Method for correction of antihypertensive preparations dosage in pregnant women with arterial hypertension

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to obstetrics, and concerns the correction of antihypertensive preparations (AHP) dosage in pregnant women with arterial hypertension. It involves Doppler ultrasound of the "mother-placenta-foetus" system. The uteroplacental misperfusion severity is evaluated. The IA or IB severity level require the AHP dosage to be reduced by 25% as compared to the initial one, while in the II severity level, the dosage is to be reduced by 50%, and in the III severity level - by 75%.

EFFECT: method provides optimised antihypertensive therapy in the pregnant women with taking into account the misperfusion severity level in the "mother-placenta-foetus" system, and as consequence, decreased number of foetal growth inhibition cases and improvement of pregnancy terminations.

5 ex

 

The present invention relates to medicine, namely to obstetrics, and is designed for optimal dosage adjustment of antihypertensive drugs in pregnant women with mild chronic hypertension on the basis of the analysis of indicators of doplerometry in utero-placental complex to improve perinatal outcomes.

There is a method to adapt the dose of antihypertensive drugs in hypertensive patients using the method of self-monitoring of blood pressure, which involves the measurement of blood pressure by the patient or his relatives. Hypertension, which are stated at average per day values of HELL more than 135/85 mm Hg, it is recommended to use low doses of antihypertensive drugs in the initial phase of treatment, starting with the lowest dosage of the drug, to reduce adverse side effects. If you have a good response to low dose of this drug, but BP control is still insufficient, increase the dosage of this drug if it good endurance (MINISTRY of health of the RUSSIAN FEDERATION ORDER of 24 January 2003, N 4 "ON MEASURES to IMPROVE the MEDICAL care of PATIENTS WITH ARTERIAL HYPERTENSION IN the RUSSIAN FEDERATION").

The disadvantages of this method is the lack of accurate specify the th on the degree of increasing the dose of antihypertensive drugs with insufficient BP control, in addition, there is no information about the necessity and nature of the correction dose of antihypertensive drugs in pregnant women with mild chronic hypertension.

It is known that a marked reduction of blood pressure with antihypertensive drugs in chronic hypertension can be beneficial for the mother, but often affects the uterine-placental blood flow, leading to intrauterine growth retardation (Von Dadelszen P, Ornstein M P, Bull S, Logan A, G, Koren G, Magee L A. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. The Lancet 2000; 355:87-92).

However, the available sources of information not found information about the possibility of dose adjustment hypertensive drugs in pregnant women, depending on the condition of the fetus.

The task was set of search criteria, allowing selection of doses of antihypertensive drugs in pregnant women with mild chronic hypertension with regard to their effects on the fetus. Accordingly, data were obtained, showing that it is necessary to assess the condition of the utero-placental perfusion using Doppler studies.

The task of the invention is the selection criteria for dose adjustment of antihypertensive drugs in pregnant women with mild chronic hypertension for Ulu who provide perinatal outcomes.

The technical result of the invention is to improve blood flow in the uterine-placental complex, reducing the number of children born with the syndrome of delayed fetal growth, and, consequently, improving perinatal outcomes in pregnant women with mild chronic hypertension.

The technical result is achieved by lowering the dose of antihypertensive drugs in pregnant women with mild chronic hypertension 25%, 50% and 75% of the original in accordance with the detected degree of disturbance of blood flow in the uterine-placental complex with Doppler studies.

Studied 37 pregnant women with mild chronic hypertension treated with antihypertensive therapy. 16 of 20 pregnant women of the main group, the dose of antihypertensive drugs was reduced by 25%, 50% and 75% depending on degree of renal blood flow in the uterine-placental complex. 17 pregnant major retrospective group were receiving antihypertensive therapy at the same dose until delivery, as well as 4 pregnant major prospective group, the blood flow in the uterine-placental complex which was within normal limits.

