RU2563824C2 - Method for preventing haemorrhage during myomectomy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to a method for preventing haemorrhage during myomectomy. The above method consists in introducing Tranexam 1.0 g dissolved in 0.9% sodium chloride 200 ml for 20-30 minutes intravenously drop-by-drop 30-45 minutes before a surgical intervention.

EFFECT: invention provides reducing perioperative blood loss and preventing coagulopathic haemorrhage during myomectomy.

6 tbl, 3 ex

Description

The invention relates to medicine, namely to obstetrics and gynecology, and can be, in particular, used to reduce blood loss when performing myomectomy, i.e. organ-saving surgery to remove myomatous nodes with preservation of the uterus.

A method of reducing blood loss is known from the practice of medicine, in which a short-term (up to 40 minutes) endovascular occlusion of the common iliac artery is performed, which allows to reduce blood supply to the internal genital organs, including the uterus, and thereby reduce intraoperative blood loss (Experience with organ-preserving operations / M.A. Kurtser, I.Yu. Breslav, M.V. Lukashina, A.M. Shtabnitsky, A.V. Panin, T.V. Alekseeva, I.V. Platitsin - Obstetrics and Gynecology - 2011 - No. 8 - S.86-90).

The disadvantages of the above method include: the need for expensive equipment, a separate room for manipulation of catheterization of blood vessels, long-term training of personnel performing intravascular manipulations, lengthening of surgical intervention and anesthetic management.

There is a method in which to reduce the blood supply to the uterus before performing the operation, it is proposed to clipping the main vessels, in particular the internal iliac arteries (Method of laparoscopic myomectomy (Patent RU No. 2407467, published December 27, 2010, IPC class: АВВ 17/42). However, this method requires high qualification of the operating team; it is technically difficult manipulation; it takes a long period of time before the main surgical intervention. In addition, there is a high risk of stated failures large vessels, followed by massive bleeding, which may lead to death.

Closest to our proposed method of the invention is a method of reducing the amount of intraoperative blood loss in organ-preserving surgical treatment of uterine fibroids, including the use of misoprostol 400 mg (1 Tikhomirov A., “Possibilities for reducing the volume of intraoperative blood loss in organ-preserving surgical treatment 1 hour before uterine surgery) treatment of uterine fibroids ", Russian Medical Journal. Mother and Child. Obstetrics and Gynecology. No. 8, 02/08/2007, Internet data: www.rmj.ru/articles_4415/htm.).

It should be noted that misoprostol is a drug that promotes spontaneous uterine contraction. According to the known pharmacokinetic data, the maximum concentration of the active metabolite of misoprostol (misoprostolic acid) in the blood plasma is reached after 15 minutes, and the half-life is 35-40 minutes.

The disadvantage of this method, compared with the proposed one, is that it is designed to reduce intraoperative blood loss due to contraction of the uterus and compression of the vessels in the myometrium only for the duration of the operation. After the end of the drug, the muscle layer of the uterus loses contractility and in the postoperative period, bleeding from vessels that are not large in diameter can be observed.

It is important to note that all of the above methods do not affect the fibrinolytic link of hemostasis at the local level.

The aim of the invention is to reduce perioperative blood loss and prevent the development of coagulopathic bleeding with myomectomy.

The specified technical result is achieved in the invention in that 30-45 minutes before surgery, the patient is injected intravenously with 1.0 g of tranexam diluted in 200 ml of a 0.9% sodium chloride solution for 20-30 minutes.

To achieve the maximum concentration of a drug substance in the blood at the time of the operation and to obtain a pronounced hemostatic effect, tranexam is administered 30-45 minutes before the operation in a total dose of 1.0 g. In addition, the introduction of the drug before surgery is convenient for medical staff during preoperative preparation.

The mechanism of action of tranexam is a specific inhibition of activation and the conversion of profibrinolysin (plasminogen) to fibrinolysin (plasmin). Tranexam inhibits fibrinolytic activity and prevents the rapid absorption of a blood clot on a damaged vessel.

