RU2760989C1 - Method for predicting the risk of necrosis of a free dermal autograft - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to transplantology and reconstructive surgery. The changes in the condition of microcirculatory blood flow in the tissues of the dermal autograft after free skin grafting are evaluated. A free split dermal autograft is used for skin grafting. The difference between the values of concentration of oxyhemoglobin in the graft tissues on the 4th, 6th and 8th days after skin grafting is determined by the optical diffusion spectroscopy method. If the increase in the concentration of oxyhemoglobin at each stage of the study is greater than 25%, the risk of necrosis of the free split dermal autograft is considered low; if the increase in the concentration of oxyhemoglobin at each stage of the study is less than 25%, the risk of necrosis of the free split dermal autograft is assessed as moderate, which requires the application of additional methods for increasing the oxygenation of the wound bed. If the dynamics of changes in the oxyhemoglobin level are negative, the risk is considered high, the dermal autograft needs to be removed to prevent local infectious complications.

EFFECT: method provides a possibility of predicting the outcome of free skin grafting.

1 cl, 8 dwg, 1 ex

Description

The invention relates to medicine, namely to general surgery, reconstructive plastic surgery, combustiology, traumatology, and can be used to predict the risk of necrosis when closing a soft tissue wound defect by free skin grafting with a split autodermotransplant.

One of the reasons for the unsuccessful outcome of free skin grafting is the unsatisfactory blood supply to the autodermotransplant. In particular, it is known that the primary signs of the germination of blood vessels supplying a free autodermotransplant are noted from the second day after its transfer to the recipient wound, and a full blood supply through the newly formed vessels begins from 5-7 days (Berlin L.B. Skin morphology after burns and free transplantation. - L .: Medicine, 1966. - 222 p.). If, for any reason, the process of angiogenesis is slowed down, and the vascular bed between the graft and the underlying tissues does not have time to recover, then necrobiotic processes grow in the graft tissue, and it is rejected from the recipient bed (Zadorozhny A.A. Dynamics of blood flow in autografts of the skin of different parts of the body in rats according to laser Doppler flowmetry / AA Zadorozhny, SI Kataev, S. Yu. Shtrygol // Methodology of flowmetry. - 2001. - No. 5. - pp. 179-196). Subjectively, it is not always possible to visually correctly assess engraftment and, therefore, the possible risk of graft rejection. As a result, timely implementation of adequate therapy aimed at stimulating the engraftment processes is impossible.

It is known that during this critical period of the first 5-7 days, the nutrition of the transplanted skin is mainly carried out diffusely - due to the penetration of the intercellular fluid from the recipient bed into the intercellular spaces of the autodermotransplant. Oxygen during this period is delivered to the cells of the autodermotransplant in two states - free, due to diffusion from the underlying tissues, and associated with hemoglobin (oxyhemoglobin) - through the vascular bed. Thus, an indicator of the activity of angiogenesis and the prognosis of the viability of the autodermotransplant in the first 5-7 days can be the amount of oxyhemoglobin in its tissue, since an increase in the amount of oxyhemoglobin indicates an increase in the number and area of functioning vessels connecting the autodermotransplant and the underlying recipient bed.

At present, optical methods for diagnosing biological tissues, which make it possible to assess the level of metabolism, hemodynamics, and changes in the biochemical composition of biological tissues, are actively developing. One of these methods is optical diffusion spectroscopy (ODS), the principle of which is based on measuring the absorption spectra of biological tissues with subsequent assessment of the concentrations of the main tissue chromophores (oxyhemoglobin, deoxyhemoglobin, melanin, water, lipids). The accuracy of the assessment of chromophore concentrations depends on many factors: the spectral range in which the measurements are carried out, the number of measurements at different distances between the source and the detector, the uniformity of light scattering and absorption in tissue, data processing algorithms, etc. (Turchin I.V. Methods of optical biomedical visualization: from subcellular structures to tissues and organs // Advances in physical sciences. - 2016. - V. 186. - No. 5. - pp. 550-567). In this regard, it should be noted that the accuracy of determining the relative changes in the concentration of chromophores in the tissue by the ODS method is significantly higher than the accuracy of determining their absolute values, since when measuring the dynamics of any value, the structure of the tissue in the measuring volume practically does not change.

