The method of treatment of postnatal pneumonia in newborns
(57) Abstract:The invention relates to medicine, namely to resuscitation, and may find application in neonatology. The method consists in the use of artificial ventilation of lungs with more intratracheal introduction pulmonary surfactant, which is used as a drug surfactant BL or surfactant-HL, which is injected from the first hours of development of respiratory insufficiency sessions for 4 to 12 h daily for 1 to 5 days in the amount of 100 to 200 mg/kg in the form of an aerosol inhalation through the alveolar nebulizer, then stop artificial ventilation. The method provides the possibility of early mitigation of ventilation parameters, reducing the time a patient on a ventilator to 5 - 6 days, significantly increases the survival of patients and enables the use of small amounts of expensive drugs pulmonary surfactant. table 1. The invention relates to medicine, more specifically to neonatology and intensive care, and may find application in the treatment of pathology of newborns.Under postnatal pneumonia (PNP) understand infiltrative lesions of the lung parenchyma, etiological swannie with virus or bacteria is umstvennoi lung ventilation (ALV) in newborns, often premature, characterized by immaturity of many systems, including the immaturity of the cellular elements of the lung tissue. Pups are characterized by the fact that the child 
progressing to respiratory failure (NAM), hypoxemia, symptoms of common infectious toxicosis, the symptoms of tracheobronchitis, change the physical data in the lungs (see the wheezing, changes in their nature, violated the uniformity of the holding of the breath, the lung fields).detected unilateral or bilateral infiltrative changes on the radiograph of the lungs, and atelectasis.Postnatal pneumonia are registered in Russia with a frequency of 200 to 10000 newborns (or about 25 thousand patients per year) with a mortality of about 30% .Etiological EOR arise from bacterial and / or viral ante-, peri - and postnatal infection and a known weakness of the immune system of newborns, especially premature. The most frequent etiological factor of the PNP are the causative agents of sexually transmitted infections (cytomegalovirus, herpes virus I and II Tina, chlamydia, Mycoplasma, Ureaplasma) and other flora: for group B Streptococcus, Pseudomonas aeruginosa, klasicheskii newborns with EOR, accompanied NAM II-III severity, is the use of mechanical ventilation with a "hard" settings, antibacterial and antiviral therapy, substitution immunoterapii and all necessary resuscitation measures aimed at the treatment of critical conditions period navorochennoy (inotropy, parenteral nutrition, and so on . Under "hard" parameters IVL understand the use of high partial pressure of oxygen in the inhaled gas mixture (FiO2- 0,8-1,0 i.e., 80-100% oxygen), high peak pressure breathing (more than 25-35 cm H2O), large amounts of supplied gas mixture (12-15 ml/kg body weight) and required positive pressure at the end of the expiratory (peep) [3, 4]. In the treatment of newborn pups severity of the child is assessed clinically and monitoring of blood gas composition, parameters of acid-base balance, metabolic index - BE. In particular, based on the value of the oxygen tension in arterial blood (PaO2), the value of which in norm should be 75-80 mm RT.article when breathing ambient air. In this case, IO (ratio of PaO2/FiO2) must be in the range 370 - 400 mm RT.article.In the last 5 years in the treatment of EOR in addition to those specified RDS newborns .There are several preparations of pulmonary surfactant: synthetic (Exosurf, Glaxo-Wellcome, USA-UK; ALEK, Britainca, UK), semisynthetic (Surfactant-TA, Tokyo Tanabe, Tokyo, Japan; Survanta, Ross/Abbott Lab. , Chicago, USA) and natural (Curosurf, Chiesi Farmaceutici, Farma, Italy; Alveofact, Thormie GmbH, Biberach, Germany; Infasurf, Forrest Labs, St. Louis, USA; CLSE, Rochester, NY, USA; Surfactant-HL  and Surfactant-BL [71.Some of the main characteristics of these products are given in table. 