RU2824264C1 - Method of treating patients with novel coronavirus infection covid-19 with spontaneous respiration - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to pulmonology, resuscitation and intensive care, infectious diseases, and can be used to treat patients with pneumonia, caused by novel coronavirus infection COVID-19 of moderate and severe severity. Nitrogen oxide is inhaled through the patient’s open mouth during spontaneous breathing from distance of 9 cm with nitrogen oxide concentration of 1,200 ppm for 5 minutes 2 times a day. Additionally, the skin surface of the patient’s anterior chest is treated with nitrogen oxide flows by scanning from distance of 9 cm with concentration of 1,200 ppm for 5 minutes 2 times a day. Procedures are carried out for 5–10 days until relief of signs of respiratory failure.

EFFECT: method enables reducing the risk of the patient’s lethal outcome due to the inhalation therapy with nitrogen oxide, which enables to prevent the development of a cytokine storm, eliminate endothelial dysfunction and acute respiratory distress syndrome, restore capillary function and protect oxygen-sensitive organs.

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Description

Field of technology to which the invention relates

The invention relates to the field of medicine, namely, to pulmonology, resuscitation and intensive care, infectious diseases and is intended for the treatment of patients with pneumonia caused by the new coronavirus infection COVID-19, including mild and moderate severity, with spontaneous breathing, thus, the treatment method can be used both in practical healthcare, as well as in the case of mass admission of patients to infectious hospitals to improve the outcome and quality of treatment.

State of the art

Known for:

1. A method for treating COVID-19 pneumonia in moderate to severe cases of the new coronavirus infection, including etiotropic antiviral, anti-inflammatory, anticoagulant therapy, as well as oxygen therapy based on the blood oxygen saturation value with the patient in a prone position with an oxygen flow of 6-15 l/min or with a constant positive pressure of an oxygen-air mixture at the end of exhalation, or with high-flow oxygen, while the patient with preserved spontaneous breathing additionally receives surfactant-BL inhalations at a dose of 75 mg for a patient weighing 70-80 kg 2-4 times a day during the therapy with a gradual transfer of the patient to breathing atmospheric air, and such inhalations are carried out for 2-5 days.

2. The method according to item 1, wherein Lopinavir/ritonovir (200 mg/50 mg) is used as etiotropic antiviral therapy, 2 tablets 2 times a day, and hydroxychloroquine 400 mg 2 times a day and 200 mg 2 times on subsequent days.

3. The method according to item 1, wherein the anti-inflammatory drugs used are the anti-interleukin drug sarilumab 400 mg intravenously with repeated administration after 12 hours, or methylprednisolone 125 mg/day for a week or methylprednisolone 125 mg/day for a week with subsequent administration of ruxolitinib 5 mg 2 times a day during the next week.

4. The method according to item 1, wherein the anticoagulant drugs used are a therapeutic dose of low molecular weight heparin - Fraxiparin 0.8 ml twice a day.

5. The method according to claim 1, wherein, in the case of a high risk of secondary bacterial infection against the background of immunosuppression, empirical antibacterial therapy with ertapenem 1000 mg/day for 7 days is used (see patent RU No. 2745535, IPC A61K 38/17, A61P 31/14, A61M 16/10, published on March 26, 2021, bulletin No. 9).

The disadvantage of this invention is the insufficient effectiveness of treatment of patients with moderate and severe cases of the new coronavirus infection.

A method of respiratory therapy for the new coronavirus infection COVID-19 in patients with respiratory failure who are spontaneously breathing is known, which consists of inhalations of nitric oxide in high doses of 160-200 ppm for 20-30 minutes twice a day until the symptoms of the disease disappear, while additional constant inhalation of nitric oxide in a dose of 20 ppm is carried out in the intervals between inhalations of nitric oxide in high doses (see patent RU No. 2769489, IPC A61M 16/10, published 01.04.2022, bulletin No. 10).

The disadvantages of this invention are the insufficient effectiveness of treatment and insufficient duration of clinical effects.

