RU2231370C2 - Method for treating patients for diseases accompanied with bronchial obstruction phenomena - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves administering auxiliary lung ventilation with air under positive constant pressure. The air is supplied via nasal mask during0.5 h. Then, a bronchial spasmolytic agent is continuously introduced into the air at a dose equal to 30-50% of mean therapeutic dose during following 0.5 h and lung ventilation is continued during 0.5 h. The treatment is applied 2-6 times a day.

EFFECT: enhanced effectiveness of treatment; reduced dose of bronchial spasmolytic.

4 cl

Description

The method relates to medicine, namely to pulmonology, and can be used to treat patients suffering from various diseases of the respiratory system, accompanied by phenomena of bronchial obstruction.

The level of technology.

For the treatment of chronic obstructive pulmonary diseases, three main groups of drugs are used to relieve bronchial obstruction: adrenomimetics (ephedrine, etc.); anticholinergics (atropine, etc.); methylxanthines (aminophylline and others).

The parenteral administration of most drugs at their high blood concentrations can cause a number of serious complications due to the toxic effects of these drugs, and combinations with ephedrine often have increased toxicity (see M.V. Weinberger, 1978).

In addition, parenteral administration of bronchodilators and taking them per os do not provide the possibility of immediate exposure to the drug.

Known methods for treating patients suffering from bronchial asthma and other obstructive pulmonary diseases by administering bronchodilators through the respiratory tract through endobronchial infusions of drugs (see, for example, RF patent No. 2066182, 09/10/96).

However, such an introduction of bronchodilators does not ensure its delivery to the alveoli and small bronchi, which reduces the therapeutic effect of the treatment, not ensuring the maximum filling of the lungs with the drug. In this regard, to achieve the clinical effect of the therapy, high doses of bronchodilators are required.

For the treatment of respiratory failure in chronic obstructive pulmonary diseases (COPD), the so-called respiratory support (lung ventilation) is used, which is divided into controlled ventilation and assisted ventilation. Auxiliary ventilation does not involve turning off the patient’s spontaneous breathing, but only supports the patient’s breathing.

In recent years, non-invasive ventilation of the lungs (NLV) has begun to be used in patients with acute respiratory failure (ARF) on the background of COPD, which does not require the application of artificial airways (tracheostomy, endotracheal tube), which significantly reduces the risk of infectious and mechanical complications during lung ventilation (see . L. Brochard et al. "Reversal of acute exacerbations of chronic obstructive lung disease by inspiratory asistance, with a fase mask" N. Engl. J. Med., 1990, -323: 1523-1529).

However, most devices for auxiliary ventilation of the lungs are bulky, which suggests their use only in a hospital setting, not allowing for auxiliary ventilation at home.

It is widely used in medicine and the treatment of patients using metered-dose aerosol inhalations of bronchodilators (Belman M. et al. "Inhaled bronchodilatores reduce dynamic hyperventilation during exercice in petients with chronic obstructive pulmonary disease". Am. J. Respir. Crit. Care Med., Mar . 1996, -153 (3): 967-975). This method is chosen by us as a prototype.

However, with this method, the intake of drugs is carried out due to the patient’s breathing, which is difficult in patients with insufficient lung function, for example, asthmatics.

In addition, this route of administration allows only limited delivery of the drug to the lungs, since most of it is deposited in the oral cavity and on the surface of the nasopharynx, which involves the introduction of large doses of the drug to achieve a clinical effect. According to estimates, with this method of drug administration, only 10-15% of the aerosol received during inhalation reaches the alveoli.

The objective of the present invention is to reduce the doses of administered bronchodilators, prevent the development of side effects from the drugs administered, increase the effectiveness of the therapy.

The task is achieved as follows. Patients with chronic obstructive diseases of the bronchopulmonary system undergo auxiliary ventilation of the lungs with air under constant positive pressure through a nasal mask, then bronchodilator is introduced continuously into the air for 0.5 hours at a dose of 30-50% of the average therapeutic single dose, followed by the continuation of the auxiliary ventilation of the lungs. Treatment is carried out 2-6 times a day, depending on the severity of the disease. The proposed method of treatment is applicable during the sleep of the patient. In patients with a tendency to worsen the disease at night, treatment is carried out in the interval from 22 to 7 hours 2-4 times per night. For assisted ventilation, you can use the device AVL-01 ("Aero").

