Broken limb blood circulation reconstruction protection device

Abstract

The invention discloses a broken limb blood circulation reconstruction protection device which comprises a blood loop for circularly perfusing perfusate into a broken limb, and the perfusate comprises nutrient substances and concentrated red blood cells which are separated from O-type whole blood and are subjected to plasma, leukocyte and platelet removal. A blood pump for driving the perfusate to circulate and a membrane type oxygenator for oxygenating vein blood are connected in the blood loop. The device provides blood circulation, oximation and constant-temperature storage environments for the separated limbs, solves the problems of ischemia and hypoxia and reperfusion injury of the separated limbs, prolongs the storage time of the separated limbs, breaks through the traditional replanting time limit of 6-8 hours of replanting of the separated limbs, and improves the survival rate of the limbs and the functions of the replanted limbs.

Description

Technical Field

[0001] The invention relates to a blood circulation reconstruction protection device for a severed limb. Background Art

[0002] In recent years, with the impact of local conflicts, natural disasters and wars, the number of trauma patients has continued to increase. In my country, trauma has always been among the top five causes of death in urban and rural areas. In Europe and the United States, trauma ranks third among causes of death, second only to cardiovascular disease and tumors. Therefore, trauma is a major public health problem that needs to be urgently addressed in countries around the world. Up to 70% of the injured are accompanied by musculoskeletal injuries of the limbs, and the incidence of limb trauma, especially limb amputation, is even higher in natural disasters and wars. Limb amputation seriously endangers the lives of the injured and has a vital impact on their quality of life after trauma. Efficient treatment must be carried out every minute. However, the repair and reconstruction of limb amputation is not only time-consuming and laborious, but also requires high technology and equipment from the rescue team. Therefore, improving the success rate of treatment of limb amputation is an important issue that needs to be urgently addressed in clinical and field rescue.

[0003] After limb amputation, due to ischemia and hypoxia, the normal metabolic process is disturbed, resulting in a series of pathological and physiological changes, such as accumulation of metabolic and toxic substances, mitochondrial edema, decreased lysosomal stability, etc., leading to cell degeneration and tissue necrosis. After the blood supply to the limb is restored, the body's inflammatory cascade effect will be stimulated, causing the functional failure of distant organs such as the heart, liver, and kidney of the injured, and in severe cases, leading to the death of the injured. Reconstructing the blood supply of the severed limb and restoring the limb function are the fundamental purposes of limb replantation in trauma surgery. At present, the demand for limb preservation by the injured is increasing day by day. However, how to preserve the severed limb, minimize the tissue damage caused by ischemia, and prolong the preservation time of the severed limb has been a research hotspot in this field in recent years. Studies have shown that severed limbs cannot be replanted after more than 6-8 hours, but a large number of injured people with limb trauma accompanied by chest and abdominal injuries, craniocerebral trauma and other complex injuries need to undergo certain life-saving operations first, or the injured need to be transferred to the rear hospital for surgery and cannot shorten the ischemia time of the severed limb, causing irreversible damage to the severed limb. Therefore, how to preserve the severed limb for a long time before limb replantation surgery, reduce tissue ischemic damage, delay tissue degeneration and necrosis, gain replantation time for patients with severed limbs, and ensure the survival and functional recovery of the severed limbs is a key issue affecting the prognosis of limb replantation.

[0004] Organ transplantation is the most effective way to treat terminal diseases. Preservation fluid and technology are crucial to the quality of donor organs and are directly related to the morbidity and survival rate after transplantation. Currently, static cold storage is the standard method for organ preservation. However, the preservation time of static cold storage is limited, and with the growing demand for donor organs, dynamic machine perfusion preservation technology has been developed. Machine perfusion is a method involving organ perfusion and controlled perfusion fluid flow, which can maintain the tension of the organ's microvascular system, provide oxygen and nutrients to support tissue metabolism, and remove toxic metabolic waste. The preservation of severed limbs is the key to successful limb replantation. At present, there has been great progress in the research on the preservation of severed limbs at home and abroad. The preservation methods include: low-temperature cold storage, organ preservation fluid preservation, hyperbaric oxygen preservation, temporary heterotopic foster care, etc.

