RU2285925C2 - Method for predicting pyoinflammatory complications in treating the cases of open long tubular bone fractures - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves determining proinflammatory interleukine-1α, anti-inflammatory interleukine-4, dienic conjugates and antioxidant activity level in patient blood serum in postoperative period. Coefficient value is calculated from suggested formula. The value is used for predicting postoperative period course.

EFFECT: high accuracy of prognosis.

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Description

The invention relates to medicine, namely to traumatology, and can be used to control the course of the wound process in the postoperative period.

The urgency of the problem of treating open fractures of long tubular bones is determined by the increase in their frequency and increase in the specific gravity of disability in the general structure of injuries [1, 2]. The complexity of this problem is due to the vastness and severity of the damage, which increases the risk of an adverse outcome (in 30-45% of cases, the development of osteomyelitis). Therefore, predicting the course of the disease can significantly change the methods of treatment with the aim of the safety of complications of diseases and reduce treatment time.

A known method for predicting the course of purulent-inflammatory postoperative complications in the clinic of abdominal surgery by determining the parameters of the immune system of patients immediately before the operation and on the second day of the postoperative period by setting the reaction of the formation of lymphocytes of the patient after incubation with autoplasma and without it [3]. An index is calculated equal to the ratio of the number of incubated cells to the number of active T-lymphocytes. With a value of the indicator greater than 1.1, a favorable course of the postoperative period is predicted, and with a value of 1.0 or less, the occurrence of purulent-inflammatory complications.

However, the method for determining rosette-forming cells using autoplasma is not specific enough, because, firstly, the patient’s autoplasma necessarily carries many factors that not only accelerate, but also inhibit the formation of outlets. These factors can be of either serum or leukocyte origin, which can affect the diurnal dynamics of the coefficient, respectively diurnal and circadian rhythms, misleading the doctor. Secondly, changes in the coefficient parameters in a rather narrow range of numbers reduces the accuracy and reproducibility of the results.

A known method for predicting the course of the fusion of a fracture of long tubular bones by determining the number of monocytes, lymphocytes, neutrophils and eosinophils per 1, 7 and 14 knocks after an injury in a unit of blood volume [8]. The fact of applying a pulsed complex-modulated electromagnetic field in the treatment after osteosynthesis is taken into account and the discriminant function F is calculated from the identified factors and a favorable fracture fusion is predicted for F> 0, and an unfavorable fracture fusion flow is predicted.

The proposed method is not objective enough, since monitoring the course of the reparative process of bone tissue is based on the interpretation of the data of the leukocyte formula, which can vary with various pathological processes. Studies are conducted over a long time, changes in discriminant function occur in a rather narrow range, which reduces the accuracy of the results.

The prototype for this invention is a method for diagnosing the development of complications and determining indications and contraindications for surgical interventions in case of combined trauma of the lower extremities and skull [4]. The severity of the condition and the possible generalization of infection are judged by increasing the content of the initial products of lipid peroxidation (LPO) and a decrease in antioxidant activity (AOS) in the blood serum of patients. The method is carried out by determining in blood serum in dynamics (1, 3, 7, 14 days) the content of primary (diene conjugates - DC) and intermediate (malondialdehyde - MDA) LPO products. To assess the state of AOS, the concentration of lipid antioxidant alpha-tocopherol (TF) and the extracellular protein ceruloplasmin (CP), which has an antioxidant effect, were determined. To assess the imbalance in the POL-AOS system, we used the integral indicator (K), which is normally 1.12, while strengthening the LPO processes, the integral indicator increases above 1.12, which indicates the development of infectious complications.

However, this method has a number of disadvantages: firstly, the study of only the parameters of the POL-antioxidants system is not sufficiently informative, since an imbalance in this system can be detected in various pathological conditions, since lipid peroxidation is a non-specific process [9]; secondly, the assessment of multicomponent antioxidant protection by studying the content of only alpha-tocopherol and ceruloplasmin is not entirely objective, since antioxidant protection is provided by a large number of compounds of both enzymatic and non-enzymatic nature [10].

