RU2629040C1 - Method for coagulopatic bleeding prevention during cesarean section - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: to prevent bleeding during caesarean section, when performing a cut of the anterior abdominal wall during caesarean section, 10 ml of 10% calcium gluconate solution and 10 ml of tranexamic acid containing 1 gram of dry matter are subsequently injected into a peripheral vein.

EFFECT: method provides prevention of coagulopathic bleeding with a decrease in perioperative blood loss in patients at risk of such bleeding.

8 tbl, 6 ex

Description

The invention relates to medicine, namely to obstetrics and gynecology, and can be used, in particular, for the prevention of coagulopathic bleeding and reduce blood loss during cesarean section.

In obstetric practice, with the aim of preventing and treating pathological bleeding that occurred during childbirth and in the postpartum period, various methods and methods for stopping them are used, taking into account the reasons that led to it (Chernukha E.A. , T.A. Fedorova // Obstetrics and Gynecology. - 2007. - No. 4. - S. 61-65).

A known method of applying compression sutures to the uterus during the period of uterine bleeding associated with uterine hypotension (B-Lynch C. A textbook of postpartum hemorrhage / C. B-Lynch, A.V. Lalonde // Duncow: Sapiens Publishinq. - 2006. - P. 468; Yaglov V.V. Uterine bleeding and hemostasis / V.V. Yaglov // Consilium medicum. - 2007. - No. 6. - P. 28-32).

In addition, a method for uterine devascularization is proposed in which ligation is performed, i.e. stitching of the main vessels feeding the uterus (Sidorenko A.V. Prevention of bleeding during cesarean section: modern possibilities / A.V. Sidorenko, E.S. Grits, L.S. Gulyaeva, V.L. Silyava // Medical journal : peer-reviewed scientific and practical journal. - 2008. - No. 4. - P. 66-67; Kurtser M.A. Ligation of the internal iliac arteries as an alternative to hysterectomy for massive obstetric bleeding / M.A. Kurtser, A.V. Panin, L.V.Sushchevich // Obstetrics and Gynecology. - 2005. - No. 4. - S. 12-15).

However, these methods of surgical hemostasis are performed already with the development of uterine bleeding and are therapeutic, not prophylactic. In addition, it should be noted that when performing surgical contraction, soft tissue eruption and sagging of sutures can be observed, and during ligation of the uterine vessels there is a high risk of damage to large vessels and adjacent organs (ureter, bladder, intestines).

A known method for the prevention of bleeding during cesarean section using balloon tamponade of the uterus (Bayev OR. Mandatory link: balloon tamponade of the uterus has become an obligatory link in the treatment of postpartum hemorrhage / O.R.Baev, Ya.G. Zhukovsky // Medical Bulletin. 2013. - No. 3 (616). - S. 14-15). The disadvantage of this method is not always a long-term positive hemostatic result.

There is a way to reduce blood loss, in which 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 (Kurtser M.A. organ-preserving operations when the placenta is ingrown / MA Kutser, I.Yu. Breslav, MV Lukashina // Obstetrics and gynecology. - 2011. - No. 8. - P. 86-90). The disadvantages of the above method include: the need for expensive equipment, a separate specialized room for manipulation of catheterization and embolization of blood vessels, specially trained medical personnel. In addition, there is a significant lengthening of the time for surgery and anesthesia.

A known method for the prevention of hypotonic uterine bleeding in the early postoperative or postpartum period using prostaglandins (Kundodyiwa T.W. Misoprostol versus oxytocin in the thirdstage of labor. / TW Kundodyiwa, F. Majoko, S. Rusakaniko // Int. J. Gynaecol. Obstetet . - 2001. - No. 75 (3). - P. 235-241; Chernukha E.A. Evolution of therapies for postpartum hemorrhage / E.A. Chernukha, T.A. Fedorova // Obstetrics and Gynecology. - 2007. - No. 4. - S. 61-65). However, this method is aimed at preventing bleeding associated with impaired uterine contractions in the early postpartum or postoperative periods.