To determine the concentration of chromophores in the surface tissue layers (up to 2 mm) can be used as contact (Kleshnin M.S., Turchin I.V. Evaluation of oxygenation in the surface layers of biological tissues based on optical diffusion spectroscopy with automated measurement calibration // Quantum Electronics. - 2019. - T. 49. - No. 7. - p. 628-632) and contactless ODS devices (O'Sullivan TD et al. Diffuse optical imaging using spatially and temporally modulated light // J. Biomed. Opt 2012. V. 17, No. 7. p. 0713111). Contact ODS devices have a probe applied to the tissue surface, in which the ends of the optical fibers are located. Some of the fibers are used to irradiate tissues with light in the optical wavelength range, while the other part is used to receive diffusely scattered light. When using non-contact ODS devices, the tissue surface is illuminated either evenly (Zherebtsov E. et al. Hyperspectral imaging of human skin aided by artificial neural networks // Biomedical optics express. - 2019. - T. 10. - No. 7. - p. 3545 -3559), or light with a certain periodic spatial structure (using structured lighting) (Gioux S. et al. First-in-human pilot study of a spatial frequency domain oxygenation imaging system // Journal of biomedical optics. -2011. - T. 16. - No. 8. - c. 086015). In this case, the diffusely scattered light is recorded by a digital camera.

To date, spectroscopic measurements carried out using optical fibers brought into contact with biological tissue are a much more accurate method for measuring the concentrations of chromophores in comparison with the method based on obtaining two-dimensional images of biological tissues with a digital camera under contactless illumination at different wavelengths. Firstly, this is due to the fact that when using contact probes of ODS devices, as a rule, the spectrum of backscattered light is recorded in a wide range of 400-1000 nm with a step of 1-2 nm, which makes it possible to analyze various features of the spectrum of backscattered radiation. , thereby providing a more accurate determination of the content of various chromophores in the tissue compared to the use of contactless ODS devices, where a limited discrete set of wavelengths is used - about 3-7. In addition, when measuring with a fiber optic probe, it is possible to select photons that have passed different paths by registering radiation backscattered by the tissue by several receiving fibers located at different distances from the fiber that delivers the probing radiation to the tissue. This allows you to measure the extinction coefficient of the tissue and, accordingly, calculate the spectrum of the absorption index, which, in turn, can be used to determine the concentration of chromophores. When using uniform illumination of the object of study, it is impossible to directly measure these values; one has to resort to rather complex methods of image processing (clustering, machine learning, etc.), in which a large number of free parameters appear, which will vary depending on the anatomical features of the structure of the skin. ... It should be noted that with the development of data processing technologies, the accuracy of measurements of chromophore concentrations performed using contactless ODS devices will increase, and with the development of hyperspectral imaging technologies, the number of spectral ranges in which backscattered radiation can be recorded increases. However, the cost of such recording devices significantly exceeds the cost of spectrometers used in contact ODS devices.

According to the literature (Lu N. et al. Sustained Poststimulus Elevation in Cerebral Oxygen Utilization after Vascular Recovery // J Cereb Blood Flow Metab. 2004. V. 24, No. 7. p. 764-770), the content of total hemoglobin reflects the blood filling of the tissue , oxyhemoglobin - oxygen supply, and deoxyhemoglobin - its consumption. Research data comparing the results obtained using ODS and standard methods for determining oxygenation (polarography, immunohistochemical analysis with a hypoxia marker) showed that the ODS method allows you to correctly determine changes in the level of oxygenation of biological tissues and identify tissue mechanisms of the resulting changes (Maslennikova AV et al. Comparative study of tumor hypoxia by diffuse optical spectroscopy and immunohistochemistry in two tumor models // J. Biophoton. 2010. V. 3, No. 12. p. 743-751; Orlova AG et al. Diffuse optical spectroscopy monitoring of oxygen state and hemoglobin concentration during SKBR-3 tumor model growth // Laser Phys. Lett. 2017. V. 14, No. 1. p. 015601).

