Surfactant for premature newborns: what is it, role, application, properties. Pulmonary surfactant Summary of the physiological role of surfactant in normal and acute lung injury

Biophysical functions

• Prevention of collapse of the alveoli and lungs during exhalation
• Support for inspiratory lung opening
• Prevention of pulmonary edema
• Stabilization and support of open small airways
• Improved mucociliary transport
• Removal of small particles and dead cells from the alveoli into the airways

Immunological, non-biophysical functions

• Phospholipids inhibit proliferation, immunoglobulin production, and lymphocyte cytotoxicity
• Phospholipids inhibit cytokines secreted by macrophages
• SB-A and SB-D promote phagocytosis, chemotaxis and oxidative damage to macrophages
• Neutralization of endogenous mediators SB-A and SB-D, which opsonize various microorganisms
• Capture of bacterial toxins SB-A and SB-D

Changes in the surfactant system in various diseases

Surfactant inhibition

The functions of a surfactant can be disturbed by many substances: blood plasma proteins, hemoglobin, phospholipases, bilirubin, meconium, fatty acids, cholesterol, etc. Oxygen and its compounds, inhalation of small particles containing silicon, nickel, cadmium, various organic compounds have a toxic effect on the surfactant , gases (eg, chloroform, halothane), numerous drugs. The relatively lower content of surfactant proteins in preterm infants compared to adults makes their surfactant system more sensitive to various damaging factors.

Primary surfactant deficiency

The importance of the surfactant system in the pathophysiology of neonatal RDS was discovered by Avery and Mead. The conclusion that the cause of RDS is a primary deficiency of surfactant due to the immaturity of type II pneumocytes was later confirmed by a huge number of clinical studies. The most pronounced features of the surfactant system in newborns with RDS: a decrease in the total concentration of all phospholipids, the relative concentration of phosphatidylglycerol, dipalmitoylphosphatidylcholine, SB-A. Surfactant begins to be synthesized by type II pneumocytes from approximately the 22nd week of gestation.

The amount of surfactant in these cells and the number of pneumocytes increase with gestational age. Newborns with RDS have a pool of surfactant of about 10 mg/kg, while in healthy newborns it is approximately 100 mg/kg.

Congenital disorders of surfactant synthesis

Currently, RDS is considered as a multifactorial disease, which is associated not only with the primary deficiency of surfactant. The main methods for diagnosing congenital disorders of surfactant synthesis are genetic and immunohistochemical analysis, lung biopsy. Genetic changes that disrupt the metabolism of surfactant and lead to a decrease in oxygenation are the causes of severe DN in the neonatal period. The first publications describing diseases associated with them date back to the beginning of the 21st century. Mutations in the genes responsible for the synthesis of SB-B, SB-C and the ABCAZ protein, which transports phosphatidylcholine and phosphatidylglycerol into lamellar bodies, which is necessary to maintain surfactant homeostasis, were identified.

Congenital SB-B deficiency is an autosomal recessive disease first described in 1993. To date, about 30-40 mutations of the gene responsible for the synthesis of this protein have been identified, which leads to a significant decrease in its production. The mutation is diagnosed with a frequency of 1 per 1000-3000 people, but clinical manifestations are extremely rare and amount to 1 per 1,000,000 live births. The disease is more common in full-term children, manifested by severe DN, complicated by pulmonary hypertension syndrome, which leads to death.

A lung disease associated with a mutation in the gene responsible for the synthesis of SB-C, and transmitted in an autosomal dominant mode of inheritance, was described by Nogee. He discovered a genetic anomaly associated with impaired synthesis of SB-C, which manifested itself as an interstitial lung disease in several generations of the same family. In 2002, another mutation of the gene responsible for the synthesis of SB-C was diagnosed. Over 40 mutations have been identified so far. The first clinical symptoms and the severity of the course of the disease are extremely variable. In 10-15% of cases, it can manifest during the newborn period. In other cases, the disease manifests itself in the first 6 months of life, which is considered a favorable prognostic sign.

