The way to prevent pneumonia and respiratory distress syndrome of adults with aspiration of gastric contents

 

(57) Abstract:

The invention relates to medicine, more specifically to anesthesiology and critical care medicine, and may find application in the prevention and treatment of critical conditions in the case of direct lung gastric contents. The method consists in the fact that the patient inkubiruut, transferred on a ventilator, conduct rehabilitation bronchoscopy, inject corticosteroids and antibiotics, and not later than 12 h of pulmonary surfactant in the form of the drug, "Surfactant-BL", sessions 4-6 hours for 2-3 days daily or continuously at a daily dose of 750-1000 mg Method provides rapid stabilization of patients and increases their survival rate when using a small total course dose of surfactant. table 1.

The invention relates to medicine, more specifically to anesthesiology and critical care medicine, and may find application in the treatment of critical conditions in cases of direct lung damage.

Syndrome of acute lung lung damage due to aspiration of gastric contents (AS) first described by Mendelssohn in 1946 [1]. The author has described the treatment of 66 women with intrapartum developed acute respiratory failure due to massive ASS.

Singakerta repetition and subsequent development of severe pneumonia or respiratory distress syndrome of adults (rdsw). These conditions develop in 90% of cases after AGES and mortality is 40 - 50%.

A number of studies provide evidence that AS is the second or third most common cause of rdsw [2, 3]. Rdsw registered in the industrialized countries at the level of from 1 to 1000 [4, 5] to 3-10,5 per 100,000 population per year [6] . For Russia, this is about 15000 - 30000 per year. Severe pneumonia and rdsw, developing due to AS, are a critical state due to respiratory failure nicardipine nature, and require for the treatment of patients use the whole Arsenal of resuscitation measures including artificial lung ventilation (ALV).

Under critical conditions imply syndrome acute lung injury (SAP) and its most severe form - respiratory distress syndrome in adults (rdsw) [7], 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.article (norm 360 - 400 mm RT.article and more). IO represents the Rel is the radio of oxygen in 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, which must be less than 18 mm RT.article the adult [4, 6, 7].

Previously, these syndromes (SOLP and rdsw) were known to doctors as "shock lung", "wet lung", nicardipine (interstitial) lung edema [4, 8 Pisson].

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, long isskustvennogo circulation, post-transfusion and reperfusion syndromes) [4, 8].

Mortality from rdsw extremely high and depends on the background on which it develops. When AS it is 40-50% [9], with multiple trauma- 50 - 60% [4, 5], sepsis - 90% [10], and in the case of development rdsw on the background of toxic shock and intestinal obstruction - 100% [11].

Currently the mainstay of treatment 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) [4, 6].

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. Lou is atrabotana in Central research radiology Institute of the RF Ministry of health (cnrri health Ministry). Surfactant-HL permitted for medical use by a Decision of the Pharmacological Committee (FC) RF Ministry of health (Protocol N3 from 15.04.99). 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 critical conditions in newborns and adults.

Some of the main characteristics of these products are given in table. 1. [12, 13, 14].

However, R is the objects of study were the introduction of preparations of pulmonary surfactant, we are not found.

In some studies, the surfactant preparations used for the treatment of meconium aspiration (sterile, original cal) in case of respiratory failure in newborns. They release meconium in the amniotic fluid occurs in connection with the intensive intestinal motility caused by hypoxia occurring during a difficult delivery or malposition of the fetus. Prevention of meconium aspiration is to prevent hypoxia.

Traditionally, to prevent AS take measures aimed at reducing the volume and acidity of gastric contents. These include fasting for 6 to 12 hours, the use of prokinetics (drugs, accelerating the evacuation of gastric contents), antacids (drugs that reduce the acidity of gastric juice, which is in the lumen of the stomach) and antisecretory drugs that reduce the secretion of hydrochloric acid goblet cells of the gastric mucosa.

Most JS often occurs in high-risk groups of patients: pregnant women in childbirth and surgery patients with "full" stomach ("full" stomach is a common term in surgery and anesthesiology). These patients, which do not require the Third group - patients with disorders of consciousness of various origins: alcohol intoxication, stroke, traumatic brain injury.