1. [6, 7, 8].There is a method of treatment of newborn pups, which provides information about the treatment of two patients suffering from severe viral (respiratory scientically virus, RSV) pneumonia . Both children were on a ventilator with a "hard" settings, and the introduction of surfactant helped to mitigate these parameters and to reduce the time spent by patients on a ventilator.There is a method of treatment of 3-week-old child with severe DN (rdsw) . The child was on a ventilator with a "hard" settings (under a lot of pressure on a breath - 58-62 cm aq.art., FiO2= 1.0, with the saturation of hemoglobin with oxygen (Sat) does not exceed 92 - 94% (norm 98 -100%). The child along with all the necessary therapy was introduced drug surfactant Exosurf at a dose of 270 mg of 4 hours after the introduction of managed SNA discharged home.There is a method of treatment of full-term infants (infants with severe respiratory failure (NAM)  . The authors analyzed the treatment of 328 patients on hard settings, mechanical ventilation (FiO2to 1.0). The aim of the study was to find out the possibility of reducing the frequency of transfer of the child to the system of extracorporeal membrane oxygenation (ecmo) - unsafe, very expensive and accompanied by a large number of complications treatment of such patients. This work was conducted in 44 neonatal centers in the form of a double-blind, randomized trial. 167 children were received in addition to standard treatment with 4 doses of natural lung surfactant (Survanta) 100 mg/kg of body weight every 6 hours. The first dose was administered 30 minutes after the inclusion of the children in the study (the criterion for inclusion in the study, in particular, was the time spent by the child on a ventilator prior to treatment with surfactant, which ranged from several hours to 5 days after birth and averaged 31 hours after birth). The authors found that the demand ecmo was lower in the group treated with ART (29,3%), in comparison with the control group (K) - (40%). In both groups the number and severity of complications (the syndrome is of n from each other. Mortality in both groups on the 28th day of life was the same. Both groups were the same, the time spent on mechanical ventilation (8 days - ST and 7 days), the time spent on oxygen support (12 days ARTICLE and 11), the time spent on ecmo (110.0 h - ST and 110.5 hours) and hospitalization time of 17.5 days (2 - 107) in the group receiving ART and 18.0 days (2 - 97).In children receiving ART was significantly more complications (and these complications were dose-dependent) from intratracheal injection (mean not only ARTICLE): 32.8% in the group with ST and 8.0% in K. These complications: hypoxia (p<0.001) and occlusion of the endotracheal tube (p<0,001).
2on the course. The authors have introduced the drug bolus (or jet) for 10 - 15 minutes. The time spent by patients on a ventilator in the group It ranged from 4 to 28 days, and in the group that received Infasurf, from 3 to 37 days. All this time the children were "hard" settings, ventilation, i.e., at high concentrations of oxygen in the inhaled gas mixture (FiO2= 0,8-1,0 or 80-100% oxygen), high peak pressure during inhalation (30 - 35 cm aq. Art. ) and high positive expiratory pressure (peep) - 8-10 cm aq. Art. In the group of children treated with surfactant IO at the beginning of treatment was in the range of from 48 to 214, and in the band from 54 to 96 mm RT.article Of the 4 children who received ART, died single; in the group To all four children survived.The technical result of the present invention is to reduce the time spent by children on a ventilator due to a change in the schema of the drug.This result is achieved by the fact that pulmonary surfactant is injected from the first hours of development of respiratory insufficiency daily for 4 to 12 hours, and enter it in the form of an aerosol in the number of 100 - 200 mg/kg within 1 to 5 days, after which artificial ventilation ceased.It is advisable ispolzovatblizhny proteins 2%.Doing professionally for the treatment of severe respiratory insufficiency II-III severity in preterm infants with respiratory distress syndrome of newborns (RDTS), traditional methods (oxygen therapy in 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 4 - 6 hours per day for 1 to 3 days. When you type the amount of surfactant was 50 mg/kgReceiving in most cases, the positive results of this treatment regimen, we attempted to use it in the treatment of very severe children with EOR, accompanied NAM II-III severity.We received the first impressive results from a 6-hour session inhalation Surfactant-HL in the form of an aerosol using a nebulizer at a dose of 100 mg/kg in the form of stabilization of the condition is very severe premature child (body weight at birth 1160 g of twins), who on the third day of life has evolved EOR. The parameters of mechanical ventilation in a child at the beginning of the ARTICLE therapy were as follows (FiO2= 0,9; PVD.