Pathophysiological Aspects of Evaluating Hemodynamics in Uterine Vessels and Quantitative Determination of Opposing Interleukin Groups in Lochia in Endometritis after Cesarean Section

The dissertation is devoted to the study of pathophysiological mechanisms of the development of endometritis after cesarean section, with an emphasis on hemodynamic changes in the uterine vessels and immunological reactions manifested as changes in the concentration of proinflammatory and anti-inflammatory interleukins in the lochia. The research is aimed at identifying early objective criteria for diagnosing inflammatory complications, which is of key importance for reducing maternal morbidity and mortality associated with postoperative purulent-inflammatory processes. The author develops approaches to differentiated diagnosis of various variants of the course of endometritis based on comprehensive laboratory and instrumental examination, including color Doppler mapping, cytological examination of lochia, and complete blood count.

Relevance of the Problem. Modern healthcare responds to the conditions that have become established in society: low birth rate, small families, and ecological adversity do not allow relying solely on the natural, "natural" course of events. Pregnancy requires intensive monitoring, preparation for childbirth, and often surgical delivery. If in the 19th century the main obstetric instrument was obstetric forceps, which helped save the mother, then in the 20th century the main instrument allowing the preservation of the health of both the mother and the child is the operation of cesarean section [104].

The increase in the frequency of cesarean section was accompanied by an 8- to 10-fold increase in the frequency of purulent-inflammatory complications compared with these indicators in spontaneous births [1, 40]. The frequency of endometritis after spontaneous births in the general population is 3-8%, in pathological births - 10-20%, after cesarean section - 30-35%, and in the group of women at high risk of developing septic complications - 55.5% [3, 32, 100, 104, 195].

In the structure of purulent-inflammatory complications, endometritis and wound infection of the anterior abdominal wall predominate. The frequency of endometritis, according to data from various authors, ranges from 6.6% to 52% [9, 155, 173]. The frequency of wound infection of the anterior abdominal wall after abdominal delivery reaches 5.5-20.4% [4, 9, 100]. The relevance of localized complications of cesarean section is determined not only by their significant frequency but also by the fact that they can become a cause of the spread of infection in some women to the peritoneum (peritonitis) or its generalization - sepsis, septic shock [44].

Unlike endometritis after vaginal births, endometritis after cesarean section has its own features, determined by the presence of additional damaged tissue areas (wounds on the uterus). Mechanical trauma of the uterus during the operation and a significant amount of suture material create favorable conditions for primary infection of tissues in the area of surgical intervention [9, 31, 40, 100].

Under conditions of inflammation, reparative processes in the wound are disrupted, and suture material, possessing a "wick effect," in some cases contributes to the spread of infection into the myometrium and the small pelvis [7, 112, 114]. According to the same authors, in 19.1% of observations in endometritis, anatomical insufficiency of the suture on the uterus was determined, and in 5.6% of cases, complete suture insufficiency was detected in combination with an abscess of the suture area. When peritonitis develops after cesarean section, complete or partial insufficiency of the suture on the uterus, upon relaparotomy, is diagnosed in 89% of women [2]. Rapid spread of the process beyond the endometrium as a result of infection of the entire thickness of the postoperative uterine suture, with possible formation of its insufficiency and generalization of infection, significantly increases the risk of maternal mortality [95, 103, 113]. According to data from B.I. Gurtov and co-authors [33], in the overwhelming majority (98%) of women, peritonitis arises precisely after abdominal delivery. The frequency of sepsis after cesarean section is 80 times higher than after spontaneous births [196], and septic shock occurs against the background of endometritis after cesarean section in 85% of cases [182]. The current frequency of peritonitis and sepsis after cesarean section is, respectively, 0.15-0.2% and 0.5-3.5%, and according to observations by some authors, the frequency of peritonitis can reach 8.7% [100, 196].

In the structure of causes of maternal mortality in the Russian Federation, they occupy 2nd-4th place, with maternal mortality from septic complications accounting for 13-15% [97, 100, 101, 112].

Early diagnosis of infectious complications is complicated by the significant spread of masked forms and the late manifestation of their clinical signs [16, 79]. In recent years, only isolated works [16, 17, 106] have been published concerning the increase in the masked course of postpartum endometritis, the manifestations of which do not always reflect the full depth and extent of involvement of the structures of the postpartum uterus in the inflammatory process. Insufficient informativeness and the absence of clear ideas about the significance of each of the used diagnostic methods of postpartum endometritis underscore the objective difficulties in diagnosing postpartum endometritis [114].

In the works of a number of authors, two variants of the course of endometritis have been identified [9, 16, 112]. In the first of them, the inflammatory process arises against the background of retention in the uterine cavity of fragments of the decidua, lochia, or placental tissue. Ultrasonographically, in this case, subinvolution of the uterus is detected from the first days of the disease, an increase in the anteroposterior size of the body and cavity of the uterus, and accumulations of heterogeneous echostructures of increased and decreased echogenicity in the uterine cavity.

In the second variant of the course of endometritis (the so-called clean form), no expansion of the uterine cavity is noted and no pathological structures are accumulated in it. Ultrasonographically, the uterine cavity is not expanded, and hyperechoic deposits are visualized on its walls; subinvolution of the uterus arises only by the 6th-7th day of the postpartum period.

The currently large number of new methods for preventing purulent-inflammatory complications after cesarean section has made it possible to reduce maternal morbidity and mortality in individual obstetric institutions, but in general, one can speak more about stabilization than about a reduction in postoperative inflammatory complications as a whole [50, 56, 57].

One of the ways to preserve the health of the mother is the improvement of methods for early diagnosis and prevention of purulent-inflammatory diseases, which allows selecting the optimal treatment tactic and preventing severe complications.