Detailed description of the method.

For a patient suffering from COPD of varying severity, non-invasive assisted ventilation with constant positive pressure in the airways is provided through a nasal mask for 0.5 h, providing positive pressure on the exhale (Continues-Positive Airway Pressure - CPAP). Air is supplied to the patient's lungs at a pressure of 8-16 cm of water.

CPAP therapy maximizes the opening of the alveoli and bronchial collaterals and prevents them from collapsing at the end of exhalation, thereby ensuring a more effective distribution of bronchodilator in the lung tissue, up to its smallest structures, i.e. maximum filling of the lungs and bronchi with the drug.

This stage of the method is preparatory and, providing maximum filling of the lungs with a drug, it can significantly reduce the dose of drugs while improving the clinical effect of the therapy by increasing the area of local effects of the drug.

Bronchodilators administered over the next 0.5 hours are fed into the circuit of the device through a dispenser (aerosol inhaler) attached to it of any known modification. A single dose of a bronchodilator, comprising 30-50% of the average therapeutic single inhalation dose, is fed into the air introduced by the device continuously for 0.5 hours.

Then they stop the flow of the drug, blocking the valve connecting the aerosol inhaler to the device, and continue assisted ventilation of the lungs under the same air pressure for another 0.5 hours. The final ventilation of the lungs allows you to consolidate the effect of the action of the bronchodilator, provides additional massage of the walls of the bronchi, while improving pulmonary blood and lymph flow, prevents the development of tracheobronchial dyskinesia, improves mucociliary transport, prevents the development of collapse on the exhale. In addition, when using sympathomimetics during an exacerbation of COPD in patients with increasing respiratory failure, exacerbation of hypoxemia and hypokalemia is possible. Ventilation of the lungs after administration of a bronchodilator helps to prevent this "reverse" action of sympathomimetics.

The number of sessions of the above therapy during the day can vary (2-6 times a day), depending on the severity of COPD.

With a mild severity (FEV1> 70% of the due), 2-3 sessions are performed per day; with moderate severity (FEV1 50-70% of the due) - 3-4 sessions per day; in severe cases (FEV1 <50%) - 5-7 sessions per day.

Chronic obstructive pulmonary disease tends to worsen at night. The most significant cause of hypoxemia in sleep in patients with COPD is considered to be hypoventilation, decreased lung capacity and fluctuations in ventilation-perfusion ratios in different phases of sleep.

Minute ventilation in patients with COPD is significantly reduced during sleep compared to wakefulness. The onset of REM sleep itself is characterized by the development of regular episodes of hypoventilation. Since patients with COPD have a physiologically increased “dead space”, rapid surface respiration during the “eye-beating” REM sleep phase leads to a more pronounced decrease in alveolar ventilation. This leads to an increase in the frequency of REM-dependent hypoxemia, and such hypoventilation is the cause of the overwhelming number of hypoxemia observed in patients with COPD during sleep.

It is possible that hypoventilation during sleep is one of the reasons for the increased resistance of the upper respiratory tract (SVDP) to the air flow, especially when NREM sleep occurs. The resulting hypoventilation, in turn, again increases the SVDP against the background of already existing impaired ventilation, which creates a "vicious circle" of respiratory disorders.

In addition, hypoventilation noted during REM sleep inevitably leads to additional ventilation-perfusion disorders in patients with COPD. In addition to the general mechanisms of hypoxemia during sleep that are common to all patients with COPD, it should be noted that in some diseases (bronchial asthma), bronchospasm in some cases develops in the evening and at night (the so-called night bronchial asthma). For such patients, the question of choosing a treatment that would prevent an attack of bronchospasm at night without disturbing the patient’s sleep is especially acute. This is not possible with conventional metered-dose inhalers.

The above tendencies for the deterioration of the condition of patients with COPD during sleep provide the prerequisites for using the proposed treatment method not only in the daytime, but also at night.

The method proposed by the authors for administering bronchodilators through constant positive air pressure supplied through a nasal mask allows for effective therapy at night, without interrupting the patient’s sleep.

The use of the method in the nighttime allows to reduce the introduction of bronchodilators in the daytime, and in some cases completely eliminate the daily administration of drugs.

