Tactics of management of pregnant women with preliminaries contractions

To date, there is no single tactic for managing pregnant women with preliminary contractions. Many domestic obstetricians believe that during the preliminary period, tranquilizers, analgesics, antispasmodics, and estrogens are indicated. F. Arias (1989) showed that in a pregnant woman with regular contractions, but without structural changes in the cervix, labor ceases after the administration of 0.015 g of morphine or 0.2 g of secobarbital, and in this case we can talk about false labor. Probably, as modern experimental and clinical data show, there is opioid inhibition of oxytocin release during pregnancy and labor.

In recent years, methods of physical influence have been developed - acupuncture.

A method for treating prolonged preliminary contractions with electroanalgesia has been developed. Electroanalgesia leads to the fact that in some pregnant women contractions completely cease and regular labor activity is established in 3-7 days, ending in spontaneous labor. The authors believe that this is due to the normalization of self-regulation processes in the central nervous system and vegetative balance. Carrying out electroanalgesia in the presence of contractions and the absence of structural changes in the cervix allows us to compare the diagnostics of the preliminary period and primary weakness of labor, to determine the interest of the central nervous system in the occurrence of labor anomalies. In these observations, the cessation of preliminary contractions, the transition of the latent phase to the active one, indicate the creation of optimal conditions for spontaneous delivery.

To select the most rational management of pregnant women, four groups of pregnant women with preliminary contractions were studied:

1. control group - no interventions were performed;
2. creation of a hormonal-vitamin-glucose-calcium background;
3. labor induction with oxytocin;
4. central regulation of uterine motor activity with diazepam (seduxen, sibazon).

A comparative analysis of the duration of labor, taking into account the duration of the preliminary period in the above groups, showed the following. The duration of labor increased in all groups except the last one. In the 2nd group, labor induction was ineffective in 34% of pregnant women, i.e. it did not lead to the initiation of regular labor. At the same time, the frequency of development of weakness of labor was the highest here - 38.5%. In this group, as in the group of pregnant women who used drug-induced sleep-rest, the highest frequency of premature rupture of membranes was noted.

The most favorable results were obtained in the groups of pregnant women who received diazepam, beta-adrenergic agonists, the bradykinin inhibitor parmidine, and prostaglandin synthesis inhibitors.

Method of central regulation with diazepam. When using diazepam (seduxen) in doses of 10-40 mg intramuscularly or intravenously, no negative effect on the body of a pregnant woman, the condition of the fetus and newborn, or uteroplacental hemodynamics was noted. It is important that the drug has a pronounced relaxing effect on the myometrium.

Method of diazepam administration. Diazepam (seduxen) is recommended to be used in a dose of 10-20 mg of standard solution (1 ampoule contains 2 ml or 10 mg of diazepam). It is preferable to administer intravenously in an isotonic sodium chloride solution in an amount of 20 ml, without admixture of other drugs, slowly, at the rate of 1 ml (5 mg) over 1 minute to avoid possible diplopia or mild dizziness that occur with rapid administration of diazepam. The total dose of the drug during the day in pregnant women should not exceed 40 mg. If there is no effect, re-administration is prescribed no earlier than 3 hours after the first injection.

This method showed the shortest duration of labor compared to other groups - 12.8 hours for first-time mothers and 7.5 hours for repeat mothers, respectively, versus 15.7 and 10.3 hours.

Weakness of labor activity was observed in pregnant women in 31% of cases in the control group versus 3.4% in the diazepam group.

It is important to note that in this group, in 63% of cases, the transition from preliminary contractions to regular labor occurred within 6 hours after the drug was administered. In 8% of pregnant women, preliminary contractions ceased and subsequently recurred 1–2 days later with normal labor. According to hysterography, spontaneous labor was established on average 8 hours after the drug was administered, ending in spontaneous labor with a total duration of labor of 10 hours.

All children were born with an Apgar score of 8-10 points, and subsequently, until discharge from the hospital, they developed without any special features.