In this regard, an increase or decrease in this parameter is not a very objective criterion for assessing the generalization of surgical infection. In addition, this method does not reflect the main pathogenetic link of purulent-inflammatory complications, namely cytokine-dependent immunodeficiencies, i.e. a shift in the cytokine balance towards pro-inflammatory or anti-inflammatory reactions [11]. This makes it difficult to objectify the stage of the inflammatory process and, as a result, the choice of adequate treatment tactics [12].

, 2) относительное содержание провоспалительного интерлейкина IL-1α-P₂ по формуле:

, 3) относительную антиоксидантную активность - Р₃ по формуле

, 4) относительное содержание антивоспалительного интерлейкина IL-4-Р₄ по формуле

.To improve the accuracy of diagnosis of the course of the wound process in the postoperative period in the blood serum of patients with open fractures, the content of diene conjugates (DC), antioxidant activity (AOA), and the content of interleukins - IL-1α, IL-4 are determined. Then calculate the following indicators: 1) the relative content of diene conjugates-P ₁ according to the formula

, 2) the relative content of pro-inflammatory interleukin IL-1α-P ₂ according to the formula:

, 3) relative antioxidant activity - P ₃ according to the formula

, 4) the relative content of anti-inflammatory interleukin IL-4-P ₄ according to the formula

.

where i is the content of lipid peroxidation products, AOS enzymes of interleukins in patients;

n is the average value of lipid peroxidation products, AOS enzymes, interleukins in healthy individuals.

значении коэффициента меньше 2,5 прогнозируют благоприятное течение раневого процесса, а при значении коэффициента, равном 2,5 и выше, прогнозируют развитие инфекционных осложнений.After that, the integral coefficient (K) is calculated by the ratio of the products of the relative content of diene conjugates and pro-inflammatory interleukin (P ₁ × P ₂ ) to the product of the relative antioxidant activity and the relative content of anti-inflammatory interleukin (P ₃ × P ₄ ), according to the formula:

a coefficient value of less than 2.5 predict a favorable course of the wound healing process, and with a coefficient value of 2.5 or more, the development of infectious complications is predicted.

The method is as follows.

On the 2nd day of the postoperative period, 10 ml of blood is taken from a cubital vein into a test tube.

The level of initial lipid peroxidation intermediates is determined at a wavelength of 232 nm [5], the total antioxidant activity is studied by the method of M.Sh. Promyslov [6].

,

антиоксидантной активности (АОА), антивоспалительного интерлейкина IL-4 по формуле:

The concentration of interleukins (IL-1α, IL-4) is determined by the method of enzyme-linked immunosorbent assay using double antibodies [7] and the ratio of diene conjugates (DC), pro-inflammatory interleukin-IL-1α is calculated by the formula:

,

antioxidant activity (AOA), anti-inflammatory interleukin IL-4 according to the formula:

To calculate the indicators, the parameters of the content of diene conjugates, antioxidant activity, pro- and anti-inflammatory interleukins in healthy people are used:

DC - 0,096 mg / lipid; AOA = 30.23%

IL-1α = 36 pg / ml; IL-4 = 32 pkg / ml;

After that, the integral coefficient (K) is calculated - the ratio of the number of populations of diene conjugates and pro-inflammatory interleukin IL-1α to antioxidant activity (AOA) and anti-inflammatory interleukin IL-4:

The coefficient parameters are interpreted as follows. If K is less than 2.5, a favorable course of the wound process in the postoperative period is predicted. If K is equal to or greater than 2.5, the development of infectious complications is predicted.

A method for predicting purulent-inflammatory complications is illustrated by the following examples.

Example 1. Patient K., 34 years old, operated on for an open fracture of the right thigh (type II B). On the second day of the postoperative period, the patient determines the content of interleukins in the blood serum.

Interleukins: IL-1α = 125 pkg / ml, IL-4 = 184 pkg / ml.

System "POL-antioxidants": DK = 1.82 mg / lipid, AOA = 17.2%

We calculate indicators of the ratio of the content of pro-inflammatory and anti-inflammatory interleukins in the test sample to the same indicators in control in healthy people:

An adverse course of the postoperative period was suggested, skeletal traction was chosen by the method of stabilization of bone fragments: subsequently, on the 3rd day after the operation, edema, hyperemia appeared around the sutures, with palpation in the middle third of the right thigh - a dense painful infiltrate of 8.5 × 6 , 0 cm, from a postoperative wound - purulent discharge. The sutures were removed, the sowing of the wound discharge gave rise to staphylococcus in association with Pseudomonas aeruginosa. The contamination of the wound by microorganisms per 1 g of tissue was 10 ⁸ .