If necessary, emergency surgical intervention under General anesthesia requiring intubation and transfer to the patient on a ventilator in patients with "full" stomach traditionally use the quick method of induction of anaesthesia, which includes the special position of the patient (reverse Trendelenburg) with a raised head end of the operating table, taking Celica, which consists in mechanical pressure on the cricoid cartilage to the squeezing of the esophagus, and finally, the exclusion of artificial ventilation through a mask. In that case, if the patient's condition and level of consciousness, before surgery, gastric lavage is carried out.

However, in some cases, the application of all of these preventive measures to prevent AS ineffective.

In the same case, if this aspiration has occurred, all efforts aimed at reducing the damaging effects on the pulmonary parenchyma acidic gastric contents. In this case, spend bronchial lavage (bronchial lavage with saline). Regarding the this these approaches are traditionally not used.

Trying to prevent the activation of Pro-inflammatory cascade induced by acidic gastric contents when exposed to the mucous membranes of the bronchial and alveolar epithelium, injected large doses of glucocorticoids. They also contribute to the prevention of bronchospasm. Further measures aimed at removing the patient from developed critical state. They consist in the transfer of the patient to the ventilation required positive pressure at the end of the expiratory (peep) and rational prescription of antibiotics.

There is a method of treating syndrome meconium aspiration (SAM) [15]. The authors conducted a retrospective analysis of treatment results of 54 infants with HIMSELF, who received drug treatment natural pulmonary surfactant Curosurf. The age of the newborn at the time of the introduction of the drug ranged from 1 to 176 hours. All of these children at the beginning of treatment condition was hard, they were immediately transferred on a ventilator with a "hard" settings and after the introduction of surfactant dose of 50 to 200 mg bolus was marked improvement. 10 children (18%) 1-2 hours after the introduction of the ARTICLE mentioned 3-4-fold increase in arterial-alveolar gradient (the rate of improvement of gas exchange in the lungs), and 33% of children t the walls of the treatment rdsw, developed including after AS by mechanical ventilation and supplemental semi-synthetic preparation of surfactant "Survanta" [16]. 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 group of patients the drug was administered at a dose of 400 mg/kg in 4 separate treatment period (for a total of 32 g per course). The second 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.

Shortcomings of traditional methods of treatment of severe pneumonia and rdsw caused by AIS, including meconium aspiration, and prevention of these conditions are

1. there is virtually no ability to prevent the development of pneumonia ilof. Michael A. Matthay from the University of California (San Francisco) and Prof. Gleen D. Rosen from Stanford University (Stanford) article about the problem AS write: "unfortunately, there is no way of therapy that would be effective to reduce the severity of lung ... when aspirating gastric contents" [9].

2. the high mortality of patients undergoing AGES, including meconium aspiration,

3. large consumption of drugs surfactant as in the treatment of patients with rdsw arising from other causes, not from AGS, including high consumption of drugs in the treatment ITSELF.

The technical result of the present invention consists in the improved survival of patients by preventing the development of pneumonia and rdsw after the incident, aspiration of gastric contents.

This result is achieved by not later than 12 hours after aspiration of gastric contents enter patient pulmonary surfactant, and enter his inhalation sessions for 4-6 hours per day or continuously for 2-3 days in the amount of 750 - 1000 mg.

It is advisable to use natural pulmonary surfactant content of phospholipids in the amount of 89%, neutral lipids - 9% and surfactant-Assoc-III severity in children and adults, suffering from acute lung injury, including rdsw, traditional ways, 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, and later applying the constant inhalation of the aerosol within 1 - 3 days, we received a significant increase in survival of patients, reduction of terms of treatment and a significant decrease in the consumption of drugs surfactant in comparison with known methods.

This fact has motivated us to conduct a special study to the possibility of preventing the development of pneumonia and rdsw in patients with AS.

If AS we have introduced the surfactant immediately after removing bronchospasm patient on a ventilator in the form of an aerosol by inhalation through a nebulizer, not later than 12 hours after AGES. Took him long sessions for 4-6 hours daily or continuously in the form of a spray through bronchial nebulizer for 2-3 days in the amount of 750 - 1000 mg.

