose of 10 mg or intravenously in 20 ml of isotonic sodium chloride solution. With a prolonged (10-12 hours) preliminary, when, after the administration of Seduxen, irregular pains continue to bother the pregnant woman and she is tired, it is necessary to introduce 10-20 ml of a 20% GHB solution. At the same time, treatment aimed at maturation of the cervix is ​​indicated.

When the cervix is ​​not ready, it is necessary to use estrogens (20,000 IU each), PG E2 preparations (prostenon, diprostone, prepedil-gel), antispasmodics (baralgin, no-shpa, etc.). It is not recommended to use shortening drugs for any kind of discoordination of labor activity.

Adequate timely treatment of discoordination of labor, as a rule, contributes to its normalization. The choice of appropriate therapy and prognosis of childbirth is carried out taking into account the age of women, obstetric and somatic anamnesis, the course of pregnancy, and an objective assessment of the condition of the fetus.

In case of discoordination of labor activity, a pathogenetically justified method of therapy is long-term epidural anesthesia.

Discoordination of labor activity may also be due to incorrect tactics of labor management, in particular repetition, unsystematic use of oxytotic drugs. In this case, an overdose of these drugs can lead to hypoxia and even death of the fetus.

A fairly common anomaly of labor activity is weakness, which is diagnosed on the basis of insufficient activity of the uterus, a decrease in the rate of smoothing of the cervix and opening of the uterine os, prolonged standing of the presenting part of the fetus at the entrance to the small pelvis and its slow advancement in accordance with the size of the pelvis. At the same time, the duration of childbirth increases, fatigue of the woman in labor is observed.

Before the appointment of labor-stimulating drugs in the presence of fatigue in childbirth, it is necessary to provide the woman with rest in the form of pharmacological sleep. Proper and timely provision of rest leads to the restoration of impaired functions of the central nervous system. In these situations, rest helps restore normal metabolism in the uterus.

In order to provide women in labor with rest, morphine, pantopon, promedol are used in combination with diphenhydramine, sibazon, etc. This scheme can be carried out by an obstetrician-gynecologist (midwife) without an anesthesiologist.

In the presence of an anesthesiologist, the steroid anesthetic viadryl (predion, prosuren, hydroxydione) is successfully used for fatigue in childbirth. Being similar to the natural metabolites of the human body, Viadryl has low toxicity and a wide range of therapeutic effects. In narcotic doses, it causes sleep similar to physiological. Among the positive qualities of Viadril, its antispasmodic and anticholinesterase action should be emphasized. From side effects it should be noted respiratory failure, the appearance of phlebitis at the injection site.

You must use the following method. For 15-20 minutes, premedication is carried out by introducing 20 mg of promedol, 25 mg of diprazine and 1 mg of metacin. To eliminate the irritating effect of Viadril on the intima of the venous vessel, the so-called "sealed" solution is introduced. To do this, 15 ml of a 2.5% solution of viadryl preheated to 35-36 ° C is drawn into a twenty-gram syringe. Then the vein is punctured and 5 ml of blood is drawn into the syringe with Viadryl (20 ml of the solution in total). Blood, mixing with viadryl, is a kind of buffer for it, when the degree of alkalinity of the solution decreases, and the protein components of the blood reduce the irritating effect of viadryl on the intima of the veins (pH of the resulting solution is 8.6). Before and after the administration of Viadril at a dose of 8-10 mg/kg. weight, 5 ml of a 0.25% solution of novocaine is injected intravenously. When using this technique, anesthesia proceeds in stages I-II.

Another way to treat fatigue in childbirth is the use of GHB - gamma-aminobutyric acid. Narcotic action of GHB of cortical origin. The drug has a pronounced hypothermic effect, does not disrupt energy metabolism, respiratory phosphorylation processes. The antihypoxant effect of GHB is realized by reducing the degree of acidosis, lactate levels, and normalizing the hormones of the pituitary-adrenal system. The drug has a sedative effect, enhancing the effect of analgesics. However, with its introduction, motor excitation is possible in the form of convulsive twitching of the limbs, impaired respiratory function. In this regard, GHB is recommended to be administered slowly (1-2 ml per minute) after the preliminary administration of sibazon (5-10 mg) at the rate of 40-60 mg/kg of the mother's weight.

Since 1971 L.S. Persianinov, N.N. Rastrigin and E.M. Kastrubin obstetric practice introduced the method of electroanalgesia. It was found that its use makes it possible to achieve a stable vegetative balance, to avoid allergic reactions that may occur when using pharmacological drugs (neuroleptics, ataractics, analgesics).

Unlike pharmacological preparations, the use of pulsed current makes it possible to obtain the so-called "fixed" stage of therapeutic analgesia, which makes it possible to maintain consciousness during the birth act, verbal contact with the woman in labor without signs of her excitement and transition to the surgical stage of anesthesia.

For therapeutic analgesia in case of fatigue in childbirth, domestic devices "Electronarkon-1", "Lenar" are used. Before applying the electrodes, 15 minutes before the start of exposure to pulsed current, premedication with promedol 1 ml of a 2% solution (20 mg), 1 ml of a 2.5% solution of diprazine (25 mg), 1 ml of a 0.1% solution of metacin (1 mg) is carried out. Before applying the electrodes, the skin of the forehead and neck is wiped with alcohol. Gauze napkins are placed under the electrodes in 8-10 layers (3x3 cm), soaked in 0.9% sodium chloride solution. The cathode (negatively charged electrode) is applied to the forehead, the anode (positively charged electrode) is placed on the area of ​​the mastoid processes. After fixing the electrodes, the device is connected. The pulse repetition rate is set within 750 Hz, the pulse duration is 0.5 ms. Then, the pulsed current slowly increases to threshold sensations (tingling, crawling) in the area of ​​the electrodes. Every 15-20 minutes it is necessary to increase the average current value by turning the "pulse current" knob or by increasing the pulse repetition rate to 1000-1500 Hz. The average value of the current in this pathology is 0.8-1.2 mA with a session duration of 1.5-2 hours.

