JP6655630B2 - Apparatus and method for simulation of surface bleeding - Google Patents

Description

  The present invention relates to the medical field, and more particularly, to the assessment of the severity of surface bleeding, for example, to determine the effectiveness of a hemostat on a wound.

  Assessing the effectiveness of a product, especially a medical product, is relevant if the protocol for validating a particular product is reliable and reproducible in a consistent and equivalent manner.

  Such reliable and reproducible protocols are not always available. For example, assessing the hemostatic performance of a product is extremely difficult due to the lack of available methods for consistent assessment of wound bleeding severity. In addition, there are no available methods that could be applied to surgery, for example, for use in clinical studies to evaluate the performance of hemostatic agents.

  Assessing total blood loss during surgery is an integral part of surgery and is considered routine care. Diverse surgical disciplines and surgery make quantitative standardization of total blood loss difficult, and an assessment has not yet been presented. With the aid of other variables such as blood pressure, total blood loss during surgery is data that is useful for the ongoing assessment of a subject's condition and the assessment / improvement of intra- and post-operative management.

  Adams et al., `` Acute in-vivo evaluation of bleeding with Gelfoam plus saline and Gelfoam plus human thrombin using a liver square lesion model in swine '' (J Thromb Thrombolysis. 2009 Jul; 28 (1): 1-5.doi: 10.1007 / s11239-008-0249-3. A publication named Epub 2008 Jul 16), used to evaluate hemostasis or residual bleeding after placement of products, especially sellfoam (produced by Baxter). The summary scale used is described. However, no indication is given as to how bleeding severity is assessed prior to randomization, particularly prior to placement of the study device, and during intraoperative inclusion / exclusion assessment. Such measures also do not appear to be adapted to be used to consistently assess the success or failure of a product for hemostasis. The proposed measure does not include the full range of possible input and output area data values for each candidate site, for example, it does not include or identify life-threatening bleeding as well as severe bleeding.

  There does not seem to be a correlation between the amount of blood associated with any score at any site and an objective measure of this amount of blood, eg, blood loss over time. Thus, there is a need for a typical score for comparable blood mass or flow at various anatomical sites and under various potentially significant conditions (covariates).

  It is an object of the present invention to provide systems and methods for simulating surface bleeding, for example, to validate bleeding severity scales for further application during surgery and / or clinical trials.

  It is an object of the present invention, inter alia, to provide a method which allows the establishment of the severity of bleeding during the randomization and intraoperative inclusion / exclusion assessment prior to the placement of the trial device.

  It is another object of the present invention to provide a surface hemorrhage severity scale that is used for a consistent assessment of the success or failure of a hemostat. It will preferably include the full range of possible input and output area data values for the bleeding severity seen during elective surgery.

  It is a further object of the present invention to provide a system and method for creating a surface bleeding model that is consistent in assessing the success or failure of hemostasis and that is independent of individual animal physiology.

  It is yet another object of the present invention to ensure that bleeding severity assessments are consistent among investigators testing a particular product, particularly in clinical trials, and that an equivalent bleeding severity is achieved, particularly during that study. It is to provide a system and a method for ensuring registration.

  A particular object of the present invention is to provide systems and methods for use in clinical trials of hemostatic products, and in particular, to determine the eligibility of patients during surgery and the success of hemostasis of a test product. is there. In particular, the objective was to ensure consistent registration of the target bleeding site of the bleeding severity to be treated and to eliminate those with too severe bleeding for the evaluation of the hemostatic product under study. Is to help ensure the safety of

  Yet another object of the present invention is to provide a system and method for recognizing a particular degree of surface bleeding and assisting the investigator in training and testing to uniformly assess such surface bleeding in clinical trials. It is to be.

  For this purpose, an apparatus and a corresponding method for simulating surface bleeding as defined in the appended claims are proposed.

  The following numbered examples illustrate features in accordance with various embodiments of the invention as described further above.

Example 1 is an apparatus for simulating surface bleeding,
The device comprises:
A blood source, especially a source of synthetic blood or blood drawn from the human body;
A pump system connected to the blood supply, wherein the pump system is configured to provide a controlled flow of the blood;
An open chamber connected to the pump system, the wound simulator having the open chamber for receiving the controlled blood flow;
The wound simulator comprises a set of replaceable plates;
Each plate is a plurality of holes arranged on the plate according to a specific pattern, wherein the specific pattern has the plurality of holes different for each plate of the set of exchangeable plates; and A plate is adapted to be removably mounted on the wound simulator to close the open chamber, such that the blood passes from the chamber through the holes of the plate mounted on the wound simulator. The said device.

  Example 2 relates to the device according to example 1, wherein the plates of the exchangeable plate set comprise holes of different surface areas, in particular of different sizes, arranged according to a specific pattern.

Example 3 relates to the device according to any one of the examples 1 or 2, wherein the holes are provided in each of the exchangeable plates at a density of at least 50 holes / cm ² , in particular 100 holes / cm ^2. .

  Example 4 relates to the device of any one of Examples 1 to 3, wherein the number and diameter of the holes in each of the exchangeable plates is set to reproduce the appearance of a bleeding surface.

  Example 5 describes the example 4 wherein the holes provided in each of the exchangeable plates have the same diameter and are preferably comprised between 0.2 mm and 1 mm, most preferably 0.5 mm. Device.

  Example 6 shows that the holes provided in each of the exchangeable plates are regularly spaced in a corresponding specific pattern, the pitch preferably being comprised between 0.4 mm and 2 mm, most preferably 1 mm The apparatus according to any one of Examples 1 to 5, wherein

  Example 7 wherein the wound simulator further comprises a drainage system for draining the blood passing through the holes of the plate and directing it to a receiver. Related to the device.

  Example 8 is a pressure monitoring system connected to a pump system, further comprising a pressure monitoring system for measuring a pressure of the blood supplied to the open chamber of the wound simulator. Device according to one of the preceding claims.

  Example 9 relates to the apparatus of any one of Examples 1 to 8, wherein the pump system further comprises a peristaltic pump provided with tubing for circulating the blood from the blood supply to the open chamber.

  Example 10 relates to the apparatus of any one of Examples 1 to 9, wherein the pump system comprises a pump controller for controlling the flow of the blood from the blood supply to the open chamber.

  Example 11 is a method for simulating a plurality of different surface bleeds, for example with the device according to any of Examples 1 to 10, wherein each surface bleed is transmitted to a wound simulator from a set of exchangeable plates. A method simulated by mounting a particular plate selected and adjusting the blood flow supplied by the pump system to a particular value.

Example 12 comprises the simulation of several sets of surface bleeding, where:
The first set of surface bleeds is simulated to represent the first surface bleeding severity, each of the surface bleeds increasing the flow of blood supplied by the pump system by more than 0 mL / min to 4.8 mL; Simulated by adjusting to a specific value chosen to be less than / min;
A second set of surface bleeds is simulated to represent a second surface bleeding severity, each of the surface bleeds not less than 4.8 mL / min of blood flow supplied by the pump system. Simulated by adjusting to a particular value chosen to be less than 0 mL / min;
A third set of superficial hemorrhages is simulated to represent a third superficial hemorrhage severity, each of the superficial hemorrhages, the flow of blood supplied by the pump system being greater than 12.0 mL / min. Simulated by adjusting to a specific value chosen to be less than 3 mL / min;
The fourth set of surface bleeding is simulated to represent a fourth surface bleeding severity, each of the surface bleeding increasing the blood flow supplied by the pump system by more than 25.3 mL / min. Simulated by adjusting to a particular value chosen to be less than 0 mL / min;
A fifth set of surface bleeds is simulated to represent a fifth surface bleeding severity, each of the surface bleeds selecting a flow of blood supplied by the pump system of 102.0 mL / min or more 11. The method of example 10, wherein the method is simulated by adjusting to a particular value.

