RU2694514C1 - Method for preventing placental dysfunction in acute gestational pyelonephritis - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to obstetrics, and can be used for preventing placental dysfunction in gestational pyelonephritis. That is ensured by the standard position therapy, infusion, antibacterial, spasmolytic, phytotherapy. Plasmapheresis is performed on the first and third day of treatment. In addition, from the first day of treatment, progesterone preparations Utrozhestan100 mg or Duphaston10 mg every 12 hours, per os, daily, before pregnancy 37 weeks + 1 day are prescribed.EFFECT: method provides effective prevention of placental dysfunction and associated obstetric complications in acute gestational pyelonephritis, safe for a pregnant woman and fetus by stabilizing a hormonal background in pregnant women, creating favorable conditions for further prolongation of pregnancy.1 cl, 5 tbl, 2 ex

Description

The invention relates to medicine, namely to obstetrics, and can be used for the prevention of placental dysfunction and associated pregnancy complications with the development of acute gestational pyelonephritis.

The frequency of pyelonephritis in pregnant women ranges from 12.2 to 38.8% (Melnikov VA, Tselkovich LS, Vysotsky TS, Balter RB Disorders of the vaginal biocenosis during gestational pyelonephritis and its recovery using culture autolactobacillus // Modern problems of science and education. - 2016. - №2. - P. 86). To date, many scientists have noted an increase in the incidence of pyelonephritis during pregnancy (Styazkina S.N., Vorobyova A.V., Makshakova N.P., Sukhikh N.V., Simanova A.A. Gestational pyelonephritis: etiology, diagnosis, treatment / / Central Scientific Herald. - 2017. - V. 2, №8 (25). - P. 50-52). The increase in the frequency of gestational pyelonephritis is associated with the increasing role of opportunistic pathogens on the background of changes in the immune and hormonal status during pregnancy (Rudenko Yu.A., Kravtsova OA, Nikulina IE, Balter RB. Pregnant women with bacterial vaginosis in conditions of unfavorable ecological environment // Higher nursing education in the Russian health care system - Ulyanovsk, 2014. - P. 95-99). It is known that the development of this pathology has a negative effect on the course and outcome of gestation. Pregnancy failure in pyelonephritis is diagnosed 5 times more often than in healthy pregnant women. In addition, the infection, penetrating into the placenta, causes its inflammatory transformation, contributing to the occurrence of impaired uteroplacental blood flow, preeclampsia, as well as delayed development, fetal hypoxia, up to its antenatal death. In the work of A.V. Khardikova et al. (2016) correlated relationship of placental-fetal blood flow with nuclear intoxication index in uncomplicated pyelonephritis in pregnant women, which is transformed into complications of pregnancy and childbirth (Khardikov AV, Petrov SV, Lyadvin A.Yu. Connection of placental-fetal blood flow with a nuclear index of intoxication in uncomplicated pyelonephritis in pregnant women // Medicine. - 2016. T. 4, No. 3 (15). P. 40-44).

The difficulties of treating this pathology during pregnancy directly affect maternal and perinatal mortality rates. According to the literature, mortality in the combination of pregnancy with pyelonephritis reaches 10%, and perinatal mortality - 7.5% (Kurbanaliev Kh.R., Chernetsova G.S. Pyelonephritis of pregnant women. A modern view on the problems of urogynecologists (Literature review) // Vestnik KRSU - 2017. - Volume 17, No. 2. - P. 33-36).

The standard amount of therapeutic measures for the detection of urinary tract infections during pregnancy includes: positional therapy, infusion, antibacterial, antispasmodic and phytotherapy, kidney stenting / microstoma and drinking mode. In complicated forms of pyelonephritis, combined intravenous antibacterial therapy, surgical treatment (nephrectomy, or reorganization of purulent-necrotic foci with their removal, decapsulation of the kidney and nephrostomy, drainage of the retroperitoneal space), plasma exchange in case of multiple organ failure are recommended. assistance in the field of “obstetrics and gynecology”, approved by order of the Ministry of Health of the Russian Federation dated November 01, 2012 572n).