Using tranexam is a safe method to limit perioperative blood loss because it does not lead to thrombosis in the vessels of the lower extremities (Svanberg L, Astedt B, Nilsson IM. Abruptio placentae - treatment with the fibrinolyticinhibitor tranexamic acid. Acta Obstet Gynecol Scand 1980; 59: 127-30 )

The use of tranexam helps reduce tissue bleeding during and after surgery on the uterus, reduces blood loss, reduces the need for transfusion of donor red blood cells, does not increase the risk of thrombotic complications (Prevention of the activation of the systemic inflammatory response syndrome during abdominal delivery of pregnant women with gestosis / A.V. Pyregov , V.A. Guryanov, L.V. Krechetova, N.K. Tetruashvili // Problems of reproduction. - 2006. - No. 6. - S. 108-110).

A distinctive feature of the proposed method is the use of tranexam before surgery, which allows you to control and prevent already at an early stage increased blood loss and coagulopathic bleeding, which are observed when performing myomectomy.

The advantage of this method is a single use of tranexam in a dose that optimally normalizes the parameters of the hemostatic system without increasing the risk of developing thrombotic conditions. In addition, with intravenous drip of tranexam for 20-30 minutes, undesirable effects on the effect of the drug are not observed. An additional advantage is the safety of the use of this method for any operations on the uterus (both obstetric and gynecological).

The practical significance of the proposed method lies in the pharmacoeconomic benefit, which is achieved by using the least total amount of hemostatic drugs and achieving a good treatment effect, as well as reducing the number of days a patient is in hospital.

The proposed method was successfully tested at the clinical base of the Department of Obstetrics and Gynecology, Faculty of Medicine, SBEE HPE "Astrakhan State Medical Academy" of the Ministry of Health of the Russian Federation at the NUZ "MSCh" in Astrakhan for the period 2009-2013. In total, 120 patients with uterine myoma were examined, who underwent a modern organ-preserving operation - laparoscopic myomectomy. All patients underwent surgery with one team using the same surgical technique.

Patients of the 1st group, 30-45 minutes before surgery, were intravenously dripped with 1.0 g of tranexam diluted in 200 ml of a 0.9% sodium chloride solution for 20-30 minutes. The drug tranexam patients of the 2nd group was not administered.

The volume of blood loss was estimated using the gravimetric method, as well as on the basis of changes in laboratory parameters in dynamics. A study was made of indicators of a general blood test (hemogram) and hemostasiogram.

The following methods were used to study the coagulation link of hemostasis:

- general coagulation tests characterizing the first phase of the blood coagulation process - the phase of prothrombinase formation: blood coagulation time according to Lee-White;

- methods characterizing the second phase of the blood coagulation process - the phase of thrombin formation: prothrombin index (IPT) according to A.J. Qwick (1935), reflecting the activity of factors of the prothrombin complex (II, VII, IX, X);

- methods characterizing the third phase of the blood coagulation process - the phase of the formation of fibrin and paracoagulation products (with pathological intravascular coagulation);

- the state of the fibrinolysis system was evaluated by studying the indicators of the fibrinolytic activity of blood cells by the time of lysis of clots of the euglobulin fraction (XIIa-dependent fibrinolysis).

In addition, the determination of the content of adhesive protein markers of endothelial dysfunction: plasma fibronectin and von Willebrand factor was carried out.

In order to identify intravascular coagulation, all patients were examined for the content of anticoagulant anticoagulant blood systems in the blood: D-dimer, PAP, antithrombin-III and protein-C system.

Table 1 presents the main laboratory parameters that allow us to evaluate the changes associated with perioperative blood loss in the observed patients.

It should be noted that the sampling of material (blood) for laboratory studies was carried out before surgery, at the end of the operation, and also after the end of the first day of the postoperative period (after 24 hours).

The results of observation and research showed the following.

Patients of the 1st group (receiving tranexam), unlike women of the 2nd group, noted a significant improvement in their general condition within 5-6 hours after the operation. This is due to the inhibitory effect of this drug on the formation of kinins and other active peptides that affect the limbic system of the brain. In addition, tranexam has its own and potent analgesic activity against opiates, which contributes to a more rapid recovery of the patient after drug anesthesia. It should be noted that we did not observe any allergic reactions or other undesirable effects on the use of tranexam with the above method.