Example 13 comprises a simulation of several sets of surface bleeding, where:
A first surface bleeding set is simulated to represent a first surface bleeding severity, wherein the first surface bleeding set comprises:
Mounting a plate with through-holes arranged according to a pattern of 1 cm 2, and the flow of blood supplied by the pump system to a specific value selected to be greater than 0 mL / min and less than 4.8 mL / min At least one surface bleed, simulated by adjusting;
Mounting a plate with through-holes arranged according to a pattern of 10 cm ² , and a specific value for the flow of blood supplied by the pump system being selected to be greater than 0 mL / min and less than 9.1 mL / min At least one surface bleed, simulated by adjusting to;
Mounting a plate with through-holes arranged according to a pattern of 50 cm ² , and a specific value for the flow of blood supplied by the pump system being selected to be greater than 0 mL / min and less than 13.5 mL / min Comprising at least one surface bleed, simulated by adjusting to
A second set of surface bleeding is simulated to represent a second set of surface bleeding severity, wherein the second set of surface bleeding comprises:
Mounting a plate with through-holes arranged according to a pattern of 1 cm ² , and a specific blood flow supplied by said pump system selected to be 4.8 mL / min or more and less than 12.0 mL / min At least one surface bleed, simulated by adjusting the value;
Mounting a plate with through-holes arranged according to a pattern of 10 cm ² , and a specific flow selected from 9.1 mL / min to less than 20.0 mL / min for the blood flow supplied by the pump system At least one surface bleed, simulated by adjusting the value;
Mounting a plate with through-holes arranged according to a pattern of 50 cm ² , and a specific flow selected from 13.5 mL / min to less than 28.0 mL / min for the blood flow supplied by said pump system Comprising at least one surface bleed, simulated by adjusting to a value;
A third surface bleeding set is simulated to represent a third surface bleeding severity, wherein the third surface bleeding set comprises:
Mounting a plate with through-holes arranged according to a pattern of 1 cm ² , and a specific flow selected by the pump system from 12.0 mL / min to less than 25.3 mL / min. At least one surface bleed, simulated by adjusting the value;
Mounting a plate with through-holes arranged according to a pattern of 10 cm ² and a specific flow selected by the pump system to provide a flow of blood of at least 20.0 mL / min and less than 71.3 mL / min. At least one surface bleed, simulated by adjusting the value;
Mounting a plate with through-holes arranged according to a 50 cm ² pattern, and a specific flow selected by the pump system to provide a flow of blood of at least 28.0 mL / min and less than 117.3 mL / min. Comprising at least one surface bleed, simulated by adjusting to a value;
A fourth surface bleeding set is simulated to represent a fourth surface bleeding severity, wherein the fourth surface bleeding set comprises:
Mounting a plate with through-holes arranged according to a pattern of 1 cm ² , and a specific flow selected by the pump system from 25.3 mL / min to less than 102.0 mL / min. At least one surface bleed, simulated by adjusting the value;
Mounting a plate with through-holes arranged according to a pattern of 10 cm ² , and a specific flow selected by the pump system from 71.3 mL / min to less than 147.4 mL / min. At least one surface bleed, simulated by adjusting the value;
Wearing a plate with through-holes arranged according to a pattern of 50 cm ² , and a specific flow selected from 117.3 mL / min to less than 192.7 mL / min for the blood flow supplied by the pump system Comprising at least one surface bleed, simulated by adjusting to a value;
A fifth surface bleeding set is simulated to represent a fifth surface bleeding severity, wherein the fifth surface bleeding set comprises:
By mounting a plate with through-holes arranged according to a pattern of 1 cm ² and adjusting the flow of blood supplied by the pump system to a specific value chosen to be 102.0 mL / min or more. Simulated, at least one surface bleed;
By mounting a plate with through-holes arranged according to a pattern of 10 cm ² and adjusting the flow of blood supplied by the pump system to a specific value chosen to be 147.4 mL / min or more. Simulated, at least one surface bleed;
By mounting a plate with perforations arranged according to a pattern of 50 cm ² and adjusting the flow of blood supplied by the pump system to a specific value selected to be greater than 192.7 mL / min. The method of example 10, comprising simulating at least one surface bleed.

  Example 14 relates to the method of any one of Examples 11 to 13, wherein the pump system comprises a pump controller for controlling the flow of the blood from the blood supply to the open chamber.

Example 15 has the following subsequent steps:
Selecting a plurality of videos of simulated surface bleeding recorded, for example, according to the method of Example 14, wherein each of the selected videos is assigned a score corresponding to the severity of surface bleeding;
Classifying the selected videos in a particular order for visualization, wherein the score of each of said videos is displayed together with the corresponding video;
At least one training video set.

  Example 16 relates to the method of example 15, wherein the videos are classified for visualization in ascending or descending order of the severity of the corresponding surface bleeding.

Example 17 includes the following subsequent steps:
Selecting a plurality of videos of simulated surface bleeding recorded, for example, according to the method of Example 14, wherein each of the plurality of videos is assigned a score corresponding to the severity of surface bleeding;
Classifying the videos in a random order for visualization, wherein the scores of each of the videos are not displayed with the corresponding videos;
A method of creating at least one test video set.

Example 18 is a method of creating at least one training video set and at least one test video set using a plurality of simulated surface bleeding videos recorded, for example, according to the method of Example 14, wherein each of the plurality of videos is Is assigned a score corresponding to the severity of surface bleeding,
Creating a training video set by selecting a portion of the plurality of videos and classifying the selected videos in a particular order for visualization, wherein each particular selection of videos is Scores and information about the plate are displayed with the corresponding video;
Creating a test video set by selecting a portion of the plurality of videos and classifying the selected videos in a random order for visualization, where each score of the video is , Not displayed with the corresponding video, and wherein the selection and / or classification of the video comprises different from the training video set.

  Example 19 is a method of training a person to be able to recognize and classify the severity of superficial bleeding, comprising displaying a plurality of training videos in a particular order, wherein the training videos are displayed. Each relates to a method of indicating a simulated surface bleed and a score corresponding to the severity of said simulated surface bleed.

  Example 20 relates to the method of example 19, wherein the training videos are displayed in ascending or descending order of the severity of the corresponding surface bleeding.

Example 21 comprises the following steps:
Displaying a plurality of test videos, each numbered in a random order, wherein each of the test videos is associated with a simulated surface bleed; Shown without a score corresponding to the severity, the test video is different from the training video and / or used in a different order;
Example 19, comprising the subsequent step of testing a person in the application of a step requiring each of the test videos to score a typical score for the severity of superficial bleeding in the order in which they were numbered Or the method of any one of 20.

Example 22 is a method of conducting a clinical test to evaluate the product's hemostatic power against surface bleeding, comprising the following steps:
a) identifying the severity of baseline surface bleeding from the patient's wound by assigning a score, said identification being based, for example, on training performed according to any one of Examples 19-21;
b) applying the product to a wound according to the specific use protocol of the product;
c) identifying the severity of surface bleeding remaining from the patient's wound by assigning a score at a predetermined time after step b), said identification being, for example, any one of Examples 19-21 Based on the training conducted according to the method.

  Example 23 relates to the method of example 22, wherein steps b) and c) are repeated several times after each identification of the severity of residual surface bleeding to assess the hemostasis of the product over time. .

  Other features and advantages of the present invention will become apparent from the following description, which is given by way of example only and not limitation, and should be read with reference to the accompanying drawings.

FIG. 1 is a schematic diagram of an apparatus for simulating surface bleeding. FIG. 2 is a perspective view of a wound simulator of the device shown in FIG. FIG. 3 is a perspective view showing a cross-sectional view of the wound simulator of FIG. FIG. 4 is an enlarged perspective view of a cross section of the open chamber and drainage system of the wound simulator of FIG. FIG. 5 is an enlarged perspective view of a replaceable plate of the wound simulator of FIG. FIG. 6a is a top view of the replaceable plate according to the first embodiment. FIG. 6b is a cross-sectional view of the replaceable plate of FIG. 6a along the line AA. FIG. 7a is a top view of a replaceable plate according to the second embodiment. FIG. 7b is a cross-sectional view of the replaceable plate of FIG. 7a along the line BB. FIG. 8a is a top view of a replaceable plate according to the third embodiment. FIG. 8b is a cross-sectional view of the exchangeable plate of FIG. 8a along the line CC.