In somnological practice, for the treatment of sleep disorders, an individual apparatus for prolonged ventilation of the upper respiratory tract and lungs during sleep with constant positive pressure -AVL-01 (Aero) is used, which we used to implement the proposed method (see S.P. Mironov and other Russian apparatus for the treatment of sleep apnea with constant positive pressure: Materials of the III international conference on restorative medicine (rehabilitation), Moscow, December 6-8, 2000, p.223-225).

The device is an adjustable compressor that can deliver a precisely metered air flow and, accordingly, maintain a certain pressure in the breathing hose, nasal breathing mask and airways of the patient. At the inlet of the air system of the apparatus, a composite air filter is installed, which allows you to clean the incoming air stream from foreign particles. After cleaning, the incoming air stream passes through a duct system that provides noise reduction, and enters the compressor inlet. The compressor is a direct current motor and multi-blade impeller placed on a vibration-absorbing base. From the compressor outlet, air flow through the breathing hose attached to the apparatus is supplied to the breathing nose mask. At the junction of the apparatus and the breathing hose there is a valve for connecting an aerosol inhaler. The air pressure, individual for a particular patient, is provided by a microprocessor-based compressor speed control system.

To implement the proposed method can be applied to any other apparatus designed for ventilation. However, the apparatus we use has several advantages. The device AVL-01 is portable, which suggests the possibility of its use not only in stationary conditions, but also by patients themselves at home after choosing a drug, its dosage and the regimen of administration by a doctor.

The clinical effectiveness of the proposed treatment is assessed by the frequency of asthma attacks, the severity of sensations of respiratory discomfort (paroxysmal cough, wheezing, difficulty sputum discharge), the peak air flow rate (PEF) before and after each session, and their fluctuations during the day, spirographic dynamics indicators (VC, FEV1). The following criteria were used: a good effect - the complete cessation of asthma attacks, a decrease or absence of respiratory discomfort, an increase in PEF of more than 30% and its fluctuations during the day less than 10%, an increase in spirographic indices by more than 1 gradation; satisfactory - the cessation of seizures while maintaining respiratory discomfort, an increase in PEF of less than 30% and its daily fluctuations of more than 10%, an increase in spirographic indices of less than 1 gradation; unsatisfactory - lack of clinical effect and dynamics of functional pulmonary parameters.

The effectiveness of the treatment of patients with chronic obstructive diseases of the bronchopulmonary system of the proposed method is confirmed by the following clinical examples.

Example 1

Patient S., 63 years old. Diagnosis: chronic obstructive bronchitis in the acute stage, pulmonary emphysema, pneumosclerosis, DN-1.

From the anamnesis it is known that for 14 years he suffers from chronic bronchitis, periodically (3-4 times a year) exacerbations are noted. Repeatedly treated in a hospital using a / b and aerosol metered-dose inhalations of bronchodilators. The condition improved slightly, inter-relapse periods were short (3-4 months).

The last exacerbation during the last 3 weeks, when cough with mucopurulent sputum intensified after acute respiratory viral infections, shortness of breath during physical exertion, fever to subfibril values, weakness, sweating.

On examination: the skin is pale, moderate acrocyanosis. In the lungs - hard breathing, scattered dry rales. Rhythmic heart sounds, heart rate-78, blood pressure 140/90 mm Hg According to the survey: in the general analysis of blood leukocytosis up to 10.3 × 109, ESR 25 mm per second.

FVD: obstructive changes at the level of small and medium bronchi: FEV1 / FVC - 51%, FEF55 - 2.23 l / s (63% of the due), PEF - 5.1 l / s (55% of the due), FEV1 - 58%

Test with ventolin positive.

According to peak flow measurements, a 30% decrease in morning exhalation flow values was noted compared to evening flow. According to polysomnography, sleep latency is increased - 43 min, efficiency is reduced - 72%, activation reaction index is increased - 36 events per hour, frequent awakenings in the second half of the night associated with coughing and suffocation attacks were recorded. The apnea-hypopnea index is 4.3 events per hour, the minimum level of SaO ₂ is 87%. Conducted therapy: sumamed 0.5 g / day, aminophylline 2.4% - 10.0 per physical. solution, theopec - 1 tab. 2 times, inhalation of ventolin (2 breaths - 200 μg × 3 r / day), inhalation of fluimucil. Against the background of the ongoing antibacterial and bronchodilator therapy, there has been a tendency to subside in acute inflammatory phenomena, however, frequent bouts of coughing and shortness of breath in the night and early morning hours persisted; during waking, the patient independently inhaled ventolin (up to 300 mcg per night).