It is known that pregnancy, labor stress and the pain component contribute to an increase in the fibrinolytic activity of puerperas, therefore, for the prevention and treatment of obstetric hemorrhage, along with complex infusion and uterotonic therapy, a method for the use of antifibrinolytic drugs in childbirth has been developed (Vasiliev S.A. Tranexam - antifibrinolytic hemostatic / S.A. Vasiliev, V.L. Vinogradov, E.G. Gemdzhyan // Thrombosis, hemostasis and rheology. - 2008. - No. 1. - P. 28-34).

In addition, a method has been developed to prevent coagulopathic bleeding and increased blood loss in the early postpartum period, in which an antifibrinolytic agent, 0.75 g tranexam diluted with 200 ml of a 0.9% sodium chloride solution, is administered intravenously dropwise 60 minutes before the expected end of labor. Sinchikhin S.P. Prevention of postpartum hemorrhage, taking into account the type of adaptation of the mother and fetus to birth stress / S.P. Sinchikhin, O.B. Mamiev, V.O. Mamiev // Russian Bulletin of the Obstetrician-Gynecologist. - 2013. - No. 6 T. 13. - S. 91-94). As already noted, this method was used for puerperas delivered through the natural birth canal.

Closest to our proposed invention is a method for the treatment of uterine fibroids, where, in order to reduce the amount of intraoperative blood loss 30-40 minutes before the start of the operation, a tranexamic acid preparation in a dose of 1000 mg is injected iv (Magakyan S.G. myomectomy. / S.G. Magakyan, S.P. Sinchikhin, L.V. Stepanyan // Patent No. 2563824 Russian Federation, IPCA 61K 31/195 (2006.01), A61K 33/14 (2006.01), A61P 7/02 ( 2006.01). - No. 2014106575/15, announced on 02/20/2014, publ., Applications 08/27/2015 Bulletin No. 24. Published on 09/20/2015. - Bulletin No. 26. - 15 pp.). However, in the specified invention does not provide data on the possible use of the developed medicinal method for cesarean section.

The present invention is aimed at preventing the development of coagulopathic bleeding in order to reduce blood loss in the perioperative period, namely before, during and after cesarean section.

The specified technical result is achieved in the invention by the fact that when performing an incision of the anterior abdominal wall during cesarean section, 10 ml of 10% solution of calcium gluconate and 10 ml of tranexamic acid preparation containing 1 gram of dry matter are sequentially injected intravenously into the peripheral vein.

The proposed dosage of the above drugs is most optimal for achieving rapid drug hemostasis in the perioperative period, as well as safe not only for the patient being operated on, but also for the newborn, since the maximum concentration of drugs in the mother’s body occurs after the fetus is removed from the uterus.

The mechanism of action of calcium gluconate is increased coagulation and rapid thrombosis of a defect in the vascular wall. This is due to the fact that calcium ions belong to the IV plasma factor of the blood coagulation system and play a role in the sequential activation of other plasma coagulation factors (II, III, Va, Xa, XIa, XIIa, XIIIa). In addition, calcium is involved in the reduction of smooth muscles of the uterus, which positively affects the prevention of uterine hypotension.

The pharmacokinetics of another drug that is used in this invention is that tranexamic acid prevents the transfer of profibrinolysin (plasminogen) to fibrinolysin (plasmin), i.e. tranexamic acid inhibits the fibrinolytic activity of the hemostatic system and slows the absorption of the resulting blood clot in the damaged vessel.

The use of tranexamic acid does not increase the systemic coagulation potential of blood in pregnant women. Therefore, the probability of developing thrombosis in this category of pregnant women is not higher than in patients who did not take this drug (Mousa N.A. Treatment for primary postpartum haemorrhage / N.A. Mousa, Z. Alfirevic // Cochrane Library, 2009, Issue 1 )

The use of tranexamic acid reduces blood bleeding during and after surgery, reduces blood loss, and therefore the need for transfusion of donor red blood cells (Pyregov A.V. Prevention of 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).

An additional important pharmacological property of tranexamic acid is its anti-inflammatory effect, which is due to the suppression of the formation of kinins, pro-inflammatory cytokines (tumor necrosis factor, interleukin 1, interleukin 2) and other active peptides involved in inflammatory and allergic reactions.