To analyze the hydration and oxygenation of tissues immediately after surgery, spectroscopy performed in the visible and / or near infrared (IR) wavelength range can be used. So, according to US patent 8060188 (publ. 11/15/2011, IPC А61В 5/00), there is a non-invasive method for predicting necrosis of a tissue site in which blood supply is impaired, including access to the specified area, collection of spectroscopic images of the specified tissue area, assessment of the viability of the specified by determining the relative concentration ratio of oxyhemoglobin and deoxyhemoglobin (oxygen saturation index), identifying areas of a tissue site below a certain threshold of an oxygen saturation index that will become necrotic without corrective action, and areas of a tissue site above a certain threshold of an oxygen saturation index that will remain viable. In this case, the wavelengths of both the visible range (430 nm, 530 nm, 565 nm) and the near infrared (within 790-1080 nm) are used.

A significant disadvantage of the analogue method is that it measures the absolute value of the ratio of the concentrations of oxy- and deoxyhemoglobin, and not the dynamics of changes in this ratio. The absolute values of the concentrations of oxy- and deoxyhemoglobin depend on the applied model of light propagation in biological tissues and the data processing algorithm. Since it is impossible to take into account all the parameters affecting the propagation of light in tissues (different thicknesses of tissue layers, scattering and absorption spectra in them, the location of blood vessels), then the reconstructed values can differ significantly from reality, limiting the applicability of the data processing method used. And the change in the concentration of a chromophore, measured at one point at different times by ODS methods, is a more stable value (a value measured with a smaller error compared to the error in measuring the absolute value of the chromophore concentration), since the thickness of tissue layers and scattering indices in them over time, they practically do not change, only the concentrations of oxy- and deoxyhemoglobin change.

A significant limitation of the analogue method is the area of application - a non-free (blood-supplied) skin flap. Some of the measurements, which are carried out in the near-infrared range, have a diagnostic depth of about 1 cm, which is sufficient to assess the risk of necrosis in the case of a non-free skin flap, but is not suitable for the case of a free autodermotransplant, since a large volume of underlying tissues falls into the sensitivity region in this range. which reduces in backscattered light the fraction of light that comes from the thin subcutaneous layer responsible for feeding the graft, and, as a consequence, reduces the sensitivity of the method to changes in the degree of oxygenation of this layer. All measurements in the visible wavelength range (500-600 nm) have a measurement depth of about 1 mm and are suitable for free autodermotransplant. The difference in the depth of diagnosis is due to the fact that in the near-infrared range the tissue absorption index is much lower than in the visible one, and, accordingly, the light spreads much deeper. Thus, the sensitivity of the method in the case of free autodermotransplant when measuring in the near IR range will be insufficient.

There is a fundamental difference in the nutrition of the tissues of the skin flap, that is, the area of tissue that retains its connection with the maternal bed through a permanent feeding pedicle, and the graft, which is completely cut off from the donor area of the skin area. In the skin flap, blood supply is maintained through the existing blood vessels, in the split autodermotransplant, nutrition for the first 4-5 days is carried out due to the diffusion of oxygen and nutrients, and then new vessels are formed that connect the graft with the recipient bed. Plasty of a skin defect with a split autodermotransplant is one of the most common operations due to its low trauma and technical simplicity, and fewer problems with the donor area. The inappropriateness of measurements in all ranges of the analogue method for assessing blood supply and predicting the development of necrotic processes in the process of free skin grafting with a split autodermotransplant is its significant drawback.

The closest analogue in terms of the technical essence of the proposed method is a method for predicting the risk of rejection of a free full-thickness skin autodermotransplant during eyelid reconstruction, known from the patent RU 2456917 (publ. 27.07.2012, IPC А61В 5/026, А61В 8/06), which is selected in as a prototype for the claimed invention. The prototype method uses an assessment of changes in the state of microcirculatory blood flow by the method of laser Doppler flowmetry, which makes it possible to assess the dynamics of capillary blood flow. The prototype method consists in the fact that after the operation from 4 to 7 days, the gradient of capillary blood flow is determined daily according to laser Doppler flowmetry between the transplanted autodermotransplant and the surrounding healthy tissues or symmetrical areas of the opposite or healthy eyelid. In the absence of a tendency to increase the gradient with its value equal to or below 15%, the risk of autodermotransplant rejection is predicted.

