A method of treating respiratory distress syndrome in adults

 

(57) Abstract:

The invention relates to medicine, more specifically to anesthesiology and critical care medicine, and may find application in the treatment of respiratory failure nicardipine of nature in critical States. The method is to use appropriate modes of artificial ventilation of lungs with more endobronchial introduction pulmonary surfactant and surfactant-BL injected from the first hours of development of respiratory insufficiency in the number of 700-1000 mg bolus or mikrostruyno, and then after 30-60 min of aerosol constantly within 15-60 h in the amount of 30-60 mg/h, after which the patient extrovert. The method provides rapid stabilization of patients and the possibility of early harsh of ventilation parameters, a significant (up to 15-60 h) reducing the time a patient on a ventilator, as well as reducing the total course dose of surfactant and a significant increase in the survival rate of patients. table 1.

The invention relates to medicine, more specifically to anesthesiology and critical care medicine, and may find application in the treatment of respiratory failure nicardipine of nature in critical States.

Under the critical condition is lung damage (SAP) and its most severe form - respiratory distress syndrome of adults (rdsw) [1], and severe bilateral pneumonia.

SAP and rdsw are characterized by the fact that the patient

develops hypoxemia refractory to oxygen therapy. In this patient, who is on artificial lung ventilation (ALV), oxygenation index (OI) for SOLP below 300 mm RT. Art. and when rdsw below 200 mm RT. Art. (norm 360 - 400 mm RT. Art. and more). IO is the ratio of the values PaO2(pressure of oxygen in arterial blood in mm RT. Art.) to the value of the FiO2(the concentration of oxygen in the inhaled air-gas mixture in %) [PaO2/FiO2],

found bilateral infiltrative changes on the radiograph of the lungs,

develops shunting blood (venous blood passes through parts of the lungs, without aeration, and may in this form to arterial blood,

reduced lung compliance and lung volumes.

All these symptoms develops in the absence of left ventricular heart failure circulation, the rate of which, with appropriate clinic, i.e., when the above-described symptoms, is the value of the jamming pressure in the pulmonary artery, kotoroe as "shock lung", "wet lung", nicardipine (interstitial) lung edema [3, 4].

SAP and rdsw registered in the industrialized countries at the level of from 1 to 1000 [5, 6] up to 3 to 10.5 per 100,000 population per year [7]. For Russia, this is about 15000 - 30000 per year.

The most common causes of the development of SAP and rdsw are sepsis and severe multiple trauma, such as a car, and various toxic conditions. The development of SAP and rdsw may occur due to direct damage to the lung parenchyma (pneumonia, aspiration of gastric contents, hot steam or air, toxic liquids and gases, lung contusion) or systemic damage to the body (sepsis, multiple trauma, traumatic brain injury, embarrassment syndrome, acute radiation damage, prolonged mechanical ventilation, complications after cardiac operations with long-term use of artificial blood circulation, post-transfusion and reperfusion syndromes) [3, 4].

Mortality from rdsw extremely high and depends on the background on which it develops. With multiple trauma and embarrassment syndrome (Krash-syndrome) mortality is 50 - 60% [3], sepsis - 90% [8], and in the case of development is of such patients is the use of mechanical ventilation, usually with a "hard" settings, i.e., a high partial pressure of oxygen in the inhaled gas mixture (FiO2= 0,8 -1,0), high peak pressure breathing (greater than 35 cm aq. Art.), large amounts of supplied gas mixture (12-15 ml/kg body weight) and required positive pressure at the end of the expiratory (peep).

These so-called "hard" settings, mechanical ventilation, are more powerful damaging factors for the flow of SAP and rdsw and often worsen the position of the patient.

During the last 5 - 7 years in the treatment of rdsw in addition to mechanical ventilation are trying to use the pulmonary surfactant preparations that have proven successful in the treatment of neonatal RDS.

