RU2700416C1 - Method for preventing somatic complications in the intra- and postoperative period in the patients with hip and knee joint hip endoprosthesis replacement - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to traumatology and orthopedics. Disclosed is a method for preventing somatic complications in the intra- and postoperative period in patients with hip and knee joint hip replacement. Method involves administering to a patient a preventive agent possessing antioxidant activity: Mexidol in injection and tablet form or Tiofan-M capsules, wherein Mexidol for injections is introduced 1 day and 1 hour before surgery and on the following postoperative day intravenously at a therapeutic dose of 2 mg/kg, then Mexidol is taken in tablets orally daily – 1 tablet (1 tablet 125 mg) in the morning and in evening for 1 month. Preparation Tiofan-M in capsules is taken 1 day and 1 hour before and on the following postoperative day once a day for one therapeutic dose 300 mg; then, the preparation is taken orally – 3 capsules (1 capsule 200 mg) once day for 1 month.

EFFECT: prevented somatic complications in patients on the part of the respiratory and cardiovascular systems in the immediate intraoperative period, and on the side of the liver and kidneys – in a more remote period after the surgical intervention, reduced time of prevention of somatic complications; method can be used in endoprosthesis replacement of large joints of lower extremities with cement fixation of endoprosthesis components.

1 cl, 8 tbl

Description

The invention relates to medicine, in particular to traumatology and orthopedics, and can find application in arthroplasty of large joints of the lower extremities with cement fixation of components of the arthroplasty.

The process of intensification of free radical oxidation and the development of oxidative stress are now recognized as a universal general biological mechanism in the development of any type of pathology. Biochemical changes in tissues caused by the intensive generation of reactive oxygen species mainly have common patterns. Some distinctive features can be identified only in the initial stages. So, in inflammatory processes, the trigger factor in the intensification of free radical processes is the “respiratory explosion”, in case of hypoxia - a violation, first of all, of the tissue respiration system, and in case of chemical damage - activation of the microsomal oxidation system. Thus, the reasons for the intensification of free radical processes may be different, but changes at the molecular level are of the same type and the processes of generation of reactive oxygen species are closely related. Common to all diseases is the strengthening of free radical processes and a decrease in the buffer capacity of antioxidant defense, a violation of its mobilization in response to an increase in the activity of the prooxidant system (PIC).

Performing a joint replacement operation in some cases (severe osteoporosis, anatomical features, the need for quick activation after surgery in old age) is possible only with the use of bone cement (CC). With an intervention accompanied by the introduction of polymerizable bone cement into the bone marrow wound, there is a high risk of an implantation syndrome that develops as a result of various types of embolic complications, as well as the toxic effect of methyl methacrylate monomer (MMA). The latter is one of the components in the preparation of CC. In the amount of 3-5% of the used dose, MMA can penetrate into the general bloodstream and lead to acute respiratory failure, severe hypotension, changes in heart rate up to a stop of blood circulation, myocardial infarction. Mortality in cement joint arthroplasty of large joints is significantly higher than in case of cementless endoprosthesis installation. However, to date in clinical practice there is no alternative to bone cement based on methyl methacrylate. The ongoing drug prophylaxis and treatment methods for the implantation syndrome are largely symptomatic.

A known method of preventing intraoperative complications by prophylactic administration of sufficiently high doses of corticosteroids to reduce the toxic effects of MMA, as well as drugs that prevent the development of embolic complications (Kornilov N.V., Voitovich A.V., Mashkov V.M., Epshtein G.G. Surgical treatment of degenerative-dystrophic lesions of the hip joint. St. Petersburg: LITO Synthesis, 1997. - p. 292). This method reduces the severity of the implantation syndrome, affecting the severity of fatty hyperglobulinemia, disorders of the aggregate state of the blood, as well as changes in the cardiovascular system caused by hypovolemia and a decrease in vascular tone.

However, the toxic effect of MMA does not eliminate this method.

A known method for the prevention of implantation syndrome in cement arthroplasty of the joints of the lower extremities, including intravenous administration of corticosteroids and means of preventing embolic complications (RF patent No. 2153879, IPC A61K 31/14, publ. 10.08.2000,). Puncture and catheterization of the femoral vein of the operated limb are preliminarily performed, and after the injection of bone cement into the bone marrow canal, a 0.03% concentration of sodium hypochlorite solution is infused through the femoral catheter at a rate of 50-60 cap. in 1 min for the first hour, and then at a speed of 30-40 cap. in 1 min for at least 3 hours with a total infusion volume of 400 ml.