A distinctive feature of the proposed method is the use of the optimal dose of two drugs (10 ml of a 10% solution of calcium gluconate and 10 ml of tranexamic acid) during cesarean section, which prevents coagulopathic bleeding, reduces intraoperative blood loss, as well as the development of postoperative complications.

An advantage of this method is that the drugs used in the invention, having different pharmacological effects, on the whole consistently complement each other at different levels of hemostasis. Calcium accelerates the formation of a blood clot in the damaged vessels of the myometrium, and tranexamic acid does not allow the resulting blood clot to quickly lyse. In general, this allows you to optimize the parameters of the blood coagulation system and reduce blood loss in patients. We consider it important that we use these drugs comprehensively before surgery. This helps to achieve maximum hemostatic effect.

An additional advantage is that the developed method can be applied both in a planned manner and in case of an urgent caesarean section, as The preparations used in the invention are used directly at the beginning of the operation - when performing an incision in the anterior abdominal wall.

The practical significance of the proposed method lies not only in clinical efficacy, but also in pharmacoeconomic feasibility, which is expressed in the use of the least total amount of drugs during and after cesarean section in view of preventing the development of perioperative complications. Moreover, in general, the drug load on the woman’s body decreases, the number of days the patient stays in the hospital decreases. This is cost-effective both for a medical institution in particular and for the healthcare system as a whole.

The proposed method has been successfully tested on the clinical basis of the Department of Obstetrics and Gynecology, Faculty of Medicine, SBEE HPE "Astrakhan State Medical University" of the Ministry of Health of Russia in GBUZ JSC "Clinical Maternity Hospital" in Astrakhan.

160 patients were under prospective observation. All women were at risk for the development of coagulopathic bleeding, given the obstetric and somatic status and / or changes in laboratory parameters of the blood coagulation system.

It should be noted that all patients underwent caesarean section with one surgical team using the same technique.

Patients were divided into the following groups / subgroups of 40 people each.

1 group (the main one) was formed by pregnant women who, during a cesarean section according to the developed method of the invention, during the incision of the anterior abdominal wall, 10 ml of a 10% solution of calcium gluconate were successively injected intravenously into the peripheral vein, and then 10 ml (1 gram of dry matter) tranexamic acid.

Group 2 (comparisons) included two subgroups, each of which also had 40 women. Subgroup 2A was formed by patients in whom 10 ml of a 10% calcium gluconate solution was injected intravenously with a prophylactic purpose during a cesarean section. Subgroup 2B was formed by women who, at the beginning of a cesarean section, were injected intravenously with 10 ml of tranexamic acid preparation (1 gram of dry matter).

Group 3 (control) consisted of patients in whom the above drugs with prophylactic purpose were not used during cesarean section.

For the prevention of hypotonic bleeding, all patients received a uterotonic oxytocin at the end of the operation according to the basic federal protocol for cesarean section.

The women we observed were comparable in age (mean age 28.3 ± 1.7 years), extragenital pathology, and obstetric-gynecological history.

To assess the effectiveness of the developed method, a comprehensive clinical, laboratory and instrumental examination of patients was performed before surgery, on the 1st and 3rd day of the postoperative period.

The volume of blood loss was estimated using the gravimetric method, measured capacity and by changes in laboratory parameters (hemoglobin and hematocrit) in the postoperative period.

Hemograms, hemostasiograms, and blood calcium were studied (table 1).

To study the hemostatic system used the following research methods:

- general coagulation tests to evaluate:

1. The first phase of the blood coagulation process, which induces the formation of prothrombinase and is estimated by the Lee-White coagulation time indicator;

2. the second phase of blood coagulation, leading to the formation of thrombin and evaluated taking into account the prothrombin index (IPT) according to A.J. Qwick, as well as reflecting the activity of factors of the prothrombin complex (II, VII, IX, X);

3. the third phase of the blood coagulation process, the formation phase of fibrin and paracoagulation products (with pathological intravascular coagulation);

- tests evaluating the state of the fibrinolysis system 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).