The amount of intraoperative (direct) blood loss in patients of the 1st group was 60% (200-230 ml) of blood loss in patients from the 2nd group (330-380 ml). The amount of discharge by drainage in patients of the 1st group during the day after the operation decreased even more pronounced, which amounted to 40% (60-80 ml) of the amount of discharge by drainage in women of the 2nd group (150-200 ml).

Thus, in patients who received tranex, the total perioperative blood loss was 53% less than in those who were not given this drug.

A study of hemogram parameters showed the following (Table 2). As can be seen from table 2, before surgery, the concentration of red blood cells and platelets in patients of both groups were comparable. At the end of the operation and 24 hours after it, these indicators decreased and had significant differences both within one group and between groups (p <0.05) (Table 2).

As can be seen from table 2, the hemoglobin level changed according to the indicators of the concentration of red blood cells in patients of both groups. Moreover, in patients of the 1st group, this indicator at the end of the operation and a day after it remained in the range of acceptable values, and its dynamics was unreliable. At the same time, in patients of the 2nd group, the concentration of erythrocytes and the level of hemoglobin decreased during the observed time intervals, and these changes were statistically significant (p <0.05).

The hematocrit significantly changed both in the dynamics of two subsequent analyzes in comparison with the initial indicators within each group, and when comparing similar data between groups.

The study of blood viscosity (Table 2) in the groups of women examined did not show any significantly significant differences in the indicators.

Thus, the analysis of hemogram changes indicates less intraoperative blood loss in patients who received tranexam before surgery compared with women in the other group.

Studying the parameters of the hemostasiogram made it possible to ascertain the development of the chronic form of DIC syndrome in all women we observed with uterine myoma (Table 3).

In the study of indicators of the procoagulant link of the hemostatic system (fibrinogen concentration, APTT, PTI), the following tendency was revealed (Table 3). The concentrations of fibrinogen and APTT at the end of the operation and one day after it in patients of both groups were within normal values. However, changes in these parameters in the dynamics, compared with the initial indicators, as well as when comparing between the corresponding groups at the end of the operation and 24 hours after it, were statistically significant (p <0.05).

In the study of platelet link of the hemostatic system (Table 3), it was noted that the indicators of platelet aggregation ability during ADP stimulation were closer to the lower limit of normal. The dynamics of these indicators was not statistically significant, however, in the 2nd group 24 hours after the operation, compared with the initial indicators, a significant increase in values was noted, which indicated changes in the hemostasis system due to the stress response of the body to surgery.

As can be seen from table 3, all patients with uterine myoma observed by us have a significant (3-4 times) increase in the content of soluble complexes of fibrin monomers (RKMF) in the blood. After surgery, this indicator increased in the group of patients who did not receive tranex. This indicates the activation of the chronic DIC and the transition of the hyper phase into hypocoagulation (into secondary fibrinolysis). However, with the use of tranexam in patients of another group, normalization of RKMF parameters was observed, which significantly reduces the risk of the formation of intravascular thrombi.

When analyzing the indicators of the components of the anticoagulant blood system, it was noted that in patients of the 1st group, the values of D-dimer and PAP significantly decreased after surgery, compared with the parameters of patients who were not administered tranex (p <0.05). This indicates the normalization of the fibrinolytic link of the hemostatic system (Table 3).

It is known that the indicators of the anticoagulant system (antithrombin-III and protein-C) decrease with DIC. Indicators of protein-C did not change in dynamics (p> 0.05).

After surgery, normalization of antithrombin-III indices was observed only in the group of patients who received tranex (p <0.05) (see Table 3).

In addition, the activation of the processes of fibrinolysis against the background of uterine fibroids is indicated by the indicators of XIIa-dependent fibrinolysis, the changes of which are statistically significant in the process of monitoring patients of the 1st group compared to women of the 2nd group, where tranexam was not used (p <0 , 05).

The dynamics of the indicators of adhesive protein markers of endothelial dysfunction (plasma fibronectin and von Willebrand factor) are statistically unreliable (p> 0.05) (Table 3).

