RU2326676C1 - Method of systemic fat embolism development prevention in perioperative period - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: hepasol A in dosage 4.0-8.0 ml/kg and 5% glucose solution are injected separately in equal dosages 40 minutes before surgery. After main operation step is complete blood is microscopically tested for fat globules. In case 10 globules of size less than 5 mcm, or one or more globules of size more than 5 mcm are found totally within 8 microscopic field, test result is considered to be positive, and Hepasol A and 5% glucose solution introduction is prolonged. In case no globules found or those found are totally less than 10 in number of size less 5 mcm test result is considered to be negative, thus Hepasol A and 5% glucose solution introduction is stopped. Blood is repeatedly tested for fat globules in 12 hours after last introduction of Hepasol A. If positive test result for fat globules is registered, Hepasol A and 5% glucose solution introduction is recommenced, and in case double negative test result is registered, Hepasol A is not introduced.

EFFECT: method allows preventing of systemic fat embolism development in perioperative period.

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Description

The present invention relates to medicine, namely to anesthesiology and intensive care.

It is known that surgical interventions on the spine, tubular bones, large joints, as well as organ transplantation or removal of adipose tissue are characterized by the risk of developing fat embolism (Kornilov N.V., Kustov V.M. Fat embolism. St. Petersburg: Morsar AB, 2001. - S.18, S.36-44).

A known method for the prevention of fat embolism, which consists in the intravenous administration of the drug lipostabil (essential) during surgery at a dose of 20-40 ml, followed by administration in the same dose for 3-4 days (Kornilov N.V., Kustov V.M. Fat embolism.St. Petersburg: Morsar AB, 2001. - P.230).

The disadvantages of this method include the fact that the effective effect of lipostabil (essentiale) is manifested only with prolonged use in large doses (1.5-2 g / day), and the introduction of a drug of 20-40 ml once or for several days affects the removal of fat globules from the blood (Klimov AN, Nikulcheva NG The exchange of lipids and lipoproteins and its disorders. - St. Petersburg: Peter Kom, 1999. - S.432-434). This was confirmed by experimental studies of the authors of the proposed method (Tvorogova S. S. Comparative evaluation of the effectiveness of drug prophylaxis and treatment of fat embolism / abstract diss. .... Ph.D., 2005. - S.14-15).

The closest in technical essence to the proposed is a method of drug prevention of fat embolism, including intravenous administration of a 5% solution of ethyl alcohol in a 5% glucose solution during surgery (Shifman E.M. Fat embolism: clinical physiology, diagnosis and intensive care ., 2nd ed. Revised and supplemented - Petrozavodsk: IntelTech, 2003. - P.23).

The disadvantages of this method include the lack of identification of markers of fat embolism and monitoring the effectiveness of the removal of fat globules from the blood. The disadvantages of this method also include the narrow therapeutic breadth of the drug and the low rate of utilization of ethyl alcohol, since even its prophylactic dose, in some cases, causes intoxication, side effects in the form of motor excitement, nausea, and vomiting.

The task of the invention is to prevent the development of fat embolism during operations with a high risk of developing this complication.

The technical result of the proposed method is to prevent the development of fat embolism in the perioperative period due to the early detection of markers of fat embolism - fat globules, their utilization, as well as the exclusion of toxic effects of the drug administered.

The technical result is achieved by the fact that the method of preventing the development of fat embolism in the perioperative period includes the intravenous administration of the drug and 5% glucose solution.

Distinctive techniques of the proposed method are that, 40 minutes before surgery, the drug “Hepasol A” and a 5% glucose solution in a volume ratio of 1: 1 are simultaneously started. "Hepasol A" is administered in a recommended dose of 4.0-8.0 ml / kg body weight at a rate of 40 drops per minute.

The difference of the proposed method lies in the fact that at the end of the main stage of the operation, a microscopic blood test is performed for the presence of fat globules, upon detection of which size is less than 5 microns in a total amount of more than 10 or size more than 5 microns in an amount of one or more fields of view, the analysis is considered positive and the introduction of Hepasol A and 5% glucose solution continue.