DETAILED DESCRIPTION OF THE INVENTION The following description is directed to the determination, recognition and evaluation of surface bleeding, particularly for determining the severity of such surface bleeding. However, all corresponding teachings are applicable to the secretion of body fluids, in particular any of the fluids to be recognized and / or evaluated for medical or scientific purposes, for example bile.

  For a reliable and reproducible assessment of surface bleeding, any surgical discipline could be used as well, i.e., independent of the consequences of blood loss in such particular surgical disciplines. There is a need to establish a scale that can also recognize the severity of surface bleeding at the target bleeding site (TBS).

  Such a scale--the SBSS, or Surface Bleeding Severity Scale--is used, for example, in any surgical procedure used in clinical trials to evaluate the performance of medical products such as hemostats. Allows for consistent and applicable bleeding assessments.

  In the case of hemostatic agents, the purpose is to ensure that hemostasis is applied when control of bleeding by conventional procedures is ineffective or infeasible, and that the severity of bleeding is not To be able to be selected for effectiveness.

  It is also important to ensure consistency in bleeding severity assessments between investigators and to ensure that only eligible bleeding reserves are registered during clinical trials.

Device for Simulating Surface Bleeding To build such a scale to assess the severity of intraoperative bleeding at the target bleeding site (TBS), simulate surface bleeding, and thus create a benchtop bleeding model It is proposed to use a device for producing.

  The specific use of this bench-top bleeding model makes it possible to simulate selected types of bleeding, so that the subsequent surgeon's assessment of surface bleeding severity at the site of target bleeding at the target bleeding site Is constructed.

  In addition, certain devices for simulating surface bleeding establish a correspondence between constant blood flow velocity (and consequent blood volume within a given time period) and the developed surface bleeding severity scale. To make things possible.

  Thanks to such a surface bleeding simulation device, it is possible to train and test the surgeon in evaluating any surface bleeding. In particular, this would be useful for training and testing surgeon investigators who must evaluate surface bleeding, for example, for testing hemostatic products.

  More generally, surface bleeding simulation devices learn how people, especially surgeons, can assess the severity of surface bleeding in any surgical situation, independent of individual animal physiology Help.

  As shown in FIG. 1, the proposed device for simulating surface bleeding comprises a source 1 of blood. Such blood can be synthetic blood, blood drawn from the human body, or any other liquid suitable for mimicking blood.

  For example, synthetic blood marketed by Jeulin, a company located in France, under the reference "Sang synthique-ref: 107175" can be used under reference. This synthetic blood has the same color and viscosity as human blood and has the advantage that it can be easily washed.

  For synthetic blood, the interface is preferably between 1% and 30% by weight, more preferably between 2% and 15% by weight, in order to adapt the surface tension of the synthetic blood and allow a homogeneous flow in the device. An activator can be added. One example of a surfactant that can be used is the product marketed by Procter & Gamble under the trademark product code PA00168831, "Fairy Original". Such surfactants include 20% to 30% of a mixture of alcohols, C10-16, ethoxylation, sulfates, sodium salts, and 5% to 10% of amines, C10-16-alkyldimethyl, N -A mixture of oxides.

  If one chooses to use blood drawn from the human body, it is preferably treated to avoid agglutination, for example by using ethylenediaminetetraacetic acid (EDTA) or citrate.

  Preferably, the temperature of the blood is controlled to a temperature close to human body temperature, that is, around 37 ° C. Alternatively, the simulation can be performed at room temperature, i.e., the blood is at a temperature between 20C and 25C.

  The simulation device further comprises a pump system 2 connected to the blood supply 1 via a specific plumbing system 4.

The pump system 2 is configured to provide a controlled flow F _in the blood. Preferably, the pump system 2 is adapted to provide a pulsed flow of blood.

Preferably, the pump system 2 comprises a peristaltic pump 21 that is provided with a pipe 4 required circulation of blood from the blood source 1 at the required flow rate F _in.

  The pump system 2 also preferably includes a pump controller 22 for complete control of the blood flow in the tubing 4 of the simulation device, in particular the volume, flow rate and direction of the blood.

Flow _{F in} the blood, regularly, preferably, it can be controlled to at least 0.1 mL / min increments, changes.

  The tubing 4 is adapted to the flow rate range in which the pump system is intended to be used.

  Preferably, the pump system 2 and corresponding tubing 4 are adapted for flow rates up to 500 mL / min, most preferably up to 250 mL / min.

  For example, the Allegro ™ family of pump systems marketed by KD Scientific, which combines a peristaltic pump system with a control unit, can be used.

  According to a particular embodiment, the piping 4 is specifically selected according to the flow rate to be used. For example, a first set of tubing 4 may be used at a flow rate up to 60 mL / min, while a second set of tubing 4 is used at a flow rate above 60 mL / min. For example, a silicone tube marketed as “Masterflex® L / S®14” can be used for flow rates up to 60 mL / min, see the reference “Masterflex® L / S®25”. Silicone tubes marketed as "" can be used at flow rates above 60 mL / min.

Simulation apparatus, which is connected to the pump system 4 further comprises a wound simulator 3 having an open chamber 31 for receiving the controlled flow F _in the blood.

  The wound simulator 3 comprises a set of exchangeable plates 32, wherein each plate 32 is adapted to be removably mounted on the wound simulator 3 to close the open chamber 31.

  As shown in FIG. 5, each plate 32 preferably comprises a plurality of holes 321 arranged in said plate 32 according to a specific pattern.

As a result, blood through the liquid inlet 311 at a particular flow F _in which is controlled by the pump system 2 enters the chamber 31 flows out of the chamber 31 through the holes 321 of the plate 32 mounted on the wound simulator 3 (See flow F _{out in} FIG. 1).

Blood flowing from the hole 321 of the plate 32 mimics the surface bleeding, the intensity of the simulated bleeding, for example, depends on several parameters, such as the arrangement of the holes 321 passing through the flow F _in and the plate 32 controlled blood I do.

  Preferably, the particular arrangement pattern of holes 321 is different for each plate 32 of the exchangeable plate set. This can simulate various bleeding surface areas that can correspond to the standard target bleeding sites encountered by surgeons during surgery.

  The arrangement pattern may have, for example, different shapes (square, rectangular, circular or any other more complex shape), different sizes, and / or provided through holes 321 with different diameters. Are said to be different from each other.

  6a, 6b, 7a, 7b, 8a and 8b show, for example, three different plates 32 included in a plate set, in which holes 321 are arranged according to three different patterns P1, P2 and P3 respectively. I have. In this case, these patterns differ from each other by having different sizes.

  Preferably, the density and diameter of the holes 321 provided in each of the exchangeable plates are set to mimic the appearance of the bleeding surface.

In particular, these holes can be provided in each of the exchangeable plates at a density of at least 50 holes / cm ² , preferably of 100 holes / cm ² .

  The diameter of the through-hole 321 can be constant, for example comprised between 0.2 mm and 1 mm, most preferably 0.5 mm. A hole diameter of 0.5 mm is actually preferred because it corresponds to the typical size of a small blood vessel.

  The holes 321 provided may be regularly spaced in a corresponding specific pattern, the pitch preferably being comprised between 0.4 mm and 2 mm, most preferably 1 mm.

In the particular embodiment of the plate shown in FIGS. 6a, 6b, 7a, 7b, 8a and 8b, the through holes 321 all have the same 0.5 mm diameter and are regularly spaced according to a square pattern (pitch 1 mm / density 100 holes / cm ² ). The only difference between the three plates in these embodiments is the area of the square pattern.

The plate 32 in FIGS. 6a and 6b corresponds to a so-called small pattern of plates, the pattern of which is a square of 1 cm ² . Such a plate comprises 100 holes of 0.5 mm diameter.

The plate 32 in FIGS. 7a and 7b corresponds to a so-called medium pattern plate, the pattern of which is a 10 cm ² square. Such a plate comprises around 1000 holes (more precisely 961 holes) of 0.5 mm diameter.

