RU2180236C2 - Method for treating the cases of burn shock - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves applying infusion therapy with human superoxide dismutase preparation added. EFFECT: enhanced effectiveness of treatment; avoided adverse side effects. 6 cl

Description

 The invention relates to medicine, namely to anesthesiology-resuscitation and combustiology, and can be used in the treatment of seriously burned.

 Numerous methods of treating burn shock are known, including carrying out infusion therapy. The main components of this therapy are the administration of crystalloid and glucose solutions; synthetic colloids; blood products (plasma, albumin); anticoagulants; disaggregants; microcirculation enhancing drugs; antihistamines; hormonal drugs; vitamins. Quantitative and qualitative calculation of infusion therapy is carried out according to well-known formulas (Evans EI et all. Fluid and electrolite requirement in severe burns. - Ann. Surg., 1952, 135, 804-815; Cristol J., Berling Ch. La reanimation urgence des brules graves. - Presse Medicale, 1961, 69, p. 2313-2316; Artz CP, Moncrief JA The triatment of burns. Philadelphia, London, Toronto: WBSaunders, 1969; Pessereau G. Les grands brutes. - Presse Med., 1968 76, 861-864; Baxter CR, Shires T. Physiological response to crystalloid resuscitation of severe burns. - Ann. NY Acad. Sci., 1968, 150, 874-94; Moore FD The body waight burn budget (basic fluid therapy for the early burns) - Surg. Clin. NA, 1970, 50, 1249-1265; Nasilowsky W. A simplified formula for carculation of the requirement for fluids in severe burned patients. - Pol. Tyg. Lek., 1971, 26, 1950-1952 and others.).

 The common disadvantages of all the above methods are the relatively low treatment efficiency and high frequency of complications that develop after removing the victims from the state of burn shock (sepsis, pulmonary edema, cerebral edema, multiple organ failure, etc.).

 A known method of treating burn shock through complex therapy, including the introduction of anticoagulants, antiplatelet agents, antihypoxants, protease inhibitors and additional administration of troxevasin at a dose of up to 500 mg per day (RF patent 1754107 from 08/15/1992).

A known method of treating burn shock, including the introduction of Ringer's solution, polyglucin, diphenhydramine, dipyrone, dipyrone, vitamin B ₆ , glucose, reopoliglyukin, novocaine, ascorbic acid, strophanthin, hemodez, aminophylline, plasma, kontrikala, heparin (RF patent 2039555 from 07.20.1995) . New in the method in relation to previously known is the additional introduction of mildronate, clonidine, trental and relanium.

 The disadvantage of the above methods is that in their implementation are not used drugs with pronounced antioxidant activity. Ascorbic acid has a weak antioxidant activity, in some cases it has a prooxidant effect and promotes the generation of reactive oxygen species.

 The closest in combination of essential features is a method of treating burn shock, in which, as part of complex infusion therapy, the victim is administered troxevasin, alpha-tocopherol, contracal in moderate therapeutic doses, tactivin and myelopid in doses 2-3 times higher than established (RF patent 1836947 from 03/30/1993).

The specified method has the following disadvantages:
- the used antioxidant alpha-tocopherol has the ability to destroy only one of the types of activated oxygen species - the hydroxyl radical (OH ^- ). At the same time, many other compounds containing unstable oxygen atoms are formed in the blood: superoxide anion radical (O ₂ ^- ), hydrogen peroxide (H ₂ O ₂ ); pergidroksilny radical (H ₂ O ^_2). singlet oxygen (O ₂ ^* ); hypogaloids (OCl ^- , OBr ^- , OI ^- ); superoxide radical ^(. RO _2), alkoxy radical ^(. RO), that the weights for burn shock and negatively affects the overall hit state;
- alpha-tocopherol inhibits only the final stage of peroxidation processes - the process of lipid oxidation and cannot reduce the intensity of oxidative stress in the early stages after thermal injury during the development of a burn shock clinic;
- alpha-tocopherol is produced in the form of an oil solution and is administered only intramuscularly, its absorption into the systemic circulation is slow, and the therapeutic effect is low.

 The aim of the invention is to increase the effectiveness of treatment of burn shock by introducing into the complex therapy of the drug superoxide dismutase person with antioxidant properties.

 Superoxide dismutase converts the radical superoxide anion into hydrogen peroxide, which is then destroyed by the catalase and glutathione enzyme system to water and oxygen. The introduction of superoxide dismutase allows you to prevent the generation of a number of toxic forms of oxygen and lipid peroxidation products formed in the period of burn shock, which can reduce damage to organs and tissues during this period of time. The use of superoxide dismutase preparations also eliminates the secondary effects of inflammatory mediators. The introduction of superoxide dismutase eliminates vascular spasm, improves microcirculation, reduces the degree of aggregation of blood cells, prevents thrombosis and has other effects.

