M. Abrahamovych, O. Abrahamovych, S. Tolopko, M. Ferko

Danylo Halytsky Lviv National Medical University

Introduction. Engaging of the different organs and systems into the pathological process, including the organs of the respiratory system, interpretated as syntropic co­ and polymorbid lesions, including the most common ­ hepatopulmonary syndrome (HPS), in many cases determines the severity of the general condition of the cirrhotic patients, leads to a significant reduction of their life quality, disability, has a decisive prognostic value at all the stages of the treatment and is the leading cause of the death of the hepatological patients.

Taking into the account the poor prognosis and high mortality (41.0 %) of the patients with the HPS, it is required the constant monitoring and paying the special attention of the physicians to such patients and also prescribing the adequate pathogenesis­based drugs to optimize the treatment.

The aim of our study was to modify the treatment of the cirrhotic patients with the hepatopulmonary syndrome of different severity degrees on the base of clarifying the characteristics of their pathogenesis and to evaluate its effectiveness.

Materials and methods. Into the study in randomized manner with the preliminary stratification by the presence of the HPS were involved 93 patients [26 women (28.0 %) and 67 men (72.0 %); aged 27 to 67 years, who were treated in Lviv Regional Hepatological Center during 2012­2015.

To elucidate the pathogenesis of the HPS for appointing the most effective pathogenetically reasonable treatment, we have determined the content of some vasoactive humoral and metabolic factors, namely the endothelium­dependent (cyclic guanosine monophosphate (cGMP), endothelin­1 (E­1)), tumor necrotizing factor α (TNF α) and the indices of the renin­aldosterone system (renin, aldosterone) in the blood plasma of the patients by ELISA. Also there were examined the gas composition of the venous blood and the acid­base balance (ABB) state. To determine the effect of the mediators of the autonomic nervous system (ANS) on the vascular tone, we have assessed its state by the registration of the heart rate variability (HRV).

After the treatment clinically and laboratory indices and life quality of the patients of the experimental group (EG) who were treated by the modified by us technique and of the control group (CG), where the patients received the standard treatment were evaluated.

Results. During the study of some pathogenetic mechanisms of the HPS it was found the inverse correlative connection between the values of carbon dioxide partial pressure, bicarbonate, standard bicarbonate, bases excess in the blood and in the extracellular fluid and the severity of the HPS, which was manifested by the progressive metabolic acidosis that required the medical correction.

With the growth of the severity of the respiratory lesions the levels of cGMP, E­1, TNF α, renin and aldosterone in the blood plasma of the cirrhotic patients were significantly (p < 0.05) increased, which made theim to be the criteria to justify the appointment of the pathogenetic treatment.

During the diagnosis of the ANS state in the cirrhotic patients with the syntropic respiratory lesions using HRV registration we proved the overwhelming influence of the sympathetic part over the parasympathetic in the patients with the I degree HPS with the directly proportional increase of the neurohormonal effects according to its severity. The modified by us method of the treatment of the patients considering the investigated pathogenic mechanisms of  the liver cirrhosis and the HPS, its severity, as well as the conventional one, gave the positive result, but by its quality parameters the conventional medical complex significantly yielded comparing to the modified by us algorithm. Statistical analysis of the questionnaires MOS SF­36 before and after the treatment indicated a significant (p < 0.05) improvement of the physical activity, vitality, mental and general health, reducing of the pain and the role of the emotional stress in disability, resulting into the improvement of the physical and mental status of the patients treated by the modified by us technique and shows its effectiveness.

Conclusions. Investigations of the indices of ABB (carbon dioxide partial pressure, levels of bicarbonate, standard bicarbonate, bases excess in the blood and in the extracellular fluid) the endothelium­dependent (cGMP, E­1), TNF α and the indices of the renin­aldosterone system (renin, aldosterone), the state of the ANS and their dependence on the severity of the HPS substantiated the advisability of including into the medical complex of the patients with the I degree HPS in addition to the detoxification, diuretic and hepatoprotective treatment the electrolyte combined isotonic solution (sodium, potassium, magnesium, calcium chloride, acetate, malate) ­ 500.0 ml intravenously once a day, pentoxifylline ­ 1 tablet (100.0 mg) twice daily, spironolactone ­ 1 tablet (25.0 mg) twice daily, carvedilol ­ 1 tablet (3,125 mg) once a day; with the II degree HPS ­ 4.0% sodium bicarbonate ­ 100.0 ml intravenously once a day, sol. Pentoxifyllini 0.05% ­ 100.0 ml intravenously once daily, valsartan ­ 1 tablet (40.0 mg) once daily, spironolactone ­ 1 caps. (50.0 mg) twice a day; with the III degree HPS ­ 4.2% sodium bicarbonate ­ 100.0 ml intravenously once a day, sol. Pentoxifyllini 0.05% ­ 200.0 ml intravenously once a day with the transition to oral use – 1 tablet (100.0 mg) of pentoxifylline twice daily, enalapril ­ 1 tablet (5.0 mg) once daily, spironolactone ­ 1 caps. (100.0 mg) twice a day. Using the modified pathogenetic reasonable treatment in the cirrhotic patients taking into account the severity of the HPS allowed us to increase its efficiency by 13.7 % and to improve the physical activity, vitality, mental and general health, reduce pain and the role of the emotional problems in disability, leading to the improvement of physical and mental status of the patients.

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