The disadvantages of this method are:

- invasiveness (femoral vein catheterization is used, on the operation side) - can become a source of infectious and embolic complications;

- It is aimed at eliminating only the toxic effects of methyl methacrylate (bone cement), but with cement arthroplasty, the combined effect is the toxic effect of cement, the exogenous reaction during hardening, mechanical trauma from the surgery itself;

- requires stationary conditions, additional equipment and additional time for the patient to stay in the intensive care unit or intensive care unit.

A known method for the prevention of complications in cement arthroplasty of large joints by the introduction of antihypoxic drugs (RF patent No. 2229089, IPC A61K 31/52, publ. 04/20/2004). A day before surgery, reopoliglukin 5-6 ml / kg is administered intravenously together with 200 mg of trental for 60-90 minutes; 12 hours before surgery, fraxiparin is administered subcutaneously at a dose of 0.3 ml; 1 hour before the use of bone cement, 1.5% reamberin 5-6 ml / kg is intravenously administered with a duration of infusion of 60-90 minutes; 2 minutes before the use of bone cement, prednisone 1 mg / kg and 2 mg of tavegil are intravenously administered; in the postoperative period within 3 days reopoliglyukin 5-6 ml / kg and 200 mg of trental are intravenously administered for 60-90 minutes; fraksiparin in a dose of 0.3 ml subcutaneously for 7 days; reamberin 1.5% - 5-6 ml / kg intravenously 60-90 min for 3 days.

However, this method is aimed only at the prevention of thromboembolic complications in the intraoperative and early postoperative period. Exercise with prednisone is dangerous for patients with hypertension. A serious water load does not take into account the characteristics of patients with kidney disease. Known morphological data show that in the first three days with cement arthroplasty there is a reaction of the lungs in the form of their edema and, if water load is also given, then hypoxia or more tragic consequences are inevitably caused.

A known method for the prevention of intraoperative complications during arthroplasty of large joints using bone cement based on methyl methacrylate (RF patent No. 2159089, IPC A61K 31/00, published on November 20, 2000). The method includes administering intramuscularly Erisod at a dosage of 0.06 mg / kg and intravenously Metafusol at a dosage of 5.7 ml / kg 30 minutes before the use of bone cement intramuscularly with an infusion duration of 30-40 minutes Erisod is an antioxidant (superoxide dismutase), has antihypoxic, anti-inflammatory and anti-cytolytic effects. It normalizes oxidative processes occurring with the participation of oxygen free radicals and prevents the destruction of cell biomembranes associated with the activation of lipid peroxidation. Methus is a saline infusion solution, the main pharmacologically active component of which is sodium fumarate - an antihypoxant that activates the adaptation of the cell to a lack of oxygen. Its action is due to participation in the reactions of reversible oxidation and reduction in the Krebs cycle. In the process of these reactions, ATP is synthesized in an amount sufficient to maintain the functions of body cells during hypoxia.

The closest analogue of the claimed invention is the patent of Kyrgyzstan (KG) No. 1967, C1, publ. 07/31/2017, which describes a method for reducing the risk of developing infectious and thromboembolic complications during knee replacement with the introduction of the antioxidant Mexidol 90 minutes before surgery for 30 minutes and then 4 hours after surgery by intravenous infusion (i.e., injection form).

However, this method of prevention is aimed at the nearest intraoperative complications and does not prevent emerging complications within a week after surgery. Bone cement implantation syndrome is prevented only as a complication of the cardiovascular system. On the first and third days, a maximum of alternative changes is observed from the respiratory and cardiovascular systems, but on the 7th day, kidney and liver disorders are actively manifested. In addition, the proposed method of prevention requires additional equipment and time for infusion therapy, which increases the time of the operation itself, and therefore the negative impact of operational stress on the patient's body.

The technical result of the claimed invention is the provision of the possibility of preventing somatic complications arising in patients both from the respiratory and cardiovascular systems in the immediate intraoperative period, and from the liver and kidneys in a more remote period after surgery, as well as simplifying the method and reducing the time of prevention of somatic complications due to the oral route of administration of the drug into the body and its prolonged protective effect.

