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3EXPERIENCE OF USING THE DRUG LONGIDASE IN COMBINATION WITH HEPARIN IN THE TREATMENT OF POST-COVID-19 PNEUMONIA
Khamdamova E.G.
Khamdamova Eleonora Gaffarovna - Senior Assistant, DEPARTMENT OF ANESTHESIOLOGY AND INTENSIVE CARE, SAMARKAND STATE MEDICAL UNIVERSITY, SAMARKAND, REPUBLIC OF UZBEKISTAN
Abstract: the World Health Organization's involvement in the fight against coronavirus began on December 31, 2019: WHO specialists first received information about an outbreak of respiratory disease in China caused by a new coronavirus. As early as January 1, 2020, a WHO-based "OutbreakResponse Support Group" was established. On January 5, the first publication about COVID-19 appeared on the official WHO website for physicians. As we know, mainly patients died from complications and in the vast majority of them were patients with widespread pulmonary tissue damage, ARDS, thromboembolic complications, sepsis. In the presenting study we provide information about using the Longidase in patients with post-COVID-19 complications associated with pneumonia. Purpose: to study and use methods of treatment of the pulmonary fibrosis using patients who had survived COVID-19 with a large lesion of the lung tissue as an example in order to provide the patient with the normal ventilation and eliminate the respiratory insufficiency. Material and methods: 37patients who had COVID-19 pneumonia with 25-65% of the lung tissue involvement were examined by X-ray, chest MSCT, coagulogram, D-dimer, C-reactive protein, lactate, procalcitonin, Ig M and G, common clinical blood tests, urine, ECG, etc. Results: Our using of heparin (unfractionated and low molecular weight heparin), solution of Longidase, along with symptomatic treatment, including noninvasive methods of oxygen therapy, contributed to resorption of fibrosis, therefore, there was an improvement in diffusion and ventilation, also there were almost no obstacles to normalization of oxygenation. Conclusions: our proposed scheme of treatment ofpost-COVID-19 pneumonia before the development of chronicization of the process had good results; duration of stay in the intensive care department of the Multidisciplinary Clinic under SamSMU averaged 8.3 bed days. Keywords: pandemic, Covid-19, pneumonia, fibrosis, longidase, heparin.
Introdaction:
The World Health Organization's involvement in the fight against coronavirus began on December 31, 2019: WHO specialists first received information about an outbreak of respiratory disease in China caused by a new coronavirus. As early as January 1, 2020, a WHO-based "Outbreak Response Support Group" was established. On January 5, the first publication about COVID-19 appeared on the official WHO website for physicians. The publication contained information about the number of sick people in Wuhan, their condition, and recommendations to the population in order to prevent the contamination with the virus. Five days later, WHO posted on its website a more extensive set of recommendations for all countries. As we know, the main causes of death are complications and the vast majority are patients with widespread lung tissue damage, ARDS, thromboembolic complications, and sepsis. The Ministry of Health of the Republic of Uzbekistan with a working group of 20 people developed a new version of "Practical recommendations for the management of patients infected with Covid-19" (Tashkent, 2021), which we followed in our practice.
COVID-19 is a potentially severe acute respiratory infection caused by the SARS-CoV-2 coronavirus. The danger of this disease is due to the development of viral pneumonia, which can lead to respiratory failure and subsequent disability of a person. Due to this fact, an essential role in recovery from coronavirus pneumonia is played by timely appeal of the patient for rehabilitation help. The program of complex rehabilitation is developed with an individual approach to each patient and depends on a number of factors, in particular, the degree of damage to the lung tissue. The duration of rehabilitation also depends on each individual case. Rehabilitation should begin as soon as the acute manifestations of pneumonia are subsided (high temperature, blood changes, etc.). The main objectives of the patient's rehabilitation after pneumonia are:
- Restoration of respiratory function of the lungs,
- Prevention of the development of pulmonary tissue fibrosis,
- Training the muscles involved in breathing,
- Treatment of pneumonia consequences (asthenia, fibrosis, etc).
Purpose: to study and use methods of treatment of the pulmonary fibrosis using patients who had survived COVID-19 with a large lesion of the lung tissue as an example in order to provide the patient with the normal ventilation and eliminate the respiratory insufficiency.
Material and methods: We studied 37 patients who had pneumonia after COVID-19, admitted for rehabilitation to the intensive care department of the Multidisciplinary Clinic of SamSMU in age from 30 to 75 years, mostly men (24 patients-64.8%). All patients underwent standard examination: coagulogram, general clinical and biochemical blood tests, D-dimer determination, C-reactive protein, chest CT scan (or chest X-ray), ECG, cardiac ultrasound with cervical doppler sonography. All patients were kept a card of intensive care. In the complex of rehabilitation were used moderate infusion therapy on demands, oxygen therapy, in some cases using of noninvasive artificial ventilation of the lungs (NIVL), breathing exercises, prone position at least 6-8 hours a day. Also, attention was drawn to the high incidence of thromboembolic complications with possibly underestimated incidence of pulmonary embolism (CT angiography in the algorithm of pulmonary embolism was not included in the standard of care during the acute period of the disease, when the patients were in specialized COVID-19 centers). The main approach to COVID-19 therapy should be preventive treatment before full complex of life-threatening conditions such as pneumonia, ARDS, sepsis is developed. We included patients after pneumonia complicated with fibrosis in the study. Based on the data of X-ray and/or MSCT we included heparin therapy into the complex of treatment of our patients with transition to the use of low molecular weight heparin preparations (clexane, enoxaparin, fraxiparin) in the recommended dosages.
