Extracorporeal Hemocorrection of Endotoxemia in Patients with Destructive Complications of Community-Acquired Pneumonia

The dissertation is devoted to the study of the pathogenesis of endotoxemia and the evaluation of the effectiveness of extracorporeal hemocorrection in patients with destructive complications of community-acquired pneumonia. The research includes an experimental part with modeling of acute lung abscess in rats, a clinicopathophysiological study of the features of the course of endotoxemia and disturbances of hemostasis in patients, as well as the development and testing of a modified program of extracorporeal hemocorrection combining plasma exchange with laser irradiation of the extracorporeally washed cytomass of blood. The work is aimed at substantiating pathogenetically grounded methods of detoxification for improving the outcomes of treatment in this category of patients.

Relevance of the Problem. Destructive complications of pneumonia have been known since the time of Hippocrates, who made detailed judgments about inflammatory diseases of the respiratory organs, in particular, about empyema of the pleura as a consequence of lung inflammation [196]. Due to a number of ecological and social processes, non-specific bronchopleural pathology is a leading cause of temporary disability and one of the main causes of disability and death from infectious diseases [57], which accounts for 3 to 6% in individuals of young and middle age without concomitant diseases [47; 268] and reaches 15–30% in patients over 60 years of age with concomitant pathology [261; 276]. Among possible pulmonary complications of community-acquired pneumonia, the following are distinguished: lung abscess and gangrene, empyema of the pleura, and multiple destruction of the lung [80; 272]. In Russia, over the past decade, there has been an increase in the frequency of pyogenic-destructive complications of severe community-acquired pneumonia [1; 8; 142]. Mortality in this case ranges from 7.2% to 28.3% [143; 191; 261], increasing up to 75% in the case of gangrenous processes [221].

Studies of the pathogenesis of destructive changes in the lungs have shown that for the development of this process, the presence of an infectious agent, impairment of bronchial patency, and cessation of blood flow in the area of inflammation are necessary. In this context, pathological processes caused by excessive accumulation of toxic products in tissues and biological fluids of the body reflect the syndrome of endogenous intoxication [50]. Endotoxins, affecting the homeostasis of the body, lead to the development of a persistent block of the microcirculatory bed around the focus of pulmonary inflammation, which makes it impossible for immunocompetent cells and antibiotics to penetrate into this area [12].

Therefore, surgical sanitation of the purulent focus, adequate antibacterial and detoxification therapy are often insufficient to prevent the development of a critical state in the patient [224]. The ineffectiveness of conservative therapy, whose mortality reaches 46.3%, prompts the development of a more active approach to the treatment of such a severe purulent process [220]. The search for approaches to active detoxification and reperfusion correction, as pathogenetically linked components of the impact of links on the pathological process, with an assessment of the effectiveness of comprehensive extracorporeal hemocorrection, appears to be an actual problem of critical care medicine [156].

The Aim of the Study. Based on a clinico-pathophysiological analysis of the mechanisms of hemostasiological disturbances and the development of endotoxemia in patients with pyogenic-destructive processes in the lungs, to substantiate the effectiveness of extracorporeal hemocorrection in the comprehensive treatment of this category of patients.

Tasks of the Study.

1. To study the features of the course of endotoxemia in experimental lung abscess and the influence of toxic factors of blood plasma on parameters of immunoreactivity of laboratory animals.

2. To study the features of the course of endotoxemia in destructive complications of community-acquired pneumonia in the process of conservative treatment of patients.

3. To identify the features of the vascular-platelet link of hemostasis and their interrelationship with other components of the system regulating the aggregate state of blood in patients with destructive complications of community-acquired pneumonia.

4. To study the dynamics of endotoxin release into the vascular bed and the character of their redistribution between plasma, erythrocytes, and urine.

5. To assess the influence of plasma exchange combined with laser irradiation of the extracorporeally washed cytomass of blood on various links of the hemostasis system, lipid peroxidation processes, and the severity of endotoxemia.