- tests for intravascular coagulation by determining the blood levels of the components of the anticoagulant anticoagulant blood systems: D-dimer, antithrombin-III, MHO and protein C.

The amount of intraoperative (direct) blood loss in patients of the 1st group was 497 ± 13.0 ml, and in the 2nd, 3rd and 4th groups, respectively, 613 ± 17 ml, 5 70 ± 10 ml, 1100 ± 120 0 ml (p≤0.05).

In patients of group 1, the amount of uterine discharge from the uterus in the first three days of the postoperative period was 20 ml daily, at the time of discharge, on the 4th day - 10 ml, i.e. total indirect blood loss in the postpartum period in this group was 70 ml. In the 2A and 2B subgroups, the total indirect blood loss was 110 ml and 85 ml, respectively. Moreover, in patients of group 4, the number of postpartum bloody discharge in the first three days daily approached 60 ml, and at the time of discharge from the obstetric hospital - 40 ml, i.e. in this group, total indirect blood loss in the postpartum period was 220 ml.

It should be noted that massive blood loss in the volume of 1800-2000 ml due to uterine hypotension was observed in two patients from the comparison group.

Thus, in patients who simultaneously and comprehensively used calcium gluconate and tranexamic acid during the caesarean section, the total perioperative blood loss was on average 40.6% less than in those patients for whom these drugs were not used for prophylactic purposes or individually, only calcium gluconate or a tranexamic acid preparation was used.

When analyzing table 2, it follows that all the studied patients before the operation observed close and adverse changes in the parameters of the blood coagulation system. After the combined use of calcium gluconate and tranexamic acid preparations in comparison with the separate use of calcium gluconate or tranexamic acid, as well as with the results of a study of patients in whom none of the above drugs were used, the following features were revealed.

The most clinically effective was the integrated use of calcium gluconate and tranexamic acid in patients of the 1st (main) group in comparison with patients of other groups (comparison and control). Clinically less effective was the separate use of the above drugs in the 2nd group in comparison with the 3rd (control) group.

As can be seen from table 2, the use of calcium gluconate helps to maintain a stable value of calcium in the blood in patients of the 1st group and 2A subgroup, while in the 2B subgroup and 3rd group there is a decrease in the level of this element in the postoperative period, which confirms the absence of compensation this ion in these groups and higher blood loss in the control group.

The use of tranexamic acid in patients of the 1st group and 2B subgroup accelerated the blocking of the activation mechanism and the conversion of profibrinolysin (plasminogen) to fibrinolysin (plasmin), which helped to reduce blood loss in the perioperative period. Moreover, in the 1st (main) group, blood loss was the most minimal, because an increase in the hemostatic effect was achieved by the synergistic effect of two drugs - calcium gluconate and tranexamic acid.

As follows from table 2, in patients of the 3rd group, positive changes in the indicators of the blood coagulation system were not observed, which was expressed in higher blood loss in this group compared to others.

It should be noted that patients who received calcium gluconate and tranexamic acid preparations, in contrast to the observed puerperas of the other three groups, noted an improvement in their general condition 3 hours after cesarean section. This condition is associated with the analgesic, anti-inflammatory and immunostimulating activity of drugs (calcium gluconate and tranexamic acid), which activate the recovery processes in the body after suffering from birth stress and drug anesthesia. It should be noted that we did not observe any allergic reactions or other undesirable effects on the use of calcium gluconate and tranexamic acid in the above method.

The practical application of the developed method of the invention is economically feasible, because contributes to the prevention of intra- and postoperative complications, and also reduces the days of hospital stay (3.5 ± 1.5 and 4.8 ± 2.4, 3.7 ± 2.1 and 6.1 ± 2.2 hospital days by 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. The present pregnancy is the fourth, complicated by severe preeclampsia. In the anamnesis, the first pregnancy ended with operative delivery due to an increase in the severity of gestosis, the second and third pregnancy were interrupted at the request of the woman at short gestation. Among the gynecological pathology, ovarian dysfunction with menstrual irregularities was noted. This pregnancy proceeded against the background of chronic pyelonephritis in the stage of unstable remission and impaired fat metabolism of the II degree. The gestational period was accompanied by polyhydramnios. Clinical data on the complicated course of pregnancy, endocrine and somatic pathology, as well as laboratory data on the presence of hypocalcemia, hypercoagulation and slowing of fibrinolysis, allowed the patient to be assigned to a high risk group for the development of coagulopathic bleeding in childbirth and early postpartum periods.

