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Instructions for medical use

Surfactant-BL
Instructions for medical use- RU No. R N003383/01

the date last change: 23.07.2010

Dosage form

Lyophilizate for the preparation of an emulsion for endotracheal, endobronchial and inhalation administration.

Compound

One vial contains 75 mg of surfactant isolated from the lungs of a large cattle and representing a mixture of phospholipids and surfactant-associated proteins.

Description of the dosage form

Freeze-dried, compressed into a tablet mass or powder of white, or white with a yellowish tint. When adding 5 ml of 0.9% sodium chloride solution to the preparation and gently mixing by pipetting (with a syringe with a needle, a suspension is taken from the vial and poured back into the vial along the wall, the procedure is repeated 4-5 times until complete uniform emulsification, a homogeneous emulsion of white with creamy or white with a yellowish tint, in which flakes or solid particles should not be observed.

Pharmacological group

Surfactant

Pharmacodynamics

Surfactant-BL highly purified natural surfactant from the lungs of cattle is a complex of substances from a mixture of phospholipids and surfactant-associated proteins, has the ability to reduce surface tension on the surface lung alveoli, preventing their collapse and development of atelectasis.

Surfactant-BL restores the content of phospholipids on the surface of the alveolar epithelium, stimulates the involvement of additional sections of the lung parenchyma into respiration and promotes removal along with sputum toxic substances and infectious pathogens from the alveolar space. The drug increases the activity of alveolar macrophages and inhibits the expression of cytokines by polymorphonuclear leukocytes (including eosinophils); improves mucociliary clearance and stimulates the synthesis of endogenous surfactant by type II alveolocytes, and also protects the alveolar epithelium from damage by chemical and physical agents, restores the functions of local innate and acquired immunity.

The experiment found that with daily inhalation administration for 10 days or for 6 months and additional observation for one month, the drug does not affect cardiovascular system, does not have a local irritating effect, does not affect the blood composition and hematopoiesis, does not affect the biochemical parameters of blood, urine and the blood coagulation system, does not cause pathological changes functions and structure internal organs, does not have teratogenic, allergenic and mutagenic properties.

It has been established that in premature newborns with respiratory distress syndrome (RDS) who are on artificial ventilation lungs (IVL), endotracheal, microfluidic or bolus administration of surfactant-BL can significantly improve gas exchange in lung tissue. With microjet administration after 30-120 minutes, and with a bolus after 10-15 minutes, the signs of hypoxemia decrease, the partial tension of oxygen in arterial blood(PaO 2) and saturation of hemoglobin (Hb) with oxygen, as well as hypercapnia decreases (partial stress decreases carbon dioxide). Restoration of lung tissue function allows switching to more physiological parameters of mechanical ventilation and reducing its duration. The use of surfactant-BL significantly reduces mortality and complication rates in newborns with RDS.

It has also been established that in adults with acute lung injury syndrome (ALS) and acute respiratory distress syndrome (ARDS), early, on the first day of ARDS, endobronchial administration of the drug halved the time spent on mechanical ventilation and in the intensive care unit and intensive care(ICU), prevents the development of purulent-septic complications associated with prolonged mechanical ventilation (purulent bronchitis and ventilator-associated pneumonia), and significantly reduces mortality in direct and indirect lung injury. A more pronounced and earlier effect of therapy is observed with the combined use of endobronchial administration of surfactant-BL and the “opening” of the lungs maneuver.

The clinic found that in patients with pulmonary tuberculosis who did not respond positively to treatment with anti-tuberculosis drugs (ATP) for 2-6 months, when a two-month course of inhalation of the drug is added to the therapy regimen, abacillation is achieved in 80.0% of patients, a decrease or disappearance of infiltrative and focal changes in the lung tissue in 100% and closure of the cavity (caverns) in 70.0% of patients. Thus, complex anti-tuberculosis chemotherapy with the addition of a course of inhalation of surfactant-BL makes it possible to receive positive result from treatment much faster and in a significantly larger percentage of patients.

Pharmacokinetics

It has been experimentally shown that after a single intratracheal administration of surfactant-BL to rats, its content in the lungs decreases after 6-8 hours and reaches the initial value after 12 hours. The drug is completely metabolized in the lungs by type II alveolocytes and alveolar macrophages and does not accumulate in the body.

Indications

1. Respiratory distress syndrome (RDS) in newborns weighing more than 800 g at birth.

2. In complex therapy Acute Lung Injury Syndrome (ALI) and Acute Respiratory Distress Syndrome (ARDS) in adults resulting from direct or indirect lung injury.

3. In the complex therapy of pulmonary tuberculosis, both in newly diagnosed patients and in case of relapse of the disease, with infiltrative (with and without decay) or cavernous clinical form, including in the presence of drug resistance of Mycobacterium tuberculosis, up to multidrug resistance.

Contraindications

I. With respiratory distress syndrome (RDS) of newborns:

1. Intraventricular hemorrhages III - IV degree.

2. Air leakage syndrome (pneumothorax, pneumomediastinum, interstitial emphysema).

3. Malformations incompatible with life.

4. DIC with symptoms of pulmonary hemorrhage

II. For ARDS and COPD in adults:

1. Disorders of gas exchange associated with left ventricular heart failure.

2. Disorders of gas exchange caused by bronchial obstruction.

3. Children under 18 years of age, as clinical trials in this age group have not been conducted and the doses have not been determined.

4. Air leakage syndrome.

III. For pulmonary tuberculosis:

1. Tendency to hemoptysis and pulmonary bleeding.

2. Children under 18 years of age, since clinical trials in this age group have not been conducted and doses have not been determined.

3. Air leakage syndrome.

Use during pregnancy and lactation

It is used according to vital indications in the treatment of ARDS.

Dosage and administration

1. Treatment of respiratory distress syndrome (RDS) in newborns.

Before starting treatment, it is necessary to correct acidosis, arterial hypotension, anemia, hypoglycemia and hypothermia. X-ray confirmation of RDS is desirable.

The drug is administered micro-stream, in the form of an aerosol through a nebulizer or as a bolus. With microjet administration, the surfactant-BL emulsion is injected slowly using a syringe dispenser (dose of 75 mg in a volume of 2.5 ml) for 30 minutes, and in the form of an aerosol through an alveolar nebulizer - the same dose for 60 minutes. Surfactant-BL can be administered as a bolus at a dose of 50 mg/kg of body weight (in a volume of 1.7 ml/kg). The second and, if necessary, the third time the drug is administered after 8-12 hours in the same doses, if the child continues to need increased concentration oxygen in the supplied gas mixture (FiO 2 > 0.4). It should be remembered that repeated injections of surfactant-BL are less effective if the first administration was delayed (late).

In the case of severe RDS (RDS type 2, which is more common in term infants due to meconium aspiration, intrauterine pneumonia, sepsis) it is necessary to use a large dose of surfactant-BL - 100 mg/kg. Repeatedly the drug is also administered with an interval of 8-12 hours, and if necessary, within a few days.

An important factor in the effectiveness of the use of surfactant-BL in complex treatment RDS in newborns is early start therapy with surfactant-BL, within two hours after birth with established diagnosis RDS, but not later than the first day after birth.

The use of high-frequency oscillatory ventilation significantly increases the effectiveness of surfactant-BL therapy and reduces the frequency adverse reactions.