Subsequently, for five days, local treatment of a purulent wound by washing the wound with a hypertonic sodium chloride solution, dressings with Levomekol ointment were used.

On day 8, a second study of interleukins was conducted.

Interleukins: IL-1α (PCG / ml) = 90, IL-4 (PCG / ml) = 133

"POL-antioxidants" - DK = 0.125 mg / lipid; AOA = 24.5%

By this time, the wound was 4.0 × 1.0 cm in size, made of fine-grained, bright red granulation tissue, and edge epithelization was noted.

Early secondary sutures were imposed. Complete healing. On the 20th day from the moment of the injury, the operation of intramedullary osteosynthesis of the hip was performed with a CITO nail. The postoperative period was uneventful.

Example 2. Patient M., 29 years old, was admitted to the hospital with a diagnosis of Open comminuted fracture (Type II) of both bones of the left tibia in the middle third with displacement of fragments. On examination, the wound is 7.0 × 2.5 cm in the middle third of the left tibia, along the outer lateral surface, the ends of the bone fragments of the tibia will stand in the wound. After 1.5 hours from the moment of receipt, the initial surgical treatment of the wound was made, the fracture was fixed by the Ilizarov apparatus.

On the second day, a study was made of the concentration of interleukins, diene conjugates and antioxidant activity

Interleukins: IL-1α (PCG / ml) = 110, IL-4 (PCG / ml) -125.

DK = 0.150 mg / lipid AOA = 19%

K = 2.45

A favorable course of the wound process is predicted, without complications. Postoperative therapy was carried out according to generally accepted methods. The postoperative period was uneventful, the wound healed by primary intention. The patient in satisfactory condition was discharged 12 days after surgery.

The proposed method for predicting purulent-inflammatory complications was carried out in 54 patients with open fractures of long tubular bones (Table 1). The diagnosis was confirmed by bacteriological and cytological studies.

In bacteriological and cytological analysis, the development of complications was detected in 25 cases, primary intention healing (without the development of complications) was observed in 27 patients, that is, the correct prognosis was recorded in 52 cases. Thus, the following characteristics of the proposed forecasting method were obtained: sensitivity and accuracy - 52/54 × 100 = 96.2%.

Table 1 The values of the integral coefficient (K) in patients with open fractures in the postoperative period on the 2nd day in various clinical groups (M ± t) Groups N DC Mg / lipid IL-1α pkg / μl IL-4 pkg / μl AOA% TO Exodus Group I n = 27 0.186 ± 0.01 * 125 ± 8 * 170 ± 7 * 15 ± 1.2 * 2.55 ± 0.03 Complications Group II n = 27 0.141 ± 0.02 * / ** 110 ± 9 * / ** 120 ± 14 * / ** 19 ± 2.2 * / ** 2.45 ± 0.01 No complications Group III n = 25 0.096 ± 0.01 36 ± 5 32 ± 2 30.2 ± 2.2 1.0 ± 0.08 Norm Note: * - the differences are significant compared with the control; ** - differences are significant between groups I and II; group I - a group of patients with purulent-inflammatory complications; II - a group of patients without purulent-inflammatory complications; III - a group of healthy individuals.

Information sources

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Claims (1)

A method for predicting the development of purulent-inflammatory complications in open fractures of the tubular bones by determining the content of diene conjugates in the blood serum, characterized in that the concentration of pro-inflammatory IL-1α, anti-inflammatory IL-4 and antioxidant activity are additionally determined in patients, their relative values are calculated with respect to the average values in healthy individuals and calculate the integral coefficient K by the formula

where P ₁ is the value of the relative content of IL-1α; P ₂ - the value of the relative content of diene conjugates; P ₃ - the value of the relative content of IL-4; P ₄ - the value of relative antioxidant activity, and with a coefficient value of 2.5 or higher, the development of purulent-inflammatory complications is predicted.