We treated three patients with AS the proposed method, and we believe the proposed scheme ART therapy optimal.

Introduction the uniform distribution of particles on the alveolar surface, that, in our opinion, is very important for sorption on it toxic components and their removal. The latter leads to the normalization of the functional state of the lung parenchyma.

Introduction surfactant sessions 4-6 hours 2-3 days, or continuously, i.e. during the entire period of possible occurrence of pneumonia or rdsw after what happened aspiration leads as to prevent destruction alveolararterial membrane due to the constant binding and excretion of toxic components and aggressive agents with bronchial secretion, and the effect of substitution therapy. During this time native surfactant inhibited aggressive components of Pro-inflammatory cascade, the activation of which is due to aspirated acidic contents of the stomach, bacterial flora present in the gastric contents, and so on, the Presence of exogenously-introduced natural surfactant in the alveolar space normalizes, as we have shown [17, 18], the structure and function of the alveolar epithelium, including alveolitis second type - producers of surfactant in the lung tissue.

The use of a preparation containing, as said above, and 2.0% surfactant-associerad the t in synthetic drugs surfactant (Exosurf), 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 [19].

2. These proteins bind antibacterial and antiviral activity of surfactants, the ability of these proteins to be active of chemoatractant in relation to alveolar macrophages, stimulate the complement-dependent and antibody-dependent capture of pathogenic bacteria and viruses alveolar macrophages, as well as the ability to resist inactivation of surfactant proteins in blood plasma that goes into the alveolar space by increasing the permeability alveolararterial membrane at rdsw [20, 21].

3. They, in addition to ogdenyou) cytokines - molecular components of Pro-inflammatory cascade [22]. The last damage alveolararterial membrane is the basic structural and functional element of pulmonary gas exchange.

The method consists in the following.

The patient caused by the aspiration inkubiruut and transferred on a ventilator. Hold him bronchoalveolar lavage with saline, injected glucocorticoids and antibiotics. Not later than 12 hours after aspiration of gastric contents in addition enter the pulmonary surfactant, via nebulizer sessions for 4-6 hours per day or continuously for 3 to 4 days in the amount of 750 - 1000 mg.

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

Example 1.

Patient M., born in 1929, history N 2215, was admitted to the hospital, cnerry (Central research radiology Institute) MOH 20.10.97 diagnosed with cancer of the sigmoid colon, obesity. 28.10.97 was executed left hemicolectomy with resection of the ileum, in 8 days - relaparotomy about the failure of the anastomosis, sanation of abdominal cavity, the imposition of a double-barreled transversality. Both operations were carried out under the th traditional intubation was impossible). 13.11.97 have any need for emergency surgery (eventtrace with risk of bleeding). Emergency tracheal intubation, despite the necessary precautions, was accompanied by significant reflux of liquid gastric contents into the tracheobronchial tree (at least 30 ml) - AGS. Urgent measures included bronchoscopic reorganization (bronchoalveolar lavage 150 ml of physiological solution), introduction glucocorticoids (200 mg hydrocortisone-succinate intratrahealno immediately after aspiration) and later in the day in connection with the re-bronchospasm still 300 mg 4 times. In addition, the patient was assigned to antibiotic - Tienam (500 mg 3 times a day), and mechanical ventilation was performed with MPCw - 7 cm aq. Art. In the first hour after AGES and forth repeatedly within 12 hours was developed severe bronchospasm, but without obvious violations of oxygenation. Given the documented nature of aspiration and clear threat to the widespread nature of the damage to your lungs, it was decided to start ART therapy. Patient after rehabilitation bronchoscopy injected drug bovine surfactant (Surfactant BL) in the form of a spray through the nebulizer, is included in the circuit of the ventilator proximal to the endotracheal is a week from the 1st to the 20th day after aspiration, signs of pneumonia was not determined. During this period the patient had no signs of hypoxemia and the oxygenation index PaO2/FiO2was not lower than 320 mm RT.article.

Result: the patient was prevented development of pneumonia or RDS after AGES, and in the process of conducting a preventive course of ART therapy was introduced 2250 mg drug Surfactant-BL.

Example 2.