When performing Doppler studies in the main prospective group, the following results were obtained. Impaired blood flow IA Stephenville place at 7 pregnant, IB degree in 4 pregnant, II degree in 3 pregnant women, the III degree 2 pregnant. 4 pregnant blood was within normal limits. In the retrospective group of blood flow disturbances IA extent occurred in 5 pregnant, IB degree in 4 pregnant, II degree in 4 pregnant women, the III degree 3 pregnant. 2 pregnant blood was within normal limits. In the main prospective group after reduction of the dose of antihypertensive drugs, depending on the degree of renal blood flow in the system "mother-placenta-fetus" at 25%, 50% and 75%, respectively repeated Doppler study of blood flow in the uterine-placental complex, which identified the improvement of blood flow in the system "mother-placenta-fetus": disorders of blood flow IA degree had 2 pregnant, IB degree-1 pregnant violations II and III have been identified. Thus, improving blood flow, up to the normalization occurred in 81.3% of pregnant women. 19 pregnant major prospective group carried the pregnancy to term. 14 pregnant major retrospective group were vodorazdelny early due to worsening functional status of the fetus. 12 of them by caesarean section in the absence of rapid and careful delivery through the birth canal. In 13 patients the main retrospective group were born children the syndrome of delayed fetal growth and required long-term treatment in the hospital.

Thus, the obtained data suggest that dose adjustment of antihypertensive medications, depending on degree of renal blood flow in the system "mother-placenta-fetus in pregnant women with mild chronic hypertension leads to improved blood flow in the uterine-placental complex, to reduce the number of children born with the syndrome of delayed fetal growth, and, consequently, to improve perinatal outcomes.

The method is as follows.

Pregnant with mild chronic hypertension receiving antihypertensive therapy, conduct Doppler study of blood flow in the uterine-placental complex, determining systole-diastolic ratio in the uterine arteries, the arteries of the umbilical cord and aorta of the fetus according to the standard technique (resurrection S.L. assessment of the status of the fetus. - Minsk: "Book House", 2004. - 303 S.; D E FitzGerald, J E Drumm "Non-invasive measurement of human fetal circulation using ultrasound: a new method" Br Med J 1977;2:1450-1451 (3 December)). Depending on the degree of blood flow disturbances in the system "mother-placenta-fetus", defined according to the classification of AN. Strizhakova and collaborators Summary A.N., Bunin A.T., Medvedev M.V. Ultrasound diagnosis in obstetrics clinic. - M.: Medicine, 1990; 239), reduce the dose of antihypertensive drugs. When the disruption of blood flow IA or IB degree, reduce the dose by 25% from the original,when the disruption of blood flow II degree 50% and the disruption of blood flow III degree - 75%. Reduce the dose of antihypertensive drugs in the presence of disturbances according to Doppler studies of the uterine arteries, the arteries of the umbilical cord and aorta of the fetus with a high degree of probability leads to normalization of blood flow in the system "mother-placenta-fetus". Based on these data, Doppler study of blood flow in the uterine arteries, the arteries of the umbilical cord and aorta of the fetus was reasonably selected for dose selection of antihypertensive drugs in pregnant women with mild chronic hypertension.

The claimed method is illustrated by the following specific examples of its implementation.

Example 1.

Pregnant K., 32 years old with a diagnosis: I timely delivery in 32 years. Gestational edema. Mild chronic hypertension. Inspection generic ways.

