General Patterns, Pathogenetic Significance, Diagnosis and Correction of Disorders of Hematoperitoneal Exchange in Diffuse Peritonitis

The dissertation is devoted to the study of hematoperitoneal exchange disorders in diffuse peritonitis from the standpoint of cell and molecular pathogenesis. The general patterns of changes in acute-phase proteins in serum and peritoneal exudate in patients with various clinico-pathogenetic variants of the course — sepsis, severe sepsis, and septic shock — are investigated. Special attention is given to the assessment of hematoperitoneal barrier permeability and the syndrome of endogenous intoxication as key pathogenetic links of the disease.

Based on clinical observations, criteria for the diagnosis and differentiated correction of hematoperitoneal exchange disorders have been developed. It has been established that an increase in permeability coefficients for acute-phase proteins and the content of medium-molecular-weight molecules in peritoneal exudate are prognostically unfavorable signs. A differentiated therapy regimen, including enteral detoxification and infusion of perfluorane, has been proposed, tested under intensive therapy conditions, and implemented in the practice of reanimation departments.

Relevance of the Problem

Despite numerous studies and achievements of modern medicine, mortality in diffuse peritonitis remains high and reaches 50–70% at the terminal stage of the disease [26, 31, 73, 105, 139].

At present, the problem of diffuse peritonitis is increasingly considered from the standpoint of the systemic inflammatory response syndrome, and patients are regarded as having abdominal sepsis [27, 67, 107, 122].

It has been established that one of the pathogenetic factors of abdominal sepsis is the disruption of hematoperitoneal exchange [23, 27, 31, 44, 129]. To assess damage to the hematoperitoneal barrier, it has been proposed to use determination of acute-phase proteins in plasma and peritoneal exudate [13, 37, 52, 155]. However, despite numerous clinical studies, sufficiently reliable criteria for assessing the severity of hematoperitoneal exchange disorders in diffuse peritonitis are still lacking, which complicates the development of pathogenetically grounded methods of diagnosis and correction [65, 127, 154].

It becomes obvious that further progress in resolving the current situation is possible only on the basis of establishing general patterns of hematoperitoneal exchange disruption in diffuse peritonitis, developing adequate diagnostic criteria, and pathogenetically grounded methods of their correction, which determined the goal and objectives of this study.

Goal of the Study

Improvement of treatment outcomes in patients with diffuse peritonitis through the development of pathogenetically grounded methods of diagnosis and correction of hematoperitoneal exchange disorders.

Objectives of the Study

1. To establish general patterns of changes in hematoperitoneal exchange of acute-phase proteins in diffuse peritonitis.

2. To assess the pathogenetic significance of hematoperitoneal exchange disorders in the development of the syndrome of endogenous intoxication in diffuse peritonitis.

3. To evaluate the clinical-diagnostic significance of endogenous intoxication indicators and hematoperitoneal exchange disorders of proteins in diffuse peritonitis.

4. To pathogenetically substantiate and clinically test methods of diagnosis and differentiated correction of hematoperitoneal exchange disorders in various clinical courses of diffuse peritonitis.

Scientific Novelty

For the first time, it has been established that changes in the selectivity and intensity of hematoperitoneal exchange are sufficiently reliable and informative criteria for determining the clinico-pathogenetic variant of the course of diffuse peritonitis.

It has been shown that hematoperitoneal exchange disorders are one of the pathogenetic factors in the development of the syndrome of endogenous intoxication in diffuse peritonitis.

The clinical-prognostic significance of hematoperitoneal exchange and endogenous intoxication indicators in diffuse peritonitis has been demonstrated — a 2–2.5-fold increase in permeability coefficients for acute-phase proteins and a 1.5–2-fold increase in the content of medium-molecular-weight molecules in peritoneal exudate are signs of an unfavorable course and outcome.

It has been proven that differentiated correction of hematoperitoneal exchange disorders, including enteral detoxification and intravenous infusion of perfluorane, is one of the ways to increase the effectiveness of intensive therapy for diffuse peritonitis.

Practical Significance and Implementation of Results

Calculation of permeability coefficients of the hematoperitoneal barrier for acute-phase proteins increases the objectivity of determining the clinico-pathogenetic variant of the course of diffuse peritonitis.

Differentiated correction of hematoperitoneal exchange disorders is one of the ways to increase the effectiveness of intensive therapy for diffuse peritonitis (patent for invention No. 2241227 dated 25.08.2003).

The main provisions of the dissertation have been incorporated into the educational process at the departments of anesthesiology and reanimatology, and pathophysiology of Kemerovo State Medical Academy, as well as at the department of anesthesiology and reanimatology of Novokuznetsk State Institute of Advanced Training. The developed scheme of differentiated therapy for hematoperitoneal exchange disorders in various clinico-pathogenetic variants of the course of diffuse peritonitis is used in the reanimation departments of City Clinical Hospitals No. 1 and 29 (Novokuznetsk) and in the reanimation department of City Clinical Hospital No. 3 (Kemerovo).

Propositions for Defense

1. In diffuse peritonitis, the selectivity and intensity of hematoperitoneal exchange are disrupted, which underlies the development of the syndrome of endogenous intoxication and determines the clinico-pathogenetic variants of the course of peritonitis: compensated — characterized by preservation of selectivity and adequacy of hematoperitoneal exchange in the presence of clinical and laboratory signs of sepsis; subcompensated — characterized by a combination of moderate disturbances of selectivity and adequacy of hematoperitoneal exchange (increased permeability for plasminogen/plasmin and alpha-2-macroglobulin, decreased permeability for lactoferrin and albumin) along with clinical and laboratory signs of severe sepsis; decompensated — characterized by a combination of pronounced hematoperitoneal exchange disorders (increased permeability coefficients for all marker proteins — plasminogen/plasmin, alpha-2-macroglobulin, lactoferrin, and albumin) along with clinical and laboratory signs of septic shock.

2. A 2–2.5-fold increase in permeability coefficients of the hematoperitoneal barrier for acute-phase proteins and a 1.5–2-fold increase in the content of medium-molecular-weight molecules in peritoneal exudate are prognostically unfavorable criteria in diffuse peritonitis.

3. Differentiated correction of hematoperitoneal exchange, including the use of enteral detoxification in the subcompensated clinico-pathogenetic variant and infusion of perfluorane in combination with enterosorption in the decompensated variant, is one of the ways to increase the effectiveness of therapeutic measures in diffuse peritonitis.

Presentation of the Work

The main provisions of the dissertation were reported and discussed at: the All-Russian Scientific and Practical Conference "Present and Future of Technology-Based Medicine" (Leninsk-Kuznetsky, 2002); the All-Russian Scientific and Practical Conference dedicated to the 60th anniversary of the formation of the Russian Academy of Medical Sciences "Current Issues of Pain Management and Intensive Therapy of Severe Craniocerebral Trauma" (Novokuznetsk, 2003); sessions of the regional society of anesthesiologists and reanimatologists (Kemerovo, 2002; Leninsk-Kuznetsky, 2003; Novokuznetsk, 2004).

Publications

On the topic of the dissertation, 14 works have been published, of which 4 are in peer-reviewed journals and 2 are patents for invention.

Structure and Volume of the Work

The dissertation is presented in 123 pages of typescript and consists of an introduction, a literature review, 3 chapters of original research results, a conclusion, findings and practical recommendations, and is illustrated with 18 tables and 12 figures. The bibliography includes 179 references, including 65 foreign sources.