= 30 cm aq.art., Peep = 8 cm aq.cent.), and hypoxemia was characterized by the value of PaO2= 56 mm RT.article IO during this session of ART therapy increased from 62 to 220 mm RT.article We continued to him the introduction of the drug in the same way in two days (72 hours), after which IO has reached 320. The child was removed from the critical state and mechanical ventilation was discontinued. Radiographically there was a significant increase in vozdushnosti" settings IVL: FiO2from 0.9 to 0.5. Nevertheless NAM remained quite pronounced and child within the next two days spent another 2 sessions of ART therapy at 100 mg/kg daily. In the process of this treatment was able to reduce FiO2to 0.3, then to remove the child from the ventilator.For treatment we used Surfactant-HL derived from the amniotic fluid of pregnant women (surfactant person) containing 93.8% of phospholipids, 4,4% of neutral lipids and 2.0% surfactant-associated proteins, which we have introduced the session for 6 hours per day in the amount of 100 mg/kg (i.e., only child received 360 mg of the drug).A positive result encouraged us to continue the research to determine the optimal modes of ART-therapy EOR in newborns.Our proposed scheme is the use of surfactant was found empirically.The introduction of surfactant in a sufficiently large dose (100 mg/kg) in aerosol form (via nebulizer) provides a uniform distribution of surfactant in the alveolar surface of the lungs due to the homogeneous structure of the population of particles (droplets) of the surfactant amount is not more than 5 μm, formed by the nebulizer, which, in our opinion, is very important for sorption on it of toxic lactante. Binding of toxic compounds on the particles of the injected surfactant and their elimination with phlegm leads to detoxification and functioning of the injected surfactant . The latter leads to the normalization of the functional state of the lung parenchyma.The introduction of surfactant in the form of an aerosol for 1 - 5 day sessions in the amount of 100 to 200 mg/kg provided relief EOR in all of our clinical observations made to date, 16 heavy DUP accompanied by respiratory insufficiency II-III severity in infants aged 1 to 28 days. Of these 16 children survived 15.The introduction of surfactant in the amount of 100-200 mg/kg due to the introduction of the aerosol sessions 4-12 hours allows you to not limit a very large number of drug, 100 mg - 1000 mg of surfactant treatment. This is particularly important given the high cost of drugs surfactant. The cost of natural surfactant preparations is 500 - 700 US $ per dose (50 - 75 mg).Our proposed scheme is the introduction of surfactant allows exuberate patient immediately after edema respiratory failure. Moreover, the use of surfactant on offer is the 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 (Survaiita) and 1.0% - 1.5% natural (Alveofact, lnfasurf 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, such as 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. These proteins bind the resistance of the native surfactant to inactivation, hemitriccus activity of surfactant in relation to alveolar macrophages, the ability stimulii and so D. [14, 15].3. They also inhibit in vitio the ability of polymorphonuclear leukocytes and alveolar macrophages to excretion (release) cytokines - molecular components provospalitelna cascade. The last damage alveolararterial membrane is the basic structural and functional element of pulmonary gas exchange .The method consists in the following.The newborn child to the clinic EOR, accompanied by severe respiratory insufficiency II-III degree of gravity located on a ventilator and require "hard" settings, ventilation, immediately after diagnostic confirmation pups injected surfactant (Surfactant-HL or Surfactant-BL) in the form of an aerosol inhalation using a nebulizer sessions 4-12 hours within 1 to 5 days at a dose of 100 - 200 mg/kg (daily) containing phospholipids 89 - 93,8%; neutral lipids 4,2 to 9% and surfactant-associated protein - 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 are selected on the basis of inhalation of 10 to 50 mg of drug per hour. Use a dilution of surfactant 50-75 mg in 5.0 ml of saline. Once in 3 days perform Reeve and with increasing oxygen tension in arterial blood (PaO2) more than 80 - 90 mm RT.article 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. Baby H-1., history N2531 (in