[0005] At present, there is still no dedicated medical instrument for the normal temperature perfusion preservation of severed limbs at home and abroad. The main method for clinical preservation of severed limbs is still low temperature refrigeration, which cannot break through the conventional preservation time limit of severed limbs. The research on technologies and devices related to the preservation of severed limbs is still in the exploratory stage. The preservation of severed limbs is a common clinical problem and a research hotspot in the field of microscopic replantation. The severed limbs cannot be replanted after the conventional time limit of 6-8 hours. This is mainly because the accumulation of metabolism and toxic substances, mitochondrial edema, and decreased lysosomal stability after ischemia and hypoxia in the severed limbs lead to cell degeneration and tissue necrosis. The absorption of toxic substances and ischemia-reperfusion injury after replantation will endanger the life of the injured. The severed limbs are often accompanied by severe contamination of the wound surface, exposure of muscle soft tissue and bones, and are prone to purulent infection or gas gangrene infection. In severe cases, sepsis can lead to life-threatening. Therefore, how to effectively avoid or reduce the infection of severed limbs during the preservation of severed limbs is a problem that must be solved. How to maintain a sterile environment and stable position of the severed limbs during the circulation perfusion is an important event for perfusion safety. During the period of circulatory perfusion of the severed limb, relevant physiological indicators need to be intelligently monitored to evaluate the perfusion effect of the severed limb in order to achieve the function of prolonging the preservation of the severed limb; in addition, temperature can affect the metabolic level of the severed limb. By intelligently regulating the ambient temperature during blood perfusion of the severed limb, the impact of temperature on ischemia and hypoxia of the severed limb can be reduced. Summary of the invention

[0006] Therefore, the present invention provides a severed limb blood circulation reconstruction and protection device, which provides blood circulation, blood oxygenation and constant temperature preservation functions for severed limbs, solves the problems of ischemia, hypoxia and reperfusion injury of severed limbs, prolongs the preservation time of severed limbs, breaks through the traditional replantation time limit of 6-8 hours for severed limbs, and improves the limb survival rate and the function of the limb after replantation.

[0007] The severed limb blood circulation reconstruction and protection device of the present invention is an extracorporeal circulation system that supports the life of a severed limb. It perfuses blood rich in leukodepleted suspended O-type red blood cells into the severed limb circulation, and drains venous blood from the severed limb to the outside of the body. After oxygenation and carbon dioxide removal by a membrane oxygenator, the blood is injected into the severed limb by a centrifugal pump.

[0008] According to one aspect of the embodiment, a blood circulation reconstruction and protection device for a severed limb is proposed, comprising a blood circuit for circulatory perfusion of a perfusion fluid into the severed limb, wherein the perfusion fluid contains nutrients and concentrated red blood cells separated from type O whole blood and from which plasma, white blood cells and platelets are removed, and the blood circuit is connected to a blood pump for driving the circulation of the perfusion fluid and a membrane oxygenator for oxygenating venous blood.

[0009] In some instances, the severed limb is stored in a sterile environment.

[0010] In some examples, the severed limb is stored in a sterile bag after the wound surface of the severed limb is closed by a VSD.

[0011] In some examples, the severed limb blood circulation reconstruction protection device also includes a temperature control system for controlling the preservation temperature of the severed limb.

[0012] In some examples, a flow meter for monitoring arterial and venous blood flow and a pressure meter for monitoring blood flow pressure are connected to the blood circuit.

[0013] In some examples, the severed limb blood circulation reconstruction protection device also includes a control system, which is configured to control the temperature control system, the blood pump and the membrane oxygenator based on the storage temperature, blood pressure and oxygenation index of the severed limb set by the user, so as to maintain the storage temperature, blood pressure and oxygenation index of the severed limb within the set range.

[0014] In some examples, the severed limb blood circulation restoration protection device further includes an interactive screen configured to display blood flow and pressure.

[0015] In some examples, a blood biochemical index monitoring device is connected to the blood circuit.

[0016] In some examples, the nutrients include: a colloidal component, a buffer for maintaining physiological pH, as well as glucose, amino acids, vitamins, and anticoagulants. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a schematic diagram of a protective device for blood circulation restoration of severed limbs.

[0018] Figure 2 It is the blood calcium value of the severed limb of Bama miniature pig preserved by the severed limb blood circulation reconstruction protection device of the present invention.

[0019] Figure 3 It is the oxygenation index of the control group and the perfusion group (the severed limbs of Bama miniature pigs preserved by the severed limb blood circulation reconstruction protection device of the present invention).

[0020] Figure 4 The device for reconstructing blood circulation of a severed limb of the present invention preserves the blood pH value of a severed limb of a Bama miniature pig.

[0021] Figure 5 The blood circulation reconstruction protection device for severed limbs of the present invention preserves the blood sodium ion value of severed limbs of Bama miniature pigs.