Thus, analyzing the data of tables 2 and 3 as a whole, it follows that all patients with uterine myoma had changes in hemogram and hemostasiogram indicators, indicating an “readiness” of the body for the development of coagulopathic bleeding. However, in patients of the 1st group after the use of tranexam, many indicators of the hemostatic system statistically significantly changed in the positive direction (p <0.05) and were in the range of normal values. Therefore, the use of the drug tranexam, blocking the activation and conversion of profibrinolysin (plasminogen) to fibrinolysin (plasmin), prevents coagulopathic bleeding, reduces the risk of pathological bleeding and, thereby, reduces the overall perioperative blood loss. The use of tranexam in a dose of 1.0 g is safe and does not lead to thrombotic conditions.

Treatment of patients of the 1st group turned out to be economically more profitable due to the prevention of intra- and postoperative complications in the form of bleeding, as well as the reduction of hospital stay days (3.5 ± 0.4 and 4.8 ± 2.2 hospital days in groups, respectively) (p <0.05).

The implementation of the proposed method is illustrated by the following clinical examples.

Example 1

Patient K., 28 years old. From the data of the anamnesis it is known that 3 years ago was the first pregnancy, which ended in an urgent birth. For 4 years, there has been observed for uterine fibroids and miscarriage. It is likely that two spontaneous miscarriages in the first trimester of pregnancy after childbirth were associated with multiple nodes of uterine fibroids (subserous and subserous-interstitial).

Gynecological examination showed that the uterine body is dense, "hilly", increased to 10-11 weeks of pregnancy, respectively, due to fibromatous nodes. According to ultrasound data: the uterus is enlarged to 11 weeks of pregnancy due to two subserous nodes located along the front wall of the uterus, 38 × 40 × 32 mm and 37 × 36 × 41 mm, respectively, as well as one interstitial-subserous node with centripetal growth, located on the back of the uterus and measuring 48 × 45 × 42 mm.

The patient was recommended to perform an organ-saving operation - myomectomy.

45 minutes before surgery, the patient was intravenously dripped with 1.0 g of tranexam diluted in 200 ml of a 0.9% sodium chloride solution for 30 minutes. No adverse clinical effects were observed with the administration of tranexam.

Under endotracheal anesthesia, laparoscopic husking of myomatous nodes was performed, followed by suturing of the muscle bed. At the end of the operation, a polyvinylchlorine tube 0.5 cm in diameter was brought into the posterior douglas space for control and removed from the abdominal cavity through the trocar opening.

Intraoperative blood loss was 200 ml. The amount of sacral discharge during the first day of the postoperative period was 150 ml. The results of laboratory tests (hemograms and hemostasiograms) are presented in table 4.

As can be seen from the presented table 4, in the hemogram there are statistically significant changes in the direction of lowering all indicators at the end of the operation, with the exception of blood viscosity. This indicates that there has been a loss of blood (as with any surgical intervention). However, after a day, these indicators stabilized, with the exception of hematocrit (to restore hematocrit indices, a longer time is needed). This positive trend is explained by the use of tranexam before surgery, which has a hemostatic and blood-preserving effect.

It can be seen from the hemostasiogram indicators that the data that testified to the "readiness" of the body for increased blood loss normalized one day after the operation (fibrinogen, RKMF, antithrombin-III, XIIa-dependent fibrinolysis, D-dimer, RAP) and their changes were statistically significant (p <0.05).

5 hours after the surgical treatment, the patient was activated with good health, which can be explained by the effect of tranexam on the limbic system.

The patient was discharged in satisfactory condition on the 3rd day of the postoperative period, i.e. two days after complex surgery on the pelvic organs.

Example 2

Patient I., 29 years old. According to the anamnesis, the patient is treated for infertility for 5 years. Uterine fibroids were first discovered 3 years ago. Over the past year, fibromatous nodes have been growing. There were no pregnancies.

A gynecological examination showed that the uterine body is dense, increased to 10 weeks of pregnancy, respectively, due to fibromatous nodes.