A congenital disorder of ABCAZ protein synthesis, inherited in an autosomal recessive manner, is a less studied, but the most common disease compared to the above. Recently, another cause of fatal surfactant deficiency in term infants has been found - a mutation of the ABCAZ gene, which is probably responsible for the maturation of lamellar bodies and the production of surfactant. The disease was first diagnosed in 2004. Currently, more than 150 mutations associated with impaired metabolism of this protein have been identified. The frequency of occurrence in the population has not been studied. Clinically, the disease proceeds as severe RDS. Pathogenetic therapy for this group of diseases has not yet been developed. In most cases, surfactant replacement therapy is performed, but the therapeutic effect is short-lived or absent. The only treatment is lung transplantation, after which the complication rate remains high. The need for its implementation is determined by the severity of DN. In most cases, the prognosis for life is unfavorable and depends on the severity of the deficiency of one of the surfactant proteins and / or ABCAZ, endogenous surfactant components, as well as the diagnostic capabilities of the clinic.

Meconium aspiration

In the presence of meconium, the phospholipid structure of the surfactant changes, its ability to reduce surface tension decreases, and a decrease in the concentration of SB-A and SB-B, LA-fraction was noted. Herting et al. compared the resistance of various surfactant preparations to the inhibitory effect of meconium in vitro. Newer synthetic drugs (Venticute, Surfaxin) proved to be more stable than modified natural ones (such as Curosurf, Alveofact and Survanta).

Bronchopulmonary dysplasia

In a newborn recovering from RDS, the amount of phosphatidylglycerol in the surfactant increases. In RDS progressing to BPD, this is less pronounced due to possible damage to type II alveolocytes, which has been noted in preterm baboons recovering from RDS. In these animals, the pool of alveolar surfactant after administration at birth and an additional 6 days on a ventilator was approximately 30 mg/kg and did not increase after the second dose.

congenital diaphragmatic hernia

The main characteristics of this disease are pulmonary hypoplasia and pulmonary hypertension. Data on the deficiency of the surfactant system in CDH are contradictory.

Pulmonary bleeding

Pulmonary bleeding is one of the causes of severe DN in newborns and develops in 3-5% of patients with RDS. Hemoglobin, plasma proteins, cell membrane lipids are surfactant inhibitors.

Clinical use of surfactant

Respiratory distress syndrome

Physiological consequences of the administration of surfactant to neonates with ARDS:

• increase in FRC;
• increased oxygenation;
• decrease in PVR;
• improvement in lung compliance.

Studies have shown a reduction in neonatal mortality and a reduction in the incidence of pulmonary barotrauma (pneumothorax and PIE) in children who were administered surfactant. Basically 2 strategies for using surfactant were tested. The first is use shortly after birth to prevent RDS and mechanical ventilation lung injury ("prophylactic use"). The second - at the age of 2-24 hours of life, after the diagnosis of RDS ("therapeutic use").

In addition to prophylactic use, the so-called early (before the age of less than 2 hours of life) is described, and the analysis of these studies also showed better results than with delayed administration: a decrease in lung barotrauma, the risk of death and the incidence of CLD.

As the clinical use of nCPAP expands, experience has shown that many newborns, even very short gestational ages, will not need mechanical ventilation and surfactant. Retrospective clinical studies have demonstrated a reduction in surfactant use in this population without an increase in BPD, mortality, or other complications of prematurity. Based on these data, large international studies have been conducted comparing early nCPAP with intubation and “prophylactic” administration of surfactant: COIN, CURPAP and SUPPORT. An analysis of these studies showed that routine early use of nCPAP and administration of surfactant only after ventilator transition reduced the risk of CLD or death compared with intubation and prophylactic surfactant administration. But if babies weighing less than 1300 g need to be intubated immediately after birth for resuscitation or due to severe DN, they should receive surfactant as soon as possible, more prophylactically.

Although the majority of newborns show a persistent clinical effect after the introduction of surfactant, about 20-30% of patients are resistant to therapy. These newborns may have other conditions besides RDS: pneumonia, pulmonary hypoplasia, PLH, ARDS ("shock lung"), or congenital heart disease. A large volume of fluid administered to the patient, especially colloidal solutions, high FiC>2, low PEEP, high TO, extreme prematurity can also reduce the effectiveness of the surfactant.