It should be pointed out that in the presence of a hypertensive syndrome, the administration of Viadril or GHB is recommended. On the contrary, in women in labor with hypotension, tachycardia, a tendency to thrombosis, in the presence of the so-called "full" stomach, the use of therapeutic electroanalgesia is the main method of therapy.

In the presence of such risk factors as a burdened obstetric and gynecological history (infertility, induced pregnancy, etc.), extragenital pathology, preeclampsia, chronic fetal hypoxia, it is advisable to choose the method of delivery by caesarean section without the above therapy.

This is due to the fact that all the factors described are dangerous for the life of a woman and her fetus with conservative management of childbirth. In addition, with discoordination of labor, complications such as uterine rupture, amniotic fluid embolism, placental abruption and, as a result, hypotonic and coagulopathic bleeding, may occur.

It must be remembered that with this pathology and the presence of a hypertensive syndrome, it is impossible to use ganglionic blockers that inhibit the secretion of catecholamines, leading not only to hypotension of the uterus, but also to the occurrence of ischemic damage to the fetal brain.

Control over the course of childbirth is carried out with constant medical supervision, cardiomonitoring monitoring of the cardiac activity of the fetus and the contractile activity of the uterus; a partogram is required. Childbirth with discoordination of labor activity must be carried out in the presence of an anesthesiologist for the timely provision of resuscitation, especially in the case of the use of viadryl, GHB. At the time of the birth of a child, a neonatologist who knows the methods of resuscitation should be in the delivery room.

Pathophysiological basis of development intrauterine hypoxia fetus

The leading role among the direct causes of perinatal morbidity and mortality belongs to fetal hypoxia. The significance of hypoxia in perinatal pathology is not limited to high stillbirth rates. Hypoxic changes in the antenatal period often lead to severe lesions of the central nervous system in a newborn child. According to the observations of a number of authors, many children who have undergone intravenous hypoxia subsequently die from its consequences. The percentage of such children is from 12.8-26.0 of the total contingent.

A special group of perinatal pathology is represented by newborns with fetal growth retardation syndrome (FGR) and low birth weight. Perinatal morbidity and mortality among this group is 5-8 times higher than in the general population. Thus, prematurely born children account for 60% of stillbirths, 50-70% of neonatal and 48-66% of infant mortality.

It is known that intranatal hypoxia can be caused by various forms obstetric complications and extragenital diseases.

The main factor in the development of the hypoxic state of the fetus is placental insufficiency. The latter manifests itself in the form of chronic or acute fetal hypoxia, which often manifests itself in a delay in its development. The frequency of detection of chronic placental insufficiency ranges from 8 to 33%, in 20-40% of cases it is the cause of perinatal morbidity and mortality. With placental insufficiency, the reserve capacity of the feto-placental system (FPS) as a whole and the fetus is significantly reduced. In this regard, the ability to develop adequate adaptive reactions under various stressful situations and extreme conditions during pregnancy and childbirth, during anesthesia, especially when combined with FGR and chronic or acute fetal hypoxia.

With severe sdfd, especially developed against the background of gestosis, the severity of gestosis, as a rule, correlates with the severity of sdfd and placental insufficiency. Moreover, according to a number of authors, fetal growth retardation can be due to both the pathology of the maternal organism, and the fetus itself and the placenta. The level of perinatal pathology in women with small fetuses is affected not only by maternal diseases leading to miscarriage, but also by long-term drug therapy for this pathology.

Several classifications of placental insufficiency syndrome can be found in the literature. For example, Kulbi et al. (1969) distinguish between chronic (throughout pregnancy), subacute (developing immediately before the onset of childbirth) and acute placental insufficiency. Botella-Llusia (1980) considers it more rational to isolate chronic (during pregnancy) and acute (during childbirth) forms in the symptom complex of placental insufficiency. However, placental insufficiency is more of a clinical than a pathophysiological or pathomorphological concept, since changes in the placenta are the result of various pathogenetic factors.

In the development of hypoxia, great importance is attached to disorders of the uteroplacental circulation and blood flow velocity.

There are a number of factors on which an adequate supply of oxygen to the fetus depends. These include maternal, including extragenital diseases, smoking and alcohol abuse. Uterine factors include a decrease in uteroplacental blood flow due to late preeclampsia or concomitant extragenital diseases, a violation of the contractile activity of the uterus, morphological changes in the spiral arteries. There are also directly placental factors, including inflammatory changes, heart attacks and thrombosis of the placenta, and fetal factors, which include Rhesus conflict, malformations, etc.

Thus, fetal hypoxia is not an independent pathology, but is due to a variety of clinical pathologies of the pregnant woman. Moreover, in the structure of perinatal mortality, fetal hypoxia ranks first, malnutrition accounts for 5.7 to 30%.

Before presenting the pathogenesis of the development of fetal hypoxia, it is necessary to know the conditions under which the fetus resides during normal physiological pregnancy. Previous studies have shown that the supply of oxygen to the fetus and under physiological conditions is reduced compared to the adult body. Moreover, the increased tolerance to oxygen deficiency in the fetus and newborn is explained by the presence of adaptive mechanisms developed even at the stage of intrauterine development, due to the action of the hypoxic factor in the embryonic period. It was found that at a gestational age of 22-23 weeks, the pH value from the umbilical cord vein (arterial blood) is 7.34 (0.04), from the umbilical cord artery (venous blood) - 7.33 (0.017). At the end of physiological pregnancy, the shift in the pH of the fetal blood towards the acidic reaction becomes greater, the pH of the arterial blood is 7.28 (0.97). There is an increase in base deficiency up to 11.05 (2.4 mmol/l of blood). Similar changes, i.e., the phenomena of metabolic acidosis, were also found in a pregnant woman.