The plate 32 in FIGS. 8a and 8b corresponds to a so-called large pattern plate, the pattern of which is a square of 50 cm ² . Such a plate comprises around 5000 holes (more precisely 5041 holes) of 0.5 mm diameter.

  This particular set of exchangeable plates 32 is particularly preferred for simulating surface bleeding, as it represents several different wound sizes that allow obtaining representative data to build a surface bleeding scale.

Other examples of plates that may be used alone or in combination with the above plates to form a plate set are as follows:
A 5 cm ² square pattern plate comprising around 500 holes of 0.5 mm diameter;
A plate of 20 cm ² square pattern, comprising around 2000 holes of 0.5 mm diameter;
A plate with a square pattern of 50 cm ² comprising around 200 holes of 0.5 mm diameter.

  Preferably, holes 321 are drilled in plate 32 according to the required pattern.

  The plate is preferably made of a material selected such that the corresponding surface tension contributes to a uniform surface flow of blood through the holes, thereby simulating a homogeneous bleeding.

  If a surfactant is used in the synthetic blood, the amount is preferably controlled depending on the hydrophobic characteristics of the material and, therefore, on the surface tension resulting from the selected material.

  Plate 32 can be made of, for example, acrylic, plexiglass, or polymethyl-methacrylate (PMMA).

  Alternatively or additionally, plate 32 may be formed of a material having a particular porosity to allow liquid to pass through the plate. The porosity is selected so that it mimics the capillary action of superficial vessels, veins, or arteries, so that it opposes the resistance to fluid passage.

  Preferably, the colors of these plates are also specifically selected according to the simulated surface bleeding. For example, to simulate surface bleeding from an organ (eg, liver), these plates are preferably colored red or made of red material. A white plate can be used to simulate bleeding from bone. To simulate bleeding from fat, a yellow plate can be used. More generally, the plate may have the color of the target tissue.

  In a preferred embodiment, the color of the plate is selected to mimic the worst that can occur during surgery with respect to the contrast between the blood and the bleeding surface (eg, bleeding from a low contrast liver). Thus, in such a case, the plate is preferably colored red or made of a red material.

  Preferably, the wound simulator 3 further comprises a drainage system 34 for draining blood that has passed through the holes 321 of the plate 32. This drainage system may be an overflow drainage 341 as shown in FIG.

The drainage system 34 is preferably designed to direct liquid from the plate 32 to be supplied by gravity, for example to a receiver 33 located in the wound simulator 3 below the open chamber 31 (FIG. 1). referring to the flow _{F G} of). In this case, the drainage system 34 may comprise, for example, a vacuum formed funnel-shaped part 342.

  The receiver 33 can comprise, for example, a wide-mouth collection bottle that can be made of high density polyethylene (HDPE).

  The volume of the receiver 33 is preferably chosen to be large enough to avoid having to change it during one simulation of a particular surface bleed. Preferably, the receiver 33 has a volume of at least 1L.

  In another embodiment, the receiver 33 is connected to the blood supply 1 such that it forms a closed loop so that the blood circulates in the simulation device. In such a case, a filter means is preferably inserted between the receiver 33 and the blood supply 1 to remove impurities which may have contaminated the blood passing through the holes 321 of the plate 32. .

  According to one particular embodiment, most of the parts forming the wound simulator 3 are made of polycarbonate. An aluminum support structure can in this case be provided to stabilize the wound simulator.

  The device for simulating surface bleeding may also include a pressure monitoring system 5 connected to the pump system 2 for measuring the pressure of the blood supplied to the open chamber 31 of the wound simulator 3. The pressure monitoring system 5 makes it possible to control the flow of blood used for the simulation of surface bleeding to remain in the physiological pressure range.

  Such devices allow for the screening of surface bleeding to simulate some types of surface bleeding and, consequently, according to their severity as assessed by a matching surgeon It is very advantageous to construct a corresponding measure for

  In particular, a plurality of different surface bleeds may be used to mount a particular plate 32 selected from a set of interchangeable plates on the wound simulator 3 using such a device to regulate the flow of blood supplied by the pump system 2. It can be simulated by adjusting the value.

Method for Constructing a Surface Bleeding Severity Scale In the following, one particular method for constructing a surface bleeding severity scale by using the above described simulation device is described.

First, straightforward idioms for qualifying and describing the severity of surface bleeding were chosen to create the following qualitative six-point general measure of surface bleeding.
0-no bleeding / hemostasis 1-minimal bleeding 2-mild bleeding 3-moderate bleeding 4-severe bleeding 5-extreme bleeding

  In addition to verbal descriptors of superficial bleeding, visual descriptors were assigned for each of the scale scores, as well as for the expected surgeon intervention. Table 1 below summarizes the characteristics of the proposed surface bleeding scale.

In the above table, the ACS-ATLS (American College of Surgeons-Advanced Trauma Life Supports) shock risk scale is defined as follows.
Class 1: contains up to 15% of the blood volume; in general, there is no change in vital signs and fluid resuscitation is usually not required.
Class 2: Contain 15-30% of total blood volume; patients often have a narrowing of the difference between systolic and diastolic blood pressure and exhibit tachycardia; body compensates for peripheral vasoconstriction Skin may begin to appear pale and cold to the touch; generally only volume resuscitation by crystalloid is needed; transfusions are generally not required.
Class 3: Including a 30-40% loss of circulating blood volume; decreased blood pressure in patients; increased heart rate and worsened peripheral perfusion deficits; fluid resuscitation and transfusion with crystalloids are usually required.
• Class 4: Including loss of more than 40% of circulating blood volume; reaching the limits of body compensation and requiring active resuscitation to avoid pups.

  The SBSS scale can be used to define whether a bleed is eligible for a trial, depending on the claimed efficacy of the test product.

  Based on the feedback of the surgeon's key opinion leaders (KOL), life-threatening bleeding (score 4 or 5) is applicable to trauma surgery or battlefield wounds, and is therefore usually a qualifying bleeding site Not included in clinical trials of hemostatic products. Although the flow rate of surface bleeding severity score 5 reflects life-threatening bleeding, it is unlikely that this level of bleeding has ever been seen in elective surgical cases. In fact, the surgeon's key opinion leaders also suggested that surface bleeding severity scores 4 and 5 were rarely seen in selected cases.

  After adapting such a qualitative measure, the simulation device can be used to determine a blood flow threshold corresponding to each of the scores of the surface bleeding severity scale. This makes it possible to construct quantitative definitions in addition to the qualitative ones described above.

  For this purpose, the surgeon can use a bench under each of the three target bleeding site (TBS) models, ie, using each of the TBS plates described above with respect to FIGS. 6a, 6b, 7a, 7b, 8a and 8b. Evaluate the top model.

  Establishing the relationship between the surface bleeding severity scale score and the blood flow velocity in the simulation device proceeds, for example, in two steps.

  First, the surgeon observes a continually increasing inflow rate to identify potential targets for the threshold of the surface bleeding scoring system.

  After these initial thresholds have been identified, the surgeon then looks at the scoring system by observing ten bleeding models at unevenly distributed increments of flow rate, each within the originally defined interval. Refine the definition.

  For example, during the first observation of a continuously increasing pump flow rate, a surgeon may identify the following thresholds as promising candidates for SBSS changes: 0, 1.0 ml / min, 3.0 ml / min, 5 0.0 ml / min, 15.0 ml / min, and 50.0 ml / min.

  Following this, the surgeon observes 10 equally distributed pump flow rates, each within the initially specified interval.

  For the hypothetical example above, for the intervals (0 ml / min and 1.0 ml / min), the surgeon observes simulated bleeding from 0 ml / min to 1.0 ml / min in 0.1 ml / min increments.

  Thus, there is a total of 50 incremental scoring (10 for each of the 5 originally defined intervals).

In the scoring process, the following steps can be used at each increment.
Step 1: Surgeon starts with a clean surface.
Step 2: Start blood flow at a given flow rate.
Step 3: Wipe the surface while the pump continues to flow at the given speed.
Step 4: After observing blood flow from the newly cleaned surface for a certain period of time (eg, 1-60 seconds, preferably at least 10 seconds), the surgeon defines the surface hemorrhage severity scale. Assigned one of the scores.