The most serious complication that occurs during treatment with surfactant is pulmonary hemorrhage. It occurs with the introduction of both synthetic and natural surfactant preparations. It is observed mainly in the smallest newborns. The appearance of pulmonary hemorrhage is associated with a functioning PDA and an increase in pulmonary blood flow after surfactant administration.

Perhaps an adequate selection of PEEP or the use of HF ventilation before the introduction of surfactant will increase its effectiveness and reduce the rate of inactivation. The use of antenatal corticosteroids increases the effectiveness of exogenous surfactant and reduces the need for repeated doses.

Currently, there is no evidence that exogenous surfactant inhibits the synthesis and secretion of endogenous and probably even has some beneficial effect on lung maturation.

Meconium aspiration

Meconium aspiration is one of the most severe respiratory illnesses in term infants. Surfactant therapy may save the life of some children with meconium aspiration. The American Academy of Pediatrics recommends the use of a surfactant for meconium aspiration.

Another method of using surfactant for aspiration is to lavage the tracheobronchial tree with diluted surfactant.

congenital pneumonia

Several clinical studies have shown improvements in lung gas exchange without associated complications. The study by Lotze et al. was aimed at identifying the benefits of surfactant in the treatment of term infants with DN, including patients with sepsis with pneumonia. Surfactant therapy increased oxygenation and reduced the need for ECMO. Recommended by the American Academy of Pediatrics.

Pulmonary bleeding

Several observational studies have shown an increase in oxygenation in children with idiopathic pulmonary hemorrhage or in pulmonary hemorrhage in patients with RDS and SAM. It is not yet the standard of care.

adult respiratory distress syndrome

The incidence of ARDS requiring mechanical ventilation in full-term and near-term infants is estimated at 7.2 per 1000 live births. A recent randomized trial of surfactant efficacy in children from birth to 18 years of age with ARDS showed no effect compared with placebo.

Bronchopulmonary dysplasia

Several studies have shown a temporary improvement in respiratory function after treatment, an improvement in the composition and function of endogenous surfactant. The use of a synthetic peptide-containing surfactant (Lucinactant) for the prevention of BPD did not affect its frequency. Of note, children in the treatment group were less likely to be hospitalized for respiratory problems after being discharged home (28.3% vs 51.1%; P=0.03).

Natural vs artificial

Both types of surfactant preparations have proven clinically effective in the treatment of RDS, but natural surfactant preparations are preferred, probably due to the content of natural surfactant proteins in it. Natural surfactants are characterized by a faster onset of action, which allows you to reduce the parameters of IVL and FO 2 earlier.

The composition of the synthetic drug lucinactant (Surfaxin) includes a combination of amino acids with activity similar to SB-B. Moya and Sinha compared its effectiveness with Exosurf, Survanta and Curosurf in international randomized multicenter trials. Lucinactant was in no way inferior to these drugs.

Natural modified surfactants differ in their composition, concentration of phospholipids, proteins, viscosity and volume of administration.

The most studied are 3 natural surfactants - beractant (Survanta), calfactant (Infasurf) and poractant alpha (Curosurf); the last of these contains the largest amount of phospholipids in the smallest volume. A meta-analysis of 5 studies comparing alfa poractant with beractant showed a reduction in mortality with alfa poractant treatment. A large retrospective study in the United States examined the outcome of treatment with three surfactant drugs (beractant, calfactant, poractant alfa) in 322 intensive care units (51,282 preterm infants) from 2005 to 2010. There was no difference in the incidence of SWS, BPD and /or mortality. The authors believe that the drugs have the same clinical efficacy.

Currently, 3 imported surfactant preparations are presented in the Russian Federation: Curosurf, Alveofact and Survanta. The efficacy of Curosurf and Alveofact was compared in 2 clinical trials with no difference in outcomes. It should be noted that the concentration of phospholipids in 1 ml of the substance in Curosurf is 2 times higher than in Alveofact.

There are domestic preparations of surfactant, but their effectiveness is unknown to the author.

Insertion technique

Surfactant is usually given as a bolus through a thin catheter inserted into the ETT. The dose, if it is considered large, is sometimes administered in 2 doses. After this, the patient is attached to a ventilator breathing circuit or assisted in the promotion of surfactant by bag breathing.