It is known that gas exchange in the placenta is similar to gas exchange in the lungs. At the same time, fetal gas exchange is more dependent on the rate of uteroplacental blood flow than on the diffusion properties of the placenta. As a result of the peculiarities of the fetal circulation (the functioning of the three arteriovenous shunts), almost all organs of the fetus receive mixed blood. In the most favorable conditions is the fetal liver, which is the only organ that receives almost purely arterial blood (oxygen saturation of about 80%). Sufficiently oxygenated blood also enters the coronary arteries and vessels that feed the brain (oxygen saturation - 68%), the lungs of the fetus, the lower part of the body are in the worst conditions. However, these tissues under normal conditions of existence do not suffer from a lack of oxygen, as evidenced by the rate of oxygen uptake by fetal tissues (4 ml of oxygen per 1 min per 1 kg of weight), equal to that of an adult. This is due to an increase in fetal cardiac output, which is 198 ml/kg compared to 70 ml/kg in adults. The heart rate increases due to increased blood flow. An important role in maintaining normal fetal homeostasis is the presence of fetal hemoglobin, anaerobic glycolysis, which is the most beneficial and economical, as it leads to the release of much less energy.

At the end of physiological pregnancy, due to the predominance of the anaerobic pathway of glycolysis, the content of lactate and pyruvate in cord blood is 2 and 1.5 times higher than in the mother's blood. In childbirth, the intensity of glycolysis processes increases slightly, which indicates the absence of an increase in oxygen deficiency in the dynamics of labor activity. Of all energy and plastic materials, glucose is the main product of metabolism. During physiological childbirth in newborns, in 46.7% of cases, the level of glucose in the umbilical cord blood is within the normal range (3.5-5.5 mmol / l), hyperglycemia is noted in 33.3%, and hypoglycemia is observed in 11.1% (level glucose 2.2 mmol/l).

The presence of the so-called natural hypobiosis was revealed in the fetus during the physiological course of pregnancy and childbirth. This is evidenced by the anaerobic pathway of glucose breakdown according to the determination of LDH and MDH in the umbilical cord blood of the fetus, the presence of hypoglycemia (glucose fluctuations from 2.1 to 3.4 mmol / l), metabolic acidosis, a decrease in the concentration of ACTH and cortisol to 22.5, respectively ( 0.8 pmol / l) and 849 (18.7 nmol / l) in cord blood and hormone levels of the pituitary-thyroid system: T3 up to 1.56 (0.02 ng / ml), T4 up to 10.83 (0. 41 ng / ml) and TSH up to 2.13 (0.1 mIU / ml), the appearance of bradycardia in the fetus in the second stage of labor. Moderate hypoproteinemia is noted: protein - 48.7 (4.5 g / l), an increase in lactate in cord blood by almost 1.4 times compared with maternal blood data up to 4.9 (0.2 μmol / l). There is also a decrease in the level of glucose, potassium, sodium and calcium compared with the values ​​in the umbilical cord blood. At the same time, with a high degree of functional readiness and structural differentiation of the endocrine apparatus, literature data indicate a decrease in its reactivity. If we take into account that at high concentrations of hormones, the processes of oxygen uptake are enhanced, the metabolism of proteins, fats and carbohydrates is accelerated, the synthesis and breakdown of lipids are stimulated, then it is under conditions of a reduced content of these hormones that the fetus creates more optimal conditions for the functioning of vital body functions. Moreover, this decrease, according to a number of authors, is of a protective and adaptive nature, ensuring the economical use of oxygen.

There is a high significant correlation between the partial tension of oxygen in the mother's blood and amniotic fluid (r=0.734), between the saturation of this substrate in the studied parameters (r=0.439), a decrease in the dynamics of labor in the pH value of the amniotic fluid from 7.258 (0.07) to 7.049 (0.012), increase in pCO2 from 42.7 (2.1) to 48.8 (2.2) mm Hg. Art. and a decrease in pO2 from 64.5 (4.0) to 47.5 (5.0 mm Hg).

In the early neonatal period, a rapid drop in glucose begins. In most newborns, even a significant decrease in its level in the blood does not entail clinical symptoms. A number of authors explain the appearance of hypoglycemia with insufficiency of the insular apparatus and glycogen-forming function of the liver and muscles in newborns, or hyperinsulism. Other researchers have shown that newborns do not have a compensatory reaction to the hypoxic factor in the form of hyperglycemia, explaining this by the immaturity of the glycogen function. That is, most authors explain hypoglycemia by immaturity or imperfection of certain systems of the newborn. At the same time, hypoglycemia is typical for both premature and healthy full-term newborns.

The concentration of urea, as the end product of protein metabolism, in cord blood is within the normal range (from 3.5 to 3.8 mmol/l). If we take into account that the synthesis of cellular protein is carried out by the tissues of the fetus mainly from amino acids and carbohydrates, then the products of its catabolism are nitrogen-containing substances (ammonia), some of which are resynthesized. The rest is excreted from the body in the form of urea and uric acid. Considering the normal values ​​of urea, it can be assumed that in the process of uncomplicated pregnancy and childbirth, there is a physiological ratio of anabolic and catabolic reactions of protein metabolism.

The most pronounced changes were found in the electrolyte balance of the blood. Cord blood shows hypernatremia, hyperkalemia. At the same time, there is a directly proportional relationship between the concentration of Na+ and K+ in plasma and erythrocytes. Their level in plasma exceeds these indicators in blood erythrocytes, that is, there is a certain dependence of their cellular reserves in fetal erythrocytes. Similar changes in the biochemical parameters of the fetal blood were also found in small children. The concentration of Ca+ in the umbilical cord blood plasma is also relatively high compared to its concentration in the mother's blood. This is due to the accumulation of Ca+ in recent months pregnancy and an increase in albumin-associated fraction. It can be assumed that a high concentration of electrolytes may be due to the existing acidosis and, as it were, a compensatory reaction of the fetus to acidotic changes in its body.

When analyzing the literature data, it was found that the fetus, during its normal existence, has a reduced reactivity, refractoriness and other vital systems of the fetus, in particular the pituitary-adrenal and thyroid systems. It has been established that these systems function from the earliest period of antenatal ontogenesis. However, by the time of birth, they remain qualitatively immature. A low phagocytic and lysozyme activity of properdin in the blood serum of newborns, which is one of the factors of nonspecific protection, was also found. There is also a low interferon-synthesizing activity of leukocytes, which is two times lower than in adults.