According to the data of multichannel external hysterography, it was revealed that after the introduction of diazepam, uterine contractions became rarer for 20-30 minutes for 3 hours - 1-2 contractions per 10 minutes; more coordinated labor activity was noted; contractions appeared in the area of the fundus and body of the uterus, and contractions were not recorded in the area of the lower segment of the uterus. The intensity of uterine contractions clearly increased, despite the fact that the duration of pauses between them lengthened. A decrease of 3-6 mm in the increased basal tone of the uterus was observed.

A possible mechanism of action of diazepam is apparently the reduction of mental stress and fear due to the normalization of central structures located in the limbic region, which is known to be affected by diazepam, regulating the contractile activity of the uterus. In the pathological course of the preliminary period, a diffuse nature of disturbances in the bioelectric activity of the cerebral cortex appears, i.e. disturbances occur in the subcortical-stem reticular formations. The main indication for the use of diazepam in preliminary contractions is disturbances in the neuropsychic status of the pregnant woman.

Changes in myometrial excitability were revealed before and every 30 minutes after the administration of diazepam (oxytocin test data). Myometrial excitability increased, becoming, according to the oxytocin test data, clearly positive at the 1-2 minute, after the administration of the drug - from the 3-4 minute. In pregnant women with high myometrial excitability, diazepam did not change the functional properties of the myometrium. These data allowed us to assume that there is another mechanism of diazepam action - due to an increase in the sensitivity of oxytocin zones, which are present in the limbic region and in turn change the reactivity of the myometrium.

Complex clinical and physiological studies in combination with determination of the body's estrogen saturation using fluorescent microscopy made it possible to develop the following method of treating the pathological preliminary period with diazepam in pregnant women with deviations in psychosomatic status.

When pregnant women with a pathological course of the preliminary period are diagnosed with a lack of estrogen readiness and an immature or ripening cervix, the following is administered: folliculin 10,000 IU intramuscularly on ether 2 times a day at 12-hour intervals; antispasmodics - 1.5% ganglerone solution - 2 ml intramuscularly or intravenously in 40 ml of 40% glucose solution; diazepam in a dose of 10-20 mg of a standard solution according to the method described above, taking into account the body weight of the pregnant woman. If there is no effect, repeated administration of the drug in a dose of 10-20 mg is prescribed no earlier than 3 hours after the first injection of the drug.

It is important to note that such treatment is also important in terms of ante- and intranatal protection of the fetus and newborn child, since with an increase in the duration of the preliminary period (especially 13 hours or more), the number of hypoxic conditions of the fetus clearly increases as a result of pathological contractile activity of the uterus, leading to disruption of the uteroplacental circulation. The frequency of asphyxia increases to 18%. A clear increase in the number of children with a low score on the Apgar scale has been established with an increase in the duration of the preliminary period.

Use of the bradykinin inhibitor parmidine in the treatment of the preliminary period.

The kallikrein-kinin system (KKS) is involved in the regulation of the reproductive system of the body. Bradykinin is the most important kinin. Bradykinin may be important during labor. Some authors point to a sharp drop in kininogen levels with the onset of labor, reaching a maximum in the second period of labor. Some doctors believe that the effect of kinins on the uterus of animals and the muscles of the human uterus during pregnancy is small and these data are contradictory. It is believed that kinin synthesis increases during pregnancy and increases especially vigorously during labor (with normal labor). Therefore, it can be assumed that kinins are actively involved in the dynamics of physiological labor. A decrease in the activity of the kinin system is noted with weak labor (lack of sufficient muscular activity of the uterus).

The activity of the KKS is one of the important factors in the occurrence of contractile activity of the uterus during labor. In some pregnancy complications, high activity of kininogenesis is observed. This circumstance led to the search for a pharmacological agent with antihypoxic and antikinin properties.

Parmidine belongs to the group of kinin antagonists and is currently practically the only drug with antibradykinin action, reducing or completely eliminating the main effects of endogenous or exogenous kinins. Parmidine selectively acts on the mitochondria of the cell during hypoxia, stabilizing their membrane, protecting against the damaging effect of peroxide reactions and thereby enhancing energy production processes. These data allow us to judge its protective role in hypoxic hypoxia of cells.

The presence of antibradykinin and antihypoxic action provides the ability of this drug to interfere with brain metabolism by regulating blood flow and permeability of brain microvessels, as well as increasing tolerance to oxygen starvation. The listed properties of parmidine can ensure the restoration of cerebral hemodynamics and metabolic processes and the creation of stable anabolism of neurocytes impaired by hypoxia.