The distinctive methods of the proposed method also include the fact that in the absence of fat globules in a blood test or if they are found to be less than 5 microns in size less than 10, also in 8 fields of view, the analysis is considered negative and the introduction of "Hepasol A" and 5 % glucose solution is stopped.

The distinguishing method of the proposed method should also include the fact that a blood test for the presence and number of fat globules is repeated 12 hours after the last injection of the Hepasol A preparation. When registering a positive analysis in the postoperative period, the introduction of the drug "Hepasol A" and 5% glucose solution in the specified dose is repeated.

If twice recorded a negative analysis for the presence of fat globules, performed at intervals of 12 hours, the introduction of "Hepasol A" is not carried out.

A comparative analysis of the proposed method and prototype shows that the claimed method differs from the known above methods. These differences allow us to conclude that the claimed technical solution meets the criteria of the invention of "novelty."

The analysis of patent and specialized literature allowed the authors to establish that the proposed technical solution has features that distinguish it not only from the prototype, but also from other technical solutions in this field of medicine. We have not found a way to prevent the development of fat embolism in the perioperative period, containing the distinctive techniques of the proposed method.

It is known that Hepasol A is a combined preparation for parenteral nutrition of patients with hyperammonemia. It has a metabolic, hepatoprotective and detoxification effect. The infusion solution contains: arginine, aspartic acid, sorbitol, nicotinamide, malic acid, Na ⁺ , K ⁺ , CI ⁺ , riboflavin, decanthenol and pyridoxine (Vidal Handbook. Russian Medicines: Handbook. M .: AstraFarmService, 2006, S. B-400-B-401).

Indication for the use of the drug "Hepasol A" is the treatment of liver failure of various etiologies. The drug is administered intravenously at a dose of 4.0-8.0 ml / kg body weight at a rate of 40 drops per minute. The introduction of the drug can be repeated every 12 hours.

The authors of the proposed method found that the introduction of the drug "Hepasol A" promotes the rapid utilization of fat globules by maintaining the initial concentration of apoprotein B and the activity of plasma lipoprotein lipase, which provide emulsifying properties of blood plasma.

The time of drug administration before surgery, equal to 40 minutes, is determined by the time of synthesis of apoprotein B in blood plasma, the substrate for which is L-arginine, which is part of the Hepasol A preparation.

Unlike the prototype, this drug is devoid of side effects, has a good therapeutic breadth of action and is easily disposed of when administered in combination with a glucose solution.

The inventive method reduces the risk of developing fat embolism by 31% -57% compared with other existing methods and improves the outcome of surgical treatment of diseases and injuries of the musculoskeletal system.

This allows us to conclude that the technical solution meets the criterion of "inventive step".

The method comprising the claimed invention is intended for use in healthcare. The possibility of its implementation is confirmed by the methods and means described in the application. The inventive method ensures the achievement of the technical result perceived by the applicant, namely, increasing the efficiency of preventing the development of fat embolism due to the early detection of markers of fat embolism - fat globules, their utilization, as well as eliminating the toxic effects of the injected drug.

From the above it follows that the claimed invention meets the condition of patentability "industrial applicability".

A method for preventing the development of fat embolism in the perioperative period is as follows:

When a patient enters the operating room, they perform puncture catheterization of the peripheral vein and begin the drip administration of Hepasol A at a dose of 4.0-8.0 ml / kg body weight at a rate of 40 drops per minute. In parallel, through an additional channel of the catheter, a 5% glucose solution is introduced into the same vein in a volume ratio of 1: 1. After 40 minutes from the start of drug administration, surgery is performed. After the main stage of the operation is completed, for example, opening and processing the medullary canal, an analysis is carried out for the presence and counting of fat globules in a smear of blood plasma by light microscopy.

If in 8 fields of vision at least one fat globule with a size of more than 5 microns or 10 globules of smaller sizes is determined, i.e. less than 5 microns, possibly drain globules, the analysis is considered positive and the introduction of the drug "Hepasol A" with 5% glucose solution in the above regimen and dosage is continued.

If the total number of globules is not more than 10, the size of which does not exceed 5 microns, in 8 fields of vision, or if there are no fat globules, the analysis is considered negative and the administration of Hepasol A with a 5% glucose solution is stopped.