With regard to thermoregulation of newborns, there is a complete readiness for the implementation of this function, on the other hand, its imperfection, immaturity, and insufficiency. At the time of the birth of the head and the whole body, as a rule, there is a lack of spontaneous movements, proprioceptive and exteroceptive reflexes, muscle atony and deep inhibition of the wakefulness function. The fetus does not respond to intense stimuli of the skin and proceptive, visual, auditory and olfactory analyzers. This functional unresponsiveness to various intense external stimuli indicates a deep inhibition of the fetal central nervous system and can simply be qualified as a deep phase of slow or paradoxical sleep. The fetus at this moment is, as it were, in a state of deep anesthesia with respiratory arrest or resembles an animal in a state of hibernation.

In connection with the foregoing, until recently, all changes in the body of the fetus were interpreted as the result of immaturity, imperfection of the vital functions of the body. However, the work of a number of researchers has shown that the fetus under physiological conditions of existence is characterized by refractoriness, hypo- or unreactivity. It is this nature of metabolic processes, according to their data, that is a kind of protection for the fetus - this ancient protective mechanism of hypobiosis. This concept is also confirmed by the works of N.I. Sirotin (1981), who showed that during hibernation the reactivity of animals decreases, while their resistance increases. These include hyporeactivity, a reduced level of metabolic processes, a predominantly anaerobic pathway for the breakdown of glucose, hypoglycemia, acidosis, etc.

Hypoxic conditions of the body, often accompanying childbirth, serve as the basis for many diseases of the fetus and newborn. The basis of hypoxic damage, first of all, is the limitation of oxygen delivery to tissues.

The existing classifications distinguish from 4 to 8 types of hypoxia and its various stages from latent to terminal. Most researchers distinguish 4 types of hypoxia: hypoxic, hemic, circulatory and histotoxic. In recent years, it is planned to add a fifth type of hypoxia - tissue hypoxia, resulting from an increase in the affinity of hemoglobin for oxygen.

Hypoxic, circulatory, hemic hypoxia may occur primarily as a result of the pathological course of pregnancy, childbirth, or disease of the fetus itself. Tissue hypoxia is a rare form and occurs secondarily as a consequence of other forms of oxygen deficiency.

There is another classification in which arterial-hypoxemic, ischemic, hemodynamic, peripheral shunting, mixed pathogenetic forms of hypoxia are distinguished.

In this case, the lack of oxygen is the leading factor in all types of hypoxia, except for tissue. There is not only a decrease in the oxygen content in the tissues, but also a violation of the processes of its utilization. The end result of oxygen starvation is a deficiency in the energy balance of the cell, insufficiency of oxidation substrates, a lack of enzymes, a decrease in the activity of coenzymes, and uncoupling of the processes of oxidation and phosphorylation. An important role belongs to changes in the Krebs cycle, which is the main donor of hydrogen atoms and reduced forms of nicotinamide adenine nucleotides.

However, fetal hypoxia cannot be completely identified with a specific level of pO2, and even a significant decrease in the partial oxygen tension of a tissue (cell) is not yet an absolute indicator of a violation of its oxygen demand, since the metabolic activity of the cell itself, i.e., cellular pO2 is not always a criterion for a hypoxic state, since with oxygen deficiency a complex of compensatory-adaptive mechanisms is activated.

The main role in adaptation to hypoxia usually plays an increase in cardiac output. Although, according to N. Alexander, with fetal hypoxia, only a reaction in the form of bradycardia is noted, cardiac output remains at a constant level. Only with the hemic form of hypoxia, there is a decrease in cardiac output and blood flow in all organs by almost 30-50%, except for the brain, where a decrease in these functions occurs only by 9%. There is a redistribution of blood flow in the brain. Hypoxia leads to vasodilation and the discharge of blood from the hemispheres into the brain stem. It is known that the reaction of the fetal brain to a change in the oxygen content is of a threshold nature: for example, a decrease in blood pO2 to 40 mm Hg. Art. does not entail changes in cerebral blood flow, but with a further decrease in pO2, cerebral blood flow increases sharply. The peculiarity of maintaining blood flow in critical areas of the brain stem is rather a protective character for the hypoxic factor and an explanation for the long-term survival of newborns in conditions of hypoxia. The reaction to a change in the partial voltage of carbon dioxide looks completely different. Any fluctuation of it leads to an increase or decrease in cerebral blood flow, a decrease in the electrical activity of the brain. An important role in the development of hypoxic syndrome belongs to the resulting acidosis, which has a significant effect on the permeability of vascular and cell membranes, tissue hydration, the rate of enzymatic catalysis, and blood clotting. Moreover, the degree of damage to organs and tissues depends on the duration and intensity of oxygen starvation, as well as on the adaptive capabilities of the fetus, the degree of maturity of its organs and systems.

The phenomena of metabolic acidosis are increasing. Oxygen deficiency and acidosis increase the permeability of cell membranes, as evidenced by the high activity of a number of intracellular enzymes (lactate-malate-succinate dehydrogenase).

The greatest changes occur in the balance of potassium. An increase in catabolic processes leads to a decrease in the formation of ATP, as a result of which potassium is not absorbed. Intracellular potassium is replaced by sodium, which draws water into the cell space, resulting in intracellular edema. Hyponatremia leads to extravascular edema of organs and tissues, contributing to the release of fluid from the vascular bed. Quantitative changes in electrolytes also lead to violations of the ratios of each electrolyte at the level of cell membranes. The Napl/Kpl, Capl/Mgpl ratio decreases, the Kpl/Capl ratio increases, which has an undeniable effect on the fetal cardiac activity.

There is also a significant restructuring of carbohydrate metabolism. So, the content of lactate increases in the liver of the mother, in the liver of the fetus and in the blood of the mother. At the same time, the patterns of lactate metabolism towards the mother are preserved? fetus, pyruvate exchange mainly mother? fetus, thus providing the fetus with an important substrate for metabolism. The strengthening of anaerobic processes in the mother's body is a response to the hypoxic factor, providing the fetus with the necessary energy substrates.

With oxygen deficiency, the sympathetic-adrenal system is activated, as a result of which catabolic processes predominate in the body. Hypoxia, limiting the resynthesis of ATP in mitochondria, causes a direct depression of the functions of various systems of the fetal body. The content of the biologically active and protein-bound plasma fraction of cortisol increases. At the same time, a large amount of catecholamines is produced, and the content of norepinephrine in the blood is 2 times higher than the amount of adrenaline. Thyroid hormones also change their hormonal direction.