There are several preparations of surfactant: synthetic (Exosurf. Glaxo-Wellcome, USA-UK; ALEK, Britanica, UK), semisynthetic (Surfactant-TA, Tokyo Tanabe, Tokyo, Japan; Survanta, Ross/Abbott Lab, Chicago, USA) and natural (Curosurf, Chiesi Farmaceutici, Farma, Italy; Alveofact, Thome GmbH, Biberach, Germany; Infasurf, Forrest Labs, St. Louis, USA; CLSE, Rochester, NY, USA; Surfactant-HL [11] and Surfactant-BL [12].

Drugs Surfactant-HL and Surfactant-BL developed at the Central research radiology Institute of the RF Ministry of health (cnrri health Ministry). Surfactant-HL time.99). Surfactant-BL approved for clinical trials in RDS infants (Protocol FC MH RF N14 from 26.09.96) and RDS adults (Protocol FC MH RF N 5 from 28.08.98). State Pharmacopoeia Committee in 1998 approved VFS on Surfactant-BL (N 42-3120-98). Clinical trials also are successful in 12 health facilities of Moscow, S.-Petersburg, Chelyabinsk and Yekaterinburg and currently more than 60 infants received treatment with this drug, and more than 40 adults and younger and older age. By the end of 1999, these tests must be completed and the reports of the clinics will be presented in the Pharmacological Committee of the Russian Federation Ministry of health for permission on his medical application. Currently in cnerry MOH created the basis for the production of drugs pulmonary surfactants with a capacity of 30 thousand bottles a year, and it will also allow the introduction of drugs in the healthcare practice for the treatment of a critical condition in newborns and adults.

Some of the main characteristics of these products are given in table. 1. [10, 11, 12].

There is a method of treatment of respiratory failure in critically ill with severe pneumonia, SAP and rdsw by IVL (and all soo is surfactant "Exosurf" [13]. The authors report on the treatment of 725 patients (364 received treatment with a surfactant, and 361 in the control group on standard treatment who received placebo (0,45% NaCl) without surfactant). The authors used the aerosol route of administration, and the drug was administered to patients not earlier than 48 hours after clinical and laboratory diagnosis rdsw, continuously for 5 days in total dose 3240 mg for the entire course; i.e., 112 mg/kg per day at the rate of introduction of 27 mg/hour. The authors found no differences neither in the possibility of mitigation options IVL, nor in patient survival compared with the control group. The time spent by patients on mechanical ventilation was similar in both groups and amounted to 16.4 0.9 days in the control (K) group and 16.0 1.0 days in the group treated with Exosurf. The time spent by patients in the intensive therapy was 16.7 0.8 in To and 18.1 1.1 days in the group treated with Exosurf. In both groups the incidence of complications and side effects was similar and only the frequency increased secretory activity in patients treated with Exosurf was significantly greater than K. the Frequency of barotrauma was 11%, including pneumothorax, pneumoperitoneum, pneumopericardium and pivotally. The study did not have children.

There is a method of treatment rdsw way the x, received treatment with a surfactant, and 17 patients in the control group who were on standard treatment and treated with placebo (0.6% of NaCl) without surfactant). Used aerosol route of administration, and Exosurf was introduced not earlier than the second day from the development of signs of respiratory distress, continuously for 5 days at 12 hours per day with a total dose of 9.0 g on the course, or 24 hours per day with a total dose of 18.0 g on a course at the rate of introduction of 140 to 150 mg/hour. Survival at 30 days was in the group treated with surfactant within 24 hours (5 days in a row), 65% in the group treated with surfactant for 12 hours per day (5 days in a row), and 56% in the placebo group, 52 per cent. Not present data on the time spent by patients on a ventilator.

Significant differences in survival, as in the previous work, was not found.

There is a method of treatment rdsw by mechanical ventilation and supplemental semi-synthetic preparation of surfactant "Survanta" [15]. The authors reported the treatment of 59 patients with this drug and used it through the endotracheal tube, not earlier than the second day from the development of symptoms of respiratory distress. Studied several variants of surfactant therapy (ART therapy). The first is the group, the drug was administered at a dose of 800 mg/kg in the form of 8 doses (total 64 g for the entire course). They found a trend towards reduced mortality. In the group of patients who received surfactant at a dose of 400 mg/kg, mortality decreased from 44% to 18%, and received the drug at a dose of 800 mg/kg from 44% to 21%. These estimates of mortality (survival) was carried out after 120 hours (5 days) after the start of treatment rdsw. About the future and the time spent with these patients on a ventilator is not reported.