Human superoxide dismutase is part of the Erisod and Rexod preparations, the manufacturing technology of which was developed by the staff of the State Scientific Research Institute for Highly Clean Biological Products (St. Petersburg). In appearance, the substance of the preparations is a white powder, hygroscopic, odorless. The substance is soluble in water and in a 0.9% solution of sodium chloride for injection. The drug is non-toxic, its administration in doses up to 0.1 g / kg was not accompanied by any manifestations of a toxic effect, with the intravenous administration of LD _{50 it has} not been established. The drugs underwent clinical trials in accordance with the decision of the Pharmacological Committee of the Ministry of Health of the Russian Federation, permission for their parenteral use in adults was obtained (VFS 42-2765-96). Human superoxide dismutase preparations have not been previously used to treat burnt ones.

туловища и верхних конечностей. Ожоговый шок 1 ст.The method is as follows: in the complex infusion therapy for patients in a state of burn shock, within 6 hours after the injury, drugs based on human superoxide dismutase (Erisod or Rexod) are additionally administered intravenously, with the dose in case of burn shock I the degree is 16-24 mg per day, in the case of burn shock II degree 24-32 mg per day and with an extremely severe degree of burn shock 32-40 mg per day. For intravenous administration, superoxide dismutase preparations are added to solutions of crystalloid, glucose and amino acids and administered intravenously; the rate of administration is from 0.5 to 2.0 mg of enzyme per hour
Example 1. Patient K., 20 years old, medical history 34690, was admitted to the clinic of thermal lesions of the Military Medical Academy 2.09.97. at 13 hours 50 minutes. The victim was at home in the kitchen, due to an epileptic seizure, she lost consciousness and fell on a burning stove. Delivered to the clinic by an ambulance team 45 minutes after the injury. Upon admission, the following diagnosis was made:
Flame burn

torso and upper limbs. Burn shock 1 tbsp.

The general condition of the victim is severe. In consciousness, somewhat inhibited. Intact skin and mucous membranes are pale, cool to the touch. Temperature 36.2 ^o C. The breathing is harsh, moderately weakened, on the right - dry rales. Respiratory rate 18 per minute. The pulse is satisfactory filling, rhythmic, with a frequency of 70 per minute. Heart sounds are muffled, no noise. Blood pressure 100/70 mm RT. Art. Central venous pressure of 20 mm of water. Art. (on the subclavian catheter). The abdomen is soft, painless in all departments upon palpation.

The victim performed the primary toilet of burn wounds, dressings with solutions of antiseptics were applied. Also performed puncture and catheterization of the right subclavian vein according to Seldinger. Started infusion therapy of burn shock. During the first day, the volume of infusion therapy was 5400 ml (including 2000 ml of Ringer's solution, 2000 ml of 5% glucose, 650 ml of Trisol solution, 750 ml of plasma). In addition, the patient drank 600 ml of fluid. The victim received the following drugs: heparin, 5 thousand units; trental of 3 ml; diphenhydramine in 2 ml of 1% solution; B vitamins (B ₁ - 2 ml of 3% solution, B ₆ - 2 ml of 2.5% solution, B ₁₂ - 200 μg each); nicotinic acid (2 ml of 1% solution); ascorbic acid (10 ml of 5% solution each); Riboxinum (on 5 ml of 2% solution); gastrocepin (2 ml each); sibazon (on 1 ml of 0,5% solution). In addition, a superoxide dismutase preparation was prescribed (Erisod at a dose of 16 mg per day, which was dissolved in crystalloid solutions and was administered continuously throughout the day). After prescribing the drug, the patient's blood gas composition and acid-base status improved. In blood tests, 15 minutes after the administration of the drug, a decrease in the luminescence of arterial and venous blood was observed (before the introduction of arteries and veins 31 and 26 mV, after the introduction of 27 and 24 mV, respectively), which directly indicated a decrease in the concentration of activated oxygen species in the obtained blood samples .

20 hours after the injury, the patient's condition remained severe, but stable, the intact skin was pale pink, warm to the touch. Body temperature 36.9 ^o C. Respiratory rate 18 per minute. Heart sounds are sonorous, blood pressure 115/70 mm RT. Art. The pulse is rhythmic, 74 beats per minute. Central venous pressure of 40 mm of water. Art. The abdomen is soft, painless. Diuresis during the observation period is 3000 ml (not less than 75-100 ml / hour). An hour later, the victim completely got out of the state of burn shock.

Scheduled treatment was prescribed, including the implementation of infusion-transfusion, antibacterial, desensitizing therapy. The victim received vitamins, anticoagulants, antiplatelet agents, symptomatic therapy. The burn disease proceeded without complications; further treatment did not have any features. To close granulating wounds, two autodermoplasty operations were performed (S = 800 cm ² from September 25 and S = 300 cm ² from 09.10). Discharged from the clinic on 10/29/1997 in satisfactory condition.