Being an active antioxidant, the drug reduces the body's need for oxygen, inhibits lipid peroxidation, reduces the amount of free radicals, and ischemia of organs and tissues.

Acting as an angioprotector, parmidine reduces the permeability of the vascular wall, improves microcirculation in the vessels, including the brain, lungs, helps to normalize the elasticity and tone of the cerebral vessels, reduces the processes of thrombus formation, prevents the formation of hemorrhages. Influencing the processes of oxidative phosphorylation, parmidine stabilizes the alveolar wall, reduces the production of kinins.

The above is the basis for including in the complex of therapeutic measures pharmacological correction of the activity of this system with the help of kinin-negative agents.

However, issues of experimental justification of the use of drugs that inhibit the kallikrein-kinin system in obstetric practice have been extremely insufficiently developed.

Method of treatment with prostaglandin synthesis inhibitors.

Rationale for the use of prostaglandin synthesis inhibitors. Prostaglandins play a role in the onset and progression of labor, and prostaglandin synthesis inhibitors can directly regulate the frequency and amplitude of uterine contractions by inhibiting prostaglandin synthesis.

It is recommended to use one of the most effective and widely used in obstetric practice indomethacin, which is most indicated for increased concentrations of endogenous prostaglandins, which clinically most often manifests itself in high amplitude and frequency of uterine contractions. Indomethacin completely suppresses uterine contractions for 1-8 hours.

Method of using indomethacin. In the absence of biological readiness for childbirth, a 200 mg solution of sigetin is first administered intravenously by drip for 2-2.5 hours, after which indomethacin is administered at a dose of 125 mg, with 1 capsule (25 mg) taken orally at first, and the second dose is administered rectally as a suppository - 1 suppository (50-100 mg). If there is no effect, after 2 hours it is again recommended to prescribe 100 mg of indomethacin. The total dose during the day should be 200-250 mg.

Indomethacin is an effective treatment for the pathological preliminary period, well tolerated by pregnant women. No negative effect of the drug on the subsequent course of labor, the condition of the fetus and newborn has been noted. The course of treatment is 3-5 days.

The second effective drug is ibuprofen. The drug is well absorbed from the gastrointestinal tract. Its absorption occurs most completely and quickly in the small intestine. After taking a single dose of 200 mg, the maximum concentration of the drug in human blood plasma is 15-30 μg / ml after 1% h. Ibuprofen intensively (up to 99%) binds to plasma proteins. Ibuprofen is eliminated quickly: 24 hours after its administration, neither the drug nor its metabolites are detected in the blood. Ibuprofen is prescribed orally in the form of tablets of 0.2 g 3-4 times a day, depending on hysterography data. The course of treatment is up to 3 days.

The most well-known adverse reactions are from the gastrointestinal tract. The development of gastropathy may be accompanied by bleeding and ulcers. Other side effects are also observed - changes in the function of the kidneys, liver, central nervous system, disorders of hematopoiesis, the occurrence of skin syndromes, the development of allergic reactions.

Method of treatment with beta-adrenergic agonists. There are isolated reports in the literature on the use of the beta-adrenergic agonist partusisten in the form of rectal suppositories during the pathological preliminary period. It is believed that inhibition of uterine contractility in pregnant women is carried out by a beta-adrenergic receptor inhibitory mechanism, i.e., due to the interaction of the endogenous beta-adrenergic agonist with the beta-adrenergic receptors of the myometrium, which is why there is a need to diagnose its condition. The partusisten test, reflecting the degree of inhibition of uterine contractility by an exogenous beta-adrenergic agonist, and the obzidan test, which can probably be used to detect excess levels of endogenous beta-adrenergic agonists and to diagnose a hyperreaction of the mother's body to an endogenous beta-adrenergic agonist, have been proposed.

We have developed a method for treating the pathological preliminary period with beta-adrenergic agonists: partusisten, brikanil (terbutaline) and alupent (orciprenaline sulfate).