The patient was registered antenatal clinic with 6 weeks of pregnancy. Profession Manager. The pregnancy was uneventful. In the third trimester was observed swelling of legs. Blood pressure rises with age of 27. Maximum blood pressure before pregnancy 150/100 mm Hg, the average level of blood pressure before pregnancy 140/80 mm Hg In the rest of the medical history is not burdened. Antihypertensive therapy before pregnancy have not been conducted. Menstrual function is not violated: 12 years for 5 days, after 28 days, the regular cycle. This pregnancy first came spontaneously. Growth 174, weight 79 kg (before pregnancy 67 kg). In 12 weeks observed in 67 GKB, the diagnosis of mild hypertension. Maximum blood pressure during pregnancy 150/100 mm Hg Therapist female consultations scheduled dopegita at a dose of 750 mg per day. Maximum blood pressure during pregnancy 150/100 mm Hg At 32 weeks was 8 GB with a diagnosis of Pregnancy 32 weeks. Head previa. Chronic placental insufficiency. Upon admission to the hospital for evaluation of blood flow in the system "mother-placenta-fetus" held Doppler study of blood flow in the uterine arteries, the arteries of the umbilical cord and aorta of the fetus on the ultrasound installation "Aloka-4000", has a sensor Doppler mapping. Using the method of ultrasonic doplerometry obtained curves of the velocity of blood flow in the uterine artery, umbilical artery, the aorta of the fetus and calculated indices of vascular resistance according to standard formulas. According to Doppler studies in this patient, after taking the original dose dopegita in the umbilical artery of systole-diastolic ratio of 2.8, in the aorta of systole-diastolic ratio of 2.7, in the right uterine artery, systole-diastolic ratio of 2.6, in the left uterine the artery of systole-diastolic ratio of 1.9. Conclusion: impaired uteroplacental blood flow and fetal-placental blood flow IA degree. Dose dopegita reduced by 25% up to 375 mg per day. In this patient, 48 hours after dose reduction dopegita according to Doppler studies in the umbilical artery of systole-diastolic ratio of 2.8, in the aorta of systole-diastolic ratio of 2.9, in the right uterine artery, systole-diastolic ratio of 1.6, in the left uterine artery, systole-diastolic ratio of 1.8. Conclusion: the blood within normal limits. Discharged after 7 days with progressive pregnancy 33 weeks. Family activities have evolved independently birth was uneventful. During childbirth was conducted anesthesia ferrous-oxygen mixture. The total duration of labour 7 hours. Waterless period of 3 hours. Water light. The baby was born alive, Mature, male, weight 3350, growth of 52, see Estimation on Apgar scale in the first minute 8 points in the fifth minute of 9 points. The mother was discharged home with your child on the 4th day. Thus, lower doses of antihypertensive drug facilitated the normalization of blood flow in the uterine-placental complex and the birth of full-term newborn without delay syndrome fetal growth.

Example 2.

Pregnant U., 29 years old diagnosed with: I timely delivery. Gestational edema. Mild chronic arterial the Naya hypertension. Inspection generic ways.

The patient was registered antenatal clinic with 7 weeks of pregnancy. Profession Manager. The pregnancy was uneventful. In the third trimester was observed swelling of legs. Blood pressure rises with age of 26. Maximum blood pressure before pregnancy 145/100 mm Hg, the average level of blood pressure before pregnancy 140/80 mm Hg In the rest of the medical history is not burdened. Antihypertensive therapy before pregnancy have not been conducted. Menstrual function is not violated: 12 years, 5 days, after 28 days, the regular cycle. This pregnancy first came spontaneously. Height 172 cm, weight 77 kg (before pregnancy 67 kg). In 10 weeks was examined in 67 GKB, diagnosed with mild arterial hypertension. Maximum blood pressure during pregnancy 155/100 mm Hg Therapist antenatal clinics assigned to atenolol dose of 50 mg per day. Maximum blood pressure during pregnancy 145/95 mm Hg At 33 weeks was 8 GB with a diagnosis of Pregnancy 33 weeks. Head previa. Chronic placental insufficiency. Upon admission to the hospital held Doppler study of blood flow in the uterine arteries, the arteries of the umbilical cord and aorta of the fetus. According to Doppler studies in this patient, after taking the original dose at which Solola in the umbilical artery of systole-diastolic ratio of 3.4, in the aorta, systole-diastolic ratio of 2.7, in the right uterine artery, systole-diastolic ratio of 2.1, in the left uterine artery, systole-diastolic ratio of 1.9. Conclusion: impaired uteroplacental blood flow and fetal-placental blood flow IB degree. Dose atenolol decreased by 25% to 37.5 mg per day. In this patient, 48 hours after dose reduction dopegita according to Doppler studies in the umbilical artery of systole-diastolic ratio of 2.8, in the aorta of systole-diastolic ratio of 2.7, in the right uterine artery, systole-diastolic ratio of 1.9, in the left uterine artery, systole-diastolic ratio of 1.7. Conclusion: the blood within normal limits. Discharged after 7 days with progressive pregnancy 34 weeks. Family activities have evolved independently birth was uneventful. During childbirth was conducted anesthesia ferrous-oxygen mixture. The total duration of childbirth 7.5 hours. Waterless period of 3 hours. Water light. The baby was born alive, Mature, male, weight 3000, height 50 cm Estimation on Apgar scale in the first minute 8 points in the fifth minute of 9 points. The mother was discharged home with the child for 5 days.