Emulsion preparation:

Immediately before the introduction of surfactant-BL (75 mg in a vial), dilute 2.5 ml of 0.9% sodium chloride solution for injection. To do this, add 2.5 ml of warm (37 ° C) 0.9% sodium chloride solution to the vial and allow the vial to stand for 2-3 minutes, then gently mix the suspension in the vial without shaking, draw the emulsion into the syringe with a thin needle, pour it back into the vial along the wall several (4-5) times until complete uniform emulsification, avoiding foam formation. The bottle must not be shaken. After dilution, a milky emulsion is formed, it should not contain flakes or particulate matter.

The introduction of the drug.

Microjet introduction. The child is intubated and sputum is aspirated from respiratory tract and endotracheal tube (ET). Importance It has correct location and compliance of the ET size with the tracheal diameter, since with a large leakage of the emulsion past the ET (more than 25% on a respiratory monitor or auscultation), as well as with selective intubation into the right bronchus or high standing of the ET, the effectiveness of surfactant-BL therapy is significantly reduced or depreciated.

Next, the respiratory cycle of the newborn is synchronized with the operating mode of the ventilator using sedatives- sodium hydroxybutyrate or diazepam, and in cases of severe hypoxia - narcotic analgesics. The prepared emulsion of surfactant-BL is injected through a catheter inserted through an adapter with an additional side entry into the ET so that the lower end of the catheter does not reach the lower edge of the endotracheal tube by 0.5 cm. The introduction is carried out using a syringe dispenser for 30 minutes without interrupting IVL, without depressurization of the respiratory circuit. For uniform distribution surfactant by various departments lungs during the administration of the drug, if the severity of the child's condition allows, the first half of the dose is administered with the child on the left side, and the second half of the dose with the child on the right side. Finishing the introduction, 0.5 ml of 0.9% sodium chloride solution is drawn into the syringe and the introduction is continued to displace the remnants of the drug from the catheter. It is advisable not to sanitize the trachea within 2-3 hours after the administration of surfactant-BL.

Aerosol administration of surfactant-BL carried out using an alveolar nebulizer included in the circuit of the ventilator synchronized with inspiration, as close as possible to the endotracheal tube to reduce drug losses. If this is not possible, it is preferable to use a microfluidic or bolus route of administration. For aerosol production and drug administration can not use ultrasonic nebulizers, since the surfactant-BL is destroyed when the emulsion is treated with ultrasound. Compressor-type nebulizers must be used.

Bolus administration of surfactant-BL. Before the introduction of the drug, as well as with microjet administration, stabilization of central hemodynamics, correction of hypoglycemia, hypothermia and metabolic acidosis. X-ray confirmation of RDS is desirable. The child is intubated and sputum is aspirated from the respiratory tract and ET. Immediately before the introduction of surfactant-BL, the child can be temporarily transferred to manual ventilation with a self-expanding Ambu bag. If necessary, the child is sedated with sodium hydroxybutyrate or diazepam. The prepared surfactant-BL emulsion (30 mg/ml) is used at a dose of 50 mg/kg in a volume of 1.7 ml/kg. For example, a child weighing 1500 g is given 75 mg (50 mg/kg) in a volume of 2.5 ml. The drug is administered as a bolus over 1-2 minutes through a catheter placed in the endotracheal tube, while the child is carefully turned to the left side and the first half of the dose is administered, then turned to the right side and the second half of the dose is administered. The introduction is completed with forced manual ventilation for 1-2 minutes with an inhaled oxygen concentration equal to the initial value on the ventilator or manual ventilation using a self-expanding Ambu-type bag. It is obligatory to control the saturation of hemoglobin with oxygen, it is desirable to control the content of blood gases before and after the administration of surfactant-BL.

Next, the child is transferred to assisted ventilation or forced ventilation and the ventilation parameters are corrected. Bolus injection of the drug allows you to quickly bring the therapeutic dose into the alveolar space and avoid the inconvenience and adverse reactions of microfluidic injection.

Full-term newborns weighing more than 2.5 kg with a severe form of RDS of the second type, due to the large volume of the emulsion, half the dose is administered as a bolus, and the second half of the dose is microfluidized.

Bolus administration can also be used for prophylactic administration of surfactant-BL. In the future, depending on the initial state and the effectiveness of therapy, the child can be extubated with a possible transfer to a non-invasive method of ventilation of the lungs with the maintenance of a constant positive airway pressure (CPAP).

2. Treatment of acute lung injury syndrome and acute respiratory distress syndrome in adults.

Treatment with surfactant-BL is performed by endobronchial bolus administration using a fiberoptic bronchoscope. The drug is administered at a dose of 12 mg/kg/day. The dose is divided into two injections of 6 mg/kg 12-16 hours apart. Multiple injections of the drug (4-6 injections) may be required until a stable improvement in gas exchange (an increase in the oxygenation index of more than 300 mm Hg), an increase in lung airiness on chest x-ray and the possibility carrying out IVL with FIO 2<0,4.

In most cases, the duration of the course of application of surfactant-BL does not exceed two days. In 10-20% of patients, the use of the drug is not accompanied by normalization of gas exchange, especially in those patients who are given the drug against the background of advanced multiple organ failure (MOF). If within two days there is no improvement in oxygenation, the administration of the drug is stopped.

The most important factor in the effectiveness of the use of surfactant-BL in the complex treatment of SOPL / ARDS is the time of the start of the drug administration. It must be started within the first day ( better than the first hours) from the moment the oxygenation index falls below 250 mm Hg.

The drug can also be administered prophylactically in case of a threat of development of COPD/ARDS in patients with chronic diseases lungs, including those with chronic obstructive pulmonary disease (COPD), as well as before extended operations on chest at a dose of 6 mg / kg per day, 3 mg / kg every 12 hours.

Emulsion preparation.

Before the introduction of surfactant-BL (75 mg in a vial), dilute in the same way as for newborns in 2.5 ml of 0.9% sodium chloride solution. The resulting emulsion, which should not contain flakes or solid particles, is further diluted with 0.9% sodium chloride solution to 5 ml (15 mg in 1 ml).

Endobronchial administration is the best way to deliver the drug. The introduction of surfactant-BL is preceded by a thorough sanitation bronchoscopy, carried out according to the standard method. At the end of this procedure, an equal amount of the drug emulsion is injected into each lung. The best effect is achieved with the introduction of the emulsion into each segmental bronchus. The volume of the injected emulsion is determined by the dose of the drug.

Most effective way The use of surfactant-BL in the treatment of SOPL / ARDS is a combination of endobronchial administration of the drug and the maneuver of "opening" the lungs, moreover, the segmental administration of the drug is carried out immediately before the maneuver of "opening" the lungs.

After the administration of the drug for 2-3 hours, it is necessary to refrain from sanitation of the bronchi and not to use drugs that enhance sputum separation.

Use of intratracheal instillation indicated in case of impossibility of bronchoscopy. The emulsion is prepared as described above. Before the introduction of the drug, it is necessary to carry out a thorough sanitation of the tracheobronchial tree, after taking measures to improve sputum drainage (vibration massage, postural therapy). The emulsion is administered through a catheter inserted into the endotracheal tube so that the end of the catheter is located below the opening of the endotracheal tube, but always above the carina of the trachea. The emulsion must be administered in two doses, dividing the dose in half, with an interval of 10 minutes. In this case, also after instillation, a maneuver of "opening" the lungs can be performed.

Treatment of pulmonary tuberculosis is carried out by repeated inhalations of the drug surfactant-BL as part of complex therapy against the background of fully developed therapy with anti-tuberculosis drugs (ATPs), that is, when the patient is empirically or based on data on the drug sensitivity of the pathogen, 4-6 anti-tuberculosis drugs are selected, which are well tolerated by the patient in the prescribed dose and combination. Only then the patient is prescribed an emulsion of surfactant-BL in inhalation at a dose of 25 mg per injection:

• the first 2 weeks - 5 times a week,
• the next 6 weeks - 3 times a week (in 1-2 days).