However, the prototype method has disadvantages. So, since the indicator of capillary blood flow is the value of the average blood perfusion within the limits of the registration time, the value of this parameter depends on the concentration of erythrocytes in the probed tissue volume and the average blood flow velocity. In particular, changes in capillary blood flow index are proportional to changes in volumetric blood flow velocity. Experimental data show that vascular spasm caused by the administration of adrenaline leads to an increase in capillary blood flow with total constant organ perfusion (Kuznetsova LV et al. Dissociation between volume blood flow and laser-Doppler signal from rat muscle during changes in vascular tone // American Journal of Physiology-Heart and Circulatory Physiology 1998 V. 274, No. 4. p. H1248-H1254). Thus, the prototype method does not always make it possible to obtain an objective and accurate assessment of the blood supply to the autodermotransplant.

The problem solved by the invention is a more objective assessment of the blood supply of the free split autodermotransplant after its placement on the recipient wound through the newly formed vessels, which makes it possible to predict the risk of necrotic changes in the free split autodermotransplant and take the necessary therapeutic and preventive measures in time.

The technical result in the proposed method for predicting the risk of necrosis of a free split autodermotransplant is achieved due to the fact that it, like the prototype method, is based on assessing changes in the state of microcirculatory blood flow in the tissues of the autodermotransplant in the period of at least 4 to 7 days after free skin plastics.

New in the proposed method for predicting the risk of necrosis of a free split autodermotransplant is that a free split autodermograft is used for skin grafting, after skin grafting by the method of optical diffusion spectroscopy, the difference between the concentration of oxyhemoglobin in the graft tissues on days 4, 6 and 8 is determined, with an increase in the concentration of oxyhemoglobin at each stage of the study, more than 25% of the risk of necrosis of a free split autodermotransplant is considered low; with an increase in the concentration of oxyhemoglobin at each stage of the study by less than 25%, the risk of necrosis of a free split autodermotransplant is assessed as moderate, which requires the use of additional methods to increase the oxygenation of the wound bed; with negative dynamics of changes in oxyhemoglobin, the risk is recognized as high, it is necessary to remove an autodermotransplant to prevent local infectious complications.

The invention is illustrated in the following figures.

FIG. 1 shows the study of the ODS apparatus by the sensor on the 4th day after free skin grafting;

FIG. 2 shows the study of the ODS apparatus by the sensor on the 6th day after free skin grafting;

FIG. 3 shows the study of the ODS apparatus by the sensor on the 8th day after free skin grafting;

FIG. 4 - view of the recipient wound bed before plastic closure;

FIG. 5 is a view of the grafts on the recipient wound immediately after the transfer;

FIG. 6 - type of grafts 4 days after free skin grafting;

FIG. 7 - type of grafts 6 days after free skin grafting;

FIG. 8 - type of grafts 8 days after free skin grafting.

The method is carried out as follows.

To assess the blood supply to the autodermotransplant, the method of optical diffusion spectroscopy (ODS) is used.

The authors found that to assess the concentrations of oxy- and deoxyhemoglobin in the surface layers of tissues (up to 2 mm), it is advisable to use the wavelength range of 500-600 nm, in which the light absorption index in tissues is sufficiently high, and, therefore, light penetrates to a relatively shallow depth - no more than 2 mm.

The contact ODS-probe is installed on a certain area of the free split autodermotransplant on the 4th day after free skin grafting (Fig. 1). The results of ODS studies (values of the concentrations of oxy- and deoxyhemoglobin) are automatically saved in the personal computer program. After 48 hours (on the 6th day after the operation), a repeated examination of the autodermotransplant is performed at the same point (Fig. 2). Further, after another 48 hours (on the 8th day after free skin grafting), a similar study of the concentration of oxyhemoglobin is performed (Fig. 3). By the numerical difference between the indicator of the concentration of oxyhemoglobin when measured with a period of 48 hours, the risk of necrosis of the autodermotransplant is determined.