Method of application of partusisten. 10 ml of the preparation containing 0.5 mg of partusisten are dissolved in 500 ml of 5% glucose solution or isotonic sodium chloride solution. Partusisten is administered intravenously by drip at a rate of 15-20-30 drops per minute. The duration of administration of the preparation is on average 4-5 hours. Subsequently, immediately after the cessation of intravenous infusion of the preparation, the latter is prescribed in tablets of 5 mg 6 times a day. To reduce tachycardia, pregnant women received finoptin at 40 mg 2-3 times a day.

A similar method was used to prepare 180 pregnant women with a preliminary period. Of these, 129 were primiparous (71.7%) and 51 were multiparous (28.3%).

Bricanil and Alupent were used in 208 pregnant women aged 18-39 years at 39-41 weeks of pregnancy. Bricanil is used orally at 5 mg, and Alupent at a dose of 0.5 mg intramuscularly. Bricanil causes a decrease in uterine contractions and a decrease in the amplitude of contractions after 30-40 minutes, and after 2-3 hours the contractions completely stop. Changes in the cardiovascular system are insignificant. The pulse quickens by 15-20 beats/min, but not more than for 20 minutes. Systolic blood pressure does not change, and diastolic pressure decreases by 10 mm Hg.

Regular labor activity occurs after 17.8 ± 1.58 hours, and the average duration of labor in primiparous women is 11.24 ± 0.8 hours versus 13.9 ± 0.8 hours in the control group without the use of drugs. The difference is statistically significant. In multiparous women, the duration of labor is 6.1 ± 0.6 hours versus 9.08 ± 0.93 in the control group. Labor was complicated by weakness of labor activity in 12.8 ± 4.9%, and in the control group - in 33.0 ± 4.7%.

When studying the condition of the fetus and newborn, it was found that the use of brikanil reduced the number of children born in asphyxia (10.6%), while in the control group this number was significant (36%). The average assessment of newborns on the Angar scale was 8.51 ± 0.095.

Alupent was administered at a dose of 0.5 mg intramuscularly. After administration of the drug, uterine contractions ceased after 40-60 minutes, but after 2-3 hours, most pregnant women again experienced weak, short, irregular contractions. Changes in the cardiovascular system were the same as with the use of Brikanil.

Spontaneous regular labor occurred 10.16 ± 1.12 hours after the administration of Alupent. The duration of labor in primiparous women was 11.3 ± 0.77 hours versus 13.9 ± 0.8 hours in the control group. Weakness of labor was noted in 18 ± 4.9%, in the control group - 33 ± 4.7%.

When using beta-adrenomimetics for the treatment of the preliminary period, a statistically significant decrease in the incidence of late toxicosis during labor was noted. When Alupent was administered, late toxicosis was noted in 16.4 ± 4.7%. This can probably be explained, on the one hand, by changes in hemodynamics, especially a decrease in diastolic arterial pressure, which closely correlates with blood flow in the intervillous space, and improvement in oxidation-reduction processes in the myometrium and placenta. A relationship was found between placental insufficiency and abnormal labor forces. On the other hand, there is a close relationship between the adrenergic system and endogenous prostaglandins, which, under the influence of beta-adrenomimetics, can improve the synthesis of prostaglandins in the placenta (especially prostacyclin type) and thereby help prevent the occurrence of late toxicosis during labor.

Contraindications to the use of beta-adrenergic agonists: hypertension in pregnancy, hypertension with blood pressure of 150/90 mm Hg and above, heart defects, insulin-dependent diabetes mellitus, hyperthyroidism, fetal malformations, stillbirth, chorioamnionitis.

Medicinal sleep-rest during the preliminary period. At night, if after the introduction of the above drugs (ciazepam, beta-adrenergic agonists, parmidine, etc.) the contractions do not stop, 20 mg of diazepam can be re-administered in combination with 50 mg of pipolfen and 40 mg of promedol solution. If the pregnant woman does not fall asleep within the next hour, she is prescribed a steroid drug - Viadril "G" in the form of a 2.5% solution intravenously, quickly in the amount of 1000 mg per 20 ml of 40% glucose solution. In order to prevent possible irritation of the punctured vein, 5 ml of 0.5% novocaine solution is administered before the injection of Viadril.