Thus, lower doses of antihypertensive drug facilitated the normalization of blood flow in the uterine-placental complex and the birth of donos the frame of the newborn, without delay syndrome fetal growth.

Example 3.

Pregnant A., 36 years old with a diagnosis: I timely delivery in 36 years. Gestational edema. Mild chronic hypertension. Inspection generic ways. The patient was registered female consultations with 7-8 weeks of pregnancy. The profession of accountant. Pregnancy proceeded against the background of the threat of premature birth in the 31st week. In the third trimester was observed swelling of legs. Blood pressure rises with 25 years. Maximum blood pressure before pregnancy 150/90 mm Hg, the average level of blood pressure before pregnancy 135/85 mm Hg Antihypertensive therapy before pregnancy have not been conducted. In the rest of the medical history is not burdened. Menstrual function is not violated: 13 years, 5 days, after 29 days, the regular cycle. This pregnancy first came spontaneously. Growth 167, weight 75 kg (before pregnancy 63 kg). Blood group A(II) second, RH - positive. In 10 weeks I went for a consultation at CDC at 67 GKB, the diagnosis of mild hypertension. Therapist female consultations scheduled dopegita at a dose of 250 mg 4 times per day. Maximum blood pressure during pregnancy 150/100 mm Hg In 31 week was 8 GB with a diagnosis of Pregnancy 31 week. Head previa. Chronic placental insufficiency. Upon receipt held Doppler study. By Dan the output of Doppler studies in this patient, after taking the original dose dopegita in the umbilical artery of systole-diastolic ratio of 3.69, in the aorta, systole-diastolic ratio of 2.7, in the right uterine artery, systole-diastolic ratio of 2.8, in the left uterine artery, systole-diastolic ratio of 2.3. Conclusion: impaired uteroplacental blood flow and fetal-placental blood flow II. Dose dopegita reduced by 50% to 500 mg per day. In this patient, 48 hours after dose reduction dopegita according to Doppler studies in the umbilical artery of systole-diastolic ratio of 2.7, in the aorta of systole-diastolic ratio of 2.7, in the right uterine artery, systole-diastolic ratio of 1.7, in the left uterine artery, systole-diastolic ratio of 1.6. Conclusion: the blood within normal limits. Discharged after 7 days with progressive pregnancy 32 weeks. Family activities have evolved independently birth was uneventful. During childbirth was conducted anesthesia and injected intramuscularly. The total duration of labour 8 hours. Waterless period of 4 hours and 10 minutes. Water light. The baby was born alive, Mature, male, weight 2950, growth 49 see score on a scale of Apgar scores in the first minute 8 points in the fifth minute of 8 points. The mother was discharged home with the child for 5 days.

Thus, lower doses of antihypertensive drug facilitated the normalization of blood flow in the uterine-placental complex and the birth to Osenovo newborn, without delay syndrome fetal growth.

Example 4.