A known method for administering oxygen therapy during spontaneous breathing in coronavirus infection includes monitoring the level of oxygen saturation of hemoglobin in the peripheral blood SpO ₂ during air breathing; when SpO ₂ decreases to a specified minimum value, the patient is transferred to oxygen insufflation, while the oxygen flow is regulated to achieve target SpO ₂ values, while the specified minimum SpO ₂ min value is calculated for the patient daily using the formula SpO _{2 min} = 91 - n _day if the duration of previous shortness of breath and / or oxygen therapy is less than 7 days, where n _day is the number of elapsed days of shortness of breath and / or oxygen therapy from 0 to 6, or SpO _{2 min} = 84% if the duration of shortness of breath and / or oxygen therapy is 7 days or more; oxygen insufflation is alternated with air breathing sessions, the latter are carried out hourly except for sleep breaks; Before the air breathing session, oxygen is insufflated into the respiratory tract, achieving by regulating its flow maintenance of the target values of SpO ₂ of 96-97% for at least 10 minutes; in addition, the respiratory rate, pulse rate and rhythm, dyspnea and the patient's well-being are continuously monitored; continuing to monitor the above indicators, the patient is transferred to air breathing until one of the following events occurs: A) a decrease in SpO ₂ to a value of SpO _2min ; B) the appearance and progression of dyspnea; C) deterioration in well-being with the patient's refusal to breathe air; D) the appearance and progression of tachypnea with a respiratory rate ≥25 per minute; D) the appearance of hemodynamically significant cardiac arrhythmia; if one of the events B-D develops during an air breathing session, SpO ₂ is recorded, limited by this event as SpO _2lim , and in order to prevent a recurrence of events B-D, a safe saturation SpO _2safe is calculated using the formula SpO _2safe = SpO _2lim +2, which is used instead of SpO _2min during the following air breathing sessions for 1 day, after which they return to SpO _2min again if one of the events B-D does not occur during the next air breathing session; alternation of oxygen insufflation with air breathing sessions is continued until events A-D disappear in the patient within 1 hour of air breathing, after which oxygen therapy is terminated (see patent RU No. 2787834, IPC A61M 16/00, published on 12.01.2023, bulletin No. 2).

The disadvantages of this invention are the complexity of calculation methods and the insufficient effectiveness of oxygen therapy.

The closest in technical essence and achieved positive effect and adopted by the authors as a prototype is a method for treating patients with a new coronavirus infection COVID-19 with high-flow oxygenation, including inhalation of nitric oxide, while inhalation of nitric oxide is carried out in both nostrils of the patient during his spontaneous breathing from a distance of 8 cm with a concentration of nitric oxide of 1100 ppm for 5 minutes 2-3 times a day, alternating during the treatment session according to individual need inhalation of nitric oxide with high-flow oxygenation, while in addition, the skin surface of the entire back of the patient in the prone position is treated with flows of nitric oxide with a concentration of 1100 ppm from a distance of 8 cm for 5 minutes 2-3 times a day for 5-10 days until the signs of acute respiratory distress syndrome are relieved (see patent RU No. 2787175, IPC A61M 16/10, A61P 11/00, A61P 31/12, published 29.12.2022, Bulletin No. 1).

The disadvantage of this invention is the insufficiently rapid improvement of clinical results.

Disclosure of invention

The objective of the proposed invention is to develop a method for treating patients with the new coronavirus infection COVID-19 during spontaneous breathing.

The technical result that can be obtained using the proposed invention is to create a method for treating patients with the new coronavirus infection COVID-19 with spontaneous breathing that can improve clinical outcomes, with no restrictions on use, an effective method, with minimal technical requirements and financial costs, rapid improvement of respiratory function, the general condition of patients, improvement of clinical results, and a significant reduction in fatal outcomes.

The technical result is achieved using a method for treating patients with the new coronavirus infection COVID-19 during spontaneous breathing, including inhalation of nitric oxide, wherein inhalation of nitric oxide is carried out through the open mouth of the patient during his spontaneous breathing from a distance of 9 cm with a concentration of nitric oxide of 1200 ppm for 5 minutes 2 times a day, wherein the skin surface of the anterior chest wall of the patient is treated with streams of nitric oxide with slow, scanning movements from a distance of 9 cm with a concentration of 1200 ppm for 5 minutes 2 times a day for 5-10 days until the signs of respiratory failure are relieved.