The specified technical result is achieved by the fact that in the method of preventing somatic complications in the intra- and postoperative period in patients with hip and knee arthroplasty by introducing a prophylactic agent with antioxidant activity into the patient’s body, according to the invention, Mexidol in injection is used as a prophylaxis and tablet form or Thiofan M in capsule form. Mexidol for injection is administered 1 day and 1 hour before surgery and the day after surgery intravenously based on a therapeutic dose of 2 mg / kg, then Mexidol is taken orally daily in tablets - 1 tablet (1 tablet 125 mg) in the morning and in the evening for 1 month. The drug Thiofan M in capsules is taken 1 day and 1 hour before and the day after surgery once a day orally at the rate of one therapeutic dose of 300 mg, then the drug is administered orally in 3 capsules (1 capsule 200 mg) once a day for 1 month.

Mexidol (ethylmethylhydroxypyridine succinate) is an antioxidant, nootropic, antihypoxant, and tranquilizer at the same time. In addition, the medication has an anticonvulsant, antiparkinsonian, antistress and vegetotropic property.

Mexidol (ethylmethylhydroxypyridine succinate) in the body acts as follows:

подавляет вредоносное действие свободных радикалов, активизирует супероксидисмутазу;

suppresses the harmful effects of free radicals, activates superoxide dismutase;

увеличивает концентрацию полярных субстанций липидов, замедляет их перекисное окисление;

increases the concentration of polar substances of lipids, slows down their peroxidation;

активизирует энергетическую способность митохондрий, за счет чего усиливаются обменные процессы в клетках;

activates the energy ability of mitochondria, due to which metabolic processes in cells are enhanced;

препятствует агрегации тромбоцитов;

interferes with platelet aggregation;

положительно влияет на мембранные свойства, оказывает стабилизирующее действие на мембраны;

positively affects membrane properties, has a stabilizing effect on membranes;

нормализует передачу импульсов в нервной ткани;

normalizes the transmission of impulses in the nervous tissue;

положительно воздействует на липидный обмен: уровень общего холестерина и ЛПНП уменьшает, а ЛПВП повышает.

positive effect on lipid metabolism: the level of total cholesterol and LDL decreases, and HDL increases.

Thiophan M (sulfane), chemical formula: bis - [(3,5-di-tert-butyl-4-hydroxyphenyl) propyl] sulfide is a highly effective polyfunctional antioxidant that simultaneously belongs to the classes of phenolic and sulfur-containing organic compounds (https: // en.wikipedia.org/wiki/%D0%A2%D0%B8%D0%BE%D1%84%D0%B0%D0%BD). One of the ways to obtain it is described in the USSR copyright certificate No. 1622369, publ. 01/23/1991 g.

Release form. Capsules containing 0.1 g (100 mg.) And 0.2 g (200 mg) of thiophan M.

Antiradical activity is associated with the fact that

- thiophan contains an aliphatic sulfur atom with pronounced antipoxic activity;

- the presence in the paraposition of an alkyl substituent allows the thiophan molecule to terminate a larger number of oxidation chains, the inhibition coefficient f = 3.7-3.8; the value of the speed of thiophan 2.3 × 10 ⁴ M ^-1 s ^-1 .

- thiophan is a bifunctional antioxidant, not only inactivates free radicals (anti-radical activity), but also reduces the rate of their formation in chain branching reactions.

- thiophan has a pronounced internal synergism, as a result of which it exceeds 1.4 to 1.7 times the total antioxidant activity of tocopherol.

The mechanism of internal synergism in sulfur-containing phenolic antioxidants has not yet been fully elucidated. It is likely that in the case of Thiophan-M, synergism manifests itself as a result of the favorable spatial mutual arrangement of its phenolic and sulfide enzymes. As a result of this, hydroperoxides and quinolide peroxide are rapidly inactivated by the sulfide enzyme with the formation of alcohols and esters, respectively, and thus the possibility of branching of the oxidation chains is prevented.

Thiophan is non-toxic, does not have cumulative and allergenic properties. The interaction of thiophan with low density lipoproteins prevents ischemia, thrombosis and embolism. Thiophan improves the rheological properties of blood, prevents an increase in its viscosity. It has anti-toxic and anti-inflammatory properties. The protective function of inflammation requires the inclusion of mechanisms of microbicidal, fungicidal and cytotoxic effects, which is accompanied by the release of toxic compounds. Thiophan reduces, and in some cases neutralizes, the effects of pathogenic factors.

The drug is used to prevent and treat many diseases, including prevents the onset and development of acute and chronic inflammatory processes, stimulates the immune system:

• normalize the activity of regulatory systems;

• increase the body's resistance to adverse environmental factors, are an adaptogen;

• improve the immune system;

• increase the detoxification activity of the liver;

• contribute to the activation of humoral immunity;

• normalize the most important indicators of blood;

• exhibit hepatoprotective and anti-inflammatory properties.