Pregnant With., 34 years old with a diagnosis: I timely online delivery at 34. Exacerbation of chronic placental insufficiency. The syndrome of delayed fetal growth, first class. Mild chronic hypertension. Crevoshay the Pfannenstiel. Caesarean section for Shutter. Spinal anaesthesia. The patient was registered female consultations with 6-7 weeks of pregnancy. Profession - seller. Blood pressure rises with 24 years. Maximum blood pressure before pregnancy 145/85 mm Hg, the average level of blood pressure before pregnancy 135/85 mm Hg Antihypertensive therapy before pregnancy have not been conducted. In the rest of the medical history is not burdened. Menstrual function is not violated: 12 years, 4 days, 30 days, regular cycle. First pregnancy two years ago, ended medical abortion patients, no complications. This second pregnancy has occurred spontaneously. Height 170, weight 78 kg (before pregnancy 69 kg). Blood group 0(1) first, a rhesus - positive. Surveyed on IGO, the result is negative. At 8 weeks was examined in 67 GKB, diagnosed with mild arterial hypertension. Physician clinics domiciliary assigned to atenolol dose of 50 mg 2 times a day. 22 and 28 weeks of pregnancy was in the hospital with the threat of interruption of pregnancy of the items. Maximum blood pressure during pregnancy 145/85 mm Hg At 32 weeks by the doctor of female consultation sent to 8 GB with a diagnosis of Pregnancy 32 weeks. Head previa. Chronic placental insufficiency. The syndrome of delayed fetal growth, first class. Mild chronic hypertension. Upon receipt held Doppler study. According to Doppler studies in umbilical artery zero diastolic blood flow in the aorta, systole-diastolic ratio of 4.5, in the right uterine artery, systole-diastolic ratio of 4.2, in the left uterine artery, systole-diastolic ratio of 3.3. Conclusion: impaired blood flow III degree. Dose atenolol decreased by 75% of the initial dose was 25 mg When you study blood flow in the system "mother-placenta-fetus" through 48 hours after, the dose of atenolol in the umbilical artery of systole-diastolic ratio of 2.9, in the aorta of systole-diastolic ratio of 3.7, in the right uterine artery, systole-diastolic ratio of 2.2, in the left uterine artery, systole-diastolic ratio of 2.0. Conclusion: the blood within normal limits. Pregnant was rodorazresheniye by caesarean section at 39 weeks due to prenatal rupture of amniotic fluid and biological immaturity generic ways in perforada 34 years. For holocaustian live a premature boy, weight 2900, growth 49 see score on a scale of Apgar scores in the first minute 8 points in the fifth minute of 9 points, transferred to the children's ward. The mother was discharged on day 7 with the child.

Thus, lower doses of antihypertensive drug facilitated the normalization of blood flow in the uterine-placental complex and the birth of full-term newborn without delay syndrome fetal growth.

Example 5.