The essence of the proposed method of treating patients with the new coronavirus infection COVID-19 with spontaneous breathing is as follows.

In addition to the standard treatment protocol for patients (etiotropic antiviral, anticoagulant, anti-inflammatory therapy) with pneumonia caused by moderate to severe NCI COVID-19 (CT-3, CT-4), who are on high-flow oxygenation with preserved spontaneous breathing using the developed manipulator, inhalation therapy with high concentrations of exogenous nitric oxide is carried out. Inhalation of nitric oxide is carried out into the open mouth of the patient during his spontaneous breathing from a distance of 9 cm with a nitric oxide concentration of 1200 ppm for 5 minutes 2 times a day, while the skin surface of the patient's anterior chest is additionally treated with nitric oxide flows with slow, scanning movements from a distance of 9 cm with a concentration of 1200 ppm for 5 minutes 2 times a day for 5-10 days until the signs of respiratory failure are relieved.

The proposed method of treating COVID-19 is applicable not only in inpatient intensive care, but also in conditions of mass admission of patients, is highly effective, safe, mobile, fully controlled, economically low-cost and with minimal time costs for the procedure per patient. All patients note the clinical effect of subjective and objective improvement of respiratory functions immediately after the procedure, the level of blood saturation increases, respiratory function is restored, biochemical tests improve, and the psychological state improves.

The method of treating patients with the new coronavirus infection COVID-19 with high-flow oxygenation must meet the following basic requirements:

- for the comfort of patients and the ability to serve a large number of them sequentially with one device, the inhalation time should not exceed 10 minutes;

- the content of nitrogen oxide in the NO-containing gas flow (NO-CGF) in the inhalation area, according to the opinion of Nobel laureate L.J. Ignarro, should be at least 100 times greater than the NO content in known inhalation gas cylinder systems (~10 ppm), i.e. be at a level of at least -1000 ppm;

- the maximum amount of nitric oxide NO entering the respiratory system during inhalation, in accordance with recommendations, should not exceed (in conventional units) 12,000 ppm ⋅ min (permissible dose 25 ppm over 8 hours);

- the maximum amount of nitrogen dioxide _NO2 entering the respiratory system during inhalation, in accordance with recommendations, should not exceed (in conventional units) 1440 ppm ⋅ min (permissible dose 3 ppm over 8 hours);

- it is impossible to allow the NO-containing gas flow to cool completely to room temperature, at which complete polymerization of nitrogen dioxide occurs with the formation of nitrogen tetroxide (2NO ₂ = N ₂ O ₄ ), which has a sharp unpleasant odor and is a strong toxic substance;

- after the completion of the inhalation session, the concentration of methemoglobin, which is formed in the blood when nitric oxide enters it and is its biological marker, should not exceed 12% or 20%.

Brief description of drawings and other materials

Fig. 1 shows a method for treating patients with the new coronavirus infection COVID-19 during spontaneous breathing, a diagram of the developed manipulator for inhalation of nitric oxide, which is a plasma-chemical generator of NO from atmospheric air and a former of an NO-containing gas flow.

In Fig. 2, the developed manipulator for inhalation of nitric oxide is intended for operation as part of the Scalpel-coagulator-stimulator SKSVP/NO-0l “PLAZON” device.

Fig. 3 also shows the main physical and chemical parameters on the axis of the NO-containing gas flow formed by the developed manipulator for inhalation, measured by the OPTIMA 7 gas analyzer manufactured by MRU GmbH (Germany).

Implementation of the invention

Examples of specific implementation of the method of treating patients with the new coronavirus infection COVID-19 with spontaneous breathing.