The duration of the course is 8 weeks - 28 inhalations, the total dose of surfactant-BL is 700 mg. During the course of treatment with surfactant-BL, according to indications, anti-tuberculosis drugs can be canceled (replaced). Chemotherapy continues after completion of the course of treatment with surfactant-BL.

Emulsion preparation:

Before use, surfactant-BL (75 mg in a vial) is diluted in the same way as for newborns in 2.5 ml of 0.9% sodium chloride solution. The resulting emulsion, which should not contain flakes or solid particles, is further diluted with 0.9% sodium chloride solution to 6 ml (12.5 mg in 1 ml). Next, 2.0 ml of the resulting emulsion is transferred into the nebulizer chamber and another 3.0 ml of 0.9% sodium chloride solution is added to it, stirring gently. Thus, 25 mg of surfactant-BL in 5.0 ml of emulsion is in the nebulizer chamber. This is the dose for one inhalation per patient. Thus, 1 bottle of surfactant-BL contains three doses for inhalation for three patients. The emulsion prepared for inhalation should be used within 12 hours when stored at a temperature of +4°C - +8°C (do not freeze the emulsion). Before use, the emulsion must be carefully mixed and warmed to 36°C-37°C.

Inhalation administration:

5.0 ml of the resulting emulsion (25 mg) in the nebulizer chamber is used for inhalation. Inhalations are carried out 1.5-2 hours before or 1.5-2 hours after a meal. For inhalation, compressor-type inhalers are used, for example, “Boreal” by Flaem Nuova, Italy or “Pari Boy SX” by Pari GmbH, Germany, or their analogues, which allow spraying small volumes of drugs and are equipped with an economizer device that allows you to stop the supply of the drug during expiration, which significantly reduces the loss of the drug.

The use of an economizer is extremely important so that the patient is given a therapeutic dose of the drug without loss (25 mg). If, due to the severity of the patient's condition, the entire volume of the emulsion cannot be used, breaks should be taken for 15-20 minutes, and then inhalation should be continued. In the presence of a large number sputum before inhalation should be carefully coughed up. If there is evidence of broncho-obstruction 30 minutes before inhalation of the surfactant-BL emulsion, it is necessary to first inhale a beta2-adrenergic agonist (at the doctor's choice), which reduces bronchial obstruction.

It is necessary to use only compressor, and not ultrasonic nebulizers, since the surfactant-BL is destroyed when the emulsion is sonicated. Before the introduction of the drug, it is necessary to carry out a thorough sanitation of the tracheobronchial tree, after taking measures to improve sputum drainage: vibromassage, postural therapy and mucolytics, which must be prescribed 3-5 days before the start of therapy with surfactant-BL in the absence of contraindications to their appointment.

Side effects

1. With respiratory distress syndrome (RDS) of newborns:

With microjet and bolus administration of surfactant-BL, obturation with the ET preparation or emulsion regurgitation may occur. This may occur if the section of the instruction “preparation of the emulsion” is not followed (use of 0.9% sodium chloride solution at a temperature below 37 ° C, inhomogeneous emulsion), with a rigid chest, high activity of the child, accompanied by coughing, crying, discrepancy between the size of the ET and the internal diameter trachea, selective intubation, injection of surfactant-BL into one bronchus, or a combination of these factors. If all these factors are excluded or eliminated, then in this case it is necessary to briefly increase the peak inspiratory pressure (P peak) for a child on mechanical ventilation. If a child develops signs of airway obstruction when not on a mechanical breath, several breaths should be taken using manual ventilation with high blood pressure to move the drug deeper. When using the aerosol method of drug administration, such phenomena are not observed. Mandatory physical and instrumental monitoring of hemodynamics and oxygen saturation of hemoglobin (Sa 0 2). Bleeding in the lungs may occur, usually within 1-2 days after administration of the drug in premature infants of low or extremely low birth weight. Prevention of pulmonary hemorrhage is early diagnosis and adequate treatment functioning ductus arteriosus. With a rapid and significant increase in the partial tension of oxygen in the blood, retinopathy can develop. The concentration of oxygen in the inhaled mixture should be reduced as quickly as possible to a safe value, maintaining the target saturation of hemoglobin with oxygen in the range of 86 - 93%. Some newborns have short-term hyperemia skin, requiring an assessment of the adequacy of ventilation parameters to exclude hypoventilation due to transient airway obstruction. In the first minutes after microfluidic and bolus administration of surfactant-BL, coarse bubbling rales on inspiration can be heard in the lungs. Within 2-3 hours after the use of surfactant-BL, one should refrain from sanitation of the bronchi. In children with intrapartum respiratory tract infection, the administration of the drug may increase sputum separation due to the activation of mucociliary clearance, which may require their rehabilitation at an earlier date.

2. For ARDS and SOPL in adults:

To date, no specific adverse reactions have been reported with surfactant-BL treatment of COPD and ARDS. various genesis was not observed.

In the case of using the endobronchial route of administration, a deterioration in gas exchange lasting from 10 to 60 minutes is possible, associated with the bronchoscopy procedure itself. With a decrease in arterial hemoglobin saturation with oxygen (Sa 0 2) below 90%, it is necessary to temporarily increase the positive end-expiratory pressure (PEEP) and the oxygen concentration in the gas mixture supplied to the patient (Fi O 2). In the case of a combination of endobronchial administration of surfactant-BL and the “opening” maneuver of the lungs, no deterioration in gas exchange was observed.

3. With pulmonary tuberculosis:

In the treatment of pulmonary tuberculosis in 60-70% of patients after 3-5 inhalations there is a significant increase in the volume of sputum discharge or sputum appears, which was not there before the start of inhalations. The effect of “easy sputum discharge” is also noted, while the intensity and soreness of cough is significantly reduced, tolerance improves. physical activity. These objective changes and subjective feelings are a manifestation of direct actions of surfactant-BL and are not side effects.

Overdose

Surfactant-BL for intravenous, intraperitoneal and subcutaneous methods administration to mice at a dose of 600 mg/kg and inhalation administration to rats at a dose of 400 mg/kg does not cause changes in the behavior and condition of animals. In no case was the death of animals. In clinical use, cases of overdose were not observed.

Interaction

Surfactant-BL cannot be used in conjunction with expectorants, as the latter will remove the administered drug along with sputum.

special instructions

The use of surfactant-BL for treatment critical conditions newborns and adults is possible only in a specialized intensive care unit, and for the treatment of pulmonary tuberculosis - in a hospital and a specialized anti-tuberculosis dispensary.

1. Treatment of respiratory distress syndrome (RDS) in newborns.

Before the introduction of surfactant-BL, mandatory stabilization of central hemodynamics and correction of metabolic acidosis, hypoglycemia and hypothermia are necessary, which adversely affect the effectiveness of the drug. X-ray confirmation of RDS is desirable.

2. Treatment of SOPL and ARDS.

The drug should be used as part of a comprehensive treatment for OMLS and ARDS, including rational respiratory support, antibiotic therapy, maintaining adequate hemodynamics and fluid and electrolyte balance.

The question of the use of surfactant-BL in OOP, combined with severe multiple organ failure (MOF), should be decided individually, depending on the possibility of correcting other components of MOF.