The INSURE (INtubate-SURfactant-Extubate) technique, which consists of intubation, surfactant administration and rapid extubation on nSRAP, has shown a decrease in the incidence of BPD. It should be noted that a stable child on nCPAP should not be specifically intubated for surfactant administration, including for INSURE.

The use of a surfactant through a thin probe during spontaneous breathing on nCPAP has been described. The technique seems promising and interest is growing. Studies have shown a reduction in the need for mechanical ventilation and the incidence of BPD.

Aerosol administration of surfactant is not yet recommended, although it continues to be investigated.

Contraindications

Relative contraindications for the introduction of a surfactant are:

• congenital anomalies incompatible with life;
• hemodynamic instability;
• active pulmonary hemorrhage.

Monitoring (before, during and after administration)

• FiO 2 >2, ventilation parameters;
• chest excursions, DO, auscultatory picture;
• SpO 2 , heart rate, blood pressure;
• chest x-ray;

Complications

Most of the complications of surfactant use are transient and rarely destabilize the patient's condition for a long time. They are mainly associated with the manipulation itself: the introduction of fluid into the trachea, turning the head, neck can lead to bradycardia, cyanosis, an increase or decrease in blood pressure, and reflux of surfactant into the ETT.

The most severe complication after surfactant administration is pulmonary hemorrhage, which occurs in 1-5% of children.

Surfactant treatment

Synthesis of a sufficient amount of surfactant in lung epithelial cells begins from the 34th week of pregnancy. Surfactant reduces the surface tension of the alveoli, is responsible for their stability and prevents the alveoli from collapsing during exhalation. The shorter the gestation period, the more likely is surfactant deficiency and associated neonatal respiratory distress syndrome. Endogenous surfactant deficiency can be compensated by surfactant replacement therapy.

Indications for the appointment of a surfactant:

• radiologically confirmed neonatal respiratory distress syndrome;
• extreme immaturity of the premature newborn;
• inspiratory oxygen concentration >0.4-0.6.

Training:

• chest x-ray;
• pulse oximetry;
• invasive blood pressure measurement;
• analysis of the gas composition of arterial blood.

Material:

• sterile gastric tube or umbilical catheter;
• sterile gloves;
• measuring tape for determining the length of the introduction;
• syringe, needle.

Holding

Stages of surfactant therapy

Endotracheal aspiration.

Laying: head in the middle position or in the position on the side.

Warm the surfactant to room temperature, do not shake. Assist with instillation: squeeze the endotracheal tube between thumb and forefinger to prevent overfilling.

Record the batch number of the drug.

Patient monitoring

Excursions of the chest, cyanosis: ECG, blood pressure, hemoglobin O 2 saturation.

Physician's tasks:

• strictly observe the doses;
• measure the length of the tube, mark it on the instillation catheter;
• collect the drug in sterile conditions;
• increase ventilator pressure.

Introduction: insert a gastric tube into the tube, during the instillation of the surfactant, the tube is squeezed by an assistant, re-introduce air to completely empty the catheter, connect the ventilator.

Alternative forms of application

Surfactant is administered through a side-ported endotracheal tube adapter, no disconnection of the device is required.

Complications:

• airway obstruction, drop in blood pressure;
• after the introduction of a surfactant, the occurrence of acute airway obstruction with an increase in pCO 2 can be compensated for by a short-term increase in airway pressure.

If possible, do not perform endotracheal aspiration for at least 6 hours after surfactant administration.

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Respiratory system

“We breathe, so we live” - this is how the poem by Georgy Lodygin begins. Indeed, a person is born with inhalation and dies with exhalation. Inhalation is the oxygen that each of our cells needs to perform their many functions.

There are 12 functional systems in the human body and the most important is the respiratory system. In addition to the respiratory function, the bronchopulmonary system also performs non-respiratory functions (excretory, thermoregulatory, speech, and others), but we will talk specifically about breathing and how to improve the functioning of the lungs and the body as a whole.

Anatomically, our lungs include bronchi, which end in bronchioles with alveoli at the ends (there are about 600 million alveoli). It is with the help of the alveoli that gas exchange is possible in the body - oxygen from the air in the alveoli passes into the blood, and carbon dioxide is removed in the opposite direction.