For a long time in obstetrics and neonatology, there was an idea that hypoxia primarily affects the enzymatic processes involved in redox processes. However, at present, the idea that any pathological condition has a deviation from the biochemical status of the organism and is a manifestation of functional or structural disorganization of biocatalytic systems and, above all, the receptor apparatus of biomembranes, is becoming more widespread.

Among the causes of changes in the structure and function of biomembranes under the action of hypoxia, one of the leading causes is the violation of free radical reactions of lipid peroxidation. Violation of the systems of protection against excessive (LPO) leads to a violation of membrane systems, modification of cellular proteins, a decrease in the production of energy spent on maintaining cell viability and the development of a pathological process.

The processes of decomposition reactions (catabolism) begin to prevail over the reaction of biosynthesis (anabolism), fats are mobilized from the fat depot, and the breakdown of triglycerides increases. The content of free fatty acids and acetone bodies increases, the amount of phospholipids and their metabolites decreases not only in full-term, but also in low-weight fetuses. The intensity of amino acid oxidation increases, the concentration of uric acid increases, the concentration of gamma-amino acid acid, the activity of monoamine oxidases change.

It is necessary to note the change in the erythrocyte parameters of umbilical cord blood, which can be considered as identical to the cellular composition of the fetal blood. So, according to the literature, the level of hemoglobin, hematocrit, the number of erythrocytes in the capillary blood of a newborn on the 1st day after birth is significantly higher than these indicators in the blood of the umbilical cord (on average 185 g/l, 56%, 5.3 per 1012/l, respectively) .

Indicators associated with the erythrocyte itself (the average volume of erythrocytes, the average content of hemoglobin in it) remain stable, i.e., these data can be used to judge the state of the erythron of the newborn.

With fetal hypoxia, there is a decrease in the number of erythrocytes, an increase in the average volume of erythrocytes, an increase in the average content of hemoglobin in an erythrocyte, and cytosis of erythrocytes. With a low fetal weight, a decrease in hematocrit, an increase in the average hemoglobin content in an erythrocyte, with a tendency to an increase in the average volume of erythrocytes, a decrease in the total hemoglobin content and the number of erythrocytes, was also revealed.

These data indicate that the presence of a hypoxic factor and gestational age undoubtedly affect the blood morphology and erythron composition not only in the fetus, but also in the newborn.

Thus, the pathogenesis of the development of chronic hypoxia can be represented in the form of the following factors: violation of the processes of oxygen supply, transport and utilization; placental insufficiency in the form of a violation of the transport, trophic, endocrine and metabolic functions of the placenta, etc. (Scheme 4).

In acute fetal hypoxia, rapid reflex reactions occur, aimed at enhancing the supply of oxygen to the fetal body: an increase in cardiac output, heart rate, changes in intrauterine respiratory movements. This at a certain stage provides an increase in the stability of the fetus with mild or short-term hypoxia. Acute hypoxia, as a rule, occurs against the background of a violation of the uteroplacental circulation (morphological and functional disorders of the umbilical cord, placenta, anomalies of labor activity). This is the most common cause of acute fetal hypoxia. Cardiovascular insufficiency, impaired function of external respiration and other pathological changes in the body of a pregnant woman can lead to this obstetric pathology. All these changes can contribute to hypoxic damage to the vital functions of the fetal body, including damage to the central nervous system and a number of parts of the brain.

In connection with the changes indicated in Scheme 4, it is necessary to carry out rational anesthesia of childbirth in women with fetal hypoxia and its low weight, because the use of narcotic analgesics without taking into account the state of the fetus can cause irreversible hypoxic damage to brain cells and lead to antenatal and perinatal losses.

Modern methods of prevention and therapy of fetal hypoxia

For several decades, there has been an active search for ways to treat intrauterine fetal hypoxia, aimed primarily at eliminating metabolic acidosis, O2 deficiency, and increasing the compensatory-protective mechanisms in the mother-fetus system in response to a lack of oxygen. It is known that various effects on the body in hypoxic conditions can create a certain conditionality and influence the mechanism of pathological effects.

Since the factor of hypoxia is assigned the leading pathogenetic significance in many urgent and non-urgent clinical situations, A.P. Kiryushchenkov’s statement that “the development effective interventions aimed at preventing and timely correction of hypoxic conditions during pregnancy and childbirth is the most important task of obstetric science and practice.

There are various ways to prevent and treat fetal oxygen deprivation. Some of them have long been well developed and have only been improved in recent years. A younger section is the physiological and therapeutic regulation of uteroplacental circulation. It is this that is read as the main, critical function in supplying the fetus with oxygen. Inadequate maternal blood flow to the placenta is considered a major factor in fetal morbidity and mortality. The expanding arsenal of methods of therapeutic effects with the help of drugs and physical methods makes it possible to correct the main manifestations of feto-placental insufficiency (FPI) in the II and III trimester of pregnancy in a significant number of women. So, at present, pathogenetic pharmacotherapy can be classified as follows:

1. Means regulating uteroplacental and fetoplacental circulation. These include vasodilators (beta mimetics, aminophylline, theophylline); means that normalize the processes of microcirculation (complain, chimes, reopoliglyukin, heparin); estrogenic drugs (estrone, estradiol propionate, sigetin).

2. Means regulating metabolic processes. These include drugs that activate glycolysis by enhancing energy production and primary phosphorylation of glucose (insulin, cocarboxylase, ATP); enhancing adequate glycolysis by blocking the release of catecholamines from the granules (donators of sulfhydryl groups) and the activity of nodal glycolysis enzymes - phosphofructokinase (sodium bicarbonate, unithiol); activating metabolic reactions of the Krebs cycle, the pentose phosphate cycle and the respiratory chain (sodium succinate, chlorpromazine, cytochrome C, sodium hydroxybutyrate); reducing oxygen consumption by tissues (gutimin), normalizing the acid-base state.

3. Means acting on the central mechanisms of regulation of functions. These are stimulants of the respiratory center (etimizol, corazol, etc.), depriming drugs chlorpromazine, GHB.