However, modern literary sources prove the insufficient effectiveness of standard therapeutic measures in pregnant women with pyelonephritis, with a high incidence of complications of drug therapy up to 10-40% (Kozak Yu.V., Kiseleva TV, Pekarev OG, Pozdnyakov I.M The use of extracorporeal detoxification methods in the treatment of pregnant women with acute gestational pyelonephritis // Medicine and Education in Siberia. - 2012. № 1. (P. 23). In his study, Yu.V. Kozak et al. (2012) suggested that membrane plasmapheresis for 1-2 days with a multiplicity of procedures from 1 to 3 and enterosorbent therapy with carbon-mineral enterosorbent SUMS-1 be included in the standard treatment of gestational pyelonephritis. The proposed method of treatment allowed the authors to reduce the course dose of antibiotics, normalize the general condition within 3-7 days and achieve clinical recovery in 98% of women. Unfortunately, the authors did not study the effect of the proposed method on the further course and outcome of pregnancy, which does not allow to judge about its 100% effectiveness in preventing and reducing the complications of gestation and perinatal losses.

In subsequent studies, additional use was proposed with traditional ultraviolet radiation therapy (UV) blood (Kozak Yu.V., Kiseleva TV, Makarov K.Yu., Kim VL Evaluation of the effectiveness of treatment of pyelonephritis in pregnant women using blood UV // Medicine and education in Siberia. -2014. - № 6. - P. 54). The authors again showed a reduction in the terms of “stopping” therapy and a reduction in the course dose of antibiotics with the additional use of UV blood, which reduces the toxic effect for the mother and fetus. However, the authors did not provide evidence of the influence of this method on the state of the uteroplacental complex and pregnancy outcomes.

There is a method of correction of placental dysfunction in pregnant women with pyelonephritis, based on early prevention of exacerbation of the disease during pregnancy by prescribing Tsunami herbal remedies (Romanenko TG. Correction of placental dysfunction in pregnant women with pyelonephritis // Health of the Woman. 2016. - №1 (107). - pp. 86-90.). The implementation of preventive measures allowed the author to reduce the frequency of threatened abortion by 1.8 times, placental dysfunction - 2.4 times. At the same time, the study does not consider the effectiveness of the drug when clinical signs of exacerbation of pyelonephritis occur during pregnancy.

It should be noted that the used treatment regimens of gestational pyelonephritis are aimed only at alleviating the symptoms of the underlying disease and do not take into account the need to influence the pronounced hormonal disorders during the combination of pregnancy and pyelonephritis to prevent placental dysfunction and complications of gestation.

The closest to the proposed method, we consider the standard treatment of acute pyelonephritis during pregnancy, which is used in all specialized medical institutions, in accordance with Order No. 572n.

The objective of the invention is to develop an effective way to prevent placental dysfunction and related obstetric complications in acute gestational pyelonephritis, safe for the pregnant woman and the fetus.

We first found an increase in the serum concentration of stress hormones — prolactin (PR), cortisol (K), and dehydroepiandrosterone sulfate (DEAS) in pregnant women with pyelonephritis (Table 1). Upon admission of pregnant women to the hospital, prior to the start of pathogenetic therapy of acute pyelonephritis, the content of PR, K and DEAS in the blood serum significantly exceeded those in the physiological course of pregnancy (Pk <0.05). In our opinion, a significant increase in stress hormones is a protective reaction of a woman’s body in response to pain, hyperthermia and stress associated with the development of acute urological pathology during pregnancy. In the dynamics, on the 4-5 day of the therapeutic measures according to the standard scheme (comparison group), we noted a sharp decrease in PR level (2 times) compared with baseline data, which can be explained by the formation of placental insufficiency against the background of the existing manifestations of endotoxicosis pyelonephritis and pregnancy (Stjazhkina, SN, Chernenkova, ML, Abdullina, IR, Mullahetova, LM, Omelina, LV. State of the placenta with gestational pyelonephritis // Modern Problems of Science and Education. 2015. No. 1 -1, p. 1329). At the same time, the concentration of total K and DEAS increased slightly in dynamics (P> 0.05) and remained significantly higher than the control values.