The main disadvantages of the above methods of treatment rdsw are low survival of patients, and in the case of synthetic drugs no difference in survival compared to the control, as well as long term (10 - 30 hours) location of the patient on a ventilator with a "hard" settings, and extremely high consumption of drugs surfactant.

Closest to the present invention is a method of treatment rdsw by mechanical ventilation and supplemental natural drug of surfactant "Alveofact", we adopted as the prototype [16]. The authors report on the treatment of 10 patients with severe rdsw caused by sepsis. They use single or double selective (in each lobar bronchus) using a bronchoscope introduction of the drug at a dose of 300 mg/kg, not early the second day from the development of sympt the improvement of the patient's condition was getting worse, additionally injected even at 200 mg/kg Of 10 patients survived 5, and 4 of them were on a ventilator with a "hard" settings from 12 to 20 days and one 7 days. At the rate of patients received from 24 to 40 grams of the drug surfactant. Thus, as in the above ways, you have a low survival rate, long-term presence of the patient on a ventilator with a "hard" settings, and high consumption of the drug.

The technical result of the present invention consists in the improved survival of patients, reducing the time the patient is on a ventilator and reducing the total dose of surfactant due to schema changes its introduction.

This result is achieved by the fact that pulmonary surfactant is injected from the first hours of development of respiratory insufficiency in the amount of 700 - 1000 mg bolus or mikrostruyno, and then after 30 - 60 minutes in a spray constantly, for 15 to 60 hours at 30 to 60 mg/hour, after which the patient extabit.

It is advisable to use natural pulmonary surfactant content of phospholipids in the amount of 89%, neutral lipids - 9% and surfactant-associated protein - 2%.

Doing professionally for the treatment of severe respiratory negotia in terms of ventilation control volume or pressure, antibiotic therapy, the use of inotropes to stabilize hemodynamics), and in the last two years with the use of additional drugs pulmonary surfactants (Surfactant-HL and Surfactant-BL), assigning them once or within 2 to 3 days in the form of a bolus instillation or mikrostruyno, we noted a more rapid improvement in oxygenation in children receiving pulmonary surfactants.

This fact has motivated us to conduct special monitoring for diseases with different modes of ART-therapy. We have introduced it, as a rule, instillation, once a day for 1 to 3 days, or in the form of an aerosol sessions for 4-6 hours a day for 1 to 3 days. When you type the amount of surfactant was 10 - 15 mg/kg

Receiving in most cases, the positive results of this treatment regimen, we attempted to use it in the treatment rdsw in adults.

Taking into account obtained in the known methods unsatisfactory results, we tried to start ART therapy from the first day, and then hours from the appearance of persistent signs of respiratory distress.

After receiving the first impressive results stabilize very heavy patient with rdsw reduce FiO2from 0.8 to 0.6 from bolus endobronchial (left and right main bronchi 500 mg each) of the drug in the first hours of the development of respiratory failure, then we did it a permanent aerosol introduction of surfactant in the amount of 60 mg/hour and watched the gradual improvement of IO to 160 - 180, and after 60 hours signs of respiratory distress had disappeared (IO = 420, FiO2= 0,21), with full recovery of airiness of the lungs on chest x-ray. Thus rdsw was stopped and the patient exuberan after 60 hours after the start of treatment, and after 3 hours after the start of ART therapy was able to reduce hardness parameters IVL, namely to reduce the concentration of oxygen in the inhaled gas mixture of 80 to 60% (or decrease FiO2from 0.8 to 0.6), and then to 45%.

For treatment we used Surfactant-BL obtained from the lung of cattle, containing 89% of phospholipids, 9% neutral lipids and 2.0% surfactant-associated proteins, which we have introduced in the amount of 60 mg/hour continuously.

A positive result encouraged us to continue the research to determine the optimal modes of surfactant therapy rdsw in adults.