Example 1. Patient D., 89 years old. Primary diagnosis: 1) Ischemic stroke (unspecified subtype according to the TOAST scale) in the left middle cerebral artery basin with the development of severe right-sided hemiparesis, hemihypesthesia, prosoparesis, mild motor aphasia. Ischemic stroke (unspecified subtype according to the TOAST scale) in the vertebrobasilar basin with the formation of an ischemic focus in the left cerebellar hemisphere. 2) Moderate coronavirus infection COVID-19. Concomitant diagnosis: Falx meningioma of the anterior third on the right. Ischemic heart disease: atherosclerotic heart disease. CHF 2A. LBBB. Hypostatic pneumonia. Hypertension stage III, uncontrolled course, CVE risk 4. Chronic anemia of moderate severity. Chronic pyelonephritis, exacerbation. Immature age-related cataract, pseudophakia of the left eye, angiosclerosis of the retina of both eyes.

Standard treatment of the underlying disease and the COVID-19 therapy protocol were administered. General condition is moderate. There were severe neurological symptoms and respiratory failure.

With the patient's voluntary consent, sessions of inhalation nitric oxide in high concentrations were performed according to the method we proposed: into the patient's open mouth during her spontaneous breathing from a distance of 9 cm with a nitric oxide concentration of 1200 ppm for 5 minutes 2 times a day, while the skin surface of the patient's anterior chest was additionally treated with nitric oxide flows with slow, scanning movements from a distance of 9 cm with a concentration of 1200 ppm for 5 minutes 2 times a day for 6 days until the signs of respiratory failure were relieved. Immediately after the first session, the patient noted an improvement in the respiratory function of the lungs, blood saturation increased to normal values. Biochemical parameters improved within 24 hours, coagulogram parameters returned to normal. Cough intensity decreased. Positive neurological dynamics were noted, cerebral circulation improved according to instrumental studies, and pronounced positive dynamics of consciousness activity from a inhibited state were noted. The patient quickly began to recover against the background of regular procedures of inhalation nitric oxide in high concentrations and exposure to NO in the anterior chest wall area. Given the patient's age, the underlying and many concomitant diseases against the background of NCI COVID-19, the prognosis could be unfavorable. According to the attending physician, high-dose NO therapy according to the proposed method quickly stopped the coronavirus infection, which was noted by laboratory and instrumental indicators and significantly accelerated the treatment of the underlying disease. Patient D. was discharged from the department on the 8th day with improvement for rehabilitation therapy.

Example 2. Patient Shch., 49 years old. Primary diagnosis: 1) Ischemic stroke (unspecified subtype according to TOAST) in the vertebrobasilar basin with formation of an ischemic focus in the left cerebellar hemisphere. Left-sided hemiparesis, left-sided hemihypesthesia, pseudobulbar dysarthria. 2) Moderate coronavirus infection COVID-19. Concomitant diagnosis: coronary artery disease. Postinfarction cardiosclerosis (AMI 2009). Mild aortic valve insufficiency. Moderate mitral valve insufficiency. CHF 2A FC 2 (NYHA) EF=55.5%. Stage 3 hypertension, CVE risk 4. Chronic pyelonephritis, exacerbation. Initial cataract, retinal angiopathy of both eyes.

Standard treatment of the underlying disease and the COVID-19 therapy protocol were administered. General condition is moderate. There were severe neurological symptoms and respiratory failure.

With the voluntary consent of the patient, sessions of inhalation nitric oxide in high concentrations were carried out according to the method proposed by us: into the open mouth of the patient during his spontaneous breathing from a distance of 9 cm with a nitric oxide concentration of 1200 ppm for 5 minutes 2 times a day, while the skin surface of the anterior chest of the patient was additionally treated with flows of nitric oxide with slow, scanning movements from a distance of 9 cm with a concentration of 1200 ppm for 5 minutes 2 times a day for 5 days until the signs of respiratory failure were relieved. Immediately after the first session, the patient noted an improvement in the respiratory function of the lungs, blood saturation increased to normal values. Biochemical parameters improved within 24 hours, biochemical parameters returned to normal. Cough intensity decreased. Positive neurological dynamics were noted. The patient quickly began to recover against the background of regular procedures of inhaled nitric oxide in high concentrations and exposure to NO in the anterior chest wall area. Respiratory function was quickly restored. Sessions with high-dose nitrogen monoxide according to the proposed method for several days relieved the clinical signs of NCI COVID-19 and improved the treatment results of the underlying disease. Patient D. was discharged from the department on the 5th day with improvement for further treatment in the infectious diseases hospital, from where he was subsequently discharged in a satisfactory condition.