Attempts to increase blood flow in the uterus by introducing substances that change the activity of the cardiovascular system (eufillin, theophylline) are of interest, but, according to recent years, the use of drugs that selectively act on the uterus and its vessels is preferable. So, one of the estrogenic drugs, sigetin, increases the volumetric blood flow rate in the uterine vessels, blood supply to the maternal part of the vessels, and promotes the transfer of substances from the mother to the fetus, namely exogenous glucose. Sigetin is successfully used during pregnancy and childbirth with initial and severe signs of fetal hypoxia. There are also some negative aspects of this drug. Since sigetin causes hyperemia of the uterus, this can lead to depletion of blood in other vital organs. This is especially necessary to take into account in hypoxia caused by blood loss. In addition, long-term use of sigetin can lead to fetal growth retardation and the development of carcinogenic lesions. It was found that when using sigetin, hemorrhage on the surface of the placenta is possible in the absence of vascularization of its fetal part. Thus, the question of the possibility of using drugs of this class in the treatment of hypoxia is rather controversial, since the protective reactions of the mother, including contractions of the uterine vessels, are very unfavorable for the fetus. In a drop in blood pressure caused by blood loss, replenishment of the systemic vessels with blood from the uterus can be of great importance in raising it in the mother and causing deterioration in the fetus.

Currently, beta-adrenomimetic agents have found wide application for the treatment of fetal hypoxia, including in preterm labor.

The introduction of terbutaline, partusisten and other drugs has a favorable effect on the indicators of cardiotocogram, CBS pO2 of the fetus and newborn due to the relaxation of the contractile activity of the uterus, due to stimulation of beta-adrenergic receptors. Magnesium sulfate has the same effect. It was revealed that the main effect of tocolytics on the fetus is the resulting changes in the cardiovascular system and fetal metabolism.

For a long time there has been an opinion about the advisability of oxygen therapy in hypoxic conditions of the fetus, especially in low birth weight during pregnancy. At the same time, an increase in the intranatal partial oxygen tension in the fetus normalizes not only its metabolism, but significantly increases the volumetric rate of uteroplacental perfusion. At the same time, the treatment of fetal hypoxia, especially during childbirth, remains controversial. There are numerous studies showing that with an increase in pO2 in the mother's blood, this indicator in the fetus increases, the level of lactate decreases, and signs of hypoxia disappear. The positive effect of oxygen in fetal hypoxia caused by entanglement of the umbilical cord, especially against the background of the use of vasodilators, is reported in their studies by G.F. Bykova et al. (1985). Along with this, there is evidence of a decrease in transplacental oxygen diffusion, no change in blood oxygen saturation in the vessels of the umbilical cord, and even the detection of acidosis and hypoxemia in the fetus with high pO2 in the mother's blood. Prolonged inhalation of oxygen can lead to hemodynamic disorders - a decrease in blood flow through the arterial duct, an increase in pulmonary vascular resistance, to which the fetus responds by narrowing the vessels of the umbilical cord, capillaries of the chorionic villi, and a decrease in the level of pO2 in the brain. Thus, when oxygen is inhaled by the mother, the fetus has an increase in pO2 from 12 to 23 mm Hg. Art., after 30 minutes with continued inhalation - a decrease this indicator up to 12 mm Hg Art. Excessive hyperoxia can cause a change in the transport of amino acids, glucose, the mother may develop hyperoxic hypoventilation, which can lead to an increase in pCO2 in her blood and in the blood of the fetus. Thus, inhalation of hyperoxic mixtures by pregnant animals in 42% of cases did not cause shifts in pO2 in the fetal brain, and in other observations it led to a significantly reversible decrease in pO2 and to respiratory failure associated with an increase in microvascular permeability. Moreover, the degree of decrease in pO2 depended on the severity of hypoxia in the mother's body.

Of great importance in the treatment of fetal hypoxia is glucose. Glucose is a valuable energy, easily digestible substance.

With the introduction of glucose, redox processes are enhanced, glycogen deposition in the liver is activated, the removal of toxins from the body and metabolic processes are enhanced. Glucose has a stimulating effect on uteroplacental circulation. Intravenous administration of glucose in the first and second half of pregnancy has favorable influence on the cardiac activity of the fetus, its motor activity, increases the resistance of the fetus to anoxia. However, in recent years, attention has been drawn to the high osmoticity of glucose solutions, which can lead to hypernatremia. Hypernatremia may be the cause of intracranial hemorrhage. Plasma hyperosmolality is especially dangerous in premature babies, which is due underdevelopment basement membrane of the endothelial cells of the capillaries of the brain, performing the function of the blood-brain barrier. These changes can lead to the "opening" of the blood-brain barrier, which facilitates the development of intracerebral hemorrhages.

It was also found that an excess of glucose in the fetal body may not always be useful in its hypoxia. So, in the experiment it was shown that when a 40% glucose solution was administered to pregnant animals in combination with oxygen inhalation under conditions of artificially created hypoxia, the desired positive effect was not achieved. An increase in lactate and pyruvate was found in the brain tissue of these fetuses. A decrease in respiratory movements was noted, which is a sign of fetal distress. With the introduction of glucose during childbirth, a number of authors note the appearance of jaundice in newborns, hypoglycemia and hyponatremia.

In addition, with the introduction of glucose with cardiotonic agents against the background of oxygen inhalation, a short-term effect is noted, followed by an increase in cord blood lactate to 5.8 (1.1 mmol/l), a decrease in oxygen tension to 28.9 (1.6 mmHg). Art.), an increase in metabolic acidosis - the pH of the blood from the fetal head to 7.15 (0.003) - and the accumulation of lipid peroxidation products without significant changes in the activity of hormones of the pituitary-adrenal system. There is also a short-term stimulation of oxygen metabolism with virtually unchanged delivery of oxygen to the tissues. The complete depletion of oxygen reserves occurs 1.5 times faster than under conditions of narcotic action, with a subsequent deterioration in these indicators.

Based on the data presented, the introduction of a 40% glucose solution with cardiotonic agents against the background of oxygen inhalation in the presence of chronic or acute fetal hypoxia should be carried out with caution, given the possibility of metabolic disturbances in the fetus.