If it is desired to ensure that the outflow velocity correlates well with the inflow velocity, the following additional steps can be performed.
Step 5: Wipe the surface while the pump continues to flow at the given speed.
Step 6: Immediately after wiping, apply a 4x4 inch stack of pre-weighed gauges to the surface and hold in place for 5 seconds.
Step 7: Immediately after the gauge is removed, it is weighed to determine the post-bleeding weight and to determine the outflow rate.

  To see if the outflow rate correlates well with the inflow rate, the gauge was then weighed immediately after the surface bleeding severity score was assigned by the surgeon for each inflow rate and TBS plate combination considered. Can be measured (step 7).

  Subtraction of the first gauge stack gives the weight of the blood alone, which is a measure of the bleeding outflow rate, taking into account the area and time of gauge application. Next, each outflow measurement is regression estimated for inflow velocity using a linear regression model and a correlation coefficient, and the corresponding 95% confidence interval is reported.

  Since the flow rate of the pump in this model increases monotonically, the resulting surface bleeding severity score represents a six-section division of the flow rate range, each division corresponding to a given surface bleeding severity score.

In detail, the notation for arbitrary ranges (also called intervals) obeys the following rules:
A range denoted by [x; y] means that both values x and y are included in the range;
•] x; y [means that both the values x and y are outside of the range;
•] x; y] means that the value x is out of the range and the value y is included in the range;
[X; y [] means that the value x is included in the range and the value y is out of the range.

  The entire procedure outlined above is then repeated for each of the three TBS models, resulting in a total of 50 scoring and 50 observed spill gauge weights for each model.

  Next, the surgeon performing the entire procedure should define a flow rate range for each of the TBS plates, thus defining the blood inflow rate (possibly correlated according to the result of the correlation with the outflow) and the surface bleeding severity scale Between each of the scores (six discrete scores in the above example).

  These ranges for each of the TBS plates can be used as is.

  Table 2 below shows a first example (Example A) of intervals defined by a skilled surgeon performing the procedure, depending on the TBS plate used.

  Table 3 below shows a second example (Example B) of intervals defined by a skilled surgeon performing the procedure, depending on the TBS plate used.

  According to another embodiment, the interval threshold corresponding to each surface bleeding severity score is averaged over three TBS models. This allows a single relationship to be defined between the flow rate and the surface bleeding severity score for all TBS models.

For example, if the resulting flow rate interval corresponds to a surface bleeding severity score of 1, within the 1, 10, and 50 cm ² TBS models] x 1 ml / min, y1 ml / min [,] x2 ml / min, y2 ml / Min [and] x3 ml / min, y3 ml / min [. Next, when the BSS is 1, the flow rate intervals finally obtained are [(x1 + x2 + x3) / 3 ml / min and (y1 + y2 + y3) / 3 ml / min. This average result may define a single surface hemorrhage severity score system that can be applied across all TBS models in subsequent medical research phases

  If the procedure is performed by several skilled surgeons, the interval can also be an average based on the interval defined by each experienced surgeon per severity score, per plate.

  According to another embodiment, one skilled surgeon determines and defines intervals for one of the TBS plates, and then those intervals correspond to the other TBS plates depending on the pattern of holes in the TBS plate. It is processed to derive the interval to be performed. Thus, these intervals are normalized to each of the surface areas of the TBS plate used for the test.

Table 4 below shows examples of normalization intervals assigned to different TBS plates, which can also be derived from the intervals defined for 1 cm ² TBS plates. In this third example (Example C), a spacing with a value rounded to a value greater than the upper unit is assigned to a 1 cm ² TBS plate, and the spacing for other TBS plates is compared to a 1 cm ² TBS area. It is calculated in consideration of the enlargement rate of the surface area. The normalization factor is given by the equation 1 + 2% ^* [expansion percentage] and the final limit of the interval corresponds to the factorized value rounded to a value above the upper unit.

  Fixing the spacing corresponding to each of the surface bleeding scale scores, possibly on the TBS plate used by the simulator, gives a quantitative final definition of the surface bleeding severity scale that can be simulated by the simulator. It is.

Learning the Surface Bleeding Severity Scale As described, the simulator allows in a rigorous and repeatable manner the simulation of a specific surface bleed at a given flow rate, which can be specified by the surgeon / investigator. It is extremely advantageous as it helps to be trained and tested to learn a well-defined surface bleeding severity scale.

  In particular, an apparatus for simulating surface bleeding can be used to create training and / or test videos of bleeding models over a range of previously defined surface bleeding severity values for each TBS plate.

  According to a non-limiting example, for each TBS model, two videos are created for each of the five equally distributed flow rates within the interval interval defining each surface bleeding severity value.

  For example, if the flow rate interval corresponding to a surface bleeding severity value of 3 is defined to be [3.0 ml / min, 5.0 ml / min], then for each TBS model, two separate surface bleeding videos would be 3 It is made at a flow rate of 0.4, 3.8, 4.2, 4.4, and 4.6 ml / min.

  The procedure for recording a video session may be similar to the scoring process shown above (Steps 1-4). Specifically, the video starts when blood begins to flow in step 2 and continues to run until step 4. In a preferred embodiment, the video recording of step 4 after wiping the TBS surface of step 3 is performed for a time between 12 and 20 seconds. The correct part of the video for the assessment of the surface bleeding severity score in this case corresponds to the first 10 seconds after the step 3 wiping of the TBS surface.

  A video of surface bleeding severity score 0 (complete hemostasis) is created by considering the five models within each TBS model. These five models aim to represent different flow rates before achieving hemostasis. In particular, the midpoint of the flow rate interval for each surface bleeding severity score ranging from 1 to 5 is conceivable.

  For example, if the flow rate interval corresponding to surface bleeding severity score 3 is defined as [3.0 ml / min, 5.0 ml / min], we consider an initial flow rate of 4.0 ml / min. . In this case, in step 2 as defined above, the video begins when blood begins to flow at a flow rate of 4.0 ml / min. Before the surface is wiped in step 3, the pump is turned off (flow rate 0.0 ml / min) and the video continues to run for at least another 10 seconds, preferably 12 to 20 seconds. Again, the correct portion of the video for the assessment of the surface bleeding severity score corresponds to the first 10 seconds after the step 3 wiping the TBS surface.

  In such an example procedure, a total of 180 videos (2 × 5 × 6 × 3 = 180) corresponding to 2 iterations, 5 flow rates each, 6 surface bleeding severity scores, and 3 TBS models are produced.

  The first set of replicates may serve as a training pool where medical research samples are created, while the second set of replicates may serve as a test pool where test samples are created. Alternatively, only one video pool is recorded, which is used for both training and testing sessions.

  After all, the superficial hemorrhage severity scale must be learned (eg, must be part of a medical study to evaluate a hemostatic product) and prepared for surgeon / investigator training and / or testing To do so, several sets of surface bleeds are simulated using the simulation device described above, and are preferably at least partially recorded as video, where the blood defining each score of the surface bleeding severity scale is measured. A set of surface bleeds is simulated for each surface bleed severity, based on the surface bleed severity scale, depending on the range of flow velocities.

For example, based on the surface bleeding severity scale defined by the average interval above, several sets of surface bleeding are simulated by the simulator and preferably at least partially recorded as video, where:
A first set of surface bleeding is simulated to represent a first surface bleeding severity, each of said surface bleeding increasing the flow of blood supplied by said pump system 2 by more than 0 mL / min. Simulated by adjusting to a specific value selected to be less than .8 mL / min;
A second set of superficial bleeding is simulated to represent a second superficial bleeding severity, each of said superficial bleeding increasing the flow of blood supplied by said pump system 2 by more than 4.8 mL / min Simulated by adjusting to a specific value chosen less than 12.0 mL / min;
A third set of superficial hemorrhages is simulated to represent a third superficial hemorrhage severity, each of the superficial hemorrhages increasing the flow of blood supplied by the pump system 2 by more than 12.0 mL / min Simulated by adjusting to a specific value chosen to be less than 25.3 mL / min;
A fourth set of surface bleeding is simulated to represent a fourth surface bleeding severity, each of said surface bleeds increasing the blood flow supplied by said pump system 2 by more than 25.3 mL / min Simulated by adjusting to a specific value selected to be less than 102.0 mL / min;
A fifth superficial bleeding set is simulated to represent a fifth superficial bleeding severity, each of said superficial bleeds increasing the blood flow supplied by said pump system 2 by more than 102.0 mL / min Is simulated by adjusting to a particular value chosen.