The introduction of the first surfactant bolus (or mikrostruyno) intratrahealno or endobronhialno using a bronchoscope (separately into the left and right main bronchi), and then in the form of an aerosol for 15 - 60 hours continuously in the amount of 30 - 60 mg/kg provided relief rdsw in all of our clinical observations made to date, 23 severe cases respiratory failure in critical States.

The introduction of surfactant in the amount of 700 - 1000 mg (bolus or mikrostruyno), and then in the form of an aerosol with a speed of 30 - 60 mg/h corresponds to the number of from 1.5 to 5 g of surfactant treatment, which is considerably less than in the known methods, characterized by the tendency to increase patient survival. This is very important, given the s to exuberate patient immediately after edema respiratory failure. Moreover, the use of surfactant on the proposed method allows the first hours of the injection of the surfactant to mitigate the parameters of mechanical ventilation (FiO2PVD- pressure on the inhale, and the amount of supplied gas mixture), and thus further eliminate damaging (lung tissue) factors IVL.

The use of a preparation containing, as said above, 2.0% of the surfactant-associated proteins, is in our opinion a very important component of the proposed method. Such proteins are absent in synthetic drugs surfactant (Exosurf) is contained in an amount of 0.1% in semi-synthetic drugs (Survanta) and 1.0% in natural (Alveofact, Infasurf and CLSE) (see tab. 1).

1. These proteins are very important for the manifestation of the ability of phospholipid surfactant to reduce surface tension at the phase boundary (the surface of the alveoli - air), while synthetic drugs, including Exosurf, do not contain these proteins. The reduction of surface tension on the surface of lung alveoli, carried out by phospholipids in cooperation with surfactant-associated proteins, facilitates the process of disclosure of the alveoli during inspiration, thus reducing the required effort of the muscles of the chest.

2. With these balkantourist of chemoatractant in relation to alveolar macrophages, to stimulate the complement-dependent and antibody-dependent capture of pathogenic bacteria and viruses alveolar macrophages, and so on [18].

3. They also inhibit in vitro the ability of polymorphonuclear leukocytes and alveolar macrophages to excretion (release) cytokines - molecular components of proinflammatory cascade. The last damage alveolararterial membrane is the basic structural and functional element of pulmonary gas exchange.

The method consists in the following.

Patient clinic with severe respiratory failure, which is on a ventilator and require "hard" settings, ventilation, immediately after diagnostic confirmation of respiratory distress syndrome bolus or mikrostruyno (intratrahealno or through the bronchoscope separately in the left and right main bronchi) to impose 700 - 1000 mg of surfactant and then after 30 - 60 minutes hold constant inhalation of the drug bovine surfactant Surfactant-BL containing phospholipids 89%, neutral lipids 9% and surfactant-associated proteins 2%. Inhalation is carried out with the help of a nebulizer, is included in the circuit of breath the ventilator, the rate of gas flow through the nebulizer poduralskogo solution. Every day perform radiographic examination of lungs, at least four times per day - the analysis of the gas composition of arterial blood and increase the oxygen tension in arterial blood (PaO2) more than 80 - 90% gradually reduce hardness parameters of mechanical ventilation. Inhalation of the drug is stopped after increasing oxygenation index up to 350-400 mm RT.article and improve the x-ray pictures.

The essence of the method is illustrated by the following examples.

Example 1.

Patient D. , 1936 year of birth, medical history, N 35291, was admitted to the clinic of cardiovascular surgery, military medical Academy 20.10.98 with a diagnosis of generalized atherosclerosis, critical ischemia of the lower extremities, gangrene of the left foot, coronary heart disease. Angina, atherosclerosis and myocardial infarction. 30.10.98 was performed surgery: aorta-femoral bypass bifurcation and necrectomy (disarticulate II - IV fingers of the left foot). The postoperative period was complicated by development of severe respiratory distress (tachypnea up to 32-36 breaths per minute, decrease in PaO2up to 58 mm RT. Art. when breathing ambient air), requiring the transfer of a patient on a ventilator. IVL, previo = 94. Radiographically determined the development of pronounced interstitial pulmonary edema. Considering hemodynamic stability, absence of any signs of heart failure, was denied the possibility of developing cardiogenic pulmonary oedema. Cause disorders of gas exchange was recognized rdsw associated with intraoperative lung damage products released into the bloodstream from esibizioni limbs.

