A method of treating respiratory distress syndrome

 

(57) Abstract:

The invention relates to medicine, namely to resuscitation, and can be used in the treatment of patients with respiratory distress syndrome. The method includes conducting drug therapy and artificial ventilation, in addition enter dismutase person and alpha-tocopherol. The method provides the inactivation of reactive oxygen species and the recovery of lung function.

The invention relates to medicine, namely to resuscitation, and can be used in the treatment of patients with respiratory distress syndrome developed after severe trauma, extensive burns, inhalation lesions, delivery, aspiration of gastric contents, as a result of developing sepsis, moved coagulopathies bleeding and other causes.

There is a method of treating respiratory distress syndrome, including artificial ventilation and drug therapy, during which part of traditional medical therapy in addition enter complamin in combination with dicinorum in pharmacologically active doses for 3-4 days (Copyright certificate 1572630 from DS treatment of respiratory distress syndrome, developed as a result of the transferred coagulopathies bleeding;

- if the process does not resolve the damaging effect of reactive oxygen species generation, which leads to the development of respiratory distress syndrome;

- with the introduction of complamin often have side effects (dizziness, headache, decreased blood pressure, and others), the drug is contraindicated in case of development of heart failure and other conditions.

Also known is a method of treatment of respiratory distress syndrome, including infusion therapy and artificial ventilation of the lungs, the implementation of which shall inhalation of nitric oxide (Bone, R. C. A new therapy for the adult respiratory distress syndrome. //N. Engl. J. Med, - 1993. - Vol. 328, 6. - R. 431-432).

The method has the following disadvantages:

- inhalation of nitric oxide does not eliminate the effect of reactive oxygen species generation, which in the body is one of the main pathogenetic factors in the development of this syndrome;

- in the process nitric oxide can interact with oxygen to form nitric acid; and with hemoglobin to form methemoglobin, which aggravates the overall SOS is e can be widely used in clinical practice.

The closest to the essential features is a method of treating respiratory distress syndrome, comprising intravenous administration of large doses (from 125 to 250 mg every 6 hours) corticosteroids for several days (Hooper RG; Kearl RA Established adult respiratory distress syndrome successfully treated with corticosteroids. // South. Med. J. - 1996, Vol. 89 - 4. - R 359-64).

The method has the following disadvantages:

the relatively low efficiency of the method is due to the fact that glucocorticoids do not have the ability to inactivate reactive oxygen species generation, which leads to the development of respiratory distress syndrome;

- the use of glucocorticoids is not possible to quickly restore the circulation and adequate gas exchange in the lungs;

- the use of large doses of glucocoticoids associated with the risk of developing side effects.

The aim of the invention is to increase the effectiveness of treatment of respiratory distress syndrome due to the introduction in the complex therapy of drugs with the ability to destroy reactive oxygen species.

Superoxide dismutase converts the superoxide anion radical to hydrogen peroxide, which then is destroyed by the enzyme catalase more toxic compared to the superoxide anion-radical reactive oxygen species, damaging macromolecules and cells. The introduction of drugs superoxide dismutase also reduces the intensity of the processes of lipid peroxidation. In addition, drugs dismutase indirectly prevent thrombosis, impaired function of the kinin system, restore the permeability of microvessels and have other effects. Introduction superoxide dismutase prevents the inactivation of nitric oxide caused by the action of superoxide anion-radical, which significantly improves pulmonary blood flow and gas exchange. Alpha-tocopherol has the ability to inactivate a different type of active forms of oxygen, singlet oxygen (Delta and Sigma), the resulting "jump" one of the electrons in the oxygen molecule to a higher energy level or, as a consequence, changes the spin of the unpaired electron. Thus, co-administration of antioxidants - superoxide dismutase person and alpha-tocopherol ensures inactivation of most types of active forms of oxygen and ensures the recovery of lung function.