3. Treatment of pulmonary tuberculosis.

In rare cases, after 2-3 inhalations, hemoptysis may occur. In this case, it is necessary to interrupt the course of treatment with surfactant-BL and continue it after 3-5 days.

Incompatibility with any anti-tuberculosis drug surfactant-BL was not noted. There are no data on interactions with aerosolized anti-tuberculosis drugs, so this combination should be avoided.

Carrying out therapy with surfactant-BL does not affect the ability to drive vehicles.

Release form

Lyophilizate for the preparation of an emulsion for endotracheal, endobronchial and inhalation administration, 75 mg.

75 mg in glass vials with a capacity of 10 ml, sealed with rubber stoppers and sealed with aluminum caps.

2 bottles are placed in a cardboard pack, 5 packs, together with an equal number of instructions for use, are placed in a cardboard box with a foam insert.

Storage conditions

In a place protected from light, at a temperature not exceeding minus 5 ° C.

Keep out of the reach of children.

If the emulsion in the opened vial is not fully used, then when stored under aseptic conditions at a temperature of +4 - +8 ° C (do not freeze the emulsion), it can be used no later than 12 hours after its preparation.

Shelf life

Do not use after the expiration date.

Terms of dispensing from pharmacies

By prescription. Used in a hospital setting.

LSR-010019/08 from 2008-12-15
Surfactant-BL - instructions for medical use - RU No.

Drug for the treatment of neonatal respiratory distress syndrome

Active substance

Surfactant

Release form, composition and packaging

Lyophilizate for the preparation of an emulsion for endotracheal, endobronchial and inhalation administration in the form of a mass pressed into a tablet or powder of white or white with a yellowish tint, prepared emulsion of white with a creamy and white with a yellowish tint, homogeneous, in which flakes or solid particles should not be observed.

75 mg - Glass vials with a capacity of 10 ml (2) - cardboard packs (5) - cardboard boxes.

pharmachologic effect

Surfactant-BL, a highly purified natural surfactant from the lungs of cattle, is a complex of substances from a mixture of phospholipids and surfactant-associated proteins, has the ability to reduce surface tension on the surface of the lung alveoli, preventing their collapse and the development of atelectasis.

Surfactant-BL restores the content of phospholipids on the surface of the alveolar epithelium, stimulates the involvement of additional sections of the lung parenchyma into respiration and promotes the removal of toxic substances and infectious agents from the alveolar space along with sputum. The drug increases the activity of alveolar macrophages and inhibits the expression of cytokines by polymorphonuclear leukocytes (including eosinophils); improves mucociliary clearance and stimulates the synthesis of endogenous surfactant by type II alveolocytes, and also protects the alveolar epithelium from damage by chemical and physical agents, restores the functions of local innate and acquired immunity.

The experiment found that with daily inhalation administration for 10 days or for 6 months and additional observation for one month, the drug does not affect the cardiovascular system, does not have a local irritating effect, does not affect blood composition and hematopoiesis, does not affect on the biochemical parameters of blood, urine and the blood coagulation system, does not cause pathological changes in the functions and structure of internal organs, does not have teratogenic, allergenic and mutagenic properties.

It has been established that in premature infants with respiratory distress syndrome (RDS) who are on artificial lung ventilation (ALV), endotracheal, microfluidic or bolus administration of surfactant-BL can significantly improve gas exchange in the lung tissue. With a microjet injection after 30-120 minutes, and with a bolus after 10-15 minutes, the signs of hypoxemia decrease, the partial tension of oxygen in arterial blood (PaO 2) and the saturation of hemoglobin (Hb) with oxygen increase, and hypercapnia decreases (the partial tension of carbon dioxide decreases ). Restoration of lung tissue function allows switching to more physiological parameters of mechanical ventilation and reducing its duration. The use of surfactant-BL significantly reduces mortality and complication rates in newborns with RDS. It was also established that in adults with acute lung injury syndrome (ALS) and acute respiratory distress syndrome (ARDS), early, on the first day of ARDS development, endobronchial administration of the drug halved the time spent on mechanical ventilation and stay in the intensive care unit ( ICU), prevents the development of purulent-septic complications associated with prolonged mechanical ventilation (purulent and ventilator-associated pneumonia), and significantly reduces mortality in direct and indirect lung injury. A more pronounced and earlier effect of therapy is observed with the combined use of endobronchial administration of surfactant-BL and the lung "opening" maneuver.

The clinic found that in patients with lungs that did not respond positively to treatment with anti-tuberculosis drugs (ATP) for 2-6 months, when a two-month course of inhalation of the drug is added to the therapy regimen, abacillation is achieved in 80.0% of patients, a decrease or disappearance of infiltrative and focal changes lung tissue in 100% and closure of the cavity (cavities) in 70% of patients. Thus, a complex anti-tuberculosis drug with the addition of a course of inhalation of surfactant-BL makes it possible to obtain a positive result from treatment much faster and in a significantly larger percentage of patients.

Pharmacokinetics

It has been experimentally shown that after a single intratracheal administration of surfactant-BL to rats, its content in the lungs decreases after 6-8 hours and reaches the initial value after 12 hours. The drug is completely metabolized in the lungs by type II alveolocytes and alveolar macrophages and does not accumulate in the body.

Indications

- respiratory distress syndrome (RDS) in newborns weighing more than 800 g at birth;

- in the complex therapy of acute lung injury syndrome (ALI) and acute respiratory distress syndrome (ARDS) in adults developed as a result of direct or indirect lung injury;

- in the complex therapy of pulmonary tuberculosis, both in newly diagnosed patients and in case of relapse of the disease, with infiltrative (with and without decay) or cavernous clinical form, including in the presence of drug resistance of Mycobacterium tuberculosis, up to multidrug resistance.

Contraindications

With respiratory distress syndrome (RDS) of newborns:

- intraventricular hemorrhage III-IV degree;

- air leakage syndrome (, pneumomediastinum, interstitial emphysema);

- malformations incompatible with life;

- DIC-syndrome with symptoms of pulmonary bleeding;

For ARDS and COPD in adults:

- violations of gas exchange associated with left ventricular heart failure;

- violations of gas exchange caused by bronchial obstruction;

- air leakage syndrome.

For pulmonary tuberculosis:

- tendency to hemoptysis and pulmonary bleeding;

- children under 18 years of age, since clinical trials in this age group have not been conducted and doses have not been determined;

- air leakage syndrome.

Dosage

Before starting treatment, it is necessary to correct acidosis, arterial hypotension, anemia, hypoglycemia and hypothermia. X-ray confirmation of RDS is desirable.

The drug is administered micro-stream, in the form of an aerosol through a nebulizer or as a bolus. With microjet administration, the surfactant-BL emulsion is administered slowly using a syringe dispenser (dose of 75 mg in a volume of 2.5 ml) for 30 minutes, and in the form of an aerosol through an alveolar nebulizer - the same dose for 60 minutes. Surfactant-BL can be administered as a bolus at a dose of 50 mg/kg of body weight (in a volume of 1.7 ml/kg). The second and, if necessary, the third time the drug is administered after 8-12 hours in the same doses, if the child continues to need an increased oxygen concentration in the supplied gas mixture (FiO 2>0.4). It should be remembered that repeated injections of surfactant-BL are less effective if the first administration was delayed (late).

In case of severe RDS (RDS of the second type, which often develops in full-term children due to meconium aspiration, intrauterine pneumonia, sepsis), a large dose of surfactant-BL - 100 mg / kg should be used. Repeatedly the drug is also administered with an interval of 8-12 hours, and if necessary, within a few days.