Ultrasound examination revealed the presence of two subserous nodes located along the front wall of the uterus, sizes 32 × 35 × 30 mm and 35 × 40 × 31 mm, respectively, as well as one interstitial-subserous node located on the back wall of the uterus and measuring 45 × 42 × 37 mm.

Given the clinical and instrumental data, the patient was recommended to perform laparoscopic myomectomy.

30 minutes before surgery, the patient was intravenously dripped with 1.0 g of tranexam diluted in 200 ml of a 0.9% sodium chloride solution for 20 minutes. Side effects when using tranexam were not observed.

Under endotracheal anesthesia, a laparoscopic myomectomy was performed. At the end of the operation, a polyvinylchlorine tube 0.5 cm in diameter was brought into the posterior douglas space for control and removed from the abdominal cavity through a trocar opening.

Intraoperative blood loss was 230 ml. The amount of sacral discharge during the first day of the postoperative period was 160 ml. The results of laboratory tests (hemograms and hemostasiograms) are presented in table 5.

As can be seen from the above table 5, the hemogram indicators tend to decrease at the end of the operation, which is to be expected with any surgical interventions even with a minimal amount of blood loss (except for blood viscosity). After 24 hours, the results of the hemogram study were leveled with the initial ones (to restore the hematocrit index, a longer time is required, in comparison with other indicators).

According to the hemostasiogram, the studied parameters returned to normal one day after the operation. Their dynamics is also reflected in table 5. These changes were significant (p <0.05).

The patient was activated 6 hours after surgery, was discharged on the 3rd day of the postoperative period.

Thus, as can be seen from examples 1 and 2, when applying the proposed method, blood loss is minimized and coagulopathic bleeding is prevented during myomectomy, hemogram and hemostasiogram parameters are normalized quickly, and the patient is quickly restored after drug anesthesia. In addition, the rapid stabilization of the clinical condition of the patient and the normalization of laboratory parameters make it possible to early discharge her from the hospital.

Example 3

Patient M., 26 years old. I went to the obstetrician-gynecologist for primary infertility. A vaginal examination showed the presence of an enlarged uterus and the presence of myomatous nodes. According to sonography: the size of the uterus corresponds to 10 weeks of pregnancy, due to two subserous nodes located along the front wall of the uterus, sizes 40 × 32 × 36 mm and 36 × 40 × 31 mm, respectively, as well as one interstitial-subserous node located on the back the uterine wall (node size 38 × 39 × 35 mm), deforming the uterine cavity.

Given the above, the patient as a first stage of treatment was recommended myomectomy, which was performed through laparoscopic access. Before surgery, in this clinical case, tranexam was not administered.

Intraoperative blood loss was 350 ml. The amount of sucrose discharge during the first day, as well as discharge through the drainage tube from the abdominal cavity was about 200 ml. In the study of laboratory indicators revealed the following (see table 6).

As can be seen from the presented table 6, in the hemogram there are statistically significant changes in the direction of lowering all the indicators at the end of the operation, which remain (or decrease further) a day after myomectomy (with the exception of blood viscosity) compared with the initial data. This indicates an increased volume of blood loss, which the patient's body could not quickly compensate for in the first hours and days after the operation.

In the hemostasiogram, almost all of the studied parameters statistically significantly changed in the negative direction, which was proved by the volume of blood loss during the operation.

The patient was activated 12 hours after the surgical treatment. Discharged on the 4th day of the postoperative period.

As can be seen from the presented example 3, with similar anatomical situations and surgical features, the total perioperative blood loss was 2 times higher than in the clinical cases indicated in examples 1 and 2.

Thus, summarizing the presented, it follows that when using the method we offer, we achieve:

- reduction of perioperative blood loss;

- prevention of the development of coagulopathic bleeding during surgical treatment of uterine tissue;

- quick recovery of the general condition of the patient in the postoperative period;

- reduction of the patient’s hospital stay.

Claims (1)

A method for the prevention of bleeding during myomectomy through the use of drugs, characterized in that 30-45 minutes before surgery, the patient is administered intravenously dropwise 1.0 g of tranexam diluted in 200 ml of a 0.9% sodium chloride solution for 20-30 minutes.