vitro fertilization), was born in the hospital N15, Moscow from the second operational premature birth at 28 weeks of pregnancy, the first fruit of the twins in the leg previa, body weight at birth 1160 with estimation on Apgar scale 5-6 points. On the third day of life symptoms of infectious toxicosis due to the development of postnatal pneumonia, with arterial hypotension and the development of decompensated metabolic acidosis. On the radiograph lung infiltrative changes on both sides, in combination with atelectasis. In connection with the development of severe respiratory failure (DN-III) the child was santourian and placed on a ventilator with the following parameters: (FiO1= 0,9, PVD.= 30 cm aq. Art., peep = 8 cm aq.cent.). Hypoxemia was characterized by the value of PaO2= 56 mm RT.article ie and IO was equal to 62. Along with the basic antibiotic therapy and the introduction of inotrope for StabiliTrak pulmonary surfactant person (Surfactant-HL) through the alveolar nebulizer dose of 100 mg/kg (120 mg). Inhalation lasted 6 hours and after 4 hours from the beginning of the ARTICLE therapy improved blood gas parameters (PaO2110 mm RT.article and FiO2was reduced from 0.9 to 0.5, i.e., IO has increased from 62 to 220 mm RT.article We continued to him the introduction of the drug in the same way in two days (72 hours), then IO reached 320, the child was removed from the critical state and mechanical ventilation was discontinued. Radiographically there was a significant increased airiness of the lungs. 10 the day the child was transferred to the pediatric unit. For treatment we used Surfactant-HL and total child received 360 mg of the drug.Example 2. Baby H-2., history N2532 (in vitro fertilization), was born in the hospital N15, Moscow from the second operational premature birth at 28 weeks of pregnancy, the second fruit of the twins in the leg previa, body weight at birth 1080 g estimation on Apgar scale 3 points in a very serious condition with irregular breathing. At 2 minutes of life were intubated and mechanically ventilated transferred on a ventilator. On the second day showed signs of infectious toxicosis due to the development of EOR. The girl noted the grayness of the skin, hypotension, decompensated metabolic ACI is stayed DN-III. The child was on a ventilator with a "hard" parameters: (FiO2= 1,0; PVD.= 25 cm aq.art., Peep = 8 cm aq. Art. ) PaO2was equal to 48 mm RT.article and IO, respectively, equal to 48. Along with the basic antibiotic therapy and the introduction of inotrope to stabilize hemodynamics child immediately after diagnosis with EOR DN-III was launched aerosol introduction of natural lung surfactant person (Surfactant-HL) through the alveolar nebulizer dose of 150 mg/kg (160 mg). Inhalation lasted 12 hours and after 6 hours from the beginning of the ARTICLE therapy improved blood gas parameters: PaO2reached 82 mm RT.article and FiO2was reduced from 1.0 to 0.6, i.e., IO has increased from 48 to 120 mm RT.article Re-introduction of the ARTICLE on the following day resulted in the decrease FiO2to 0.4; PaO2reached 120 mm RT.article and IO rose to 300 mm RT.article After three days from the beginning of the ARTICLE therapy significantly increased airiness of the lung tissue, DN disappeared and the child was removed from the ventilator. All newborn received 320 mg of Surfactant-HL on the course of therapy. On the 12th day after birth and moved EOR the child was transferred to the II stage of nursing.Example 3. Child,, history N2454, was born in the hospital N15, Moscow from the first premature Rola at birth 1950, assessment on a scale of Apgar scores 5-7 points. The child was in serious condition due to the increase of the RDTS. At the age of 1 hour of life were intubated and mechanically ventilated transferred on a ventilator with a "hard" parameters: (FiO2= 1,0; PVD.