головы, туловища, верхних конечностей. Ожоговый шок 2 ст.Example 2. Patient F., 39 years old, medical history 34920, was admitted to the clinic of thermal lesions of the Military Medical Academy 09/18/96. He was injured on September 17, 1996 at the dacha as a result of falling into a fire while intoxicated. During the day I did not seek medical help, during this time I drank about 10 liters of water. Delivered to the clinic by ambulance, non-narcotic analgesics were administered on the way to the victim, no infusion therapy was carried out. Upon admission, the following diagnosis was made:
Flame burn

head, trunk, upper limbs. Burn shock 2 tbsp.

The general condition of the patient was regarded as severe. Consciousness is clear. The intact skin is pale pink, cool to the touch. Body temperature 36.2 ^o C. The vesicular breathing with a harsh tint. Respiratory rate 22 per minute. The pulse is satisfactory filling, rhythmic, with a frequency of 100 per minute. Heart sounds are clear, pure. Blood pressure 130/70 mm RT. Art., central venous pressure - 40 mm of water. Art. on the femoral catheter. The tongue is dry, covered with a whitish coating. The abdomen is soft, somewhat painful on palpation in the right hypochondrium. Ortner's symptom is positive. The liver is enlarged, protrudes from the edge of the costal arch by 3 cm. In blood tests: moderate blood concentration (Нb 150 g / l); arteriovenous hypoxemia (pO ₂ art. = 68 mm Hg, pO ₂ veins = 27 mm Hg); compensated metabolic acidosis (pH 7.3; SBE = -4.5, ABE = -3.3); hypoproteinemia (total protein 50 g / l).

The victim had a toilet for burn wounds, dressings with iodopiron solution were applied. A puncture and catheterization of the right femoral vein according to Seldinger was performed, and infusion therapy of severe burn shock was started taking into account the delay in starting therapy and the peculiarities of self-help. During the first day, the volume of infusion therapy was 5700 ml (including 2800 ml of Ringer's solution, 400 ml of hemodesis, 1500 ml of 10% glucose, 500 ml of aminosteril, 500 ml of plasma). The patient drank 1100 ml of liquid. Drug therapy included the introduction of the following drugs: anticoagulants (heparin in 5 thousand units every 6 hours), antiplatelet agents (trental in 3 ml), antihistamines (diphenhydramine in 2 ml of 1% solution), B vitamins (B ₁ 2 ml of 3% solution, B ₆ 2 ml of 2.5% solution, B ₁₂ - 200 μg each), nicotinic acid (2 ml of 1% solution), ascorbic acid (10 ml of 5 % solution), riboxinum (5 ml of 2% solution each).

The victim was also prescribed the drug “Erisod” at a dose of 24 mg per day, which was dissolved in ringer and glucose solutions, was administered at a rate of 1 mg per hour continuously throughout the day. After prescribing the drug, an improvement in the gas composition of the blood was noted after 15 minutes: increased pO ₂ art. up to 93 mmHg Art. , pO ₂ veins. up to 38.4 mm Hg; indicators of the acid-base state improved (SBE = -1.1; ABE = -0.3). At the same time, a decrease in the luminescence of arterial and venous blood was noted (before the introduction of the artery and vein 37 and 41 mV, after the introduction of 34 and 36 mV, respectively), which indicated a decrease in the concentration of activated forms of oxygen in the obtained blood samples.

12 hours after the injury, the patient's condition remained severe, but stable. In the mind, adequate. The skin is pale pink, warm to the touch. Body temperature 38.1 ^o C. Respiratory rate 22 per minute. Blood pressure 130/90 mm RT. Art. The pulse is satisfactory filling, rhythmic, with a frequency of 120 beats per minute. Central venous pressure of 110 mm of water. Art. (on the femoral catheter). Diuresis during the observation period - 2800 ml (not less than 75-100 ml / hour). Anemia (Нb 100 g / l, erythrocytes - 3.0 • 10 ¹² ), hypoproteinemia (total protein 49 g / l) was noted in blood tests. According to clinical data, the injured man got out of the state of burn shock.

головы, туловища, конечностей. Ожоговый шок III ст.Example 3. Patient S., 38 years old, medical history 34962, was admitted to the clinic of thermal lesions of the Military Medical Academy at 18 hours 09/19/97. He was injured in an accident at an oil refinery. It was delivered to the clinic by ambulance 6 hours after the injury. Infusion therapy at the prehospital stage was not carried out, narcotic and non-narcotic analgesics were administered. Upon admission, the diagnosis was made:
Flame burn

head, trunk, limbs. Burn shock III Art.