Example 1. A method for the prevention of somatic complications in the intra- and postoperative period in patients with hip and knee arthroplasty using Mexidol.

Mexidol for injection is administered 1 day and 1 hour before surgery and the day after surgery intravenously based on a therapeutic dose of 2 mg / kg, then Mexidol is taken orally daily in tablets - 1 tablet (1 tablet 125 mg) in the morning and in the evening for 1 month.

Example 2. A method for the prevention of somatic complications in the intra- and postoperative period in patients with hip and knee arthroplasty using Thiofan M.

The drug Thiofan M in capsules is taken 1 day and 1 hour before and the day after surgery once a day orally at the rate of one therapeutic dose of 300 mg, then the drug is administered orally - 3 capsules (1 capsule 200 mg) once a day for 1 month.

To determine the effectiveness of prophylactic action, a clinical study of the effectiveness of the use of Mexidol, Tocopherol and Thiofan-M preparations was performed. Patients were divided into groups: group 1 (control), without the use of drugs (50 people) - the patient was managed according to standard methods; Group 2 (64 people) using Tocopherol - 1 capsule 3 times a day the day before surgery and after for 1 month; Group 3 (43 people) using Mexidol - the day and 1 hour before and the day after the operation, Mexidol solution was administered intravenously at a therapeutic dose of 2 m g / kg, then the patient was taken orally - no 1 tablet in the morning and evening on for 1 month. Group 4 (25 people) used the drug Thiofan-M. The drug was used the day and 1 hour before and the day after surgery once a day orally at a dose of 300 mg, then the patient was taken orally - 3 capsules once a day for 1 month.

The fastest and most accurate blood count, which can signal the onset of inflammatory processes, destruction of bone tissue in the human body, is CRP, or a study on C-reactive protein (norm <5 mg / l). The level of protein in a blood test directly depends on the degree of neglect of the disease. The highest concentration of protein indicates that the body has an infection of a bacterial or parasitic origin, or a tumor, trauma, or necrotic process. A sharp jump in the level of C-reactive protein can be observed in case of tissue injury, when 6 hours after receiving damage, its level rises, and after 12 hours it increases several times.

Fibrinogen is also one of the blood factors known as “rheumatic tests” (normal 2-4 g / l). The levels of fibrinogen and other rheumatic factors increase sharply in the blood with inflammation or tissue damage. The level of fibrinogen in the blood rises with acute inflammatory diseases, as well as with tissue necrosis. Fibrinogen is a protein in the acute phase of inflammation. This means that the concentration of fibrinogen can increase dramatically in any condition caused by inflammatory processes or tissue damage. Its level directly affects the increase or decrease in ESR. The dynamics of fibrinogen during the entire observation period in the case of a favorable perioperative period in all observation groups is within the acceptable values of the norm. Therefore, any deviations from the norm in the postoperative period should alert the doctor and require correction in the treatment of the patient.

Deviations in the level of uric acid in the blood can be caused by relatively harmless factors, and even diurnal fluctuations (in the evenings its concentration increases) (the norm for women is 150-350 mmol / l, for men - 210-420 mmol / l). Blood urea levels decrease with many liver diseases. This is due to the inability of damaged liver cells to synthesize urea, which, in turn, leads to an increase in the concentration of ammonia in the blood and the development of hepatic encephalopathy.

Renal failure manifests itself with the loss of the glomerulus of the ability to filter blood metabolites through itself. This can happen suddenly (acute renal failure) in response to the disease, the introduction of drugs, poisons, damage. Sometimes this is a consequence of chronic kidney diseases (pyelonephritis, glomerulonephritis, amyloidosis, kidney tumors, etc.) and other organs (diabetes, hypertension, etc.). Urea levels should be interpreted inseparably from creatinine.

Creatinine is one of the metabolites of the biochemical reactions of amino acid-protein metabolism in the body. The formation of this compound occurs continuously and is associated with metabolic processes in muscle tissue. Therefore, there are maximum and minimum limits for the norm of creatinine, which take into account all these points and talk about the normal functioning of the organs (the norm for women is 53-97 mmol / l, for men - 62-115 mmol / l).

ESR values are considered normal for women up to 25 mm / h, for men - up to 10 mm / h.