The patient underwent an emergency cesarean section, the indications for which were a severe degree of preeclampsia and a scar on the uterus after the previous surgical delivery. During a cesarean section, when performing an incision in the anterior abdominal wall, 10 ml of 10% calcium gluconate solution and 10 ml of tranexamic acid containing 1 gram of dry matter were intravenously injected sequentially.

Intraoperative blood loss according to the gravimetric method was 490 ml. During the operation, a good contraction of the uterus and the absence of uterine bleeding were noted. Subsequent monitoring of the patient for three days showed normal involution of the uterus and a tendency to a decrease in postpartum discharge.

The results of laboratory tests (hemograms and hemostasiograms) are presented in table 3. As can be seen from table 3, the hemogram has statistically significant changes in the direction of lowering all indicators during the first days after surgery, with the exception of blood viscosity. This indicates that there has been a loss of blood (as with any surgical intervention). However, three days after the operation, these indicators stabilized, with the exception of hematocrit (to restore the hematocrit indices, a longer time is needed). This positive trend is explained by the use of calcium gluconate and tranexamic acid preparations at the beginning of the operation, which had a strong hemostatic effect, reduced intraoperative blood loss, prevented the development of bleeding and impaired uterine contractility.

Table 3 shows that those hemostasiogram indicators (fibrinogen, RKMF, antithrombin-III, XIIa-dependent fibrinolysis, calcium, D-dimer, MHO), which indicated before the operation that the body was “ready” for increased blood loss, while taking gluconate preparations calcium and tranexamic acid had statistically significant positive changes in dynamics (p <0.05). In addition, hemogram values in this puerpera confirmed low intraoperative blood loss.

It should be noted that three hours after the surgery, the patient was activated. This is probably due to the anti-inflammatory, analgesic and anti-allergic properties of tranexamic acid due to the suppression of the formation of kinins and other active peptides, which has a beneficial effect in protecting against surgical stress and prevents the development or progression of multiple organ failure syndrome. In addition, calcium ions, stimulating the sympathetic nervous system of the body, contribute to increased adrenaline excretion of adrenaline, thereby increasing the body's resistance to the development of an infectious-inflammatory reaction.

The patient was discharged on the 4th day of the postoperative period, i.e. 4 days after cesarean section.

Example 2

Multiparous patient E., 28 years old, without a history of reproductive losses, was admitted to the obstetric hospital with a diagnosis of Pregnancy 38 weeks. Severe preeclampsia. Mixed gluteal presentation of the fetus. Large fruit. Obesity 2 degrees.

The cesarean section was performed on an emergency basis due to the combination of the above gestational complications. During the operation, calcium gluconate and tranexamic acid preparations were not used. Intraoperative blood loss was 980 ml. Analysis of hemogram indicators, hemostasiograms, as well as methods for assessing blood loss before surgery, on the first and third days of the postoperative period confirmed high intraoperative blood loss and persistent changes in hemostasiogram (table 4).

Thus, in similar clinical situations indicated in examples 1 and 2, the total blood loss in the puerpera in this case was 1.9 times higher than in the patient from the previous clinical example, where the developed method of the invention was used.

Example 3

The first pregnant patient M., 26 years old, was admitted to the obstetric hospital for planned surgical delivery due to symphysitis and the presence of a large fetus in the period of 39 weeks of pregnancy. Pregnancy proceeded against the background of anemia of the II degree (Hb 86 g / l), frequent colds (4 times per pregnancy), the threat of termination of pregnancy. Among gynecological pathology, chronic adnexitis, primary infertility was noted, about which specific treatment was carried out in the pregravid period. According to the results of the examination, changes in the parameters of the blood coagulation system were noted, which made it possible to attribute this patient to the high-risk group for the development of coagulopathic bleeding.