The patient within 1 hour after a diagnosis through the bronchoscope separately in the left and right main bronchi was introduced drug Surfactant-BL in the amount of 500 mg each, and then 30 minutes later started the constant inhalation of the preparation of Surfactant-BL at a speed of 60 mg/hour via nebulizer, included in the circuit of the ventilator. 3 hours after the beginning of surfactant therapy IO increased from 94 to 160 and was maintained at this level at a constant inhalation of Surfactant-BL during the day. Performed 24 hours after the beginning of the ARTICLE-therapy x-ray examination revealed a significant positive trend, the decrease of intensity of interstitial pulmonary edema and increase the lightness. By the end of the first day after the start of therapy showed an increase in oxygenation index is achala of a drug the patient was excubitor, inhalation surfactant stopped (total time for the treatment was introduced to 4.6 g of the drug). On the 25th day after the operation the patient was discharged from the hospital in satisfactory condition.

Example 2.

Patient A., born in 1945, history N 2074, was admitted to the hospital Central research radiology Institute (cnrri) MOH 21.11.98 with a diagnosis of biliary cirrhosis. 07.12.98 was performed surgery: liver transplantation. The postoperative period was complicated by development of colonic adhesive obstruction that led to relaparotomy on the fifth day after surgery. The effects paralytic ileus has been preserved in the future, which was accompanied by inadequate function of external respiration (high standing of the diaphragm) and demanded a longer trigger the ventilator apparatus RV-740 with FiO2= 0,4. On the ninth day of AV in the background-resolved intestinal obstruction marked deterioration of blood gas composition IO = 160, diffuse alveolar infiltration on x-ray of the lungs in the absence of signs of left ventricular failure. Cause disorders of gas exchange was recognized rdsw moderate severity associated with d is Ronchi was introduced Surfactant-BL 350 mg each bronchus and after 60 minutes started the constant inhalation of the drug aerosol Surfactant-BL at a speed of 40 mg/hour via bronchial nebulizer, included in the circuit of the ventilator. The inhalation was continued for 15 hours. The change of gas composition of blood marked the end of the first hour of drug administration, after 2 hours of IO has increased from 160 to 235 after 5 hours up to 275, 17 hours ART-therapy - up to 308 and gas exchange parameters remained stable. Patient exuberan after graduating from ART therapy. 44 the day after surgery the patient was discharged in satisfactory condition. All patient received 1.30 grams of Surfactant-BL on therapy.

Example 3.

Patient G. , 1951 birth, was admitted to the clinic of cardiovascular surgery, military medical Academy 15.04.99 with a secondary diagnosis of infectious endocarditis of the aortic valve. 21.04.99 operation: the reorganization of the heart chambers and prosthetic aortic valve under conditions of extracorporeal circulation and cold cardioplegia. The duration of being on the heart-lung machine - 424 min, the duration of cross-clamping of the aorta 296 minutes Operation ended at 4 a.m 22.04.

In the nearest postoperative period the patient developed multi-organ failure, abnormalities in the hemostatic system, and therefore produced a massive blood transfusion was used is respiratory failure, accompanied by a decrease in oxygenation index and growth index of lung injury. On the x-ray light in this period was determined by interstitial edema on both sides, blurred pulmonary pattern, srednevekovye shadows in both lungs. IO = 156, FiO2= 0.6 index of lung injury by Murray = 1,92. On the basis of radiographic, clinical, and laboratory data was diagnosed rdsw. After 3 hours after diagnosis rdsw patient through the bronchoscope was introduced Surfactant-BL 500 mg in each main (left and right) bronchi, and then after 30 minutes with a speed of 35 mg/hour via nebulizer continuously during the 2 days spent inhalation of the drug. After 3 hours of inhalation of surfactant at the same FiO2= 0,6 IO rose from 156 to 266, and an index of lung damage fell to 1.27 1.92, while PaO2rose from 93 to 159 mm RT. Art. Within two days of IO was maintained at FiO2(0,45-0,55) on the level of 240 - 260 Units.