In the experimental work of Yu.Yu. Chebotaryova et al. (2017) established the value of glucocorticoid disregulation in the development of gestational pyelonephritis and placental insufficiency in animals (Chebotareva Yu.Yu., Ovsyannikov V.G., Khutieva M.Ya., Podgorny IV The role of glucocorticoid disregulation in the development of gestational pyelonephritis, placental insufficiency in the experiment // Nephrology. - 2017. - V. 21, No. 5. - P. 76-79). In addition, the important role of the increasing activity of the adrenal glands of the fetus in the initiation of labor activity is known (IA Salov. Non-developing pregnancy (pathogenesis, clinic, diagnosis, treatment): Abstract. Diss. Doctor of Medical Sciences, M., 1998. - 42 p .; NF Khvorostukhina. The relationship of prolactin and steroid hormones in women with fetal fetal death, the principles of their medical correction: Abstract of thesis ... Candidate of Medical Sciences, Volgograd, 2003. - 25 p.). It is possible that an increase in the serum concentration of total K and DEAS is due to an increase in fetal corticosteroids under conditions of formation of placental dysfunction and fetal hypoxia in acute gestational pyelonephritis.

Given the importance of progesterone (P) in the genesis of complications of gestation, we also conducted a parallel study of this hormone in the dynamics in pregnant women with acute pyelonephritis (Table 2).

Initially, on admission, a slight decrease in the level of P in pregnant women with acute pyelonephritis (Pk> 0.05) was found. A significant decrease in the hormone concentration (1.5 times in relation to the control parameters) was found on the 4-5th day of the standard therapy (comparison group, Pk <0.05), which, in our opinion, is also associated with the formation of placental dysfunction in combination pregnancy and pyelonephritis.

When studying the content of a specific marker of the fruit part of the placenta trophoblastic beta-1-glycoprotein (TBG), there was a slight decrease in its level before the start of treatment of gestational pyelonephritis (Table 3). At the same time, the concentration of a specific marker of the maternal part of the placenta, a placenta-specific alpha-1-microglobulin (PAMG-1), with the development of acute pyelonephritis, increased 1.5 times compared with the control group (Pc <0.05). In the dynamics, at 4-5 days of standard therapeutic measures, a further increase in PAMG-1 was observed against the background of a significant decrease in TBG (1.3 times), which indicates the progression of violations of the protein-synthetic function of the fetal component of the uteroplacental complex and may cause damage to the fetus / embryo.

Analysis of the results of the study of the “zone of pregnancy” proteins once again proves the formation of placental insufficiency during the development of acute gestational pyelonephritis, which is accompanied by multidirectional changes in the synthesis of specific TBG and PAMG-1 proteins.

It should be noted that, despite violations of the hormonal status and synthesis of gravidary proteins revealed in the dynamics, only 29.7% of pregnant women (n = 11) in the comparison group had clinical signs of threatening abortion (pulling pain in the bottom) abdomen, increased uterine tone during palpation) and hemodynamic disturbances in the uterine arteries, which can be explained by the adequate use of antispasmodic drugs in the complex of standard measures.

We first proposed a method for the prevention of placental dysfunction, which consists in the simultaneous use, against the background of standard therapy of acute pyelonephritis, progesterone preparations (Utrogestan © at a dose of 100 mg or Dyufaston® 10 mg every 12 hours, orally, from the 1st day of pyelonephritis treatment, daily , until gestational age 37 weeks + 1 day) and 2 sessions of discrete plasmapheresis on the 1st and 3rd day of treatment of gestational pyelonephritis, to prevent a sharp decrease in serum concentrations of PR and P, as well as progressive age The level of K and DEAS (4-5 days), thereby stabilizing the hormonal background for further prolongation of pregnancy.