According to another example, several sets of surface bleeds are simulated on said simulator, preferably at least partially based on the surface bleeding severity scale defined by skilled surgeons, summarized in Table 3 above. Video as a video, where:
A first surface bleeding set is simulated to represent a first surface bleeding severity, wherein the first surface bleeding set comprises:
Mounting a plate 32 with through holes 321 arranged according to a 1 cm ² pattern, and the flow of blood supplied by the pump system 2 is selected to be greater than 0 mL / min and less than 4.8 mL / min At least one surface bleed, simulated by adjusting to a specific value;
Mounting a plate 32 with through holes 321 arranged according to a pattern of 10 cm ² , and the flow of blood supplied by the pump system 2 is selected to be greater than 0 mL / min and less than 9.1 mL / min At least one surface bleed, simulated by adjusting to a specific value;
Mounting a plate 32 with through holes 321 arranged according to a pattern of 50 cm ² , and the flow of blood supplied by the pump system 2 is selected to be greater than 0 mL / min and less than 13.5 mL / min Comprising at least one surface bleed, simulated by adjusting to a particular value;
A second set of surface bleeding is simulated to represent a second set of surface bleeding severity, wherein the second set of surface bleeding comprises:
Mounting a plate 32 with through-holes 321 arranged according to a 1 cm ² pattern, and the flow of blood supplied by the pump system 2 is selected to be at least 4.8 mL / min and less than 12.0 mL / min. At least one surface bleed, simulated by adjusting to a certain value;
Mounting a plate 32 with through holes 321 arranged according to a pattern of 10 cm ² , and the flow of blood supplied by the pump system 2 is selected to be at least 9.1 mL / min and less than 20.0 mL / min. At least one surface bleed, simulated by adjusting to a certain value;
Mounting a plate 32 with through-holes 321 arranged according to a pattern of 50 cm ² , and the flow of blood supplied by said pump system 2 is selected from 13.5 mL / min to less than 28.0 mL / min. At least one surface hemorrhage simulated by adjusting to a particular value;
A third surface bleeding set is simulated to represent a third surface bleeding severity, wherein the third surface bleeding set comprises:
Mounting a plate 32 with through-holes 321 arranged according to a pattern of 1 cm ² , and the flow of blood supplied by the pump system 2 is selected to be at least 12.0 mL / min and less than 25.3 mL / min. At least one surface bleed, simulated by adjusting to a certain value;
Mounting a plate 32 with through holes 321 arranged according to a pattern of 10 cm ² , and the flow of blood supplied by the pump system 2 is selected to be greater than or equal to 20.0 mL / min and less than 71.3 mL / min. At least one surface bleed, simulated by adjusting to a certain value;
Mounting a plate 32 with through-holes 321 arranged according to a pattern of 50 cm ² , and the flow of blood supplied by the pump system 2 is selected to be at least 28.0 mL / min and less than 117.3 mL / min. At least one surface hemorrhage simulated by adjusting to a particular value;
A fourth surface bleeding set is simulated to represent a fourth surface bleeding severity, wherein the fourth surface bleeding set comprises:
-Mounting a plate 32 with through-holes 321 arranged according to a pattern of 1 cm ² and the flow of blood supplied by the pump system 2 is selected to be greater than or equal to 25.3 mL / min and less than 102.0 mL / min; At least one surface bleed, simulated by adjusting to a certain value;
Mounting a plate 32 with through holes 321 arranged according to a pattern of 10 cm ² , and the flow of blood supplied by the pump system 2 is selected to be greater than or equal to 71.3 mL / min and less than 147.4 mL / min. At least one surface bleed, simulated by adjusting to a certain value;
Mounting a plate 32 with through-holes 321 arranged according to a pattern of 50 cm ² , and the flow of blood supplied by the pump system 2 is selected to be at least 117.3 mL / min and less than 192.7 mL / min. At least one surface hemorrhage simulated by adjusting to a particular value;
A fifth surface bleeding set is simulated to represent a fifth surface bleeding severity, wherein the fifth surface bleeding set comprises:
Mounting a plate 32 with through-holes 321 arranged according to a 1 cm ² pattern and adjusting the flow of blood supplied by the pump system 2 to a specific value selected to be 102.0 mL / min or more At least one surface bleed, simulated by:
Mounting a plate 32 with through-holes 321 arranged according to a pattern of 10 cm ² and adjusting the flow of blood supplied by the pump system 2 to a specific value selected to be 147.4 mL / min or more At least one surface bleed, simulated by:
Mounting a plate 32 with through holes 321 arranged according to a pattern of 50 cm ² and adjusting the flow of blood supplied by the pump system 2 to a specific value selected to be greater than 192.7 mL / min. Comprising at least one surface bleed, simulated by performing

  For the surface bleeding severity scale defined by the intervals summarized in Table 2 or Table 4 above, the definitions of various sets of simulated and preferably at least partially video recorded surface bleeding are: It can be easily estimated from the above procedure described for the intervals in Table 3.

  After simulating and recording all required surface bleeding sets, at least one training video set is created using the training video pool, and a set of test videos is created using the test video pool.

  This training video set can be prepared by selecting 36 videos from the training video pool, for example, within each TBS, each 2 videos are sampled for surface bleeding severity values.

  Since the surface bleeding severity score represents a series of flow velocity discretizations, the video within each surface bleeding severity value is preferably sampled to be representative of bleeding occurring at flow rate intervals corresponding to that value. You.

  For example, if two videos of each surface bleeding severity value are sampled, then three videos of flow velocity near the midpoint of the flow velocity interval will have 90% (30% each) sampling opportunities, On the other hand, videos near the end of the flow interval have 10% (5% each) sample opportunities.

  For example, if the flow interval corresponding to a surface bleeding severity value of 3 is defined to be [3.0 ml / min, 5.0 ml / min], the flow rates 3.4, 3.8, 4.2, 4 Bleeding videos at .4 and 4.6 ml / min are available for training set sampling. In this case, from these five videos, videos corresponding to flow rates of 3.8, 4.2, and 4.4 ml / min have a 30% selection opportunity, respectively, with 2.4 and 4.6 ml / min. Two videos are randomly sampled (no replacement) so that the videos of bleeding flow rate each have a 5% selection opportunity.

  This sampling is performed for each score in each TBS, resulting in a total of 36 training videos, with 12 videos for each TBS.

  The test videos are sampled from a pool of previously created test videos. The test video is preferably sampled in a manner similar to that described for the training video. Specifically, two videos were sampled for each superficial bleeding severity value, so that three videos of flow velocity near the midpoint of the flow velocity interval had 90% (30% each) sampling opportunities. On the other hand, videos near the end of the flow interval have 10% (5% each) sampling opportunities. Even though the sampling method is the same as for the training video, the results of sampling the test video may be different from the results of sampling the training video.

  Such sampling also allows for a selection of a total of 36 test videos.

  Simulate and record two videos of five flow rates unequally distributed in the interval segment defining each surface bleeding severity score as described above (a total of 180 videos), then 36 training videos and 36 videos Instead of sampling between those videos to obtain a test video of each, first indicate for each surface bleeding severity score and for each TBS which two flow rates should be used to simulate surface bleeding Sampling can be performed. As a result, only the flow rates selected from the sampling are simulated and video recorded. Using such an alternative, 2 replicates (1 for training, 1 for testing), 2 flow rates each, 6 surface bleeding severity scores, and a total of 72 videos corresponding to 3 TBS models (2 × 2 × 6 × 3 = 72) is created.