The multilevel nature of inflammation, as a general reaction of the organism, justifies the study of both immunological reactions and hemodynamics in the uterine vessels of women after cesarean section.

The above stated predetermined the goal of the present research: to study the pathophysiological features of the development of the inflammatory process when various variants of endometritis arise after the operation of cesarean section.

To solve the stated goal, the following tasks were formulated:

1. To study the features of hemodynamics in the uterine vessels of women during an uncomplicated puerperium after cesarean section.

2. To determine early signs of disruption of hemodynamics in the uterine vessels during the development of inflammatory complications after cesarean section.

3. To evaluate the concentration of pro- and anti-inflammatory interleukins in lochia as predictors of the occurrence of endometritis after cesarean section.

4. To study the cellular composition of lochia among women after cesarean section during uncomplicated puerperium and inflammatory complications, and to determine the diagnostic significance of the leukocyte intoxication index of lochia.

5. To determine the possibility of using the complete blood count for predicting the occurrence of inflammatory complications after cesarean section.

6. To study the features of the clinical course of various variants of endometritis after cesarean section in modern conditions.

7. To develop principles for selecting pathogenetic therapy for endometritis after cesarean section, taking into account the results of laboratory and instrumental examination.

Scientific Novelty. For the first time, on the basis of a comprehensive analysis, the mechanisms of formation of the inflammatory process of the uterus in various variants of endometritis after cesarean section have been elucidated, and early, objective criteria for diagnosing the inflammatory process have been identified. For the first time, using color Doppler mapping (CDM), the hemodynamics of the uterus in women after cesarean section with different courses of the postoperative period have been studied in detail (in the uterine, arcuate, radial, and basal arteries, in the anterior and posterior walls in the area of the uterine suture, on the 2nd, 4th, and 6th day of the puerperium). Early signs of disruption of uterine hemodynamics upon the development of inflammatory complications after cesarean section have been determined. For the first time, the results of a comparative study of changes in the level of proinflammatory (IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in the lochia of women with different courses of the postoperative period have been obtained. Correlational relationships between the concentration of various groups of cytokines, hemodynamic changes in the uterus, and features of the clinical course of women after cesarean section have been established. On the basis of the principles of evidence-based medicine, the possibility of using the indicator of the change in the number of leukocytes in the blood after the operation, compared with the preoperative level, to predict inflammatory complications after cesarean section has been established. In cytological examination of lochia, the LII indicator, calculated according to the formula of V.K. Ostrovsky [83], was used for the first time for diagnosing inflammatory complications after cesarean section.

Basic Propositions of the Dissertation, Presented for Defense

1. The pathophysiological features of the occurrence of endometritis after cesarean section are disruptions of hemodynamics in the uterine vessels, expressed in increased vascular resistance of the basal arteries in the area of the uterine suture, as well as in pronounced lateralization of blood flow in the ascending branches of the uterine arteries.

2. Inflammatory complications after cesarean section are accompanied by disruptions in the system of mediators of intercellular interaction: intensification of the production of proinflammatory cytokines (IL-6, IL-8); an increase in the ratio of pro- and anti-inflammatory cytokines against the background of a decrease in anti-inflammatory cytokines (IL-10).

3. The principles for selecting a pathogenetically grounded variant of local treatment of endometritis after cesarean section are the presence or absence of pathological substrate in the uterine cavity, as well as dynamic evaluation of the effectiveness of the conducted therapy.

Practical Significance. The work substantiates the advisability of studying hemodynamics in the uterine vessels for early differentiated diagnosis of inflammatory complications after cesarean section. The sensitivity and specificity of criteria of hemodynamic disturbances for early diagnosis of inflammatory complications after cesarean section have been established. Data have been obtained on disturbances in the balance of pro- and anti-inflammatory cytokines in the lochia during the development of purulent-inflammatory complications after cesarean section. Correlational relationships between the cytokine level and indicators of vascular resistance of the uterine vessels after cesarean section have been revealed. The possibility of using the indicator of the change in the number of leukocytes in the blood after the operation, compared with the preoperative number, to assess the risk of developing inflammatory complications has been established. Statistically significant differences in the LII of lochia among women with uncomplicated puerperium and inflammatory complications after cesarean section have been obtained.

Dissertation Defense. The main provisions and results of the research were presented in the form of publications and reports at the All-Russian Scientific and Practical Conference "Medical-Biological and Ecological Problems of Human Health in the North" (Surgut, 2000); the II District Conference of Young Scientists of the KhMAO (Surgut, 2001); the Interregional Conference "Actual Questions of Obstetrics, Gynecology, and Perinatology" (Moscow-Surgut, 2002, 2003); the IV Interuniversity Scientific Conference of Young Scientists and Students (Izhevsk, 2004); the IV Interregional Scientific and Practical Conference (Tomsk, 2004); the District Scientific and Practical Conference "Actual Problems of Obstetrics and Gynecology" (Langepas, 2004), the VI Congress of Young Scientists and Specialists (Tomsk, 2005); the City Scientific and Practical Conference "Modern Approaches to Preserving Reproductive Health and Preventing Intrauterine Infections" (Surgut, 2005).

Publication of Research Results. Nine printed works have been published on the dissertation topic.

Volume and Structure of the Dissertation. The dissertation is presented on 178 pages of typed text, illustrated with 20 figures, 41 tables, and 1 scheme, and consists of an introduction, a literature review, materials and methods of research, results of own research, a conclusion, conclusions, practical recommendations, and a list of references. The bibliographic index contains 196 sources, of which 134 are by domestic and 62 by foreign authors.