The general condition of the patient was regarded as severe. Consciousness is clear, somewhat inhibited. Intact skin integument is pale, cyanotic, cold to the touch. Body temperature 36.0 ^o C. The respiration is vesicular, no wheezing. Respiratory rate 26 per minute. The pulse is satisfactory filling, rhythmic, with a frequency of 125 per minute. Heart sounds are clear, pure. Blood pressure 150/90 mm RT. Art., central venous 0 mm of water. Art. (on the subclavian catheter). The tongue is dry. The abdomen is soft, painless in all departments upon palpation. The liver is enlarged, protrudes from the edge of the costal arch by 2.5-3 cm. Anuria. In blood tests: hemoconcentration (red blood cells 5.9 • 10 ¹² ; hematocrit 55%; hemoglobin 170 g / l); arterial hypoxemia (pO ₂ art. = 77 mmHg); metabolic acidosis (pH 7.25; BE = -7.5); hypoproteinemia (total protein 48 g / l).

The victim had a toilet for burn wounds, dressings with iodopiron solution were applied. A puncture and catheterization of the right subclavian vein according to Seldinger was performed, and infusion therapy of severe burn shock was started. During the first day, the volume of infusion therapy was 19,400 ml (including 8800 ml of Ringer's solution, 8800 ml of 5% glucose, 800 ml of Mafusol solution, 1000 ml of plasma). The patient drank 350 ml of liquid. Drug therapy included the introduction of the following drugs: anticoagulants (heparin in 5 thousand units every 6 hours), antiplatelet agents (trental in 3 ml), antihistamines (diphenhydramine in 2 ml of 1% solution), B vitamins (B ₁ 2 ml of 3% solution, B ₆ 2 ml of 2.5% solution, B ₁₂ - 200 μg each), nicotinic acid (2 ml of 1% solution), ascorbic acid (10 ml of 5 % solution), metabolic correctors (riboxin in 5 ml of 2% solution), gastrocepin (in 2 ml), sibazon (in 1 ml of 0.5% solution).

In addition, the patient was prescribed a superoxide dismutase drug (Erisod) at a dose of 32 mg per day, which was dissolved in the Ringer's solution and was administered at a rate of 1.8 mg per hour continuously throughout the day. After prescribing the drug, an improvement in the gas composition of the blood was noted after 15 minutes: the pO ₂ in arterial blood increased to 97 mm Hg, blood saturation increased to 95%); slightly improved indicators of acidic ground state (pH 7.3, BE = -3.5). Also, during this period of time, a decrease in the luminescence of arterial and venous blood was observed (before the introduction of arteries and veins 68 and 53 mV, after the introduction of 45 and 36 mV, respectively), which directly indicated a decrease in the concentration of activated oxygen species in the obtained blood samples.

18 hours after the injury, the patient's condition remained severe, but stable. In the mind, adequate. The skin is pale pink, warm to the touch. Body temperature 38.2 ^o C. Respiratory rate 26 per minute. Heart sounds are weakened, blood pressure 140/80 mm RT. Art. The pulse is satisfactory filling, rhythmic, with a frequency of 104 beats per minute. Central venous pressure of 60 mm of water. Art. The abdomen is soft, painless. Diuresis during the observation period is 5000 ml (not less than 75-100 ml / hour). Blood tests showed anemia, hypoproteinemia, moderate metabolic acidosis and arteriovenous hypoxemia. The victim emerged from a state of burn shock 20 hours after admission to the clinic according to clinical data.

 In the future, the burn disease proceeded without complications, the patient was given parenteral nutrition, infusion-transfusion, antibacterial, desensitizing therapy. The victim received vitamins, anticoagulants, antiplatelet agents, symptomatic therapy. Local treatment: dressings with antiseptics, water-soluble ointments, necrolytic therapy. Surgical treatment to restore the skin: autodermoplasty from 10/15/97; 11/12/97; 11/21/97. The skin is completely restored. The patient was discharged from the hospital on December 4, 1997 in a satisfactory condition.

Claims (6)

 1. A method of treating burn shock, including carrying out infusion therapy using antioxidants, characterized in that the patient is administered intravenously human superoxide dismutase preparations in a dosage determined depending on the severity of the burn shock.  2. The method according to p. 1, characterized in that the patient is administered the drug "Erisod".  3. The method according to p. 1, characterized in that the patient is injected with the drug Rexod.  4. The method according to p. 1, characterized in that the patient is administered superoxide dismutase preparations in a dose of 16-24 mg per day with mild burn shock.  5. The method according to p. 1, characterized in that the patient is administered superoxide dismutase preparations at a dose of 24-32 mg per day in severe burn shock.  6. The method according to p. 1, characterized in that the patient is administered superoxide dismutase preparations in a dose of 32-40 mg per day with extremely severe burn shock.