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"Emergency medicine" 7 (62) 2014

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Treatment of endothelial disorders in newborns undergoing severe asphyxia at birth

Authors: Ovcharenko S.C., Mezhirov N.M., Kravtsov D., Danilov V.V. — Kharkiv national medical University, Department of pediatric surgery and pediatric anesthesiology

Categories: Medicine of emergency

Sections: Specialist manual

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The problem of therapy of systemic inflammation response (SIR) is relevant in the modern medicine. Currently, no approach to solving it is developed. Pathogenesis of SIR includes three basic levels: appearance of endotoxin, increased production of cytokines and endothelial activation. Given the pathogenesis levels, the SIR therapy has three directions. The first is antibacterial therapy, in which the use of antibiotics of cytostatic action is preferred. The second is cytokines therapy. Currently, treatment schedules are being developed, the difficulty lies in the selection of dosage, as cytokine levels are individual and vary widely. The third direction in the treatment of SIR is influence on endothelial activation.

Deproteinized hemodialysate of vealers blood is an aggregate of a number of physiologically active ingredients, which stimulate oxygen uptake by tissues in the presence of hypoxia, provide increased glucose transport across biological membranes, increase intracellular ATP synthesis, and increase the proportion of aerobic glycolysis. Stimulation of oxygen uptake upon hypoxia leads to the fact that anaerobic metabolism normalizes in vascular endothelium, release of prostacyclin and nitric oxide, which possess vasodilation effect, occurs. The result is a reduction in vascular resistance.

Study objective: to determine the effect of deproteinised hemodialysate on endothelial activation in infants with SIR suffered severe asphyxia at birth.

All studied patients were in critical condition due to cardiorespiratory and cerebral inefficiency. Artificial lung ventilation (ALV) has been carried out from the first days of life with modern apparatus.

Patients are divided into groups: group I — infants who received standard therapy, corresponding to the treatment protocols for severe asphyxia and hypoxic-ischemic central nervous system injury (34 people); group II — infants, the standard therapy of whom included deproteinised hemodialysate of vealers blood in a dose of 0.5 ml/kg per day (16 people).

The object of the biochemical study was venous blood. The study included: quantification of thrombocytes, indices of functional activity of endothelium – derivatives of nitric oxide, and quantitative indicator of endogenous intoxication — average weight molecules (AWM), ceruloplasmin was studied to detect inflammation.

The study results were processed using the statistical software package for general use Statisticafor Windows version 6.0 of descriptive statistics for the indicators measured in quantitative scales, we used the median and the average value, distribution of all analyzed quantitative indicators was conducted according to Kolmogorov-Smirnov criterion, the nonparametric criterion of Mann — Whitney was used for determining a difference between the groups.

The obtained data allow suggesting that both groups are initially homogeneous.

The AWM dynamics is representative of the observed patients: children who received standard therapy, the level of AWM corresponds to the upper limits of normal values for the third and fifth days of the disease, but an increase in normal values occurs on the seventh day, which indicates the appearance of endogenous intoxication. Absolutely opposite pattern is observed in patients who received deproteinised hemodialysate of vealers blood: throughout the study the AWM levels were within normal values and, moreover, were two times lower than in the previous group, i.e. endogenous intoxication doesn’t develop in infants treated with deproteinised hemodialysate of vealers blood, which undoubtedly has a positive effect on the course and outcome of the disease.

A dynamic study of indicators of nitrites indicates their same level on the third and fifth day of the disease in both groups of infants. On the seventh day of the disease, the children, who received deproteinised hemodialysate of vealers blood in complex intensive therapy, have the same nitrite level, and the children of the first group have a significantly increased level indicating endothelial activation. We believe that the cause of endothelial activation is a persistent inflammatory process, as evidenced by increased levels of ceruloplasmin during the study.

Thrombocyte level in patients who received deproteinised hemodialysate of vealers blood was significantly higher on the third, fifth and seventh day of the disease than in patients who received standard therapy. Furthermore, it should be noted that the children received the preparation have normal thrombocyte level on the seventh day, while it barely reaches the lower limit of normal in the other group of children.

Many studies show that an increase in the release of nitric oxide occurs in the vascular endothelium under the action of the preparation, but to our knowledge this did not happen. On the contrary, the nitrite level in the group of patients, in the complex intensive therapy of whom the deproteinised hemodialysate of vealers blood had been used, was significantly lower on the seventh day than the patients, who had received standard therapy. Similar data were obtained by Kuninaka T., Senga Y., and they explain the fact that in the conditions of oxidative stress components of the preparation carry out blockade of lipid peroxidation and prevent the synthesis of nitric oxide, which allows such an antioxidant effect.

In the neurological status of all children we primarily observed a syndrome of cerebral suppression, as well as a multiple organ injury syndrome with a dramatic suppression of physiological reflexes, as well as signs of hemodynamic instability that required the prosthetics of respiratory function. When analyzing the indicators of neurological status in the two groups, a significant decrease in terms of resuscitation of the CNS functions in the group of children, the standard therapy of whom included the deproteinised hemodialysate, was found. A rapid stabilization of hemodynamic parameters, more express activation of physiological and tendon reflexes were observed.

The period of stay in the ICU of the children treated with the preparation was three days less (11 bed days) than of the children, who received standard therapy (14 days).

Thus, the results of this study show that the children, the complex intensive therapy of whom included the deproteinised hemodialysate of vealers blood, had a decrease in endothelial activity, resuscitation of normal thrombocyte level without inflammation and endogenous intoxication by the seventh day of the disease, which was accompanied by a decrease in the duration of ALV, positive dynamics of neurological pattern and reducing of time of stay in the intensive care unit.

Conclusions. Application of the deproteinised hemodialysate of vealers blood in the complex intensive therapy of infants suffered severe asphyxia at birth has a positive effect on the pathogenic process due to reducing inflammation and endothelial activity.

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