In fact, the alveoli are microscopic air bubbles, covered on the outside with a network of blood vessels. When you inhale, the alveoli expand, and when you exhale, they contract. From the inside, the alveoli are covered with a layer of a special substance - a surfactant, which prevents air bubbles from sticking together when exhaling, because. The surfactant changes the surface tension in the alveoli—increasing inhalation tension as the alveoli expand and decreasing exhalation surface tension as the alveoli contract.

The role of the surfactant

In the alveoli, the surfactant guarantees the passage of vital oxygen into the blood (capillaries) to supply the cells of the body with oxygen and thus resists cell hypoxia. With hypoxia (lack of oxygen), metabolism slows down, the immune system does not work well, cells cannot fully feed and function. The main symptoms of hypoxia are drowsiness, lethargy, chronic fatigue, unwillingness to move, mental retardation, shortness of breath when moving, and cravings for sweets (during hypoxia, glucose quickly burns out and there is a need for it).

Surfactant is essential for proper lung function. When a premature baby is born, there is a risk that the baby will not be able to breathe on its own, because. the formation of the surfactant layer ends by 9 months of gestation (oxygen to the developing fetus enters through the umbilical cord along with the blood of the expectant mother).

Pulmonary surfactant was first isolated and described in 1957. The word "surfactant" comes from the English phrase "surfactant" - surf (ace) act (ive) a (gen) ts, "surface" in English means "surface".

The basis of the surfactant is fats (lipids, 90% of them, of which 85% are phospholipids) and proteins (10%).

Surfactant is produced by epithelial cells - pneumocytes and transported to the alveoli. Damage to pneumocytes (for example, by microorganisms pneumocystis that cause pneumocystis pneumonia) or insufficiency of their functioning leads to a deficiency of surfactant, and this leads to impaired gas exchange in the lungs, lack of oxygen in the cells.

During respiration, surfactant is constantly consumed and re-formed, however, if pneumocytes are damaged, under the influence of external factors, surfactant may not be enough. It has been found that surfactant production also decreases with age.

The role of the surfactant, in addition to providing a breathing mechanism, is to protect the lungs from foreign and various chemical agents, as well as from bacteria and viruses, preventing them from entering the blood (bactericidal and immunomodulatory function of the surfactant). At the same time, the spent surfactant is excreted through the bronchi along with sputum, taking with it dust particles, toxins and bacteria captured by macrophages.

When inhaling polluted air containing automobile exhausts, gasoline vapors, acetone, dust of household and construction chemicals, toxic smoke and tar when smoking, the surfactant layer of the alveoli suffers (these chemical toxic substances clog the alveoli and block the production of surfactant). All these factors can lead to the development of diseases of the bronchopulmonary system. The function of the surfactant is also impaired by overheating and hypothermia of the body and by an increase in the concentration of carbon dioxide in the air (for example, in a stuffy room).

It has been established that in chronic bronchitis, the amount of surfactant in the alveoli is reduced, and this contributes to an increase in the viscosity of sputum in the lungs and colonization of the bronchial tree by microbes, causing an inflammatory process. Pneumonia is an inflammation of the lung tissue with a primary lesion of the alveoli, in which there is an accumulation of fluid from small blood vessels.

When there is not enough surfactant in the alveoli, the body spends additional energy and increases the load on the respiratory muscles - the diaphragm, external intercostal muscles and the muscles of the upper shoulder girdle.

By the way, during physical training and stress, a strong consumption of surfactant occurs, so such people are recommended to take additional fat intake.

Surfactant and fat intake

The fats we consume during metabolism in the body turns into fatty acids, which go first to the formation of a surfactant, then to the construction of cell membranes.

While the benefits of consuming fat are obvious, many people switch to the now fashionable low-fat diet (be afraid of cholesterol and obesity), in which the level of surfactant decreases, which means that oxygen absorption and transport to cells is inhibited.

Fats are directly related to full-fledged respiration and the supply of oxygen to cells (and they get fat not from fats, but from carbohydrates).