Superoxide dismutase person is part of the preparations "Erised and Rexed", manufacturing technology which developed by Coburg). In appearance substance drugs is a white powder, hygroscopic, odourless. The substance is soluble in water and in 0.9% sodium chloride solution for injection. The drug is non-toxic, putting it in doses up to 0.1 g/kg was not accompanied by any manifestation of a toxic effect when administered intravenously LD50is not installed. The drugs were in clinical trials in accordance with the decision of the Pharmacological Committee of Ministry of health of RF, obtained permission for their parenteral administration in adults (VFS 42-2765-96). For the treatment of respiratory distress syndrome drugs dismutase person has not previously been used.

The method is as follows: drug therapy of patients with developed respiratory distress syndrome administered drugs on the basis of human superoxide dismutase (drug Ariad" or "Rext") in doses of from 16 to 40 mg per day of alpha-tocopherol in a dose of from 100 to 300 mg per day. In this case, preparations of human superoxide dismutase administered intravenously and through inhalation (using ultrasonic inhalers), and alpha-tocopherol, intramuscularly or orally. Intravenous preparations of superoxide dismutase EXT the place from 0.5 to 2.0 mg of enzyme per hour.

Example 1. Patient I., 1975, p., (22 years), history 34824, was admitted to the hospital thermal lesions of the Military medical Academy 10.09.1997, 15 h 20 min 1 h 20 min from the moment of injury. The victim did paint work inside a metal tank self-contained breathing apparatus. From sparks exploded vapor necrocracy. Immediately after the explosion, the patient developed bleeding from the nose, appeared hoarseness. When the receipt was put the following diagnosis: Multifactor defeat. Flame burn the head, trunk, upper extremities. Burns of the respiratory tract. Severe burn shock. Barotrauma. Poisoning by carbon monoxide severe.

Was performed puncture and catheterization of the left femoral vein by the Seldinger started infusion therapy of burn shock. If fibrobronchoscopy discovered the presence of soot up to the level of segmental bronchi, pronounced hyperemia of the mucosa, submucosal lesions of hemorrhage. Established microrheology PVC-tube with a diameter of 1.4 mm, through which began insufflation of oxygen with a bulk velocity of 5 l per minute. Performed toilet burn wounds, bandages wrapped around with a solution of itaperuna. The victim is placed on fluidizing the plasma and 250 ml of 10% albumin). In addition, the patient drank 800 ml of liquid. Medical therapy included the introduction of the following medications: anticoagulants (heparin), antiplatelet, nicotinic acid, antihistamines (demerol), b vitamins (B1B6B12), ascorbic acid, metabolic proofreaders (Riboxin). In connection with the victim inhalation defeat introduced 110 mg of prednisolone. The volume of infusion therapy for the second day was less - 2800 ml (including 260 ml of plasma and 250 ml of 10% albumin). From a state of burn shock came on 2 days after injury. He was appointed the planned therapy, including the infusion of crystalloids (global, dial, latosol, Mapusa to 1200 meters per day), 5% and 10% glucose (1200-1600 ml per day), transfusion solutions of amino acids (daily 500 ml aminosteril), plasma (500-750 ml daily), 10% albumin (100 ml), single-group blood on the testimony (250-750 ml per day). Starting from the third day, was appointed Meronem (1 g 4 times daily). The patient received gastrotsepin, Almagel, trental, heparin, nicotinic acid, vitamins b and C, vitamin complex "Centrum". The probe was introduced nutrient mixture "Supra-Plus 1.5 liters per day. Daily completed the rehabilitation fibrobronchoscopy.

Since 24.09.1997, the patient's condition stabilized. Improved respiratory function, however, the victim continued mechanical ventilation modes of Assisted-CMV and later STMV. 26.09.1997, the victim was transferred to spontaneous breathing, 06.10.1997, in a state of moderate severity the victim was transferred to a General ward. Further treatment of any of the features were not. Discharged from the clinic who drank in the clinic thermal lesions Military medical Academy, 24.09.1997 Within 3 days prior to injury was addicted to alcohol. Had been injured in the workplace in the ignition oiled clothing. When applying put the following diagnosis:

Flame burn the head, torso, right arm. Burn shock of the first degree.