The patient started therapy with constant positive pressure (CPAP - 10 cm water. Art.) With a dosed supply of 80 mcg of salbutamol into the inhaled air continuously for 0.5 h 3 times a night and 1 time per day.

During treatment, nightly attacks of bronchial obstruction were stopped; according to peak flowmetry, the difference between evening and morning airflow values decreased by 10%.

Example 2

Patient V., 48 years old. Diagnosis: chronic obstructive bronchitis, pneumosclerosis. From the anamnesis: for 5 years he suffers from chronic bronchitis, periodically (1-2 times a year) exacerbations are noted.

This exacerbation - within 1.5 weeks, when shortness of breath appeared during physical exertion, cough with difficult to separate mucopurulent sputum, subfibrillation, weakness, sweating.

In the lungs - hard breathing, scattered dry rales, mainly in the upper sections; Heart rate - 76 per minute.

In the general analysis of blood leukocytosis up to 15 × 109, ESR - 21 mm per second.

ATS: FEV1 - 70%, FEV1 / FVC - 60%, FEF55 - 72% of due, PEF - 68% of due.

Conducted therapy: theophylline 1 tab. 3 r / d per os, inhalation of salmeter in 2 breaths - 50 mcg × 2 times a day., Antibiotic therapy.

The treatment did not produce a tangible effect. Shortness of breath, frequent bouts of coughing, shortness of breath persisted. With breathing difficulties, the patient independently inhaled an additional 50 micrograms of salmeter.

The treatment has begun with the proposed method with a dosed supply of salmeter in the inhaled air of 15 mcg for 0.5 h, 1 time at night and 1 time in the afternoon.

After the treatment, bronchial obstruction attacks were stopped, an increase of FEV1 / FVC by 15%, PEF - by 40% was noted.

There were 5 patients under observation in the therapeutic department of the Rehabilitation Center (average age - 57.3 ± 11.2 years). Of these, in three patients, the main diagnosis is chronic obstructive bronchitis in the acute stage; in 2 patients - infectious-allergic bronchial asthma in the acute stage.

In all patients, bronchial obstructive syndrome prevailed in the clinical picture, worsening in the night and early morning hours. It was not possible to achieve complete stabilization of the state against the background of systemic and inhalation use of corticosteroids and bronchodilators, including prolonged ones (inhalation of a cereal before bedtime).

Against the background of the use of constant positive pressure therapy with the introduction of low doses of 2 antagonists (3 patients) or anticholinergics (2 patients) into the supplied air, a significant improvement in clinical and instrumental indicators was achieved: according to the results of spirometry performed immediately after awakening, an increase in FEV1 / FVC was noted by 20 ± 5%, FEF25-75 by 31 ± 6%, PEF by 42 ± 11%. Night episodes of bronchial obstruction stopped, according to polysomnography, sleep structure parameters improved (sleep efficiency increased on average from 73.5 ± 6.3% to 86.1 ± 4.1%, the number of EEG activation reactions decreased on average from 32.2 to 18.1 events per hour). At the same time, a decrease in the dose of applied 2 antagonists was noted by an average of 42.3% compared with the initial level.

Claims (4)

1. A method of treating patients with chronic obstructive diseases of the bronchopulmonary system by inhalation of bronchodilators, characterized in that they perform auxiliary ventilation of the lungs with air under constant positive pressure supplied to the patient through a nasal mask for 0.5 h, then continuously into the air for the next 0 , 5 hours a bronchodilator is administered at a dose of 30-50% of the average therapeutic single dose, followed by continued auxiliary ventilation for 0.5 hours; treatment is carried out 2-6 times a day. 2. The method according to claim 1, characterized in that the treatment is carried out during sleep of the patient. 3. The method according to claims 1 and 2, characterized in that for patients with a tendency to worsen the disease at night, treatment is carried out in the interval from 22 hours to 7 hours 2-4 times per night. 4. The method according to claims 1 to 3, characterized in that for the auxiliary ventilation of the lungs use the device "Aero".