Example 3. Patient M., 72 years old. Primary diagnosis: 1) Ischemic stroke (unspecified subtype according to the TOAST scale) in the blood supply zone of the right middle cerebral artery with the formation of cerebral infarction in the right parietal lobe with the development of left-sided hemiparesis, left-sided hemihypesthesia, prosoparesis on the left. 2) Moderate coronavirus infection COVID-19. Concomitant diagnosis: Diabetes mellitus type 2. Diabetic foot syndrome, neuroischemic form. Condition after exarticulation of 1 toe of the right foot. Diabetic nephropathy. CKD. Chronic pyelonephritis in the acute stage. Mild chronic iron deficiency anemia. Hypertension stage III, stage 3, risk 4. CHF 2A. FC 2.

Standard treatment for the underlying disease, diabetes mellitus, and the COVID-19 treatment protocol were administered. General condition is moderate. There were severe neurological symptoms, complications of diabetes mellitus, and respiratory failure.

With the patient's voluntary consent, sessions of inhaled nitric oxide in high concentrations were performed according to the method we proposed: into the patient's open mouth during her spontaneous breathing from a distance of 9 cm with a nitric oxide concentration of 1200 ppm for 5 minutes 2 times a day, while the skin surface of the patient's anterior chest was additionally treated with nitric oxide flows with slow, scanning movements from a distance of 9 cm with a concentration of 1200 ppm for 5 minutes 2 times a day for 10 days until the signs of respiratory failure were relieved. Immediately after the first session, the patient noted an improvement in the respiratory function of the lungs, blood saturation increased to normal values. Biochemical parameters improved within 24 hours, biochemical parameters normalized, inflammation markers decreased. Cough intensity decreased. Positive neurological dynamics were noted, cerebral circulation improved according to instrumental studies. The patient quickly began to recover against the background of regular procedures of inhaled nitric oxide in high concentrations and exposure to NO in the anterior chest wall area. Given the patient's age, the underlying and many concomitant diseases, including diabetes mellitus, against the background of NCI COV1D-19, the prognosis could be unfavorable. High-dose NO therapy according to the proposed method quickly stopped the coronavirus infection, which was noted by laboratory and instrumental indicators and significantly accelerated the treatment of the underlying disease. Patient D. was discharged from the department on the 17th day with improvement for rehabilitation therapy.

Nitric oxide is known to suppress the replication of the SARS virus - severe acute respiratory syndrome caused by the SARS-CoV-1 coronavirus in 2003. A powerful direct antiviral effect of NO on the new coronavirus infection COVID-19 has been revealed. Inhaled nitric oxide therapy in the proposed method can quickly prevent cytokine storm, eliminate endothelial dysfunction, eliminate ARDS, restore capillary function and protect oxygen-sensitive organs.

In total, nitric oxide treatment according to the proposed method was carried out with voluntary consent in 16 patients with mild to moderate lung damage due to COVID-19, who were spontaneously breathing. All patients who received high-dose inhalation NO therapy survived and recovered. There were no fatal outcomes. Patients fully recovered in vital functions.

The proposed invention has the following advantages compared to the prototype and other known technical solutions:

- rapid increase in the effectiveness of treatment of patients with mild to moderate pneumonia caused by COVID-19 during spontaneous breathing, due to direct antiviral action;

- significant increase in patient survival;

- improving clinical outcomes;

- rapid improvement of respiratory function;

- significant reduction in fatal outcomes.

References

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Claims (1)

A method for treating patients with moderate to severe pneumonia caused by the new coronavirus infection COVID-19, including inhalation of nitric oxide, characterized in that inhalation of nitric oxide is carried out through the open mouth of the patient during his spontaneous breathing from a distance of 9 cm with a concentration of nitric oxide of 1200 ppm for 5 minutes 2 times a day, in addition, the skin surface of the anterior chest wall of the patient is treated with streams of nitric oxide with scanning movements from a distance of 9 cm with a concentration of 1200 ppm for 5 minutes 2 times a day, the procedures are carried out for 5-10 days until the signs of respiratory failure are relieved.