It is not for nothing that people with lung diseases are strongly recommended to use fats, and traditional medicine recipes for lung diseases contain components such as butter, milk, baked milk and lard, they advise externally rubbing badger and bear fat.

Production and application of surfactant

The world has learned how to produce surfactant from natural products - the lungs of cattle and pigs, as well as from the lungs of dolphins and whales (as you know, whales and dolphins breathe with their lungs. A whale inhales and exhales about two thousand liters of air in 1 second). The best surfactant was found in whales - a whale has about 300 liters of it, while a person has only 30 - 40 milliliters (the largest whale fishery in Japan, which, along with other areas of improving the nation's health, improved the health of the Japanese).

In Russia, there are patents for natural surfactants, for example, according to one of them, 2 g of surfactant can be isolated from 1 kg of light cattle.

There is experience of using the obtained surfactant for respiratory disorders in newborns, as well as for the prevention of pneumonia and even pulmonary tuberculosis in the Central Research Institute of Tuberculosis of the Russian Academy of Medical Sciences.

What fats are good to eat

It is especially useful to consume fats that provide polyunsaturated omega-3 fatty acids. Without them, surfactant and cell membranes are poorly formed (they are 90% fats - lipids), sex hormones are not produced enough (they are synthesized from fats), the brain and eyes are poorly nourished (these organs contain a lot of fatty structures), etc.

Omega-3 fatty acids are found in linseed oil, fish fats - mackerel, herring, salmon, tuna, and if tuna contains 3.5% of these acids, then linseed oil contains 70%. Flax seeds and chia seeds are also rich in these fatty acids.

Fish oil contains omega-3 fatty acids and is the cheapest and most effective supplement for replenishing surfactant and normalizing all body systems. Now fish oil is sold in capsules and its specific taste is not even felt when taken (fish oil manufacturers, both Russia and America, are on the iHerb website (iHerb - I'm a herb)). It is recommended to take fish oil with food for a month 2-3 times a year.

In health food stores, online stores sell "Omega-3 for the lungs" - unrefined linseed oil, which is infused with currants, marshmallows, raspberries and currants, cedar resin and licorice. The inclusion of these herbs improves the drainage function of the lungs and the activity of the ciliated epithelium of the respiratory tract, through which dust, germs and viruses are disposed of.

To compensate for the deficiency of surfactant, Konstantin Zabolotny (doctor - pediatrician, nutritionist) recommends adding at least 6 tablespoons of linseed oil to food per day. For example, I dress salads with linseed oil, add a teaspoon of this oil to cottage cheese (as recommended by the famous doctor of medical sciences Ivan Neumyvakin), or simply pour oil on a piece of bread, while getting satisfaction from the right food.

I think you've learned a little more about breathing and the need for healthy fats to help you be healthier.

In many ways, we can take care of our health ourselves, having useful knowledge in this area. Subscribe to my news - interesting articles about food, plants and a healthy lifestyle.

ID: 2015-12-1003-R-5863

Kozlov A.E., Mikerov A.N.

State Budgetary Educational Institution of Higher Professional Education Saratov State Medical University im. IN AND. Razumovsky Ministry of Health of Russia, Department of Microbiology, Virology and Immunology

Summary

The surface of the alveolar epithelium in the lungs is covered with a surfactant necessary for respiration and adequate immune protection. Pulmonary surfactant is composed of lipids (90%) and a number of proteins with different functions. Surfactant proteins are represented by SP-A, SP-D, SP-B and SP-C proteins. This review discusses the main functions of surfactant proteins.

Keywords

Pulmonary surfactant, surfactant proteins

Review

The lungs perform two main functions in the body: providing respiration and the functioning of immune defense mechanisms. The correct performance of these functions is associated with pulmonary surfactant.

Surfactant is synthesized in the lungs by type II alveolar cells and secreted into the alveolar space. The surfactant covers the surface of the alveolar epithelium and consists of lipids (90%) and proteins (10%), forming a lipoprotein complex. Lipids are represented mainly by phospholipids. Deficiency and/or qualitative changes in the composition of pulmonary surfactant have been described in tuberculosis, neonatal respiratory distress syndrome, pneumonia, and other diseases. .