The introduction of promedol (20-40 ml), sibazon (5-10 ml), as an anesthesia for childbirth, leads to depression of tissue respiration in the mother with impaired respiratory enzymes, an increase in the oxygen delivery time to 12.6 (1.7 s), a critical constant up to 12.4 (1.1 s), increased anaerobic processes of glycolysis, lactic acidemia with simultaneous activation of LPO processes in cord blood, which indicates the possible occurrence of violations of the vital functions of the fetus and newborn, especially in the presence of a small fetus. Therefore, the method of choice for labor pain relief in women with a small fetus, with hypoxia is the use of pharmacological protection of the fetus (electroanalgesia in combination with reduction for the mother with doses of GHB - 28.4 mg / kg of weight, sibazon - 0.07 mg / kg, droperidol - 0 .03 mg/kg).

Pharmacological protection of the fetus helps to reduce the degree of acidosis: an increase in pH to 7.22 (0.01), lactate level from 6.2 (0.2) to 3.4 mmol / l, normalization of hormones of the pituitary-adrenal and thyroid systems of the fetus, indicators glycolysis, positive dynamics of CTG of a full-term fetus in 90.4%.

In the event of acute fetal hypoxia due to abnormalities in labor activity, impaired uteroplacental blood flow, pharmacological protection of the fetus is carried out by intravenous administration of subnarcotic doses of drugs such as GHB. at the rate of 14.2-28.4 mg/kg of body weight of a woman, sibazon 0.07 mg/kg or droperidol 0.03 mg/kg. In the presence of a small fetus, a combination of GHB with sibazon is necessary (14.2 and 0.035 mg/kg, respectively). With positive dynamics on CTG, a second dose is administered after 45 minutes - 1 hour. If there is no effect, it is necessary to consult the issue of early operative delivery. Thus, in order to pharmacologically protect the fetal CNS from hypoxic damage in a parturient woman due to fetal hypoxia and their low weight, to reduce the side effects of drugs on the fetus and newborn during labor, it is necessary to use drugs that have an antihypoxic effect in reduced doses for the mother.

The transport of drugs across the placenta is a complex and little-studied problem. The placental barrier is functionally similar to the hematoliquor barrier. However, the selective ability of the hematoliquor barrier is carried out in the direction of the blood-cerebrospinal fluid, and the placental barrier regulates the transfer of substances from the mother's blood to the fetus and in the opposite direction.

The placental barrier differs significantly from other histo-hematic barriers in that it is involved in the metabolism of two organisms that have significant independence. Therefore, the placental barrier does not belong to the typical histo-hematic barriers, however, it plays an important role in protecting the developing fetus.

The morphological structures of the placental barrier are the epithelial cover of the chorionic villi and the endothelium of the capillaries located in them. Syncytiotrophoblast and cytotrophoblast have high absorption and enzymatic activity. Such properties of these layers of the placenta largely determine the possibility of penetration of substances. An essential role in this process is played by the activity of nuclei, mitochondria, endoplasmic reticulum and other ultrastructures of placental cells. The protective function of the placenta is limited to certain limits. Thus, the transition from mother to fetus of proteins, fats, carbohydrates, vitamins, electrolytes, constantly contained in the mother's blood, is regulated by mechanisms that have arisen in the placenta in the process of phylo- and ontogenesis.

Studies of transplacental transport of drugs were carried out mainly on the means used in obstetrics. There is evidence from experiments with chemicals illustrating the rapid transition from mother to fetus of ethyl alcohol, chloral hydrate, gaseous general anesthetics, barbiturates, sulfa drugs, and antibiotics. There is also circumstantial evidence of morphine, heroin and other drugs passing through the placenta, as newborns from drug-addicted mothers show withdrawal symptoms.

More than 10,000 children with limb deformities (phocomelia) and other pathological signs, born to women who took thalidomide during pregnancy, are another sad proof of transplacental drug transfer.

The transfer of drugs across the placental barrier occurs through all the mechanisms discussed above, of which passive diffusion is of the greatest importance. Non-dissociated and non-ionized substances pass through the placenta quickly, and ionized - with difficulty. Facilitated diffusion is possible in principle, but has not been proven for specific drugs.

The transfer rate also depends on the size of the molecules, since the placenta is impermeable to substances with a molecular weight of more than 1000. This is due to the fact that the pore diameter in the placenta does not exceed 10 nm and therefore only low molecular weight substances penetrate through them. This barrier is especially important for short-term use of certain substances, such as neuromuscular junction blockers. However, with prolonged use, many drugs can gradually penetrate into the body of the fetus.

Finally, proteins such as gamma globulin can enter through pinocytosis.

Chervertic ammonium bases, as well as muscle relaxants (decametonite, succinylcholine) penetrate the placenta with difficulty, due to their high degree of ionization and low lipid solubility.

From the body of the fetus, drugs are excreted by reverse diffusion through the placenta and renal excretion into the amniotic fluid.

Therefore, the content of a foreign substance in the body of the fetus differs little from that of the mother. Considering the fact that the binding of drugs to blood proteins in the fetus is limited, their concentration is 10-30% lower than in the mother's blood. However, lipophilic compounds (thiopental) accumulate in the liver and adipose tissue of the fetus.

Unlike other barrier functions, placental permeability varies widely during pregnancy, which is associated with the increasing needs of the fetus. There is evidence of an increase in permeability towards the end of pregnancy. This is due to changes in the structure of the boundary membranes, including the disappearance of the cytotrophoblast and the gradual thinning of the syncytiotrophoblast of the placental villi. The permeability of the placenta in the second half of pregnancy does not increase to all substances introduced into the mother's body. So, the permeability of sodium bromide, thyroxin and oxacillin is higher not at the end, but at the beginning of pregnancy. Apparently, a uniform or limited supply of a number of chemicals to the fetus depends not only on the permeability of the placental barrier, but also on the degree of development of the most important fetal systems that regulate its needs and homeostasis processes.

The mature placenta contains a set of enzymes that catalyze drug metabolism (CYP) and transport proteins (OCTNl/2, OCN3, OAT4, ENTl/2, P-gp). Enzymes can be produced during pregnancy, therefore, the metabolic processes occurring in the placenta, as well as the duration of the use of drugs, should be taken into account when deciding whether the fetus may be exposed to a substance circulating in the blood of a pregnant woman.

