Some Pathophysiological Mechanisms of Neonatal Respiratory Distress Syndrome

The dissertation is devoted to the study of pathophysiological mechanisms of neonatal respiratory distress syndrome (RDS), associated with a primary surfactant deficiency and subsequent impairment of external respiratory function. The research encompasses analysis of changes in the respiratory system, hemodynamic parameters, gas transport function of blood, acid-base equilibrium, as well as lipid peroxidation processes and antioxidant defense in newborns with RDS. Special attention is given to the influence of the syndrome stage and modes of mechanical ventilation on the severity of respiratory and hemodynamic disorders.

The work includes a literature review, materials and methods of investigation, as well as three chapters of original results devoted to external respiration and gas transport function of blood, features of the cardiovascular system and hemodynamics, and lipid peroxidation and antioxidant activity. Data on presentation at scientific and practical conferences and publications on the research topic are presented.

Respiratory Distress Syndrome (RDS) of the newborn is a severe disorder of breathing in the first days of life, caused by a primary deficiency in the quantity and/or quality of surfactant, leading to increased surface tension at the air-alveolar interface and impaired alveolar opening during the first breath (Volodin N.N., 2007; Greenough A., Robertson N.R.C., 1999). The consequences of this condition include tissue hypoxia, water-electrolyte imbalance, metabolic disorders, acid-base disturbances, activation of free radical oxidation processes, and polyorgan dysfunction (Fanaroff A.Avroy, Martin J.Richard., 1992).

Untimely and not always adequately conducted therapy of RDS in newborns contributes to high mortality, ranging according to various authors from 49 to 56% (Samsygina G.A., 1990; Grebennikov V.A., 1995; Sotnikova K.A., 1995; Shabalov N.P., 2004; Gomella T.L., 1995). The complexity of treating this pathology lies in the combination of severe respiratory disorders with significant hemodynamic disturbances (Lewandowski K. et al., 1995).

The primary method of respiratory therapy in critically ill newborns is continuous positive airway pressure and mechanical ventilation. The effectiveness of these methods has been thoroughly evaluated in numerous studies (Petty T.L., 1996, Luce J.M., 1998, Murray J.F. et al., 2000, Musante G. et al., 2001, Piantadosi C.A., 2004). Special importance is currently attributed to surfactant replacement therapy, whose significance is difficult to overestimate. However, in the absence of economic feasibility for surfactant administration, it becomes necessary, depending on the severity of respiratory and hemodynamic disorders, to select optimal ventilation parameters and modes, which also yield positive results.

Research Objective

Analysis of changes in the respiratory system, hemodynamic parameters, and metabolic disorders in newborns with RDS, studying functional and pathogenetic characteristics for improving diagnosis and pathogenetically grounded therapy.

Research Tasks

1. To assess the status of external respiratory function and the surfactant-alveolar complex, the oxygen transport system, and acid-base status indicators during mechanical ventilation in newborns with RDS.

2. To elucidate the pathogenesis of existing hemodynamic disorders and their changes when newborns with RDS are transitioned to mechanical ventilation.

3. To study free radical oxidation processes and antioxidant defense against the background of comprehensive therapy.

4. To pathogenetically substantiate the diagnosis and treatment of RDS in newborns.

Scientific Novelty

For the first time, an evaluation of external respiratory function in newborns during the development of RDS has been conducted; the change in hemodynamic status before and after the initiation of respiratory therapy has been studied; and a link between cardiovascular system maladaptation and the stage of RDS as well as the degree of "aggressiveness" of mechanical ventilation has been established.

For the first time, a functional-quantitative analysis of surfactant-alveolar complex impairment in RDS of newborns has been performed, as well as its normalization during the course of comprehensive therapy.

The mechanisms of metabolic disorders, free radical oxidation and acid-base status, and the oxygen transport system have been studied, and pathogenetic variants of their correction have been determined.

A diagnostic complex and treatment program for RDS in newborns has been substantiated.

Scientific and Practical Significance

The obtained data, refining the understanding of the features of external respiratory function in newborns with RDS, pertain to the domain of fundamental knowledge, as they expand our understanding of the staging of its course for subsequent prognosis and therapy.

It has been demonstrated that the identified pathogenetic mechanisms of hemodynamic disorders in newborns with RDS and during their transition to mechanical ventilation depend on the stage of the syndrome, which determines the severity of disorders and the principles of resuscitative measures.

The conducted evaluation of lipid free radical oxidation processes and the antioxidant system during treatment confirms the possibility of using mexidol and ascorbic acid at various stages of respiratory distress syndrome.

Main Propositions for Defense

1. Impairment of external respiratory function in newborns with RDS is associated with a reduction in the quantity and function of surfactant, detected by a decreased phospholipid level in lavage fluid, which leads to increased surface tension at the air-alveolar interface and promotes the development of atelectasis, reduced tidal volume, and subsequent hypoxemia and decompensated acidosis, which in combination with hemodynamic disorders reduces oxygen delivery to tissues.

2. In newborns with RDS, there is a reduction in stroke volume and stroke index, cardiac output and cardiac index, mean arterial pressure, and circulating blood volume, while simultaneously an increase in total peripheral vascular resistance is observed as a compensatory-protective response, the degree of which depends on the severity of the condition, and an increase in central venous pressure promotes the progression of RDS and may lead to the development of pulmonary edema and secondary surfactant deficiency.

3. In newborns with RDS, the state of lipid peroxidation and antioxidant activity is characterized by a decrease in erythrocyte catalase activity and an increase in the content of hydroperoxides and malondialdehyde; therapy of the indicated condition with mexidol slows the initiation processes, and ascorbic acid also reduces the levels of accumulated lipid peroxidation products.

Dissertation Research Presentation

Materials of the dissertation research have been reported and discussed at the scientific and practical conference of SOGMA "Young Scientists in Medicine" — Vladikavkaz, 2008; the 10th jubilee scientific session dedicated to the 70th anniversary of SOGMA — Vladikavkaz, 2009; and the international scientific and practical conference "Development of Industrial and Ecological Safety in the 21st Century" — Vladikavkaz, 2009.

Publications

Six works on the dissertation topic have been published, presenting the main propositions of the dissertation.

Scope and Structure of the Dissertation

The dissertation comprises 189 pages of computer text in Times New Roman 14 and consists of an introduction, a literature review, materials and methods of investigation, three chapters of original results and their discussion, conclusions, findings, and practical recommendations. The work contains 19 tables, is illustrated with 18 figures. The bibliographic reference lists 82 domestic and 192 foreign sources.