When conducting 2 sessions of discrete plasmapheresis on the 1st and 3rd day of treatment of pyelonephritis in pregnant women, 30-50% of the circulating plasma volume is removed and replaced with saline and hydroxyethylated starch solution ("Voluven 6%", by Fresenius Kabi). A starch solution of 6% is a plasma substitute of a new class, which has minimal side effects and, along with its inherent hemodynamic and rheological properties, is an ideal infusion medium for the correction of hypovolemia, hemorheological disorders and colloid osmotic insufficiency (Serov VN, Baranov I. I. Solutions of hydroxyethylated starch in obstetric and gynecological practice // Russian Medical Journal., 2006. - V. 14., №1. - P. 3-6). The use of discrete plasmapheresis on the 1st and 3rd day of treatment of pyelonephritis in pregnant women allows you to prevent a sharp decrease in PR for 4-5 days, due to the excretion of endotoxicosis products and normalization of the function of the placenta, as well as a progressive increase in K and DEAS for 4-5 days, due to the stabilization of the fetus.

The method of discrete plasmapheresis is as follows:

1) Two cubital veins are punctured.

2) Make the introduction of plasma-solution. The amount of solution injected before the start of blood exudation depends on hemodynamic parameters and ranges from 100 to 200 ml (0.9% saline). If necessary, the introduction of plasma substitutes is carried out simultaneously with the exudation of blood.

3) Blood exfusion (350-450 ml) is carried out in plastic containers of the “Gemakon 500/300” type.

4) The blood cells are separated from plasma in refrigerated centrifuges of type OC-6M, TsPR5-01 or CR-412 using 3000 rpm at + 22 ° C, rotor code 24 for 7 minutes.

5) Plasma is removed by plasma extractor, blood cells are reinfused to the patient after dilution with 100 ml of 0.9% sodium chloride.

6) Repeat the entire cycle in the same sequence 2 times (depending on the patient's weight and portability of the procedure), which allows you to remove 500-700 ml of plasma (without hemoconservative). The volume of plasma substitution in a single session is 1000-1500 ml, of which saline is 500-1000 ml and hydroxyethyl starch solution 130/04 (Voluven 6%, Fresenius Kabi) 500 ml.

In parallel, for the purpose of correcting hypoprogesteronemia, pregnant women with acute pyelonephritis from the 1st day of complex therapy add progesterone drugs to the treatment Urogestan © in a dose of 100 mg or Dyufaston® 10 mg every 12 hours, orally, from the 1st day of pyelonephritis treatment, daily, until gestational age 37 weeks + 1 day. With a gestation period of 37 weeks + 1 day - 41 weeks (from the first day of the last menstruation), pregnancy is considered full-term, and childbirth is classified as “normal.” (OR Baev, L. Komissarova, T. Puchko, O. Vasilchenko, E. T. Malbakhova, O. L. Polyanchikova, E. M. Shifman. The basic protocol for the management of labor // Obstetrics and gynecology. - 2011. - № 4. - P. 3-14). The effectiveness of the use of progesterone drugs for stopping the clinical symptoms of threatened abortion is known. However, in order to prevent placental dysfunction, these drugs have not been used to date.

The method was applied in 19 pregnant women with a gestation period from 10 to 36 weeks (main group) from the first day of conservative treatment of pyelonephritis. Determination of serum hormone concentrations in pregnant women was carried out on the 4-5th day of the proposed method of treatment (Table 4).