An important factor in the effectiveness of the use of surfactant-BL in the complex treatment of RDS in newborns is the early start of therapy with surfactant-BL, within two hours after birth with an established diagnosis of RDS, but not later than the first day after birth.

The use of high-frequency oscillatory ventilation significantly increases the effectiveness of surfactant-BL therapy and reduces the frequency of adverse reactions.

Emulsion preparation:

Immediately before the introduction of surfactant-BL (75 mg in a vial), dilute 2.5 ml of a 0.9% solution for injection. To do this, 2.5 ml of warm (37 ° C) 0.9% sodium chloride solution is added to the vial and the vial is allowed to stand for 2-3 minutes, then the suspension is gently mixed in the vial without shaking, the emulsion is drawn into the syringe with a thin needle, poured back into the vial along the wall several (4-5) times until complete uniform emulsification, avoiding foam formation. The bottle must not be shaken. After dilution, a milky emulsion is formed, it should not contain flakes or solid particles.

The introduction of the drug.

Microjet introduction. The child is pre-intubated and sputum is aspirated from the respiratory tract and endotracheal tube (ET). It is important to correctly locate and match the size of the ET to the diameter of the trachea, since with a large leakage of the emulsion past the ET (more than 25% on the respiratory monitor or auscultation), as well as with selective intubation into the right bronchus or high standing of the ET, the effectiveness of therapy with surfactant-BL is significantly reduced or depreciated. Next, the respiratory cycle of the newborn is synchronized with the mode of operation of the ventilator using sedatives - or diazepam, and in cases of severe hypoxia - narcotic analgesics. The prepared surfactant-BL emulsion is injected through a catheter inserted through an adapter with an additional lateral entry into the ET so that the lower end of the catheter does not reach the lower edge of the endotracheal tube by 0.5 cm. without depressurization of the breathing circuit. For uniform distribution of the surfactant in different parts of the lungs during the administration of the drug, if the severity of the child's condition allows, the first half of the dose is administered with the child on the left side, and the second half of the dose with the child on the right side. Finishing the introduction, 0.5 ml of 0.9% sodium chloride solution is drawn into the syringe and the introduction is continued to displace the remnants of the drug from the catheter. It is advisable not to sanitize the trachea for 2-3 hours after the administration of surfactant-BL.

Aerosol administration surfactant-BL carried out using an alveolar nebulizer included in the circuit of the ventilator synchronized with inspiration, as close as possible to the endotracheal tube to reduce drug losses. If this is not possible, it is preferable to use a microfluidic or bolus route of administration. Ultrasonic nebulizers cannot be used to obtain an aerosol and administer the drug, since the surfactant-BL is destroyed when the emulsion is treated with ultrasound. Compressor-type nebulizers must be used.

Bolus administration of surfactant-BL. Before the introduction of the drug, as well as with microjet administration, stabilization of central hemodynamics, correction of hypoglycemia, hypothermia and metabolic acidosis are carried out. X-ray confirmation of RDS is desirable. The child is intubated and sputum is aspirated from the respiratory tract and ET. Immediately before the introduction of surfactant-BL, the child can be temporarily transferred to manual ventilation with a self-expanding bag of the Ambu type. If necessary, the child is sedated with sodium hydroxybutyrate or diazepam. The prepared emulsion of surfactant-BL (30 mg/ml) is used at a dose of 50 mg/kg in a volume of 1.7 ml/kg. For example, a child weighing 1500 g is given 75 mg (50 mg/kg) in a volume of 2.5 ml. The drug is administered as a bolus over 1-2 minutes through a catheter placed in the endotracheal tube, while the child is carefully turned to the left side and the first half of the dose is administered, then turned to the right side and the second half of the dose is administered. The introduction is completed with forced manual ventilation for 1-2 minutes with an inhaled oxygen concentration equal to the initial value on the ventilator or manual ventilation using a self-expanding Ambu-type bag. It is obligatory to control the saturation of hemoglobin with oxygen, it is desirable to control the content of blood gases before and after the administration of surfactant-BL.

Next, the child is transferred to assisted ventilation or forced ventilation and the ventilation parameters are corrected. Bolus injection of the drug allows you to quickly bring the therapeutic dose into the alveolar space and avoid the inconvenience and adverse reactions of microfluidic injection.

Full-term newborns weighing more than 2.5 kg with a severe form of RDS of the second type, due to the large volume of the emulsion, half the dose is administered as a bolus, and the second half of the dose is microfluidized.

Bolus administration can also be used for prophylactic administration of surfactant-BL. In the future, depending on the initial state and the effectiveness of therapy, the child can be extubated with a possible transfer to a non-invasive method of ventilation of the lungs with the maintenance of a constant positive airway pressure (CPAP).

2. Treatment of acute lung injury syndrome and acute respiratory distress syndrome in adults.

Treatment with surfactant-BL is performed by endobronchial bolus administration using a fiberoptic bronchoscope. The drug is administered at a dose of 12 mg/kg/day. The dose is divided into two injections of 6 mg / kg every 12-16 hours. Multiple injections of the drug (4-6 injections) may be required until a stable improvement in gas exchange (an increase in the oxygenation index of more than 300 mmHg), an increase in airiness of the lungs on chest X-ray and the possibility of IVL with FiO 2< 0.4.

In most cases, the duration of the course of application of surfactant-BL does not exceed two days. In 10-20% of patients, the use of the drug is not accompanied by normalization of gas exchange, especially in those patients who are given the drug against the background of advanced multiple organ failure (MOF). If within two days there is no improvement in oxygenation, the administration of the drug is stopped.

The most important factor in the effectiveness of the use of surfactant-BL in the complex treatment of SOPL / ARDS is the time of the start of the drug administration. It must be started within the first day (better than the first hours) from the moment the oxygenation index falls below 250 mm Hg.

The drug can also be administered prophylactically in case of a threat of development of SOPL / ARDS in patients with chronic lung diseases, including chronic obstructive pulmonary disease (COPD), as well as before extended chest operations at a dose of 6 mg / kg per day, 3 mg / day. kg after 12 hours

Emulsion preparation. Before the introduction of surfactant-BL (75 mg in a vial), dilute in the same way as for newborns in 2.5 ml of a 0.9% sodium chloride solution. The resulting emulsion, which should not contain flakes or solid particles, is further diluted with 0.9% sodium chloride solution to 5 ml (15 mg in 1 ml).

Endobronchial administration is the best way to deliver the drug. The introduction of surfactant-BL is preceded by a thorough sanitation bronchoscopy, carried out according to the standard method. At the end of this procedure, an equal amount of the drug emulsion is injected into each lung. The best effect is achieved with the introduction of the emulsion into each segmental bronchus. The volume of the injected emulsion is determined by the dose of the drug.

The most effective way to use surfactant-BL in the treatment of SOPL/ARDS is a combination of endobronchial administration of the drug and the maneuver of "opening" the lungs, moreover, the segmental administration of the drug is carried out immediately before the maneuver of "opening" the lungs.

After the administration of the drug for 2-3 hours, it is necessary to refrain from sanitation of the bronchi and not to use drugs that enhance sputum separation. The use of intratracheal instillation is indicated if bronchoscopy is not possible. The emulsion is prepared as described above. Before the introduction of the drug, it is necessary to carry out a thorough sanitation of the tracheobronchial tree, after taking measures to improve sputum drainage (vibration massage, postural therapy). The emulsion is administered through a catheter inserted into the endotracheal tube so that the end of the catheter is located below the opening of the endotracheal tube, but always above the carina of the trachea. The emulsion must be administered in two doses, dividing the dose in half, with an interval of 10 minutes. In this case, also after instillation, the lung “opening” maneuver can be performed.