Laboratory control is performed 12 hours after the last administration of Hepasol A.

After each positive result of the analysis for the presence of fat globules, Hepasol A and a 5% glucose solution in the recommended dose are infused.

Prevention of fat embolism with the introduction of “Hepasol A” is stopped with a double negative analysis performed at intervals of 12 hours.

The proposed method is illustrated by an example of a specific implementation.

Extract from the medical history of patient A., 57 years old, weight 85 kg, which was diagnosed with bilateral coxarthrosis on the right of the III-IV degree, on the left - the II degree. Contracture of the right hip joint, was admitted to the clinic of traumatology and orthopedics for surgical treatment. From concomitant pathology noted chronic obstructive bronchitis, gastric ulcer in remission.

Clinical, biochemical blood tests and urine tests performed during the preoperative period were normal.

The patient underwent a planned operation - total cement endoprosthetics of the right hip joint with the ESI design. Patient A. was admitted to the operating room with blood pressure - 140/80 mm Hg. Art., pulse - 76 per min. After puncture catheterization of the peripheral vein, a parallel infusion of Hepasol A and a 5% glucose solution was started, in a volume ratio of 1: 1, at a rate of 40 drops per minute. After this, a puncture of the subarachnoid space and intrathecal administration of a 0.5% solution of marcaine 20 mg were performed. Sedation of the patient was provided by the introduction of a solution of Relanium - 10 mg, dosed with infusion of diprivan - 400 mg. The operation began 40 minutes after the start of the Hepasol A infusion with 5% glucose solution.

The course of anesthesia is smooth until the stage of implantation of the femoral component of the prosthesis, which was performed using bone cement at 45 minutes after the start of the operation. At this stage, a short-term decrease in blood pressure to 90/50 mm Hg was noted, which did not require any measures and quickly stabilized independently at the previous figures - 110/80 mm Hg. Art. At the stage of implantation of the femoral component, blood was drawn from the central vein for analysis of the presence of fat globules.

In a smear of blood plasma, in 8 fields of view, 20 fat globules of 0.1-0.2 microns in size were found, 4 - 1-2 microns in size. The analysis is positive. It was decided to continue the Hepasol A infusion started with surgery with a 5% glucose solution. Prior to the end of the operation, hemodynamic parameters were stable, NPV 12-16, hemoglobin saturation - 97% -99% with oxygen insufflation through a nasal catheter - 2 l / min.

The duration of the operation is 90 minutes, the duration of the anesthetic benefit is 130 minutes. Blood loss amounted to 600 ml, the volume of infusion therapy - 2200 ml. The infusion of the drug "Hepasol A" at a dose of 5 ml / kg with 5% glucose solution was completed one hour after the end of the operation.

In the postoperative period, a double analysis of blood plasma smears was performed (12 and 24 hours after the operation): there were no fat globules. Repeated infusion of Hepasol A in the early postoperative period was not performed.

The postoperative period was uneventful. The patient was discharged from the clinic on the 10th day after the operation.

In the above example, at the stage of implantation of the femoral component of the endoprosthesis, a massive influx of bone marrow fat into the vascular bed occurred, which was clinically manifested by a decrease in blood pressure and confirmed by laboratory tests. The introduction of “Hepasol A” allowed the fat entering the vascular bed to be fragmented into smaller globules that are not dangerous in terms of embolism.

Repeated blood tests for the presence of fat globules performed 12 and 24 hours after surgery were negative. Therefore, a single infusion of 500.0 ml of Hepasol A, started 40 minutes before surgery, was enough to prevent the development of fat embolism at the intraoperative stage and in the postoperative period.

The authors of the proposed method conducted comparative clinical studies of the prevention of fat embolism using "Hepasol A" and well-known drugs - Essential H, 5% solution of ethyl alcohol.

For this, patients undergoing total hip arthroplasty were divided into three groups.

The first group consisted of 70 patients who, to prevent the development of fat globulemia, before and during the operation, the drug “Hepasol A” and 5% glucose solution were administered.

The second group consisted of 85 patients who received Essential N during and after surgery.