If the indicator of oxyhemoglobin concentration in dynamics increases by more than 25% at each stage of measurement with a 48 hour interval, then the processes of angiogenesis and repair are adequate, additional intervention is not required, and the risk of autodermotransplant necrosis is considered low.

If the change in the increase in the concentration of oxyhemoglobin in the tissue of the autodermotransplant is less than 25%, then the risk of necrosis of the autodermotransplant is assessed as moderate, and its successful engraftment requires the use of additional therapeutic methods to increase the oxygenation of the wound bed (VAC-therapy, antiplatelet and anticoagulant therapy, etc.) ).

With negative dynamics of changes in the concentration of oxyhemoglobin in the tissue of the autodermotransplant, the risk of necrosis is recognized as high, it is necessary to remove the autodermotransplant to prevent local infectious complications.

With a measurement period of less than 48 hours, the difference in the concentration of oxyhemoglobin may not be significant. In addition, frequent dressings in conditions of an insufficiently formed vascular network between the graft and the recipient bed lead to additional trauma to the graft, its displacement along the plane. With more than 48 hours, the period of registration of the oxygen status of the autodermotransplant, therapeutic measures may be ineffective.

Clinical example. Patient K., born in 1965, was admitted to the department of purulent surgery of GBUZ NO "GKB No. 30 of the Moscow region of Nizhny Novgorod" on October 27, 2019 with the following diagnosis: "Type I diabetes mellitus. Target level НbАlс> 7.5%. Diabetic foot syndrome, neuroischemic form, Wager IV. Wet gangrene of the 1,2,3 toes of the right foot ”. The general condition of the patient is of moderate severity. Complaints at the time of admission: fever up to 38.8 ° C, local edema of the distal foot, hyperemia of the right foot, pain syndrome. On October 27, 2019, an emergency operation was performed: amputation of 1, 2, 3 toes of the left foot with resection of the corresponding heads of the metatarsal bones. After the operation, a wound with dimensions of 14 × 8 cm and a depth of 3 cm was formed. According to the results of a microbiological examination of the wound discharge, the presence of Enterobacter aerogenes 10 ⁷ CFU / ml was revealed. Conservative treatment in the postoperative period was complex and included all the components necessary for patients with diabetic foot syndrome: complete unloading of the affected limb for the period of hospital treatment, antibacterial (imipenem 500 mg 3 times a day), detoxification (saline 500 ml 1 time day), analgesic (ketonal 2.0 2 times a day), gastroprotective (omez 20 mg 2 times a day), vitamin and antioxidant (tocopherol 200 mg 2 times a day, ascorutin 2 tablets 3 times a day), antihypoxant ( actovegin 500 ml i.v. drip 1 time per day), antiplatelet (aspirin 500 mg 1 time per day), antihyperglycemic therapy (aktrapid 4ED 3 times a day, Protafan 15U 2 times a day). Local treatment in phase I of the wound process consisted of daily dressings, including debridement of the purulent focus with 0.1% Prontosan solution, covering the wound with a sterile gauze napkin with Oflomelid water-soluble ointment, chemical necrolysis with chymitrypsin. After the transition of the wound process to the II phase, local treatment included the treatment of the wound with metluracil ointment with atraumatic dressings "Branolind".

On November 10, 2019, a decision was made to perform the dermal-plastic stage of treatment. The wound closure method is free skin grafting with a split graft. On the scale of the Research Institute named after I.I. Janelidze the readiness of the recipient zone for free autodermoplasty was estimated at 17 points (Fig. 4). On 10.11.19, free autodermoplasty was performed with a split graft 0.35 mm thick.

Received three autodermotransplants (No. 1, No. 2, No. 3, see Fig. 5) were transferred to the recipient wound, while additional fixation with sutures was not performed. A gauze bandage with iodopyrone was applied to the donor wound. A gauze bandage soaked in a solution of aqueous chlorhexidine was applied to the recipient wound. The first dressing of the donor zone was performed on the 8th day, the recipient zone - on the 4th day after surgery, focusing primarily on the degree of saturation of the dressings with wound exudate. On the 4th day after surgery, when changing the dressing, there were no clinical signs of non-viability of autodermotransplants: the grafts were pale pink in color, which is normal for this time period, tightly fixed to the wound bed (Fig. 6).