Treatment of pulmonary tuberculosis is carried out by multiple inhalations of the drug surfactant-BL as part of complex therapy against the background of a fully developed therapy with anti-tuberculosis drugs (ATPs), that is, when 4-6 anti-TB drugs are selected empirically or based on data on the drug sensitivity of the pathogen, which in the prescribed dose and combination are well tolerated by patients. Only then the patient is prescribed an emulsion of surfactant-BL in inhalation at a dose of 25 mg per injection:

- the first 2 weeks - 5 times a week;

- the next 6 weeks - 3 times a week (in 1-2 days). The duration of the course is 8 weeks - 28 inhalations, the total dose of surfactant-BL is 700 mg. During the course of treatment with surfactant-BL, according to indications, anti-tuberculosis drugs can be canceled (replaced). Chemotherapy continues after completion of the course of treatment with surfactant-BL.

Emulsion preparation: before use, surfactant-BL (75 mg in a vial) is diluted in the same way as for newborns in 2.5 ml of 0.9% sodium chloride solution. The resulting emulsion, which should not contain flakes or solid particles, is further diluted with 0.9% sodium chloride solution to 6 ml (12.5 mg in 1 ml). Next, 2.0 ml of the resulting emulsion is transferred to the nebulizer chamber and another 3.0 ml of 0.9% sodium chloride solution is added to it, stirring gently. Thus, 25 mg of surfactant-BL in 5.0 ml of emulsion is in the nebulizer chamber. This is the dose for one inhalation per patient. Thus, 1 bottle of surfactant-BL contains three doses for inhalation for three patients. The emulsion prepared for inhalation should be used within 12 hours when stored at a temperature of +4°C - +8°C (do not freeze the emulsion). Before use, the emulsion must be carefully mixed and warmed to 36°C-37°C.

Inhalation administration: 5.0 ml of the resulting emulsion (25 mg) in the nebulizer chamber is used for inhalation. Inhalations are carried out 1.5-2 hours before or 1.5-2 hours after a meal. For inhalation, compressor-type inhalers are used, for example, "Boreal" from Flaem Nuova, Italy or "Pari Boy SX" from Pari GmbH, Germany, or their analogues, which allow spraying small volumes of drugs and are equipped with an economizer device that allows you to stop the supply of the drug during expiratory time, which significantly reduces the loss of the drug. The use of an economizer is extremely important so that the patient is given a therapeutic dose of the drug without loss (25 mg). If, due to the severity of the patient's condition, the entire volume of the emulsion cannot be used, breaks should be taken for 15-20 minutes, and then inhalation should be continued. If there is a large amount of sputum before inhalation, it should be carefully coughed up. If there is evidence of broncho-obstruction 30 minutes before inhalation of the surfactant-BL emulsion, it is necessary to first inhale a beta 2-adrenergic agonist (at the doctor's choice), which reduces bronchial obstruction. It is necessary to use only compressor, and not ultrasonic nebulizers, since the surfactant-BL is destroyed when the emulsion is sonicated. Before the introduction of the drug, it is necessary to carry out a thorough sanitation of the tracheobronchial tree, after taking measures to improve sputum drainage: vibromassage, postural therapy and mucolytics, which must be prescribed 3-5 days before the start of therapy with surfactant-BL in the absence of contraindications to their appointment.

Side effects

1. With respiratory distress syndrome (RDS) of newborns:

With microjet and bolus administration of surfactant-BL, obturation with the ET preparation or emulsion regurgitation may occur. This can occur if the section of the instruction "preparation of the emulsion" is not followed (use of 0.9% sodium chloride solution at a temperature below 37 ° C, inhomogeneous emulsion), with a rigid chest, high activity of the child, accompanied by coughing, crying, discrepancy between the size of the ET and the inner diameter of the trachea, selective intubation, the introduction of surfactant-BL into one bronchus, or a combination of these factors. If all these factors are excluded or eliminated, then in this case it is necessary to briefly increase the peak inspiratory pressure (P peak) for a child on mechanical ventilation. If the child shows signs of airway obstruction when he is not on a mechanical breath, it is necessary to take several respiratory cycles using manual ventilation with increased pressure to move the drug deeper. When using the aerosol method of drug administration, such phenomena are not observed. Mandatory physical and instrumental control of hemodynamics and saturation of hemoglobin with oxygen (SaO 2). Bleeding in the lungs may occur, usually within 1-2 days after administration of the drug in premature infants of low or extremely low birth weight. Prevention of pulmonary bleeding consists in early diagnosis and adequate treatment of a functioning ductus arteriosus. With a rapid and significant increase in the partial tension of oxygen in the blood, retinopathy can develop. The concentration of oxygen in the inhaled mixture should be reduced as quickly as possible to a safe value, maintaining the target saturation of hemoglobin with oxygen in the range of 86-93%. In some newborns, short-term hyperemia of the skin is noted, requiring an assessment of the adequacy of mechanical ventilation parameters to exclude hypoventilation due to transient airway obstruction. In the first minutes after microfluidic and bolus administration of surfactant-BL, coarse bubbling rales on inspiration can be heard in the lungs. Within 2-3 hours after the use of surfactant-BL, one should refrain from sanitation of the bronchi. In children with intrapartum respiratory tract infection, the administration of the drug may increase sputum separation due to the activation of mucociliary clearance, which may require their rehabilitation at an earlier date.

2. For ARDS and SOPL in adults:

To date, no specific adverse reactions have been observed in the treatment of surfactant-BL with SOPL and ARDS of various origins. In the case of using the endobronchial route of administration, a deterioration in gas exchange lasting from 10 to 60 minutes is possible, associated with the bronchoscopy procedure itself. With a decrease in arterial hemoglobin saturation with oxygen (SaO 2) below 90%, it is necessary to temporarily increase the positive end-expiratory pressure (PEEP) and the oxygen concentration in the gas mixture supplied to the patient (FiO 2). In the case of a combination of endobronchial administration of surfactant-BL and the maneuver of "opening" the lungs, no deterioration in gas exchange was observed.

3. With pulmonary tuberculosis:

In the treatment of pulmonary tuberculosis in 60-70% of patients after 3-5 inhalations there is a significant increase in the volume of sputum discharge or sputum appears, which was not there before the start of inhalations. The effect of "easy sputum discharge" is also noted, while the intensity and pain of coughing is significantly reduced, and exercise tolerance is improved. These objective changes and subjective sensations are a manifestation of the direct action of surfactant-BL and are not side reactions.

Overdose

Surfactant-BL when administered intravenously, intraperitoneally and subcutaneously to mice at a dose of 600 mg/kg and when administered by inhalation to rats at a dose of 400 mg/kg does not cause changes in the behavior and condition of animals. In no case was the death of animals. In clinical use, cases of overdose were not observed.

drug interaction

Surfactant-BL cannot be used in conjunction with expectorants, as the latter will remove the administered drug along with sputum.

special instructions

The use of surfactant-BL for the treatment of critical conditions of newborns and adults is possible only in a specialized intensive care unit, and for the treatment of pulmonary tuberculosis - in a hospital and a specialized anti-tuberculosis dispensary.

1. Treatment of respiratory distress syndrome (RDS) in newborns.

Before the introduction of surfactant-BL, mandatory stabilization of central hemodynamics and correction of metabolic acidosis, hypoglycemia and hypothermia are necessary, which adversely affect the effectiveness of the drug. X-ray confirmation of RDS is desirable.