The results of the dynamic study of hormones showed (Table 4) that after using plasmapheresis in patients with progesterone in the main group of pregnant women, the concentration of PR and P in serum at 4-5 days was significantly higher than the studied indicator of patients receiving standard treatment (comparison group) , while there was no significant difference in the content of P in comparison with the indices during the physiological course of pregnancy of similar periods of gestation (Pk> 0.05). In addition, we did not observe a further increase in the total K and DEAS for 4-5 days of the proposed treatment in the main group. The level of these hormones in pregnant women of the main group was 1.3-1.4 times lower than similar values of K and DEAS in the comparison group (P <0.05).

When studying the dynamics of a specific marker of the fetal part of the placenta TBG in pregnant women of the main group, it was stated that the synthesis of TBG was restored to the values of the control group on the 4-5th day of treatment (Table 5). And the content of PAMG-1 in this group was significantly reduced (1.4 times) relative to the initial data. Moreover, the obtained results of protein determination had significant differences with similar parameters of the comparison group for all periods of gestation (P <0.05).

Observation of pregnant women was carried out throughout the gestation period. Analysis of the course and outcomes of pregnancies in combination with acute pyelonephritis showed a high incidence of complications of gestation using standard treatment methods. The risk of abortion within 2-4 weeks after discharge of pregnant women from the hospital occurred in 83.8% of women in the comparison group (n = 31). In the main group, manifestations of the threat of interruption were found only in 1 patient (5.3%).

Violations of the uteroplacental blood flow (Ia degree) when performing ultrasound for 1 month after treatment were ascertained in 29 pregnant comparison groups (78.4%), and hemodynamics of II degree (16.2%) were detected in 6 women of this group. In addition, in 16 pregnant women (43.2%), according to the results of an ultrasound scan, 1 month after the postponed gestational pyelonephritis, the shortage of water and premature maturation of the placenta were found. The proportion of diagnostics of gestational hypertension and preeclampsia during prolongation of pregnancy was 54.1% and 40.5%, respectively.

Premature birth ended 75.7% of pregnancies in women of the comparison group (n = 28). Moreover, in 15 pregnant women (40.5%), premature delivery by cesarean section was performed in connection with the development of pre-eclampsia. The frequency of miscarriage in this group was 10.8% (n = 4). It should be noted that a high percentage of obstetric complications in the comparison group is most likely due to the pathogenetic features of pyelonephritis combined with pregnancy, an unstable hormonal background due to a disruption of the interaction in the mother-placenta-fetus system and the lack of therapeutic measures aimed at prevention of placental insufficiency. In the main group, the additional use of discrete plasma exchange on the 1st and 3rd days of standard treatment, as well as progesterone drugs from the 1st day, contributed to the prolongation of pregnancy in all cases. The successful outcome of pregnancy and the birth of living children was established in 100% of observations in women of the main group.

Thus, discrete plasma exchange at the 1st and 3rd days of conservative treatment of acute pyelonephritis, as well as the parallel use of progesterone drugs, can prevent the progressive decrease of PR, P and TBG by 4-5 days of inpatient treatment, as well as a sharp rise in serum concentration. K, DEAS and PAMG-1 in response to the formation of placental insufficiency and fetal hypoxia in this pathology, helping to stabilize the hormonal levels in pregnant women and creating favorable conditions for cial prolongation of pregnancy.

Example 1. Patient N., 26 years old. Clinical diagnosis: Acute gestational pyelonephritis. Pregnancy 17.4 weeks.