[0022] Figure 6 This is the cell morphology of the control group and the perfusion group (the severed limbs of Bama miniature pigs preserved using the severed limb blood circulation reconstruction protection device of the present invention). DETAILED DESCRIPTION

[0023] like Figure 1 The blood circulation reconstruction and protection device for severed limbs includes: a blood storage device, a blood pump, a membrane oxygenator, a sterile environment for carrying severed limbs, a temperature control system, a monitoring system and a control system. The blood storage device, the blood pump, the membrane oxygenator, and the severed limbs in the sterile environment are connected to form a blood circuit. The blood storage device can be a blood bag. The blood pump drives the blood to circulate extracorporeally. The blood pump can be a peristaltic pump, and the blood flow rate can be changed by controlling the rotation speed of the peristaltic pump. The membrane oxygenator oxygenates the venous blood, and the oxygenated blood can enter the blood circulation system (local blood circulation) of the severed limb. The sterile environment for carrying the severed limb can adopt any existing technology, such as a closed cavity or a sterile bag. The temperature control system controls the temperature of the sterile environment. A monitoring system is connected to the blood circuit. The monitoring system includes a flowmeter for monitoring the arterial and venous blood flow and the amount of bubbles, a pressure gauge for monitoring the blood flow pressure, a thermometer for monitoring the blood temperature, and a biochemical parameter monitoring device such as electrolytes, blood sugar, metabolic waste, liver and kidney function, and osmotic pressure. In one embodiment, a blood circulation reconstruction protection device for a severed limb may include a box, in which a blood storage device, a blood pump, a membrane oxygenator, a sterile environment for carrying the severed limb, a temperature control system and a control system are encapsulated, and the temperature control system controls the temperature of the entire box.

[0024] The control system connects the blood pump, membrane oxygenator, temperature control system and monitoring system, and controls the blood pump, membrane oxygenator and temperature control system based on the user's settings and the monitoring of the monitoring system. For example, the control system includes a controller and an interactive screen, under the control of the controller: the user sets the temperature of the sterile environment and the speed of the blood pump through the interactive screen, the temperature control system adjusts the temperature of the sterile environment to the set value, the blood pump operates at the set speed, so that the blood pressure in the blood circuit is kept within a reasonable range, and the interactive screen implements the display of the monitoring system's monitoring results, such as the temperature of the sterile environment, the pressure, flow, temperature, bubble volume and blood oxygen saturation of the blood in the blood circuit, and the electrolytes, blood sugar, metabolic waste, liver and kidney function and osmotic pressure measured by the biochemical parameter monitoring equipment connected to the blood circuit.

[0025] The perfusion fluid is prepared by using leukoreduced suspended O-type red blood cells. As a universal blood type, O-type can be adapted to various blood transfusions, and can be used for perfusion of various blood types. The use of leukoreduced suspended red blood cells can reduce the occurrence of immune responses caused by leukocytes. The HLA antigens of leukocytes in the transfused blood can activate the effector cells or T-cell long-lived antibodies of the recipient, causing certain serious transfusion reactions, and the antibodies of blood products (mostly present on leukocytes) can directly cause transfusion reactions with related antigens in the recipient, such as hemolytic febrile transfusion reactions and transfusion-related acute lung injury. Removing leukocytes can minimize their occurrence. In the preparation process of the present invention, the main method is to explore the ratio of the perfusion fluid to normal saline, so that it can play the best role and achieve the best storage conditions.

[0026] The perfusate contains concentrated red blood cells separated from whole blood and freed of plasma, leukocytes, and platelets, and nutrients mixed with the concentrated red blood cells. The nutrients contain a colloid component, a buffer for maintaining physiological pH, as well as glucose, amino acids, vitamins, and anticoagulants. The colloid component contains human serum albumin and dextran 40. The buffer for maintaining physiological pH contains sodium chloride, potassium chloride, disodium hydrogen phosphate, and potassium dihydrogen phosphate.

[0027] For example, the following nutrients are added to 1-2 units of concentrated red blood cells: human serum albumin (50-90g / L), dextran 40 (5-10g / L), buffer to maintain physiological pH (sodium chloride 5-10g / L, potassium chloride 0.1-0.3g / L, disodium hydrogen phosphate 1-2g / L, potassium dihydrogen phosphate 0.1-0.3g / L), glucose (3-6mmol / L), amino acids (arginine 2-6mmol / L), vitamins (vitamin B1 5-25mg / L, vitamin D 25-35mg / L), and anticoagulants (heparin sodium 20000-30000u).