  For training, 36 training videos are preferably configured as a training set, where these videos are represented separately for each TBS situation, in ascending order of flow rate. In this way, the surgeon is trained in visually increasing bleeding flow rates and their association with surface bleeding severity values.

  After training, each surgeon is presented with a different set of test videos than those used during the training phase.

  Based on the 36 test videos obtained from the sampling as described above, one or more test video sets may be prepared. Here, the selected test video is completely randomized.

  Each video of the selected test video can be displayed several times.

  According to a first example, a test video set is created by displaying 36 selected test videos three times in a random order. Thus, such an example test video set comprises a series of 108 test videos that are randomly displayed.

  According to a second example, a test video set is created by displaying 36 selected test videos in random order and 6 test videos selected from the sampling for each TBS corresponding to a score of 0. Is done. Thus, such an example test video set comprises a series of 42 test videos that are displayed at random.

  Preferably, the test video set is prepared to comprise the same number of videos for each surface bleeding scale score. Alternatively, the number of test videos for score 0 is greater than for other surface bleeding scale scores.

  Several different sets of test videos can be prepared with different display orders of the selected test videos.

  Before conducting clinical trials to test the hemostatic performance of the product, each surgeon enrolled in the trial as an Investigator is trained and tested to assess the severity of surface bleeding according to the definition of the score .

  First, the investigator is given a description of the surface bleeding severity scale and the corresponding visual descriptor, for example, based on the information shown in Table 1 above.

  Presumably, a set of videos is displayed to the investigator, which shows the plate 32 used to simulate the various surface bleeds used in the training and testing videos, without blood flow.

  After viewing the set of 36 training videos, the investigator is tested on a test video set (eg, a 42 video test set or a 108 video test set). For each video in the set of test videos, the investigator is required to assign a single surface bleeding severity score.

  The registration of the investigator in a clinical trial depends on the successful recognition of the severity of surface bleeding in the trial video, and its success depends on the degree of knowledge required for the clinical trial.

  Clinical trials are, in fact, always based on the reference surface bleeding severity scale trained and tested by the investigator, but the criteria for recognizing the severity of surface bleeding may vary from clinical trial to clinical trial.

  For example, in a potential example of a clinical trial, a bleeding severity of 1, 2, or 3 is eligible for inclusion in the clinical trial, but a bleeding score of 0, 4, and 5 Is not eligible for inclusion. In addition, the surface bleeding severity score also determines hemostasis (success) and non-hemostasis (failure). A score of 0 defines hemostasis, and a surface bleeding severity score greater than 0 corresponds to non-hemostasis (failure). Such examples of rules for clinical trials are summarized in Table 5 below.

  Using such proposed clinical trials, each investigator's trial will determine the appropriate percentage of trial eligibility and the percentage of successful hemostasis success.

  Because it is important for the investigator to be able to distinguish between eligible and unqualified bleeding sites at baseline and between haemostasis and non-haemostasis, these parameters should be reviewed prior to clinical trial participation and subject enrollment. A minimum score must be achieved. The minimum positive recognition rate may e.g. correspond to 90%.

  If the investigator fails, retraining and retesting will continue. Preferably, the investigator can try three times to meet the minimum score for both parameters. Minimum scores for both parameters must be achieved within a single trial. If the investigator fails to achieve the minimum score after three attempts, the physician will not be allowed to participate in the clinical trial.

Clinical Trials for the Evaluation of Hemostasis Products If the investigators are trained and the test is successful, they can perform defined clinical procedures to test the hemostat product under investigation.

  The following describes examples of possible procedures for assessing the effectiveness of a hemostatic product, also referred to as a hemostatic implant material.

  The properties of an ideal local hemostat may vary according to the surgical specialty, but the rapid and effective management / stopping of bleeding; the ability to create effective contact with the bleeding surface; acceptable safety properties And several properties are universally valuable, including reliable, easy handling and speed of preparation.

  Assessment of the safety and efficacy of hemostatic agents can be performed by performing certain clinical trials.

  Prior to the trial, the investigator is trained on the proper application of the hemostatic product.

  Subjects undergoing surgery may be eligible for enrollment in a clinical trial. This may relate to subjects undergoing either open or laparoscopic procedures, such as, for example, cardiothoracic surgery, abdominal surgery, spine surgery, soft tissue surgery, mastectomy, or orthopedic lower limb surgery.

  The investigator performs surgery, including conventional methods of hemostasis (compression, ligation, cauterization, etc.), according to his standard procedures. Prior to surgery, the test hemostatic product is prepared according to the corresponding instructions for use.

  Preferably, a dedicated stopwatch is used to track the time of hemostat application and hemostasis evaluation.

  Hemostasis is assessed by the Investigator using the specific surface bleeding severity scale learned.

Scores are assigned at intermittent times until hemostasis is achieved, for example, at the following times:
Baseline-when assessing intraoperative eligibility;
A first time point (eg, 3 minutes);
A second time point (eg, 6 minutes); and a third time point (eg, 10 minutes).

  Bleeding severity assessments can be made by one or more investigators but must be performed independently.

  In the case of an assessment by two investigators, hemostasis is considered when both investigators have assigned a score of 0 at the same assessment time. All other scores are considered a failure to stop bleeding. Target bleeding sites are assessed at all time points until hemostasis is achieved.

  If hemostasis is not achieved, the investigator may use any means necessary to control bleeding.

  Next, the efficacy of the hemostatic product under study is evaluated by processing and comparing all data collected during the procedure.

  In addition to the advantages described above, the devices and methods for simulating surface bleeding presented herein help surgeons to define a diagnosis with respect to the severity of bleeding, thus allowing the surgeon to easily and quickly It can help select the hemostat to use.

  The proposed apparatus and method for simulating surface bleeding also involves a harmonization in the recognition of surface bleeding, and thus a harmonization of diagnostic methods and practices among surgeons, which is generally positive for the health of the patient.

  Another advantage of the proposed device and method for simulating surface bleeding is that it is possible to avoid performing in vivo tests on animals for testing of hemostatic products, which is therefore a very positive ethical Has a positive effect.

Reference "Acute in-vivo evaluation of bleeding with Gelfoam plus saline and Gelfoam plus human thrombin using a liver square lesion model in swine" (J Thromb Thrombolysis. 2009 Jul; 28 (1): 1-5.doi: 10.1007 / s11239 -008-0249-3.Epub 2008 Jul 16)

Claims (22)