Admission: complaints of weakness, pain in the lumbar region, more to the right, increased body temperature to 38 ° C. The disease duration is 4 hours. After the examination and verification of the diagnosis, standard pyelonephritis therapy was started: positional therapy, antispasmodics, infusion therapy in a volume of 15 ml / kg body weight, antibiotics (Cefazolin 1.0 ip / m 2 times a day), cannephron 2 pills 3 times a day . On the 1st and 3rd day of standard therapy, discrete plasmapheresis was added to the treatment, with removal of 1500 ml of plasma and replacement with 1500 ml of physiological saline, 6% "Voluven" 1000 ml for two sessions of plasmapheresis. From the 1st day, hormone therapy was prescribed (Utrozhestan ©, 100 mg orally, every 12 hours, daily). On the background of therapy, the pregnant woman noted an improvement in overall well-being. Examination results: on admission, the concentration of prolactin was 68.2 ng / ml, cortisol - 210.7 ng / ml, DEAS - 1.04 μg / ml, progesterone - 54.5 ng / ml, TBG - 58.5 μg / ml PAMG-1 - 80.3 ng / ml; On the 4-5th day of treatment, prolactin decreased to 59.8 ng / ml, cortisol - 183.4 ng / ml, DEAS - 0.81 µg / ml, PAMG-1 - 56.9 ng / ml, and the increase progesterone - up to 74.2 ng / ml and TBG - up to 67.5 µg / ml. The conclusion of ultrasound: Pregnancy 18.2 weeks.

On the 6th day, the pregnant woman was discharged from the urology department under the supervision of a local obstetrician-gynecologist with a recommendation to continue taking Utrogestan ©, 100 mg orally, every 12 hours, daily until 37 weeks gestational period + 1 day. In the future, the pregnancy was uneventful. Delivery in time through the birth canal. A boy was born with an Apgar score of 8-9 points, a weight of 3.410 grams, height 51 cm.

Example 2. Patient K., 28 years old. Clinical diagnosis: Acute gestational pyelonephritis. Pregnancy 31 week.

Upon receipt of a complaint of weakness, pain in the lumbar region and in the lower abdomen, an increase in body temperature to 37.8 ° C. Disease duration 2 days. After the examination and verification of the diagnosis, complex intensive therapy was started. Against the background of standard pyelonephritis treatment, hormone therapy (Dyufaston® 10 mg every 12 hours, inside) and discrete plasmapheresis on the 1st and 3rd day were prescribed for 1 day. Removed only 1500 ml of plasma. Plasma substitution was made with saline 1500 ml, 6% "Voluven" 1000 ml during two plasmapheresis sessions. After all procedures, the pregnant woman noted a satisfactory condition.

Examination results: at admission, the concentration of prolactin was 184.3 ng / ml, cortisol - 256.5 ng / ml, DEAS - 0.90 μg / ml, progesterone - 87.6 ng / ml, TBG - 145.6 μg / ml PAMG-1 - 120.5 ng / ml; on the 4-5th day of treatment, a slight decrease in prolactin to 168.7 ng / ml, cortisol to 191.3 ng / ml, DEAS - 0.65 μg / ml, PAMG-1 - 79.2 ng / ml was noted. The content of progesterone on the 4-5th day increased to 106.4 ng / ml, and TBG - to 164.7 µg / ml. The conclusion of ultrasound: Pregnancy 31.5 weeks. On the 6th day of treatment, the pregnant woman was discharged from the urology department under the supervision of a local obstetrician-gynecologist with a recommendation to continue taking Duphaston® 10 mg every 12 hours orally, until the gestational period of 37 weeks + 1 day. In the future, the pregnancy was uneventful. Delivery in time through the birth canal. A girl was born with an Apgar score of 8-9 points, a weight of 3,630 grams, height 50 cm.

As can be seen from the description and examples given, the use of progesterone Urozhestan © in a dose of 100 mg or Dyuhoston® in a dose of 10 mg every 12 hours, orally, every day before the term of full-term pregnancy (37 weeks + 1 day) and discrete plasmapheresis on the 1st and 3rd day of treatment is a reliable way to prevent placental dysfunction and obstetric complications associated with it.

Claims (1)

Method for preventing placental dysfunction in gestational pyelonephritis, including standard positional therapy, infusion, antibacterial, antispasmodic, phytotherapy and plasmapheresis, characterized in that it is additionally prescribed progesterone progesterone from the first day at a dose of 100 mg or Duphaston® 10 mg every 12 hours, inside Every day, before the gestational age of 37 weeks + 1 day, and plasmapheresis is performed on the first and third days of treatment.