Pregnant With., 34 years old with a diagnosis: I operational premature birth at 34 weeks. Exacerbation of chronic placental insufficiency. The syndrome of delayed fetal growth, second degree. Mild chronic hypertension. Crevoshay the Pfannenstiel. Caesarean section for Shutter. Spinal anaesthesia. The patient was registered female consultations with 6-7 weeks of pregnancy. Profession - seller. Blood pressure rises with 24 years. Maximum blood pressure before pregnancy 145/85 mm Hg, the average level of blood pressure before pregnancy 135/85 mm Hg Antihypertensive therapy before pregnancy have not been conducted. In the rest of the medical history is not burdened. Menstrual function is not violated: 12 years, 4 days, 30 days, regular cycle. First pregnancy two years ago, ended medical abortion patients, no complications. This second pregnancy has occurred spontaneously. P the article 170, weight 78 kg (before pregnancy 69 kg). Blood group 0(I) first, a rhesus - positive. Surveyed on IGO, the result is negative. At 8 weeks was examined in 67 GKB, diagnosed with mild arterial hypertension. Physician clinics domiciliary assigned to atenolol dose of 50 mg per day. 23 and 27 weeks of pregnancy was in the hospital with a threatened miscarriage. Maximum blood pressure during pregnancy 145/85 mm Hg At 34 weeks by the doctor of female consultation pregnant sent to 8 GB with a diagnosis of Pregnancy 34 weeks. Head previa. Chronic placental insufficiency. The syndrome of delayed fetal growth, second degree. Mild chronic hypertension. Upon receipt held Doppler study. According to Doppler studies in umbilical artery zero diastolic blood flow in the aorta zero diastolic blood flow in the right uterine artery, systole-diastolic ratio of 4.2, in the left uterine artery, systole-diastolic ratio of 3.3. Conclusion: impaired uteroplacental blood flow and fetal-placental vnutriporovogo flow of III degree. Antihypertensive therapy is not canceled, as due to acute placental insufficiency pregnant was rodorazresheniye by caesarean section in term poradek is. The head of the extracted live a premature boy, weight 1350, growth 40 see score on a scale of Apgar scores in the first minute 5 points in the fifth minute of 6 points, was transferred to the neonatal intensive care unit on a ventilator. The mother was discharged on day 7. The child was transferred to the II stage of nursing.

Delayed diagnosis of disorders of blood flow in the uterine-placental complex is not allowed to adjust the dose of antihypertensive drugs in this patient, that has led to the need for early delivery and premature birth of the child requiring long-term hospital treatment.

Thus, the proposed method provides improved blood flow in the system mother-placenta-fetus, reducing the number of children born with the syndrome of delayed fetal growth, and thereby improves perinatal outcomes.

The method for correcting the dose of antihypertensive drugs in pregnant mild chronic hypertension, including the determination of the degree of disturbance of blood flow in the uterine-placental complex with Doppler study of the system "mother-placenta-fetus" and when IA or IB disturbance reduce the dose of antihypertensive drugs by 25% from the original, with II degree of violations by 50%, III - degree of 75%.



 

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7 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention is related to medicine, in particular to urology, and is related to removal of residual concrements in patients who sustained surgical procedure. For this purpose patients who sustained surgical procedure receive irrigation of kidney cavities with litholytical solution, which contains ampicillin in amount of 0.1 - 0.3 wt % and complexon in amount of 4-5 wt %. As complexon they use either trilon B or sodium citrate or their mixture with content of each in the mixture of 2-2.5 wt %. Irrigation is carried out at solution temperature of 36.8-37.2°C and constant speed of litholytical solution feed, which is selected within the limits of 1-10 ml/min.

EFFECT: method provides for possibility of simultaneous removal of concrements of various composition and prophylaxis of complications stipulated by kidney injury because of residual concrements and bacterial infection.

1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine and pharmacy, namely to agents for inhibition of development or progression of liver cancer in hepatitis C positive patients suffering from cirrhosis, wherein the agent contains three types of amino acids, namely isoleucine, leucine and valine, wherein mass ratio of isoleucine, leucine and valine makes 1:1.5-2.5:0.8-1.7.

EFFECT: invention provides effective inhibition of development or progression of liver cancer in hepatitis C positive patients suffering from cirrhosis.

18 cl, 1 ex, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine, in particular to gynecology and deals with hormonal treatment of disease or disorder and increase of fertility in woman who needs it. For this purpose, regimens of continuous with more than 50-day duration introduction of combination of ethinylestradiole in dose from 5 mcg to 50 mcg and levonorgestrel in dose from approximately 0.05 mg to approximately 1.5 mg is suggested. Further, estrogen is introduced during period from 2 to 10 successive days.

EFFECT: due to "estrogen bridge" between cycles of hormonal therapy, inventions ensure reduction of number of unplanned bleedings in second and following cycles of intake in comparison with regimens, which include after the cycle finishing days, free of hormonal therapy, and minimisation of symptoms, conditioned by break between cycles.

64 cl, 10 dwg, 21 tbl, 10 ex

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