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Photo 1: Microinfusion pump SN-50C6T
Heparin was used for 2-3 days in a dose of 20-21 units per hour, using infusomats. Then we switched to low-molecular-weight heparin in a dose corresponding to the body weight, subcutaneously 2 times a day for 5 -7 days. Then antiaggregants (clopidogrel preparations, most often it was Zilt, KRKA in a dose of 75 mg per day), or anticoagulant, direct Xa factor inhibitor rivaroxaban- Xarelto in a dose of 10-15 mg per day were prescribed for therapy. Control was carried out by coagulogram and D-dimer indices. In order to eliminate lung tissue fibrosis, we used Longidase intramuscularly in a dose of 3000 units once every 3-5 days, 7-10 injections, which has hyaluronidase enzymatic activity, antioxidant, immunomodulatory and moderately pronounced anti-inflammatory effect. Treatment of comorbid conditions (concomitant diabetes mellitus, CHD, hypertension) and complications was carried out in accordance with clinical guidelines, standards of medical care for these diseases, conditions and complications. The practice of assessing the appropriateness of the use of drugs outside demands specified in the instructions for medical use, is generally recognized in the world. In current conditions of spread of a new coronavirus infection and limited evidence base on COVID-19 treatment, the use of «off-label» (not for its intended purpose) medications to provide medical care to patients with COVID-19 is based on international recommendations as well as consensus expert opinions based on an assessment of the benefits and risks of «off-label» therapy.
Results of the study: As a result of the conducted therapy of post-COVID-19 pneumonia at stage of fibrosis we observed positive changes in the condition of the patients under study: blood oxygen saturation was normalized, physical data on the lungs significantly improved, coagulogram and D-dimer level were decreased to normal values. Objectively, the clinical picture was confirmed by stable normal blood saturation, ECG data, blood tests, repeated radiological data and MSCT results. Here is an example of a clinical case:
Pic.1. Patient T., 54 years old, before the start of fibrosis treatment.
Pic.2. Patient T.,54 years old after fibrosis treatment on day 11.
Pictures 1 and 2 show the X-ray of patient T., 54 years old, who was admitted to the intensive care unit of the Multidisciplinary Clinic of SamSMU 3 months after he had survived COVID-19, complicated with pneumonia and 70% lung damage, was treated after the acute period as an outpatient in a private clinic, but there was no effect. He was admitted in an extremely severe, critical condition, with marked hypercoagulability, high D-dimer values, blood saturation below 70%. The appropriate standard therapy for ARDS was carried out using oxygen therapy with the help of the Yuwell (China) device for NIVL in CPR mode. Continuous heparin therapy, symptomatic and life-sustaining therapy were started immediately after hemodynamic parameters were stabilized and longidase was used. In this case the desired result was achieved, the patient came out of the serious condition completely, was discharged to the home regime and soon started his work activities.
Discussion: For patients with acute respiratory failure due to COVID-19 it is recommended to use step-by-step approach in the choice of respiratory therapy to improve the results of treatment: for mild ARDS (PaO2/ FiO2 200300 mmHg or SpO2 80-90% by air breathing) standard oxygen therapy (through face mask or nasal cannulas), high-flow oxygenation (HFO) or noninvasive AV (NIVL) in combination with prone positioning are recommended, in moderate and severe ARDS (PaO2/FiO2 usually less than 150 mm Hg. or SpO2 less than 75% when breathing with air) tracheal intubation and invasive artificial ventilation combined with prone position are prescribed. In the vast
majority of cases (28 cases) we used high-flow oxygenation through nasal cannulas or face mask in combination with prone positioning, in the remaining cases (9 patients) we used NIVL in combination with prone positioning. There were 1 fatal case, when lung lesion according to MSCT was more than 75%, late appeal for help, categorical refusal from NIVL. In the rest situations - satisfactory and good results. Patients with relatively satisfactory results received additional treatment in the rehabilitation center and in the departments of the Multidisciplinary Clinic of SamSMU.
Conclusions: Thus, we consider the tactics of intensive therapy we use in patients who underwent COVID-19 with large lesions of lung tissue, with the phenomena of ARDS and pulmonary fibrosis quite reasonable, providing patients with normal ventilation, contributes to the elimination of fibrosis (or its significant reduction) and respiratory failure; NIVL is preferable to use (compared with high-flow oxygenation) only in patients with comorbidities - COPD, chronic heart failure.
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