By the end of the second day of administration of the drug, improvement was noted in the oxygenation of arterial blood, with a simultaneous decrease in the concentration of oxygen in the inhaled mixture, and expressed a positive x-ray dynamics. After 49 hours after the start of injection of the surfactant Malinois in the surgical intensive care unit.

Example 4.

The victim K. , age 17, history N 7865. Delivered in the clinic military surgery BMA "ambulance" 14.04.99 in critical condition. Circumstances of injury: shot down by car. Diagnosed with severe concomitant injury to the head, chest and abdomen. Open craniocerebral injury, brain injury of moderate severity. Extensive scalped wound to the face and scalp. The fracture of the left zygomatic bone bruise of the left facial nerve. Closed chest trauma, fracture of III-V of the left ribs, bruised lung, closed abdominal trauma with damage to the liver, hemorrhages in the mesentery of the small intestine, the pancreas head, continuing intraperitoneal bleeding. Acute massive blood loss (2000 ml). Traumatic shock III degree.

When receiving completed: laparotomy, wound closure liver, cholecystotomy, primary surgical treatment of wounds of the head.

On the third day after admission for traumatic disease was complicated by the syndrome of acute lung injury. Thus, the patient was noted severe hypoxemia refractory to oxygen therapy. The partial pressure of oxygen in arteria is through the bronchoscope into the left and right main bronchi bolus put on 500 mg of Surfactant-BL and then for 14 hours the patient continued administration of the drug in aerosol form constantly through the nebulizer 60 mg/hour.

After 5 hours after the start of ART therapy, the patient noted a pronounced positive dynamics of blood gas composition: PaO2increased from 66 to 96 mm RT. Art. when FiO2= 0,8; i.e., IO up to 120 mm RT. Art. After 7 hours at the same FiO2PaO2amounted to 122, and IO 152 mm RT. Art. Continued inhalation for 12 hours at a dose of 30 mg/h was possible to reduce the partial pressure of oxygen in the feed gas mixture to 0.4 with a stable PaO2= 98 -106 mm RT. Art. Thus IO increased to 240 - 265 mm RT. Art. After that, in connection with a stable improvement in oxygenation the patient was exuberan. All patient received 2200 mg of Surfactant-BL. After 7 days moved from ICU to General ward.

To date, the proposed method were treated 23 patients with acute respiratory failure in critical States. All patients were treated respiratory failure within 15 - 60 hours. Died three patients from nulegacy reasons: the girl is 13 years 10 days after leaving rdsw from brain swelling and herniation before surgery syndrome (reason development rdsw - drowning in fresh water) and two cancer patients, 10 and 14 days after exit RSD.

Before is to significantly improve the survival of patients. Mild respiratory distress reached us in all patients, while in the method prototype in 5 cases out of 10 treated. The survival rate of our patients was 21 out of 23 who received the treatment, and the method-prototype 5 out of 10.

2. The method can significantly reduce the time spent by the patient on a "hard" settings, mechanical ventilation up to 2-8 hours and the total duration of no more than 60 hours; i.e. provides rapid elimination of iatrogenic factors lung damage, as well as factors of damage associated with over rdsw that is very important for the prevention of fibrosis of the lung is the most frequent complications in surviving patients.

3. The method reduces the amount of preparation surfactant; it ranges from 1.5 to 5 g per course of treatment, while in the method-prototype 18 - 25 g, as shown in the equivalent semi-synthetic preparation of surfactant - 32-64,

Note that the cost of treatment of the prototype is estimated at 35,000 to $ USA [19].

4. An important advantage of the proposed method is the use of the preparation of Surfactant-BL - natural lung surfactant containing 89% of phospholipids, 9% neutral lipids, and the nature of the more effective functioning of the surfactant, solely due to the properties of the surfactant-associated proteins, namely their immunomodulatory and anti-toxic properties, especially with regard to lung tissue. It should be recalled that in the method prototype using surfactant containing 1.0% of these proteins, and in ways analogous to using a synthetic drug Exosurf 0 - 0,1%.