6. To develop a pathogenetically grounded program of extracorporeal hemocorrection in patients with destructive complications of community-acquired pneumonia.

Scientific Novelty. For the first time, a method of modeling acute lung abscess in small laboratory animals — rats — has been developed (priority certificate for the patent application No. 2004111923 dated 19.04.04). The experiment established that the acute destructive process in the lungs is accompanied by a decrease in the functional activity of phagocytes against the background of intensification of lipid peroxidation processes and significant depression of the activity of the antioxidant defense system of erythrocytes.

The endotoxemia syndrome arising in destructive processes in the lungs of patients is characterized by phase changes in composition and dynamic redistribution of low- and medium-molecular-weight substances between plasma and erythrocytes. Maximum impairment of toxin excretion is observed in patients during the formation of the syndrome of multiple organ insufficiency. At the same time, an increase in the functional activity of platelets was identified against the background of endotheliopathy, which at the initial stages of development is associated with active inflammation in the lung tissue. The revealed depression of fibrinolysis contributes to the progression of microthrombosis, which manifests as disseminated intravascular coagulation.

It was established that plasma exchange combined with laser irradiation of the extracorporeally washed cytomass in patients with destructive complications of community-acquired pneumonia leads to a decrease in the content of low- and medium-molecular-weight substances both in plasma and in erythrocytes and a significant increase in their content in urine, which testifies to the deblockade of the body's detoxification system regardless of the severity of the disease. This modified hemocorrection causes a decrease in the activity of the coagulation system, the degree of thrombinemia, and stabilization of the plasmin system against the background of reduced intensity of lipid peroxidation and restoration of the activity of the antioxidant system.

Theoretical and Practical Significance of the Study. The obtained data deepen the understanding of the significance of endogenous intoxication and disturbances of the regulation of the aggregate state of blood in the formation and progression of pyogenic-destructive complications of community-acquired pneumonia, and reveal the mechanisms of realization of hemocorrection during the conduct of extracorporeal therapy.

The results obtained can serve as a basis for conducting further studies of the clinico-pathogenetic aspects of endogenous intoxication and disturbances of rheological parameters in experiments and in patients with destructive complications of community-acquired pneumonia and endogenous intoxication of another etiology, and for further clinical development of pathogenetically grounded methods of detoxification in patients with destructive diseases of the lungs.

Presentation of the Work. The materials of the dissertation were reported at the international conference "Critical and Terminal States. Pathophysiology and Therapy" (Moscow, 2002), the scientific-practical conference "20 Years of OKB No. 1 named after A.N. Kabanov" (Omsk, 2003), the scientific-practical conference "Actual Problems of Pathophysiology" (Saint Petersburg, 2004), the conference "Reanimatology. Its Role in Modern Medicine" (Moscow, 2004), the second international conference "Pathophysiology and Modern Medicine" (Moscow, 2004), the jubilee scientific-practical conference "Specialized Medical Care" dedicated to the 75th anniversary of the medical service and the 10th anniversary of the formation of the multidisciplinary hospital of the Main Directorate of Internal Affairs of the Sverdlovsk Region (Yekaterinburg, 2005), the Sixth International Conference "Diseases of Civilization in the Aspect of the Teachings of V.I. Vernadsky" (Moscow, 2005), the International Youth Medical Congress "Saint Petersburg Scientific Readings" (Saint Petersburg, 2005).

Publications. Ten works have been published on the topic of the dissertation.

The following statements are presented for defense.

1. The development of destructive complications of community-acquired pneumonia is accompanied by endotoxemia, which is of a phase character and is caused by the accumulation of low- and medium-molecular-weight substances and products of lipid peroxidation as a result of impaired functioning of the antioxidant defense system of erythrocytes.

2. In destructive complications of community-acquired pneumonia, an increase in the functional activity of platelets is observed, and as the severity of the disease increases, disturbances of hemorheological parameters occur.

3. Plasma exchange combined with laser irradiation of the extracorporeally washed cytomass possesses a more significant rheocorrectionary and detoxification effect compared to traditional plasmapheresis.