Surfactant proteins are SP-A, (Surfactant Protein A, 5.3%), SP-D (0.6%), SP-B (0.7%), and SP-C (0.4%). .

The functions of the hydrophilic proteins SP-A and SP-D are associated with immune defense in the lungs. These proteins bind lipopolysaccharide of gram-negative bacteria and aggregate various microorganisms, affect the activity of mast, dendritic cells, lymphocytes and alveolar macrophages. SP-A inhibits the maturation of dendritic cells, while SP-D increases the ability of alveolar macrophages to capture and present antigens, stimulating adaptive immunity.

Surfactant protein A is the most abundant protein in pulmonary surfactant. It has pronounced immunomodulatory properties. The SP-A protein affects the growth and viability of microorganisms by increasing the permeability of their cytoplasmic membrane. Moreover, SP-A stimulates macrophage chemotaxis, influences the proliferation of immune response cells and the production of cytokines, increases the production of reactive oxidants, increases phagocytosis of apoptotic cells, and stimulates bacterial phagocytosis. Human SP-A consists of two gene products, SP-A1 and SP-A2, whose structure and function are different. The most important difference in the structure of SP-A1 and SP-A2 is amino acid position 85 of the collagen-like region of the SP-A protein, where SP-A1 has cysteine ​​and SP-A2 has arginine. Functional differences between SP-A1 and SP-A2 include their ability to stimulate phagocytosis, inhibit surfactant secretion. In all these cases, SP-A2 is more active than SP-A1. .

The functions of the hydrophobic proteins SP-B and SP-C are associated with the provision of respiration. They reduce the surface tension in the alveoli and promote even distribution of the surfactant on the surface of the alveoli. .

Literature

1. Erokhin V.V., Lepekha L.N., Erokhin M.V., Bocharova I.V., Kurynina A.V., Onishchenko G.E. Selective effect of pulmonary surfactant on different subpopulations of alveolar macrophages in tuberculosis // Topical issues of phthisiology. - 2012. - No. 11. - P. 22-28.
2. Filonenko T.G., Distribution of surfactant-associated proteins in fibrous-cavernous pulmonary tuberculosis with active bacterial excretion // Tauride Medical and Biological Bulletin. - 2010.- No. 4 (52). - S. 188-192.
3. Chroneos Z.C., Sever-Chroneos Z., Shepherd V.L. Pulmonary surfactant: an immunological perspective // ​​Cell Physiol Biochem 25: 13-26. - 2010.
4. Rozenberg O.A. Pulmonary surfactant and its use in lung diseases // General Reanimatology. - 2007. - No. 1. - pp. 66-77
5. Pastva A.M., Wright J.R., Williams K.L. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease // Proc Am Thorac Soc 4: 252-257.-2007.
6. Oberley R.E., Snyder J.M. Recombinant human SP-A1 and SP-A2 proteins have different carbohydrate-binding characteristics // Am J Physiol Lung Cell Mol Physiol 284: L871-881, 2003.
7.A.N. Mikerov, G. Wang, T.M. Umstead, M. Zacharatos, N.J. Thomas, D.S. Phelps, J. Floros. Surfactant protein A2 (SP-A2) variants expressed in CHO cells stimulate phagocytosis of Pseudomonas aeruginosa more than do SP-A1 variants // Infection and Immunity. - 2007. - Vol. 75. - P. 1403-1412.
8. Mikerov A.N. The role of surfactant protein A in the immune protection of the lungs. Fundamental research. - 2012. - No. 2. - S. 204-207.
9. Sinyukova T.A., Kovalenko L.V. Surfactant proteins and their role in the functioning of the respiratory system // Bulletin of the Surgical University of Medicine. - 2011. - No. 9. - pp. 48-54

Filterable List

Instructions for medical use

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

Last Modified Date: 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 bovine lung surfactant, which is 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, 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 pulmonary 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 pathogens 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 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 ( 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 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

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

2. In the complex therapy of acute lung injury syndrome (ALI) and acute respiratory distress syndrome (ARDS) in adults that have developed as a result of 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 Mycobacterium tuberculosis drug resistance, 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, since clinical trials in this age group have not been conducted and 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 injection, the emulsion of surfactant-BL 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 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 the 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 0.9% sodium chloride 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.