The third group consisted of 39 people who were intravenously injected with a 5% solution of ethyl alcohol in a 5% glucose solution during the operation.

To study the blood for the presence of fat globules, blood was drawn from the central vein at the following stages: intraoperative - before the operation, during the treatment of the medullary canal, at the end of the operation and in the postoperative - on the first, second, third day after the operation.

Detection and calculation of fat globules in a smear of venous blood plasma stained with Sudan III was performed using light microscopy (Diagnosis of fat globulemia in injuries and bone operations: Method. Rivers: compiled by N.V. Kornilov, A.V. Voytovich, V .M. Kustov. - SPb., 2000 .-- 24 s).

Before surgery, the analysis for the presence of fat globules was negative in all patients.

Comparative results of the frequency of detection of fat globules at the intraoperative stage are presented in table 1.

Table 1 A drug N ZhG / N without ZhG Absolute risk Chance Hepasol A 38/32 0.54 * 1.17 * Essential N 67/18 0.79 * 3.76 * 5% alcohol solution 26/13 0.67 2.03 * - p <0.05 (χ ² with Yates correction)

where N FG - the number of patients with a positive analysis for the presence of fat globules,

N without GH - the number of patients with a negative analysis for the presence of fat globules.

From the presented table 1 it follows that at the intraoperative stage, the administration of “Hepasol A” significantly (p <0.05) reduced the absolute risk and chance of developing fat embolism compared with the introduction of essentials I. Reducing the relative risk (COP) of developing fat embolism in the group administration of “Hepasol A” in comparison with the group of administration of essential H was 31%, and the NNT indicator characterizing the number of patients who need to be treated with essentiale to get the same effect as when using “Hepasol A" is 4.

The introduction of "Hepasol A" also significantly reduced the absolute risk and chance of developing fat embolism in the early postoperative period (see table 2).

table 2 A drug N ZhG / N without ZhG AR Chance COP NNT Hepasol A 11/59 0.15 *** 0.18 *** 0 one Essential N 30/55 0.35 * 0.54 * 56% 5 5% alcohol solution 14/25 0.36 ** 0.56 ** 57% 5 - ** - p <0.05 (χ ² with Yates correction)

where N FG - the number of patients with a positive analysis for the presence of fat globules,

N without ZhG - the number of patients with a negative analysis for the presence of fat globules,

AR - the absolute risk of developing fat embolism,

COP - reduction of the relative risk of developing fat embolism,

NNT is an indicator that characterizes the number of patients who need to be treated with this drug to get the same effect.

From table 2 it follows that the COP in the administration group of “Hepasol A” compared with the administration group of Essential H was 56%, and with the administration group of the alcohol solution - 57%. The NNT in the last two groups compared with the group “Hepasol A" amounted to 5 people.

Thus, the data presented characterize a significantly more pronounced prolonged prophylactic effect of preventing the development of fat embolism from the introduction of "Hepasol A".

The drug "Hepasol A" is well tolerated by patients and does not have severe side effects.

Claims (1)

A method for preventing the development of fat embolism in the perioperative period, including the simultaneous administration of a 5% glucose solution and another drug, characterized in that Hepasol A is used as another drug, which is started at a dose of 4.0-8.0 ml / kg separately from a 5% glucose solution, these funds are administered in equal volumes 40 minutes before the operation, at the end of the main stage of the operation, a microscopic blood test is performed for the presence of fat globules, if detected in 8 fields vision in the total number of more than 10 globules, the size of which is less than 5 microns, or in the amount of one or more globules larger than 5 microns, the analysis is considered positive and the introduction of the drug "Hepasol A" and 5% glucose solution continue, and in the absence of fat globules or if they are found to be smaller than 5 microns in total less than 10 globules, the analysis is considered negative and the administration of Hepasol A and a 5% glucose solution is stopped, and the blood test for the presence of fat globules is repeated 12 hours after the last injection “Hepasol A” arata and, if a positive test for the presence of fat globules is recorded, the administration of the “Hepasol A” preparation and a 5% glucose solution is repeated, and if a double test, with an interval of 12 hours, is recorded, a negative test for the presence of fat globules the drug "Hepasol A" is not carried out.