2. Treatment of SOPL and ARDS.

The drug should be used as part of a comprehensive treatment of SOPL and ARDS, including rational respiratory support, antibiotic therapy, maintaining adequate hemodynamics and water and electrolyte balance.

The question of the use of surfactant-BL in OOP, combined with severe multiple organ failure (MOF), should be decided individually, depending on the possibility of correcting other components of MOF.

3. Treatment of pulmonary tuberculosis.

In rare cases, after 2-3 inhalations, hemoptysis may occur. In this case, it is necessary to interrupt the course of treatment with surfactant-BL and continue it after 3-5 days.

Incompatibility with any anti-tuberculosis drug surfactant-BL was not noted. There are no data on interactions with aerosolized anti-tuberculosis drugs, so this combination should be avoided.

Influence on the ability to drive vehicles and control mechanisms

Carrying out therapy with surfactant-BL does not affect the ability to drive vehicles.

Pregnancy and lactation

It is used according to vital indications in the treatment of ARDS.

Application in childhood

The drug is used to treat respiratory distress syndrome (RDS) in newborns weighing more than 800 g at birth. Contraindicated in:

Intraventricular hemorrhages III-IV degree;

- air leakage syndrome (pneumothorax, pneumomediastinum, interstitial emphysema);

- malformations incompatible with life;

- DIC-syndrome with symptoms of pulmonary bleeding;

Contraindicated in children under 18 years of age for the treatment of ARDS, SOPL and pulmonary tuberculosis, since clinical trials in this age group have not been conducted and doses have not been determined.

Terms of dispensing from pharmacies

By prescription. Used in a hospital setting.

Terms and conditions of storage

In a place protected from light, at a temperature not exceeding minus 5 ° C. Keep out of the reach of children. Expiration date - 1 year.

The administration of surfactant-BL is carried out by endotracheal spraying to newborns with respiratory distress syndrome, who are undergoing mechanical ventilation. The introduction of the drug is carried out through the endotracheal tube micro-stream through the side adapter or inhalation in the form of an aerosol using an alveolar nebulizer.

With microjet injection, the emulsion of surfactant-BL is injected slowly (dose of 75 mg / mg in a volume of 2.5 ml) for 60-90 minutes, and in the form of an aerosol through an alveolar nebulizer - the same dose for 2-3 hours. The drug is administered 1 or 2 times at a dose of 75 mg/kg as a 3% emulsion (30 mg in 1 ml of 0.9% NaCl solution). In the case of severe respiratory distress syndrome (respiratory distress syndrome type 2, due to mixed etiology - immaturity of the lungs and the presence of infection) - 100 mg / kg. Repeatedly the drug is administered with an interval of 6-10 hours, if necessary - after a few days.

Emulsion preparation. Immediately before the introduction of surfactant-BL - 75 mg of lyophilized powder in a vial is diluted with 2.5 ml of 0.9% NaCl solution for injection. For this, 2.5 ml of a 0.9% NaCl solution (room temperature) is added to the vial. The bottle must not be shaken. After 1-2 minutes, the suspension in the vial is gently mixed in a circular motion without shaking, it is drawn into the syringe with a needle for intravenous injection and poured back into the vial along the wall several times (2-3), the needle is changed to a thin one (needle for intravenous injection). m injections N 2) and again repeat the procedure 2-3 times until complete emulsification, avoiding the formation of foam. After dilution, it forms milky emulsion, it should not contain flakes or solid particles. The bottle is heated to 30-34 degrees C, but not more than 36 degrees C.

The introduction of the drug. The child is pre-intubated and immediately prior to the introduction of surfactant-BL, sputum is aspirated from the respiratory tract and endotracheal tube. Through an adapter with an additional side entrance to the trachea, using a syringe pump or drip for 60-90 minutes, the prepared preparation is infused. To evenly distribute the surfactant in different parts of the lungs during the infusion of the drug to the child, if the severity of the condition allows, carefully change the position of the body for several minutes: turn to the right-left side, raise the head or foot end. The procedure is completed with several forced breaths of the patient. It is advisable not to debride the trachea for several hours after the administration of the surfactant.

Aerosol administration of surfactant-BL is carried out using a nebulizer included in the circuit of the ventilator as close as possible to the endotracheal tube to reduce drug losses. It is also desirable to use ventilators that allow the surfactant aerosol to be delivered synchronously with a breath. An aerosol of the surfactant-BL preparation cannot be created using an ultrasound device (nebulizer or inhaler), because the surfactant is destroyed by ultrasonication of the emulsion. Only non-US alveolar nebulizers should be used for aerosol production and drug administration.

You should consult your doctor before using SURFACTANT-BL. These instructions for use are for informational purposes only. For more complete information please refer to the manufacturer's instructions.

Clinical and pharmacological group

12.062 (Drug for the treatment of neonatal respiratory distress syndrome)

pharmachologic effect

Highly purified natural surfactant derived from cattle.

A complex of substances from a mixture of phospholipids and surfactant-associated proteins; reduces the surface tension of the pulmonary alveoli, preventing their collapse and the development of atelectasis. Restores the content of phospholipids on the surface of the alveolar epithelium, stimulates the involvement of additional sections of the lung parenchyma in breathing; promotes the removal of toxic substances from the alveolar space along with sputum. Increases the activity of alveolar macrophages and inhibits the expression and excretion of cytokines by polymorphonuclear leukocytes; stimulates the synthesis of endogenous surfactant by type II alveolocytes and protects the alveolar epithelium from damage by chemical and physical agents.

When inhaled, it does not affect the cardiovascular system, does not have a local irritating effect, does not affect the composition of the blood and hematopoiesis, with the exception of short-term (1 day after stopping the drug at doses of 200 and 400 mg/kg) lymphopenia and granulocytosis due to an increase in the number of rod- and segmented neutrophils. In the future, the composition of peripheral blood is completely normalized. Does not affect the biochemical parameters of blood, urine and the blood coagulation system, does not cause pathological changes in the functions and structure of internal organs.

In premature newborns with respiratory distress syndrome, endotracheal administration of the drug during mechanical ventilation improves gas exchange in the lung tissue. 30-120 minutes after administration, the signs of hypoxemia decrease, the partial pressure of oxygen in the arterial blood and the saturation of Hb with oxygen increase, and hypercapnia (partial pressure of carbon dioxide) decreases, which allows you to switch to more physiological parameters of mechanical ventilation (reduce toxic oxygen concentrations in the inhaled gas). mixtures up to 40%, as well as to reduce the total duration of apparatus breathing). Significantly reduces mortality and morbidity in newborns with respiratory distress syndrome.

Pharmacokinetics

After 6-8 hours after a single intratracheal administration, the concentration of surfactant in the lungs decreases and reaches the initial value after 12 hours.

The drug is completely utilized in the lungs and does not accumulate in the body.

SURFACTANT-BL: DOSAGE

Respiratory distress syndrome of newborns on mechanical ventilation: endotracheally (by spraying micro-stream through the endotracheal tube and side adapter) and inhalation (in the form of an aerosol using a bronchoalveolar nebulizer). Micro-jet is injected slowly - a dose of 75 mg in a volume of 2.5 ml for 60-90 minutes, in the form of an aerosol through an alveolar nebulizer - at the same dose for 2-3 hours. The drug is administered 1-2 times at a dose of 75 mg / kg in the form 3% emulsion (30 mg in 1 ml of 0.9% solution). In the case of severe respiratory distress syndrome (type 2, due to mixed etiology - immaturity of the lungs and the presence of infections) - 100 mg / kg. Repeatedly the drug is administered with an interval of 6-10 hours, if necessary - after a few days.