Further, the respiratory cycle of the newborn is synchronized with the mode of operation of the ventilator using sedatives - sodium oxybutyrate or diazepam, and in cases of severe hypoxia - narcotic analgesics. The prepared surfactant-BL emulsion is administered 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. The administration is carried out using a syringe dispenser for 30 minutes without interrupting IVL, without depressurization of the respiratory 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 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 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 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 for 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 the concentration of inhaled oxygen 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 microjet 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 of mechanical ventilation 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 initiation of 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 patients with chronic lung diseases, including those with chronic obstructive pulmonary disease (COPD), as well as before advanced chest surgery 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 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.

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 administration:

• 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” by Flaem Nuova, Italy or “Pari Boy SX” by Pari GmbH, Germany, or their analogues, which allow spraying small volumes of drugs and 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, he cannot use the entire volume of the emulsion, you should take breaks for 15-20 minutes, and then continue inhalation. 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 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 during sonication of the emulsion. 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 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 (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 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. It is necessary to reduce the concentration of oxygen in the inhaled mixture 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 of the skin, requiring an assessment of the adequacy of the 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 (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 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.

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 for ARDS 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 each in 10 ml glass vials, 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.

Best before date

Do not use after the expiration date.

Terms of dispensing from pharmacies

By prescription. Used in a hospital setting.

R N003383/01 dated 2008-12-15
Surfactant-BL - instructions for medical use - RU No.

Lung surfactant, consisting mainly of phospholipids and protein, performs a wide range of protective functions, the main of which is anti-atelectatic. A pronounced lack of surfactant leads to the collapse of the alveoli and the development of acute respiratory failure syndrome - RDSN (respiratory distress syndrome of newborns). The surfactant reduces the surface tension in the alveoli, ensures their stability during breathing, prevents their collapse at the end of the exhalation phase, ensures adequate gas exchange, and performs an anti-edematous function. In addition, the surfactant is involved in the antibacterial protection of the alveoli, increases the activity of alveolar macrophages, improves the function of the mucociliary system, and inhibits a number of inflammatory mediators in acute lung injury syndrome (ALS) and acute distress syndrome (ARDS) in adults.
In case of insufficient production of one's own (endogenous) surfactant, exogenous surfactant preparations are used, obtained from the lungs of a person, animals (bovine, calf, pig) or synthetically.
The chemical composition of mammalian lung surfactant has much in common. Surfactant isolated from human lungs contains: phospholipids - 80-85%, protein - 10% and neutral lipids - 5-10% (Table 1). Up to 80% of alveolar surfactant phospholipids are involved in the process of recycling and metabolism in type II alveolocytes. The surfactant includes 4 classes of proteins (Sp-A, Sp-B, Sp-C, Sp-D), each of which is encoded by its own gene. The main mass of proteins is Sp-A. Preparations of endogenous surfactant of various origins differ somewhat in content from phospholipids and proteins.
Surfactant is synthesized and secreted by type II alveolocytes (a-II). On the alveolar surface, the surfactant consists of a thin phospholipid film and a hypophase containing membrane formations. This is a very dynamic system - more than 10% of the total surfactant pool is secreted hourly.

Table 1. Phospholipid composition of alveolar surfactant in the lung of an adult

Studies, including multicenter studies, have shown that the early use of surfactant preparations for respiratory distress syndrome in newborns can significantly reduce mortality (by 40-60%), as well as the incidence of multisystem complications (pneumothorax, interstitial emphysema, bleeding, bronchopulmonary dysplasia, etc.). ) associated with the neonatal period in preterm infants.
In recent years, pulmonary surfactant preparations have begun to be used in the treatment of ALI/ARDS and other lung conditions.
Currently known preparations of pulmonary surfactant differ in the source of production and the content of phospholipids in them (Table 2).
In Russia, surfactant therapy has been used only recently, primarily in neonatal intensive care units, thanks to the development of a domestic natural surfactant preparation. Multicenter clinical trials of this drug have confirmed the effectiveness of the use of pulmonary surfactant drugs in the treatment of critical conditions and other respiratory diseases.

Table2. Pulmonary surfactant preparations