Was performed puncture and catheterization of the right subclavian vein by the Seldinger started infusion therapy of burn shock. The volume of infusion therapy for the first day after the injury was 11900 ml, of which 1280 ml of plasma and 200 ml of 10% albumin. Medical therapy included the introduction of the following medications: anticoagulants (heparin), antiplatelet, nicotinic acid, antihistamines (demerol), b vitamins (B1B6B12), ascorbic acid, metabolic proofreaders (Riboxin). Burn shock was leaking heavily, with pronounced symptoms of hemoconcentration (Hb - 180 g/l) and metabolic acidosis (pH 7,27). The victim was released from the burn shock after 26 hours after injury. He was appointed the planned therapy, including the infusion of crystalloids, 5% and 10% glucose, transfusion solutions of amino acids (aminosteril), plasma, 10% albumin, blood. The patient received antibiotic therapy gastria the test mixture "Supra-Plus" by 1.5 liters a day.

On a background of treatment the patient's condition remained serious, but stable, 28.09.97. about 14 hours, the victim suddenly complained of a feeling of lack of air. Objectively: the skin is pale gray, tachycardia and 132, tachypnea up to 35 per minute, auscultation of the lungs is breathing hard with a lot of wet coarse-bubble wheeze on the inhale and the exhale. Appeared productive coughing, red sputum. The blood was arterial hypoxemia (Rho2art.=70.5 mm RT.CT.) and a sharp increase in the level of active forms of oxygen in arterial and venous blood (109 and 117 mV).

Started conservative therapy (breathing oxygen through a nasal catheter, the introduction of diuretics and glucocorticoids), which led to some improvement in General condition. During the next day the casualty's condition continued to deteriorate. Unstable hemodynamics with a tendency toward hypotension (heart rate up to 140 beats per minute, blood pressure - 95/40 mm RT.cent.), requiring inotropic support with dopamine at a dose of 9.5 g/kg/min for all day. Respiratory rate of 35 per minute on the background inhalation of oxygen through a nasal catheter at a speed of 5 l per minute. In the lungs Astana hypoxemia (Rho2art.=65 mm RT. Art., saturation of the blood, 74%). On radiographs of the chest - signs of bilateral swelling of the lungs, By the end of the day the victim developed a detailed clinical picture of respiratory distress syndrome in adults.

Given the growing phenomenon of cardiovascular and respiratory failure, was performed tracheal intubation, and started artificial lung ventilation apparatus "Engstrm Erica" (Sweden) in the CMV mode. The victim was assigned drugs Erised" intravenous dose of 30 mg per day of alpha-tocopherol intramuscularly at a dose of 300 mg per day. 20 minutes after the start of therapy was observed sharp decrease in the level of reactive oxygen species in the artery and vein - to 21 and 26 mV, respectively. The victim has improved gas composition of the blood (Rho2art. = 95 mm RT.cent.), normal acid-base status (pH 7,31, VE -1,5).

In the period from 30.09.97 on 10.10.97 the patient's condition was severe. The period of burn disease was complicated by the development of toxic myocarditis and toxic hepatitis. The victim was conducted infusion-transfusion therapy and prolonged mechanical ventilation modes CMV, Assisted - CMV and later SIMV. The victim continued to get preovolos a significant decrease in the levels of active forms of oxygen in arterial and venous blood. On a background of treatment the patient's condition has stabilized, 10.10.97 the victim was transferred to an independent breath. Further treatment of any of the features were not. He was discharged 09.12.1997, in a satisfactory condition.

A method of treating respiratory distress syndrome, including medical therapy and artificial ventilation of the lungs, characterized in that therapy is additionally injected drugs with antioxidant properties - dismutase person and alpha-tocopherol.

 

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