= 30 cm aq.art., Peep = 7, see aq.CT.) while PaO2was equal to 42 mm RT.article and IO is equal to 42. On the third day of life (and being on a ventilator) the child has developed right-sided pneumothorax and increased symptoms of infectious toxicosis were revealed bilateral infiltrate on the chest radiograph. Diagnosed with EOR DN-III. One hour after radiographic confirmation EOR child started ART therapy preparation of Surfactant-BL (natural surfactant from the lung of cattle) at a dose of 100 mg/kg (200 mg per 6-hour session). The drug was administered in an aerosol inhalation via nebulizer daily for 5 days. 48 hours after the beginning of the ARTICLE therapy had positive dynamics of blood gases and increasing PaO2UP to 90 mm RT.article and FiO2managed to reduce to 0.6. Thus IO increased from 42 to 150. Despite the stabilization, the child's condition remained severe due to continued infiltrative changes on the radiograph of the lung and persistent DN-II, ART therapy bit FiO2to 0.5, and then on the 4th day to 0.3 (IO - 240 mm RT.cent.). In connection with the closing of pneumothorax during the 5-day ART therapy, the child was transferred to a ventilator (IO - 320 mm RT.cent.), and on the same day mechanical ventilation was discontinued. By day 15, the child was transferred to the pediatric unit. Only child received in the process of ART therapy 1000 mg of Surfactant-BL and was on a ventilator for 5 days.Example 4. Child F., history N3176. The girl was born in the hospital N15, Moscow from the second preterm birth at 32 weeks gestation, weighing 2120 g, with rating on a scale of Apgar 6-7 points. From the first hours of life the child was in serious condition due to the growing phenomena of RDTS and at the age of 2.5 hours the child was santourian and placed on a ventilator with a "hard" parameters: FiO2= 0,8; PVD.= 25 cm aq.art., Peep = 7 cm aq.cent.), while PaO2was equal to 60 mm RT.article and IO is equal to 75 mm RT.article On the second day, the child has developed bilateral pneumothoraces and EOR. The child had a drainage of the pleural cavities and started inhalation aerosol Surfactant-BL through the alveolar nebulizer dose of 100 mg/kg (200 mg per session). Inhalation was carried out for 4 hours and PaO2increased at the end of this session from 60 to 80 mm RT.art., but it was not possible to reduce FiO2 is in the next 3 days was re-conducted sessions of ART therapy. On the third day ART therapy closed pneumothorax and for 5 days significantly decreased hypoxemia (PaO2increased from 80 mm RT.article up to 120 mm RT.art., and FiO2managed to reduce to 0.3, respectively, IO increased to 360 mm RT.article By the end of 6 days of clinical and radiographic signs EOR disappeared and the child was removed from the ventilator. Total patient received within 4 days 800 mg surfactant. On day 7, the girl was transferred to the intensive care unit at the second stage of nursing.To date, the proposed method of treatment 16 newborns with EOR, accompanied DN-II-III degree of severity. One child died from sepsis.The proposed method is compared with the known has a number of significant advantages.1. The method can significantly reduce the time spent by patients on a ventilator to 5-6 days, and being on "hard" settings, mechanical ventilation up to 3 days, whereas in the method-prototype of the patients were on the "hard" settings, the ventilator to 31 days. This drastic reduction in time spent newborns with PNP on mechanical ventilation is important to prevent the development of bronchopulmonary dysplasia - threatening complications of pathology neonatal period in children with lung immaturity.2. Some as in method prototype - one of the four. The severity of the condition in our study was similar to the newborn in a method prototype. In our case, when joining in ART therapy IO in children was in the range of 42 to 75 mm RT.art., in the method prototype from 48 to 214 mm RT.article Moreover, as can be seen from the examples, two children prior ART-therapy had a one - or two-sided pneumothorax, a condition that is associated with the use of "hard" settings IVL amid profound immaturity of the lungs and which is a contraindication to the use of drugs surfactant.3. The method allows the use of a small amount of surfactant preparations (300 - 1000 mg for the entire course).It should be noted that drugs of natural pulmonary surfactants are expensive and the cost of such a course prototype is estimated at up to 20,000 USD. (Bottle of 60 - 100 mg drug costs 500 - 700 $ [17, 18].4. An important advantage of the proposed method is the use of drugs Surfactant-HL and Surfactant-BL - natural pulmonary surfactants containing 89% - 93.8% of phospholipids, 4,2% - 9% neutral lipids, and characterized by a high content of surfactant-associated protein - 2,0%.The method developed by the staff of the Central scientific studies the CSO Institute of Pediatrics and children's surgery MZ the Russian Federation and is clinically tested with 16 full-term and premature infants with postnatal pneumonia, accompanied NAM II-III degrees, with positive effect.REFERENCES
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