After using the indicated dose of Viadril, a woman quickly, literally within the first 3-5 minutes and without the stage of arousal, falls asleep, which continues against the background of the preliminary administration of diazepam, pipolfen and promedol.

Viadril (predion for injection) relaxes muscles well, does not have a significant effect on breathing and the cardiovascular system, and due to its weak effect on carbohydrate metabolism, it can be used in diabetes mellitus.

Instead of Viadryl, sodium oxybutyrate can be used intravenously in a dose of 10-20 ml of a 20% solution. The drug is usually well tolerated; it does not significantly affect the cardiovascular system, respiration, liver, or kidneys. With rapid intravenous administration, motor excitation, convulsive twitching of the limbs and tongue are possible.

Calcium antagonists. Recognition of the importance of the role played by calcium ions in myometrial contractions has allowed them to be used for the preparation of pregnant women and the treatment of the pathological preliminary period.

We used nifedipine according to the following method: 3 nifedipine tablets of 10 mg each were administered alternately at 15-minute intervals (total dose 30 mg). 160 pregnant women were examined. The duration of the preliminary period was more than 12 hours.

In the group of primiparous women, the overall percentage of somatic diseases was 27%, complicated pregnancy in 65.5% of pregnant women. In the group of multiparous women, somatic diseases were detected in 34.2%, complicated pregnancy in 31.5%.

In 63.7% of women, a persistent tocolytic effect was achieved after using nifedipine. The average duration of labor in primiparous women was 15.4 ± 0.8 hours, in multiparous women - 11.3 ± 0.77 hours. Labor was complicated by weakness of labor in 10.6% of cases. Rapid and precipitous labor was observed in 4.3 ± 0.85%. No negative effects of nifedipine on the body of the mother, fetus, or newborn child were found.

The main clinical indications for the use of calcium antagonists in the treatment of pregnant women in the preliminary period are:

• the presence of frequent uterine contractions with symptoms of discomfort, sleep and rest disturbances;
• a combination of uterine contractions with symptoms of fetal dysfunction caused by a long preliminary period;
• the presence of increased uterine tone and symptoms of impaired fetal vital activity;
• contraindications to the use of other drugs (beta-adrenergic agonists, prostaglandin synthesis inhibitors, etc.);
• the presence of cardiovascular pathology in pregnant women.

Combined treatment with calcium antagonists, beta-adrenergic agonists and glucocorticoids. In pregnant women with a high risk of developing weakness of labor activity, with poor tolerance of beta-adrenergic agonists, a scheme of combined use of the calcium antagonist - nifedipine, beta-adrenergic agonist - partusisten and glucocorticoids - dexamethasone in half doses has been developed.

Combined tocolysis with calcium antagonists and beta-adrenergic agonists allows the use of significantly lower doses of these drugs; fewer changes in the ECG in the mother and heart rate in the fetus; the frequency of severe side effects is higher when using partusisten alone.

Glucocorticoids (cexamethasone at a dose of 12 mg/day) inhibit prostacyclin synthesis for 2 days, reduce the degree of postnatal hypoxia by increasing pulmonary surfactant, which improves the transfer of oxygen through the alveolar membranes, increase the synthesis of renal PG and arachidonic acid, and in clinical conditions lead to a shortening of the duration of labor and the onset of labor.

Thus, when developing tactics for managing pregnant women with a pathological preliminary period, it is necessary to proceed from a number of considerations. Firstly, various psychogenic factors are of great importance in the pathogenesis of this complication, especially in women with signs of underdevelopment of the reproductive system and insufficiently expressed readiness for childbirth. Secondly, it is obvious that a pregnant woman experiencing unusually painful contractions of the uterus, as well as constant pain in the lower abdomen and sacrum, needs adequate rest and the cessation of debilitating pain. Therefore, in the complex therapy of the pathological preliminary period, antispasmodics, antispasmodic analgesics and adrenergic agents (brikanil, utopar, ritodrin, partusisten, ginepral, alupent, brikanil, etc.) should be more widely used. These substances allow for highly effective reduction of unproductive uterine contractions, creation of complete rest, prevention of fetal dysfunction, relaxation of the uterus and improvement of uteroplacental circulation, which ultimately leads to a reduction in perinatal morbidity and mortality rates.