A device for simulating surface bleeding,
The device comprises:
-Blood supply source (1);
A pump system (2) connected to the blood supply (1), wherein the pump system (2) is configured to supply a controlled flow of the blood;
A wound simulator (3) having an open chamber (31) connected to the pump system (2), the open chamber (31) for receiving the controlled blood flow;
With
Said wound simulator (3) comprises a set of exchangeable plates (32);
- the set plate (32), said has a plate plurality of holes arranged according to a specific hole pattern (32) (321), said holes are spaced regularly phase, the replaceable plate Each plate of the set has a specific hole pattern having a different surface area than the other plates of the set; and each plate (32) of the set has the wound to close the open chamber (31). Adapted to be removably mounted on a simulator (3) so that said blood flows from said chamber (31) to said hole (321) of said plate (32) mounted on said wound simulator (3). ) through to flow out,
The pump system may be configured such that, in response to the plate attached to the wound simulator, the blood flow rate may be less than a specific value within an interval defining a particular degree of surface bleeding severity within the surface bleeding severity scale. The device wherein the device is adjusted to a value and adapted to achieve a surface bleeding severity corresponding to the surface bleeding set .   The device of claim 1, wherein the blood is synthetic blood or blood drawn from a human body. 3. The device of claim 1 or 2, wherein the particular hole pattern has a different pattern or surface area . 4. The apparatus of claim 3, wherein the particular hole pattern has a square hole pattern . It said bore (321) comprises replaceable plate (32) of are provided with a density of at least 50 pores / cm ^2, respectively, according to any one of claims 1 to 4. It said bore (321) comprises replaceable plate (32) of which is provided at a density of 100 pores / cm ^2, respectively, according to any one of claims 1 to 4.   7. The method according to claim 1, wherein the number and the diameter of the holes (321) provided in each of the exchangeable plates (32) are set to reproduce the appearance of a bleeding surface. apparatus.   The device according to claim 7, wherein the holes (321) provided in each of the exchangeable plates (32) have all the same diameter.   The device according to claim 7, wherein the holes (321) provided in each of the exchangeable plates (32) have all the same diameter, said diameter being comprised between 0.2 mm and 1 mm.   8. The device according to claim 7, wherein the holes provided in each of the exchangeable plates (32) have all the same diameter, said diameter being 0.5 mm.   The device according to any of the preceding claims, wherein the holes (321) provided in each of the exchangeable plates (32) are regularly spaced in a corresponding specific pattern.   11. The holes (321) provided in each of the exchangeable plates (32) are regularly spaced with a pitch comprised between 0.4 mm and 2 mm in a corresponding specific pattern. An apparatus according to any one of the preceding claims.   11. The method according to any one of the preceding claims, wherein the holes (321) provided in each of the exchangeable plates (32) are regularly spaced at a pitch of 1mm in a corresponding specific pattern. apparatus. The wound simulator (3) further comprises the plate (32) culvert system for guiding the blood to drain receptacle to (33) the blood that has passed through the hole (321) in (34), Apparatus according to any one of the preceding claims.   A pressure monitoring system (5) connected to the pump system (2) for measuring a pressure of the blood supplied to the open chamber (31) of the wound simulator (3). The device according to any one of claims 1 to 14, further comprising (5).   The pump system (2) further comprises a peristaltic pump (21) provided with a pipe (4) for circulating the blood from the blood supply (1) to the open chamber (31). The device according to any one of claims 15 to 15.   The pump system (2) according to any of the preceding claims, wherein the pump system (2) comprises a pump controller (22) for controlling the flow of the blood from the blood supply (1) to the open chamber (31). The device according to item. 18. A method for simulating a plurality of different surface bleeds using the device according to any one of claims 1 to 17, wherein the method comprises simulating several sets of surface bleeds. Each set of surface bleeding represents the degree of surface bleeding severity within the surface bleeding severity scale,
Each surface bleed causes the wound simulator to wear a particular plate selected from a set of replaceable plates, and to alter the blood flow supplied by the pump system to a particular severity. The foregoing method, wherein the method is simulated by adjusting to a particular value within an interval defining the degree and achieving a degree of severity of surface bleeding corresponding to the set of surface bleeding . · First surface bleeding set is simulated to represent the first surface bleeding severity, each surface bleeding greater than 0 mL / min flow of the blood supplied by the pump system 4. Simulated by adjusting to a specific value chosen to be less than 8 mL / min;
A second set of surface bleeds is simulated to represent a second surface bleeding severity, each of the surface bleeds not less than 4.8 mL / min 12 Simulated by adjusting to a specific value selected to be less than 0.0 mL / min;
A third set of superficial hemorrhages is simulated to represent a third superficial hemorrhage severity, each of the superficial hemorrhages being capable of controlling the flow of blood supplied by the pump system by more than 12.0 mL / min 25 Simulated by adjusting to a specific value chosen less than 3 mL / min;
A fourth set of surface bleeding is simulated to represent a fourth surface bleeding severity, wherein each of the surface bleeding changes the blood flow supplied by the pump system by more than 25.3 mL / min. Simulated by adjusting to a specific value selected to be less than 0.0 mL / min;
A fifth surface bleeding set is simulated to represent a fifth surface bleeding severity, wherein each of the surface bleeds causes the blood flow supplied by the pump system to exceed 102.0 mL / min. 19. The method according to claim 18, simulated by adjusting to a particular value selected. · First surface bleeding set is simulated to represent the first surface bleeding severity, said first surface bleeding set,
Mounting a plate with through holes arranged according to a hole pattern having a surface area of 1 cm ² and selecting the blood flow supplied by the pump system to be greater than 0 mL / min and less than 4.8 mL / min At least one surface bleed, simulated by adjusting to a particular value;
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 10 cm ² and selecting the blood flow supplied by the pump system to be greater than 0 mL / min and less than 9.1 mL / min At least one surface bleed, simulated by adjusting to a particular value; and mounting a plate with through holes arranged according to a hole pattern having a surface area of 50 cm ² , and said pump system At least one surface bleeding simulated by adjusting the flow of blood supplied by the method to a particular value selected to be greater than 0 mL / min and less than 13.5 mL / min;
A second set of surface bleeding is simulated to represent a second set of surface bleeding severity, wherein the second set of surface bleeding comprises:
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 1 cm ² and reducing the blood flow supplied by the pump system from 4.8 mL / min to less than 12.0 mL / min At least one surface bleed, simulated by adjusting to a particular value selected;
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 10 cm ² , and reducing the blood flow supplied by the pump system from 9.1 mL / min to less than 20.0 mL / min At least one surface bleed simulated by adjusting to a particular value selected; and mounting a plate with through-holes arranged according to a hole pattern having a surface area of 50 cm ² and said pump At least one surface bleeding simulated by adjusting the blood flow supplied by the system to a specific value selected from 13.5 mL / min to less than 28.0 mL / min;
A third surface bleeding set is simulated to represent a third surface bleeding severity, wherein the third surface bleeding set comprises:
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 1 cm ² and reducing the blood flow supplied by the pump system to between 12.0 mL / min and less than 25.3 mL / min. At least one surface bleed, simulated by adjusting to a particular value selected;
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 10 cm ² , and reducing the blood flow supplied by the pump system to more than 20.0 mL / min and less than 71.3 mL / min At least one surface bleed simulated by adjusting to a particular value selected; and mounting a plate with through-holes arranged according to a hole pattern having a surface area of 50 cm ² and said pump At least one surface hemorrhage simulated by adjusting the blood flow supplied by the system to a specific value selected from 28.0 mL / min to less than 117.3 mL / min;
A fourth surface bleeding set is simulated to represent a fourth surface bleeding severity, wherein the fourth surface bleeding set comprises:
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 1 cm ² , and reducing the blood flow supplied by the pump system from 25.3 mL / min to less than 102.0 mL / min At least one surface bleed, simulated by adjusting to a particular value selected;
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 10 cm ² , and reducing the blood flow supplied by the pump system from 71.3 mL / min to less than 147.4 mL / min At least one surface bleed simulated by adjusting to a particular value selected; and mounting a plate with through-holes arranged according to a hole pattern having a surface area of 50 cm ² and said pump At least one surface bleeding simulated by adjusting the blood flow provided by the system to a specific value selected from 117.3 mL / min to less than 192.7 mL / min;
A fifth surface bleeding set is simulated to represent a fifth surface bleeding severity, wherein said fifth surface bleeding set comprises:
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 1 cm ² , and a specific value selected for the blood flow supplied by the pump system to be at least 102.0 mL / min At least one surface bleed, simulated by adjusting to
Mounting a plate with through-holes arranged according to a hole pattern having a surface area of 10 cm ² and a specific value selected for the blood flow supplied by the pump system to be at least 147.4 mL / min. At least one surface hemorrhage simulated by adjusting to; and mounting a plate with through-holes arranged according to a hole pattern having a surface area of 50 cm ² , and said pump being supplied by said pump system 19. The method of claim 18, comprising at least one surface hemorrhage simulated by adjusting the blood flow to a particular value selected to be greater than or equal to 192.7 mL / min.   21. The method according to any one of claims 18 to 20, wherein each of the simulated surface bleeds is recorded as a video. A plurality of simulated surface bleeding videos are used to create at least one training video set and at least one test video set;
A score corresponding to the severity of surface bleeding is assigned to each of the plurality of videos;
The training video set is created by selecting some of the videos of the plurality of videos and classifying the selected videos in a particular order for visualization, wherein a particular selection of each video is performed. Scores and information about the plate are displayed with the corresponding video,
The test video set is created by selecting a subset of the plurality of videos and classifying the selected videos in a random order for visualization, where the score of each video is 22. The method of claim 21, wherein the training video set is not displayed with the corresponding video and the selection and / or classification of the video is different from the training video set.

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