Patient I. , 1934 birth, history N 2096, was admitted to the hospital, cnerry health Ministry 29.09.98 diagnosed with cancer of the output section of the stomach cachexia. The patient was examined and preparation for surgical treatment. 15.10.99 the patient was taken to the ICU from the ward: a critical condition, coma, traces of vomit on the face, dry rales over the entire surface of the lungs. The saturation of hemoglobin with oxygen (SatO2) 92% at FiO2equal to 0.21. The patient was transferred to the ventilation mode normogastria with peep -7 cm aq. Art., FiO2= 0,4 (apparatus Puritan Bennett 740). Bronchoscopy - traces of food masses in the tracheobronchial tree. Neurological condition seen as dynamic cerebral circulation. Along with traditional therapy after AS (IVL, bronchoscopic sanitation, glucocorticoid - hydro dose of 1000 mg in aerosol form during 6 hour sessions inhalation for two days in a row. Control radiographs at 2 and 3 day signs of pneumonic infiltration no. The oxygenation index is not less than 300 mm RT.article within two days of ART-therapy. Patient exuberan over 3 days on the background of reduced consciousness, was transferred to the surgery Department. The chest radiograph on day 7 showed no pulmonary pathology. The patient received a total of 2000 mg surfactant and after three days was excubitor. Development of pneumonia or rdsw he has not occurred.

Example 3.

Patient G., born in 1945, history N 2074, was admitted to the hospital, cnerry health Ministry 21.11.98 with a diagnosis of generalized lymphoma, post-plastic surgery of the esophagus, the small intestine, respiratory failure. Upon admission to the intensive care unit in a critical condition, confused consciousness, shortness of breath up to 40 per minute, hypoxemia: SatO2= 40% (PaO2= 25 mm Hg) at FiO2= 0,21. The condition rapidly deteriorated for several hours before admission. On the chest x - ray shows signs of incipient pneumonic infiltration characteristic of the state after AGES. Bronchoscopy - fibrinous deposits on the vocal cords and the walls of the trachea, a small amount of food masses in podvenechnom Proa transferred to mechanical ventilation with peep, equal to 8 cm aq.art., hydrocortisone - succinate (400 mg intratrahealno), antibiotics - Tienam (500 mg three times a day), optimization of hemodynamics (trental intravenous). With the aim of preventing the development of severe pneumonia and rdsw was immediately initiated the introduction of Surfactant-BL: at a dose of 750 mg daily in the form of a spray through the nebulizer, which lasted for three days continuously. After a few hours of treatment with surfactant marked improvement in oxygenation (index PaO2/FiO2went from 180 to 280 4 hours and up to 320 12 hours after the start of ART-therapy). 24 hours after the start of ART therapy on the chest x-ray showed reduction infiltrative changes, and on the 3rd day of recovery lightness of the lung tissue. During the third day the patient discontinued colortherapy and it is translated into the somatic compartment. Throughout the course spent 2250 mg of Surfactant-BL.

To date, the proposed method is carried out prevention of the occurrence of pneumonia and rdsw in 3 patients. All three patients, using the specified schema prevention, managed to prevent the development of acute lung injury: pneumonia or rdsu.

The proposed method is compared with iswe rdsw patients after AGES and thereby improve their survival.

2. The method requires a small amount of the drug surfactant to prevent pneumonia and rdsw for which treatment in accordance with known methods require 10 to 20 times more of these expensive drugs. Note that the cost of treatment of the prototype is estimated at 35,000 to $ USA [23].

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 characterized by a high content of surfactant-associated proteins was 2.0%. This, from our point of view, provides a more effective functioning of the surfactant and rapid normalization of pulmonary function and gas exchange.

The method developed by the staff of the Central research radiological Institute of the RF Ministry of health and was clinically tested 3 patients with aspiration of gastric contents with a positive result.

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The way to prevent the artificial lung ventilation and intratracheal injection of surfactant and glucocorticoids followed by antibiotic therapy, characterized in that the surfactant used "surfactant BL", which impose no later than 12 h after aspiration of gastric contents, and enter his inhalation sessions over 4 to 6 hours daily, or continuously for 2 to 3 days at a daily dose of 750 - 1000 mg

 

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