The method developed by the staff of the Central research radiological Institute of the RF Ministry of health and the staff of the Military medical Academy and was clinically tested in 23 patients with the syndrome of acute respiratory distress syndrome adults with a positive result.

REFERENCES

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2. Ashbaugh D. G., D. B. Bigelow Petty, T. L., Lewin. Acute respiratory distress in adults.// Lancet.- 1967.-Vol. 2.- P. 319 - 323.

3. Silber, A. P. Studies of critical medicine. Volume 2. Respiratory medicine. Petrozavodsk, 1996. - 368 S.

4. Pison U., Bock J. C., Pietschmann, S., Veit, S., Slama K. The adult respiratory distress syndrome: pathophysiological concepts related to the pulmonary surfactant system.//In: Surfactant Therapy for Lung Disease. - N. Y., 1995. - P. 169-198.

5. Chan, C. Y. J., Barton, T. L., D. K. Rasch Colfosceril in an infan Am. Rev. Respir. Dis. - 1993. - Vol. 147. - P. 218-233.

7. Falcke. The management of severe ARDS. In the book: Actual problems of anesthesiology and critical care medicine. TRANS. from English. Arkhangelsk And Tromsø. 1998, S. 240 - 247

8. Martin M. A., Silverman H. J. Gram-negative sepsis and the adult respiratory distress syndrome // Clin. Infec. Dis. - 1992. - Vol. 14. - P. 1213-1228.

9. Grinev, M. C., Kulibaba D. M., Novozhilov Century. N. Clinical aspects Toshiko septic shock in peritonitis. // The Bulletin of surgery.- 1995.- So 154.- N 1.- S. 7-11.

10. Boncuk-Dayaniki P., H. W. Taeusch Essential and nonessential constituents of exogenic surfactants. Surfactant Therapy for Lung Disease. Ed. Robertson B. and Taeusch, H. W. - N. Y., 1995. - P. 217-238.

11. Rosenberg, A. A., Silgan A. A., Aliev A. A. and other Way of getting lung surfactant. 1995 (priority), 1996 (per) N 2066197. Bulletin of inventions No. 25, 1996.

12. Rosenberg, A. A., Silgan A. A., Aliev A. A. and other Way of getting lung surfactant. 1995 (priority), 1996 (per) N 2066198. Bulletin of inventions No. 25, 1996.

13. Anzueto a, Baughman R., K. Guntupalli et al. An international randomized, placebo-controlled trial evaluating the safety and efficacy of aerosolized surfactant in patients with sepsis-induced ARDS. New England J Med., 1996; 334: 1417-1421.

14. Weg J., H. Reines, R. Balk et al. Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced ARDS. J Am Med. Assoic., 1994; 272:1433-1438.

15. Gregory T. J., W. J. Longmore, Moxely M. A. et al. Surfactant replation following survanta supplementaion in patients with acute respiratoru distress syndrinistration in patients with severe adult respiratory distress syndrome and sepsis. Am J Respir Crit Care Med., 1996; 154: 57-62.

17. Gunter A. , Sceger W. Resistance to surfactant inactivation. In: Surfactant Therapy for Lung Disease. Ed. Robertson B. and Taeusch, H. W. - N. Y. , 1995. - P. 269-292.

18. van Iwaarden, J. F., van Golde L. M. G. Pulmonary surfactant and lung defense. In: Surfactant Therapy for Lung Disease. Ed. Robertson B. and H. W. Taeusch, N. Y., 1995. - P. 75 -92.

19. F. X. McCormack, R. J. Mason Surfactant therapy in adult respiratory distress syndrome. // In: Surfactant Therapy for Lung Disease. - N. Y., 1995. - P. 573-600.

A method of treating respiratory distress syndrome in adults, including artificial ventilation of lungs and endobronchial introduction of natural lung surfactant, characterized in that as the surfactant used in the surfactant-BL, which is injected with of prvih hours development of respiratory insufficiency in the amount of 700 - 1000 mg bolus or mikrostruyno, and then after 30 - 60 min in a spray constantly, for 15 to 60 h in the amount of 30 - 60 mg/h, after which the patient extrovert.

 

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