Immediately before the introduction of 75 mg of lyophilized powder, dilute with 2.5 ml of a 0.9% solution of sodium chloride for injection. To do this, 2.5 ml of warm (36 ° C) 0.9% sodium chloride solution is added to the vial and the vial is allowed to stand for 2-3 minutes, then the suspension is gently mixed in the vial without shaking, the emulsion is drawn into the syringe with a thin needle, poured back into the vial along the wall several times (4-5) until complete uniform emulsification, avoiding foam formation. The bottle must not be shaken. After dilution, a milky emulsion is formed, devoid of flakes or solid particles.

The introduction of the drug

The newborn is preliminarily intubated and immediately before the introduction of Surfactant-BL, sputum is aspirated from the respiratory tract and endotracheal tube. Through an adapter with an additional side entrance to the trachea using a syringe pump or drip, for 60-90 minutes, the prepared drug is infused. To evenly distribute the surfactant in different parts of the lungs, during the infusion of the drug to the child, if the severity of the condition allows, carefully change the position of the body for several minutes: turn to the right-left side, raise the head end. The procedure is completed with several forced breaths of the patient. It is advisable not to debride the trachea for several hours after the administration of the surfactant.

Aerosol administration is carried out using a nebulizer included in the ventilator circuit as close as possible to the endotracheal tube to reduce drug losses. It is desirable to use devices that allow the surfactant aerosol to be delivered synchronously with inspiration. To obtain an aerosol and administer the drug, it is necessary to use only non-ultrasound bronchoalveolar nebulizers, because. the surfactant is destroyed by ultrasonication of the emulsion.

Acute lung injury syndrome and respiratory distress syndrome in adults: endobronchially, using a fiberoptic bronchoscope, at a dose of 12 mg/kg of body weight per day, divided into 2 injections of 6 mg/kg, performed after 12-16 hours. The drug is administered as 1.5 % emulsion (15 mg in 1 ml of 0.9% sodium chloride solution). Multiple injections of the drug (4-6 injections) may be required until a stable improvement in gas exchange (up to an increase in the oxygenation index of more than 300 mm Hg), radiographic picture and the possibility of mechanical ventilation with FiO2 less than 40%.

In most cases, the duration of the course of application of Surfactant-BL does not exceed two days. In 10-20% of patients, the administration of the drug is not accompanied by normalization of gas exchange (especially in patients with severe multiple organ failure). If within 2 days there is no improvement in oxygenation, the administration of the drug is stopped.

Rules for preparing an emulsion

75 mg of lyophilized powder is diluted in the same way as for newborns, in 2.5 ml of 0.9% sodium chloride solution. The resulting emulsion is diluted with an additional 0.9% sodium chloride solution to 5 ml, obtaining a 1.5% emulsion of the drug (15 mg in 1 ml of a 0.9% sodium chloride solution).

The introduction of the drug

Endobronchial administration of the drug is preceded by a thorough rehabilitation bronchoscopy, carried out according to the standard method, at the end of which an equal amount of the drug emulsion is injected into each lung. Best effect achieved with the introduction of the emulsion into each segmental bronchus. The volume of the injected emulsion is determined by the dose of the drug.

Intratracheal instillation is indicated in the absence of the possibility of bronchoscopy. The emulsion is prepared as described above. Before the introduction of the drug, it is necessary to carry out a thorough sanitation of the tracheobronchial tree, after taking measures to improve sputum drainage (vibration massage, postural therapy, mucolytics in the absence of contraindications to their appointment). The emulsion is administered through a catheter inserted into the endotracheal tube so that the end of the catheter is located below the opening of the endotracheal tube, but always above the carina of the trachea. The emulsion must be administered in 2 doses (dividing the dose in half), with an interval of 10 minutes.

For tuberculosis (after the selection of multicomponent antimycobacterial therapy) - inhalation before or 1.5-2 hours after a meal at a dose of 25 mg 5 times a week for the first 2 weeks, then 3 times a week for the next 6 weeks. Course duration - 8 weeks, 28 inhalations.

SURFACTANT-BL: SIDE EFFECTS

Newborns: short-term reflux (retrograde release of the drug emulsion), which is eliminated by several forced breaths of air or an oxygen-air mixture (when using the aerosol method of administration, such phenomena are not observed); bleeding in the lungs 1-2 days after administration in premature infants with low birth weight; retinopathy - with a rapid and significant increase in the partial tension of oxygen in the blood; short-term hyperemia of the skin (requires an assessment of the adequacy of mechanical ventilation parameters to exclude hypoventilation due to transient airway obstruction).

Adults: No specific side effects have been identified. With endobronchial administration - deterioration in gas exchange lasting 10-60 minutes, associated with the actual procedure of bronchoscopy.

Indications

• respiratory distress syndrome of newborns.
• acute lung injury syndrome and respiratory distress syndrome in adults (incl.
• against the background of multiple trauma,
• sepsis
• aspiration of gastric contents,
• endogenous intoxication,
• massive blood loss and multiple blood transfusions,
• the use of AIC during cardiac surgery,
• severe pneumonia).

Contraindications

• intraventricular hemorrhages III-IV st.
• in newborns;
• pneumothorax;
• pneumomediastinum;
• interstitial emphysema;
• gas exchange disorders
• associated with LV insufficiency and bronchial obstruction.

special instructions

The use of Surfactant-BL is possible only in a specialized intensive care unit.

newborns

An important factor in the effectiveness of the use of Surfactant-BL in the complex treatment of neonatal respiratory distress syndrome is the timely initiation of therapy, during the first day (better than the first hours) after birth. The use of high-frequency oscillatory ventilation significantly increases the efficiency and reduces the frequency of adverse reactions.

Before the introduction of Surfactant-BL, it is necessary to stabilize the central hemodynamics and maintain adequate diuresis. Spontaneous breathing of the child is unacceptable. In the event of the presence or occurrence of spontaneous breathing during the administration of the drug, it is necessary to correct the ventilation parameters or use drug synchronization with the ventilator. It is necessary to check the correct location (depth of standing) of the endotracheal tube.

After administration of the drug, it is possible rapid rise partial tension of oxygen and a decrease in the partial tension of carbon dioxide, as well as CBS of the blood. In this regard, it is necessary to regularly monitor these indicators. You should simultaneously change the parameters of mechanical ventilation in accordance with the degree of oxygenation of the blood to reduce the risk of developing hyperoxia. Before the introduction of the drug, it is necessary to correct metabolic acidosis (reduces the effectiveness of the drug). In the first minutes after the microjet injection of Surfactant-BL, coarse bubbling rales on inspiration can be heard in the lungs. Within 4-6 hours after administration, one should refrain from draining the contents of the bronchi. In children with intranatal respiratory tract infection, the administration of the drug may increase sputum separation due to the activation of mucociliary clearance, which requires their rehabilitation at an earlier date.

Prevention of pulmonary bleeding during the administration of the drug consists in early diagnosis and adequate treatment of a functioning ductus arteriosus.

adults

Therapy must be started within the first day (better than the first hours) from the moment the oxygenation index falls below 200 mm Hg. The question of the use of Surfactant-BL in the syndrome of acute lung injury, combined with severe multiple organ failure, should be decided individually, depending on the possibility of correcting other components of multiple organ failure.

In the event of a decrease in the level of Hb oxygenation after the administration of the drug by more than 10%, it is necessary to temporarily increase the level of positive end-expiratory pressure and FiO2.