[0028] By sealing the wound of the severed limb through VSD, the exposure of soft tissue and bone tissue on the wound surface is greatly reduced, the risk of wound infection is reduced, and at the same time, wound exudation is reduced, providing closed perfusion conditions for the blood circulation of the severed limb; in addition, VSD will reserve a medical PVC tube channel, and medical PVC tubes of different sizes can connect the blood circuit of the severed limb blood circulation reconstruction protection device to the main artery and vein of the severed limb to establish a complete circulation perfusion pathway for the severed limb. After the reconstruction of the severed limb blood circulation and the closure of the wound surface are completed, the severed limb is wrapped as a whole in a disposable sterile bag. At the same time, the sterile bag has the function of fixing the severed limb during perfusion to prevent it from moving during perfusion. In addition, by intelligently regulating the ambient temperature during blood perfusion of the severed limb, the impact of temperature on ischemia and hypoxia of the severed limb is reduced.

[0029] An example of the application of a device for reconstructing blood circulation in a severed limb is given below.

[0030] 1. Establishment of Bama miniature pig amputation model

[0031] Ten healthy adult male Bama miniature pigs weighing 24-30 kg were divided into a perfusion group and a control group. The pigs were fasted for 12 hours before surgery and anesthetized with intramuscular injection of ketamine (10 mg / kg) combined with endotracheal intubation. Propofol was diluted with 5% glucose injection at a ratio of 1:5 and continuously dripped through the ear vein to maintain anesthesia. After successful anesthesia, the piglets were fixed on the operating table, the right hind limb was depilated, routine disinfection and draping were performed, and an arc-shaped surgical incision was designed in the groin area. The skin and subcutaneous tissue were cut open, and the femoral artery, vein and femoral nerve were separated and ligated from the proximal end using microsurgical techniques. The ipsilateral iliac artery and vein and pudendal artery and vein were ligated, and then the right hind limb was quickly severed with a wire saw at the ligation plane; the severed limb was stored at room temperature for 3 hours, and the ischemic model of the severed limb was established. After the severed limb model was established, the vascular cannulation of the severed limb was performed, and the heparinized anticoagulation protection of the severed end blood vessels was performed through the catheter. Finally, the catheter was connected to the arterial and venous ends of the severed limb external bypass perfusion instrument.

[0032] Preparation of perfusion blood

[0033] 2. Treatment of severed limbs

[0034] The control group received no treatment.

[0035] Perfusion group: After the severed limbs were stored at room temperature (26°C) for 3 hours, blood perfusion was continued using a severed limb blood circulation reconstruction protection device, with a perfusion volume of 150 ml / min, the perfusion environment temperature set to 26°C, and the volume fraction of the membrane oxygenator set to 10%. After perfusion for 12 hours, the severed limbs were replanted;

[0036] 3. Limb replantation in Bama miniature pig amputation model

[0037] After the severed limbs of Bama pigs were perfused with extracorporeal blood circulation at the specified time in the above groups, limb replantation surgery was performed. After the Bama pigs were successfully anesthetized according to the above method, routine fixation, disinfection and draping were performed, the negative pressure closed drainage device and vascular connection device of the stump of the limb were removed, and the stump and the wound of the limb were flushed with anticoagulant flushing fluid, with emphasis on flushing the blood vessels and surrounding tissues. The ex vivo limb was shortened by 3mm using a ring saw, and the femoral artery and vein stumps and surrounding fascia tissues were appropriately freed and trimmed to reduce blood flow obstruction caused by vascular traction and compression. First, a suitable micro-bone plate was selected to fix the femoral stump, and an electric drill was used to drill holes in the femur in turn, measure the depth, and then implant an appropriate number of bone screws to firmly fix the femoral stump. After the femoral fixation was completed, vascular and nerve anastomosis was performed under a microscope. The distance between the arteries and veins of Bama pigs is about 2 mm. 11-0 micro sutures are used to interrupt the anastomosis of the femoral artery and vein. When anastomosing the blood vessels, the two ends of the blood vessels are appropriately freed to reduce vascular tension, and the lumen is intermittently flushed with anticoagulant solution. After the vascular anastomosis, a vascular patency test is used to detect the effect of the vascular anastomosis. If the lumen in the arteriovenous anastomosis segment is filled, it means that the anastomosis is unobstructed. Then, 10-0 micro sutures are used to interrupt the anastomosis of the sciatic nerve. After flushing the wound with antibiotic saline, sufficient bleeding is stopped. Finally, the muscle layer and skin of the severed limb are sutured in turn, and the incision is disinfected with iodine and then bandaged with sterile dressings.

[0038] 4. Postoperative observation and recording of limb replantation in each group

[0039] Observe and record the skin color of the replanted lower limb, the presence of edema, thrombosis, skin and soft tissue infection and necrosis, etc.; compare the color of the replanted limb with that of the healthy limb. If the color is pink like the healthy side, it proves that the replanted limb is fully perfused. If the distal end of the replanted limb is pale, it indicates femoral artery crisis and insufficient arterial perfusion. If the distal end is dark purple, it indicates that venous congestion and poor return are observed.