During cesarean section, the developed and described method was applied. Intraoperative blood loss was 510 ml. The general condition of the puerperas and blood counts confirmed a slight loss of blood during cesarean section surgery (table 5).

Example 4

The nulliparous patient Z., 27 years old, was admitted for planned delivery with a diagnosis of Pregnancy 40 weeks. Preeclampsia is moderate. Polyhydramnios. Herniated disc.

This pregnancy was complicated by anemia of the first degree (Hb 91 g / l), gestational pyelonephritis and frequent colds. Together, the indicated obstetric and somatic pathology, as well as changes in the hemostasiogram (table 6), allowed to attribute the woman in labor to the high risk group for bleeding in the perioperative period.

A cesarean section was performed, taking into account the impossibility of delivery through the natural birth canal due to the associated extragenital pathology. Intraoperative blood loss amounted to 1100 ml. The results of the study objectively confirmed the indicated blood loss (table 6).

In similar clinical situations indicated in examples 3 and 4, blood loss during surgical delivery of a patient where the developed method of the invention was not used was 1.5 times higher than in a pregnant woman who used calcium gluconate and tranexamic acid preparations.

Moreover, as can be seen from examples 1 and 3, when applying the proposed method, both in the primiparous and the multiparous blood loss is maximally reduced and there is no excessive bleeding during cesarean section. In addition, low intraoperative blood loss contributed to an improvement in the somatic state of puerperas in the postoperative period and early discharge from the obstetric hospital.

To compare the effectiveness of the integrated use of calcium gluconate and tranexamic acid from their separate use, we present the following two clinical examples.

Example 5

Multiparous patient I., 28 years old, was admitted for surgical delivery by a diagnosis of Pregnancy 39 weeks. Preeclampsia is moderate. Defective uterine scar. Large fruit. Obesity 2 degrees.

A caesarean section was performed due to the combination of the above gestational complications. At the beginning of the operation, 10 ml of a 10% calcium gluconate solution was injected at the moment of cutting the anterior abdominal wall. Intraoperative blood loss was 600 ml. Analysis of hemogram indicators, hemostasiograms, as well as methods for assessing blood loss before surgery, on the first and third days of the postoperative period confirmed a relatively low intraoperative blood loss (table 7).

Example 6

The first-born patient A., 27 years old, was admitted to the obstetric hospital with a diagnosis of Pregnancy 35 weeks. Premature detachment of a normally located placenta. Dichoric diamniotic twins.

This pregnancy was complicated by anemia of the first degree (Hb 91 g / l) and frequent threats of abortion at different stages of gestation. The level of hemoglobin before surgery was 88 g / l. Blood loss before surgery was 200 ml. Together, the indicated obstetric and somatic pathology, as well as changes in the laboratory parameters of the blood coagulation system (table 8), allowed to attribute the woman in labor to the high risk group for bleeding in the perioperative period.

An emergency operation performed cesarean section. At the beginning of the operation, 10 ml (1 gram of dry matter) tranexamic acid was injected iv. Intraoperatively confirmed the detachment of a normally located placenta in a volume of 15%. Blood loss during surgery was 560 ml. The results of the study objectively confirmed the indicated blood loss (table 8).

As can be seen from examples 5 and 6, the volume of blood loss is 1.1 times greater with the separate use of calcium gluconate and tranexamic acid preparations almost in comparison with the complex (simultaneous) use of these drugs during cesarean section.

Thus, summarizing the foregoing, it follows that when using our proposed method is achieved:

- prevention of coagulopathic bleeding during cesarean section;

- reduction of perioperative blood loss;

- 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 coagulopathic bleeding in Caesarean section by the use of drugs, characterized in that when performing an incision of the anterior abdominal wall, 10 ml of 10% calcium gluconate solution and 10 ml of tranexamic acid preparation containing 1 g of dry matter are sequentially injected intravenously into the peripheral vein.