An instrumental study of the concentrations of oxy- and deoxyhemoglobin was carried out using an ODS-device described in the work of M.S. Kleshnin, I.V. Turchin. Evaluation of oxygenation in the surface layers of biological tissues based on optical diffusion spectroscopy with automated measurement calibration // Quantum Electronics. - 2019. - T. 49. - No. 7. - With. 628-632.

An instrumental examination revealed that the concentration index of oxyhemoglobin in graft No. 1 was 9.5 µM / L, in graft No. 2 - 9.9 µM / L, in graft No. 3 - 8.7 µM / L. On the 6th day after plastic surgery, graft No. 1 retained a pale pink color, the concentration of oxyhemoglobin was 9.3 μM / L (negative dynamics); most of the graft No. 2 acquired a pinkish-cyanotic hue, which visually confirms the activation of the processes of angiogenesis between it and the recipient bed, the concentration of oxyhemoglobin is 14.3 μM / L (an increase in the concentration of oxyhemoglobin by more than 25%); in graft No. 3, a smaller part of the tissues has a pink-cyanotic color, the concentration of oxyhemoglobin is 10.3 μM / L (an increase in the concentration of oxyhemoglobin by less than 25%) (Fig. 7). To minimize the risk of necrosis of free autodermotransplant No. 3, it was decided to apply VAC-therapy for 2 days. On the 8th day of the postoperative period, most of the graft No. 1 was lysed, the engraftment area was 35%, the concentration of oxyhemoglobin was 8.5 μM / L (preservation of negative dynamics); the engraftment area of the graft No. 2 was 85%, the concentration of oxyhemoglobin was 18.4 μM / L, that is, an increase in the concentration of oxyhemoglobin compared with the previous measurement by more than 25%; after applying an additional method of exposure (VAC-therapy) to improve integration with the wound bed of graft No. 3, the area of its engraftment was 80%), the concentration of oxyhemoglobin was 12.2 μM / L (an increase in the concentration of oxyhemoglobin by less than 25%) (Fig. 8) ... After 4 days, we observed complete necrosis of graft No. 1, after which it was removed to prevent local infectious complications.

Thus, using the proposed method, it is possible to non-invasively predicting the risk of necrosis of a free split autodermotransplant to determine further treatment tactics: with an increase in the concentration of oxyhemoglobin at each stage of the study by more than 25%, the risk of necrosis of a free split autodermotransplant is considered low; with an increase in the concentration of oxyhemoglobin at each stage of the study by less than 25%, the risk of necrosis of a free split autodermotransplant is assessed as moderate, which requires the use of additional methods to increase the oxygenation of the wound bed; with negative dynamics of changes in oxyhemoglobin, the risk is recognized as high, it is necessary to remove an autodermotransplant to prevent local infectious complications.

The possibility of carrying out the invention is confirmed by the available methods and means described in the application, therefore, the proposed technical solution meets the criterion of the invention "industrial applicability".

The analysis of the patent and medical scientific literature showed that the proposed method contains features that distinguish it not only from the prototype, but also from other options for assessing the risk of free graft rejection. These differences allow us to conclude that the proposed technical solution meets the criterion of the invention "novelty".

Claims (1)

A method for predicting the risk of necrosis of a free autodermotransplant, based on the assessment of changes in the state of microcirculatory blood flow in the tissues of an autodermotransplant in the period from at least 4 to 7 days after free skin grafting, characterized in that a free split autodermotransplant is used for skin grafting, after skin grafting by the method optical diffusion spectroscopy determine the difference between the concentration of oxyhemoglobin in the tissues of the autodermotransplant on the 4th, 6th and 8th days, with an increase in the concentration of oxyhemoglobin at each stage of the study by more than 25%, the risk of necrosis of the free split autodermotransplant is considered low; with an increase in the concentration of oxyhemoglobin at each stage of the study by less than 25%, the risk of necrosis of a free split autodermotransplant is assessed as moderate, which requires the use of additional methods to increase the oxygenation of the wound bed; with negative dynamics of changes in oxyhemoglobin, the risk is recognized as high, it is necessary to remove an autodermotransplant to prevent local infectious complications.

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