Discussing the role of histo-hematic barriers in the selective distribution of drugs in the body, it is necessary to note at least three more factors influencing this process. First, it depends on whether the drug is in the blood in free or protein-bound form. For most histo-hematic barriers, the binding form of the substance is an obstacle to their entry into the corresponding organ or tissue. So, the content of sulfonamides in the cerebrospinal fluid correlates only with the part that is in the blood in a free state. A similar picture was noted for thiopental in the study of its transport through the blood-ophthalmic barrier.

Secondly, some biologically active substances contained in the blood and tissues or introduced from the outside (histamine, kinins, acetylcholine, hyaluronidase) in physiological concentrations reduce the protective functions of histo-hematic barriers. Opposite action provide catecholamines, calcium salts, vitamin P.

Thirdly, under pathological conditions of the body, histo-hematic barriers are often rebuilt, with an increase or decrease in their permeability. The inflammatory process in the membranes of the eye leads to a sharp weakening of the blood-ophthalmic barrier. When studying the entry of penicillin into the cerebrospinal fluid of rabbits in control and experiment (experimental meningitis), its content was 10-20 times higher in the latter case.

Therefore, it is difficult to imagine that even substances that are similar in structure according to the distribution profile will behave in a similar way. This is due to the fact that this process depends on numerous factors: the chemical structure and physicochemical properties of drugs, their interaction with plasma proteins, metabolism, affinity for certain tissues, the state of histo-hematic barriers.

Today, the term "placenta" no longer surprise anyone. Modern girls are much better informed about pregnancy and childbirth than their grandmothers and mothers. However, most of this knowledge is superficial. Therefore, today we want to talk about what the placental barrier is in the womb. At first glance, what's incomprehensible here? The baby seat has the ability to protect the developing embryo from harmful effects and toxic substances. In fact, this organ is a real mystery and a miracle of nature.

under protection

The placental barrier is a kind of immune system. It serves as a boundary between two organisms. It is the placenta that ensures their normal coexistence and the absence of an immunological conflict. The first trimester of pregnancy is the most difficult. Partly because the placenta is not yet formed, which means that the body of the embryo is completely unprotected. From about 12 weeks, she is fully included in the work. From now on, she is ready to perform all her functions.

How is the placenta arranged?

This is an important point, without which we cannot continue our conversation. The very word "placenta" came to us from Latin. It translates as "cake". Its main part is special villi, which begin to form from the first days of pregnancy. Every day they branch out more and more. At the same time, inside them is the blood of the child. At the same time, maternal blood enriched with nutrients enters from the outside. That is, the placental barrier primarily has a separating function. This is very important, since this organ regulates the exchange of substances between two closed systems. According to this statement, the outer and inner sides of the placenta have a different structure. Inside it is smooth. The outer side is uneven, lobed.

barrier function

What does the concept of "placental barrier" include? Let's deviate a little more towards the physiology of the ongoing processes. As already mentioned, it is the unique villi that provide the exchange of substances between the woman and the embryo. Maternal blood brings oxygen to the baby and the fetus gives carbon dioxide to the pregnant girl. while they have one for two. And therein lies the greatest mystery. The placental barrier separates maternal and fetal blood so well that they do not mix.

At first glance, it seems unimaginable, but the two vascular systems are separated by a unique membrane septum. It selectively skips what is important for the development of the fetus. On the other hand, toxic, harmful and dangerous substances linger here. Therefore, doctors say that starting from the 12th week, the expectant mother can already relax a little. The placenta is able to protect the body of the child from many adverse factors.

Only the most important

All necessary nutrients and oxygen pass through the placental barrier. If the doctor observes the pathology of fetal development, he may prescribe special drugs that increase the blood supply to the placenta. This means that they increase the amount of oxygen that enters the baby. However, not all so simple. The membrane septum retains the bacteria and viruses contained in the mother's blood, as well as antibodies that are produced during the Rhesus conflict. That is, the unique structure of this membrane is tuned to preserve the fetus in a variety of situations.

It should be noted the high selectivity of the partition. The same substances that have got through the placental barrier overcome this boundary in different ways in the direction of the mother and fetus. For example, fluorine very easily and quickly penetrates from a woman to a baby, but does not pass back at all. The situation is similar with bromine.

What regulates metabolism?

We have already told the reader that the placental barrier separates the maternal and fetal lymph. How did nature manage to launch such a perfect mechanism of regulation, when what is needed penetrates the barrier, and what is harmful is delayed? In fact, we are talking about two mechanisms here at once. Next, let's take a closer look at each of them.

First of all, we are interested in how the supply of vital, nutrient elements is regulated. Everything is quite simple here. Lipids and carbohydrates, proteins and vitamins are constantly present in the mother's blood. This means that the body can develop a balanced scheme. It will initially imply that the concentration of certain substances in the blood of the mother and child is different.

placental permeability

It is much more difficult when we are talking about toxic substances that enter the body of a pregnant woman. The placental barrier separates lymph and blood. This means that those toxins that have passed through the mother's bloodstream will not get in their pure form to the fetus. However, after passing through the natural filters (liver and kidneys) in a residual form, they can still harm the baby. The fact is that substances (chemicals, drugs) that accidentally enter the mother's body are much more difficult to stop. They often tend to overcome the placental barrier.

Limited barrier functions

Nature could not foresee the development of modern industry. Therefore, the products of chemical production relatively easily pass the natural barrier. They pose a threat to the growth and development of the fetus. The degree of penetration through the placenta depends on the properties and characteristics of a particular substance. We will only mention a few points, in fact there are many more. Thus, medicinal substances with a molecular weight (less than 600 g / mol) pass through the placental barrier much faster. At the same time, those that have a lower rate practically do not penetrate. For example, these are insulin and heparin, which can be prescribed without fear during pregnancy.

There is another sign. Fat-soluble substances cross the placenta much better than water-soluble ones. Therefore, hydrophilic compounds are more desirable. In addition, physicians know that the probability of penetration of a substance through the placenta depends on the residence time of the drug in the blood. All medications long-acting are more dangerous than those that are rapidly metabolized.