[0040] 5. Detection indicators after replantation of severed limbs

[0041] Blood was collected from the ear vein of Bama pigs to analyze and evaluate the blood routine, liver and kidney function and other indicators of Bama pigs after replantation; blood oxygen saturation, hematocrit, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB) and other related indicators of the replanted limbs were monitored. The ultrastructural pathological changes of skeletal muscle tissue, blood vessels and nerve tissues of the amputated limbs were observed by transmission electron microscopy; and the changes of apoptosis, autophagy, necrosis and other indicators of skeletal muscle tissue, blood vessels and nerve tissues of the amputated limbs were detected by immunohistochemistry.

[0042] Figure 2 The blood circulation reconstruction protection device for severed limbs of the present invention preserves the blood calcium value of a severed limb of a Bama miniature pig for 12 hours. Figure 3It is the oxygenation index of the severed limb of Bama miniature pig preserved for 12 hours by the control group (control) and the severed limb blood circulation reconstruction protection device of the present invention. Figure 4 This is the blood pH value of the severed limb preserved by the severed limb blood circulation reconstruction protection device of the present invention for 12 hours in the Bama miniature pig. Figure 5 The blood circulation reconstruction protection device for severed limbs of the present invention preserves the blood sodium ion value of the severed limbs of Bama miniature pigs for 12 hours. The device of the present invention can better maintain the blood sodium ion value, blood pH value, and blood calcium value of the severed limbs within the normal range, and the oxygenation index is always at a normal value. Figure 6 The cell morphology of the Bama miniature pig's severed limb preserved for 12 hours in the control group and the device for blood circulation reconstruction of severed limbs of the present invention. The non-perfused limbs showed obvious inflammatory cell infiltration in the muscle tissue and muscle necrosis, while the blood cell morphology of the perfused group was better maintained.

Claims

1. A blood circulation reconstruction and protection device for a severed limb, characterized in that: The invention comprises a blood circuit for circulating a perfusion solution to the severed limb, wherein the perfusion solution contains nutrients and concentrated red blood cells separated from type O whole blood and free of plasma, white blood cells and platelets. The blood circuit is connected to a blood pump for driving the circulation of the perfusion solution and a membrane oxygenator for oxygenating venous blood.

2. The blood circulation reconstruction and protection device for severed limbs according to claim 1, characterized in that: The severed limbs were stored in a sterile environment.

3. The blood circulation reconstruction and protection device for severed limbs according to claim 2, characterized in that: The severed limb was sealed with VSD and then stored in a sterile bag.

4. The blood circulation reconstruction and protection device for severed limbs according to claim 3, characterized in that: Also included is a temperature control system for controlling the preservation temperature of the severed limb.

5. The blood circulation reconstruction and protection device for severed limbs according to claim 4, characterized in that: The blood circuit is connected with a flow meter for monitoring arterial and venous blood flow and a pressure meter for blood flow pressure.

6. The blood circulation reconstruction and protection device for severed limbs according to claim 5, characterized in that: The device also includes a control system, which is configured to control the temperature control system, the blood pump and the membrane oxygenator based on the storage temperature, blood pressure and oxygenation index of the severed limb set by the user, so as to maintain the storage temperature, blood pressure and oxygenation index of the severed limb within the set range.

7. The blood circulation reconstruction and protection device for severed limbs according to claim 6, characterized in that: Also included is an interactive screen configured to display blood flow and pressure.

8. The blood circulation reconstruction and protection device for severed limbs according to claim 1, characterized in that: The blood circuit is connected with a blood biochemical index monitoring device.

9. The blood circulation reconstruction and protection device for severed limbs according to claim 1, characterized in that: The nutrients include: colloidal components, buffers for maintaining physiological pH value, glucose, amino acids, vitamins and anticoagulants.

10. The blood circulation reconstruction and protection device for severed limbs according to claim 9, characterized in that: The following nutrients are added to 1-2 units of the concentrated red blood cells: 50-90 g / L human serum albumin, 5-10 g / L dextran 40, 5-10 g / L sodium chloride, 0.1-0.3 g / L potassium chloride, 1-2 g / L disodium hydrogen phosphate, 0.1-0.3 g / L potassium dihydrogen phosphate, 3-6 mmol / L glucose, 2-6 mmol / L arginine, 15-25 mg / L vitamin B, 25-35 mg / L vitamin D and 20000-30000 u of heparin sodium.

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