White blood cells are cells responsible for the body's immune defense. Each type of cells of the leukocyte series has its own function. Neutrophils - destroy a bacterial infection found in the blood. Lymphocytes are responsible for immune memory. Monocytes - absorb foreign agents that enter the bloodstream. Eosinophils are “responsible” for the fight against allergens. There are many more functions of white blood. The leukocyte rate depends on the age of people - in children there are more immune cells than in adults. The leukocyte composition of a healthy person is as follows:

Neutrophils - 55% (of which 47-72% are segmented, 1-6% are stab-nucleated);

Lymphocytes - 35%;

Monocytes - 5%;

Eosinophils - 2.5%;

Basophils - 0.5-1%.

During the first hours after surgery, there is an increased content of blood lymphocytes in all observation groups. During the first day, a sharp drop in the number of lymphocytes was detected as a response to surgical aggression. The lymphocytic “failure” observed in the first postoperative month is restored for the next observation period and reaches preoperative values by 3-4 months. Thus, regular changes in the dynamics of indicators of acute phase proteins and a careful study of the results of general clinical analysis can serve as the basis for monitoring rehabilitation treatment in the postoperative period, as well as timely signaling about possible complications and adequacy of the treatment process.

The analysis of tables 1-8 shows that when studying the dynamics of CRP, there is a significant positive reaction with the use of Mexidol and Thiophan-M (indicators are almost the same 32 ± 3.7 on the first day and a sharp decrease in values on the 7th day 20.3 ± 7, 6 which remain within these limits for 2 months).

Dynamics of uric acid - a significant protective effect of the studied drugs was observed in the first week, the indicators are significantly lower than in the comparison groups Thiofan-M 426.4 ± 12.2 and Mexidol - 459.2 ± 4.6. Then there is an increase in the values in all groups, but by the end of the 2nd month in the group using Thiophan-M, the values reach 433.7 ± 4.8 and when using Mexidol - 469.6 ± 2.13. Indicators return to normal in the group using Thiophan-M by the end of the 5th month, in the group with Mexidol by the 6th, in the remaining groups only by the end of the year.

Studying the dynamics of urea, it was found that the level of urea remains within normal limits only in the first day. An exception was the results in patients with Mexidol, who remained within normal limits throughout the observation period. In the remaining groups there is an increase in the level of urea from the third to the 7th day. The maximum performance in this period has a group with cement endoprosthetics (22.3 ± 0.44 mmol / l). The plateau of maximum values lasts up to 2 months, except for the group using Thiophan-M, which is approaching normal indicators by the end of the month.

Indicators of creatinine values reveal that the results of a study of all groups throughout the observation period are within the established norm.

Leukocytosis occurs from the first day of observation. The maximum indicators in all groups are determined on the 3rd day. By the 5th day there is a significant decrease in the level of leukocytosis, but only the group with the use of Thiophan-M remains within the normal range. The results of the study of leukocytes gradually return to normal only by the second month of observation. In the same period there is a lymphocytic failure - there is no cellular immunity. The lymphocytic “failure” observed in the first postoperative month is restored for the next observation period and reaches preoperative parameters by 3-4 months, with the exception of the group using Thiophan-M, the indicators of which come to normal by the end of the 2nd month.

Thus, the analysis of the above studies confirms the achievement of the claimed technical result, which consists in ensuring the possibility of preventing somatic complications arising in patients both from the respiratory and cardiovascular systems in the immediate intraoperative period, and from the liver and kidneys in a more remote period after surgery . The simplification of the proposed method and reducing the time for the prevention of somatic complications is ensured by the oral method of introducing the drug into the body and its prolonged protective effect.

Claims (1)

A method for the prevention of somatic complications in the intra- and postoperative period in patients with hip and knee arthroplasty by introducing a prophylactic agent with antioxidant activity into the patient’s body, characterized in that Mexidol in injection and tablet form is used as a prophylactic agent with antioxidant activity or Thiofan M in capsules, and Mexidol for injection is administered 1 day and 1 hour before surgery and the next day after e operations are intravenously based on the therapeutic dose of 2 mg / kg, then Mexidol is taken orally daily in tablets - 1 tablet (1 tablet 125 mg) in the morning and evening for 1 month, and Thiofan M in capsules is taken for 1 day and 1 hour before and the day after surgery once a day orally at the rate of one therapeutic dose of 300 mg, then the drug is administered orally - 3 capsules (1 capsule 200 mg) once a day for 1 month.