Procedure for flushing a blood pump

Abstract

Devices, systems, and procedures are provided that are based on a technique for flushing a blood pump. The technique may include providing a blood pump with an impeller and providing a fluid containing bicarbonate. The technique may involve the fluid flowing through a first gap between a bearing and an outer surface of a rotatable shaft connected to the impeller, the bearing and the gap being arranged within the lumen of a tubular element. Depending on the fluid flow rate and the impeller speed, the fluid can flow through the first gap and into a second gap between the bearing and a surface of the impeller facing the bearing. The bicarbonate reduces the denaturation and adsorption of blood proteins in the gap(s).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Applications 63 / 312,277, filed February 21, 2022, and 63 / 398,991, filed August 18, 2022, which are incorporated by reference in their entirety into this application. TECHNICAL FIELD

[0002] The present disclosure relates to a blood pump, in particular an intravascular blood pump, for supporting blood flow in a blood vessel of a patient and a method for flushing such a pump during operation while it is inserted into a patient. BACKGROUND

[0003] There are various types of blood pumps, such as axial blood pumps, centrifugal blood pumps, or mixed types, where blood flow is caused by both axial and radial forces. An example of a blood pump is the Impella series of blood pumps (e.g., Impella 2.5). ® , Impella CP ® , Impella 5.5®, etc.), which are products of Abiomed, Danvers, Massachusetts. Intravascular blood pumps can be inserted into a patient's blood vessel, such as the aorta, using a catheter.

[0004] Some pump designs utilize a flushing fluid to prevent blood from entering the mechanism and to mitigate the effects of blood on the pump mechanisms. Typically, the flushing fluid contains an anticoagulant such as heparin (usually the sodium salt of heparin). The heparin is designed to prevent blood from clotting in gaps between pump sections, such as an impeller shaft and the housing. Heparin is a commonly used anticoagulant, typically administered in controlled doses.

[0005] In one example, the irrigation fluid is delivered through a irrigation cassette, which passes through a filter assembly and an internal irrigation lumen into a blood pump catheter, which directs the irrigation fluid through the catheter to a irrigation channel in the motor assembly. The flow of the irrigation fluid is regulated by an automatic controller.

[0006] However, such conventional techniques typically lead to denaturation of circulating proteins and deposition of biomaterial in the spaces between pump components. SHORT SUMMARY

[0007] In various aspects, a blood pump may be provided. The blood pump may comprise a tubular body having a distal end and a proximal end and a lumen extending therethrough, the lumen having a central axis. An impeller may be connected to a flexible shaft disposed at least partially within the lumen. A bearing may be disposed within the lumen around a portion of the flexible shaft. The bearing may be configured to form a first gap in the radial direction between an outer surface of the flexible shaft and an inner surface of the bearing, and may be configured to form a second gap in the axial direction between the bearing and a surface of the impeller facing the bearing. The blood pump may be configured such that a fluid containing a bicarbonate flows through the first gap and into the second gap.In some embodiments, the first gap may be 4-9 µm. In some embodiments, the second gap may be 90-110 µm.

[0008] In some embodiments, the bicarbonate may be sodium bicarbonate. In some embodiments, the fluid may contain 12.5 mEq / L to 100 mEq / L sodium bicarbonate, e.g., 25 mEq / L to 50 mEq / L sodium bicarbonate. In some embodiments, the fluid may contain a pharmaceutical therapeutic or prophylactic agent, such as an anticoagulant or a patient-specific pharmaceutical treatment (e.g., a small molecule drug). In some embodiments, the fluid may further contain aqueous dextrose.

[0009] In some embodiments, the concentration of the bicarbonate-containing liquid in a volume defined by the first gap may be at least 50% of the total liquid in the first gap. In some embodiments, the first gap may be filled with the bicarbonate-containing liquid. In some embodiments, the concentration of the bicarbonate-containing liquid in a volume defined by the second gap may be no more than 40% of the total liquid in the second gap.

[0010] In various aspects, a system may be provided. The system may include a pump as disclosed herein and a flushing bag containing the bicarbonate-containing liquid, wherein the flushing bag may be operatively connected to the pump. In some embodiments, the first gap may be 4-9 µm. In some embodiments, the second gap may be 90-110 µm.

[0011] In some embodiments, the bicarbonate may be sodium bicarbonate. In some embodiments, the fluid may contain 12.5 mEq / L to 100 mEq / L sodium bicarbonate, e.g., 25 mEq / L to 50 mEq / L sodium bicarbonate. In some embodiments, the fluid may contain a pharmaceutical therapeutic or prophylactic agent, such as an anticoagulant or a patient-specific pharmaceutical treatment (e.g., a small molecule drug). In some embodiments, the fluid may further contain aqueous dextrose.

[0012] In some embodiments, the concentration of the bicarbonate-containing liquid in a volume defined by the first gap may be at least 50% of the total liquid in the first gap. In some embodiments, the first gap may be filled with the bicarbonate-containing liquid. In some embodiments, the concentration of the bicarbonate-containing liquid in a volume defined by the second gap may be no more than 40% of the total liquid in the second gap.

[0013] In various aspects, a kit may be provided. The kit may include a pump as disclosed herein. The kit may include an irrigation bag containing the bicarbonate-containing liquid. The kit may include an irrigation cassette configured to connect the irrigation bag to the pump.

[0014] In various aspects, a method for flushing a pump may be provided. The method may include providing a pump with an impeller, as disclosed herein, and a fluid containing a bicarbonate. The method may include flowing the fluid through a first gap between a bearing and an outer surface of a rotatable shaft connected to the impeller, wherein the bearing and the gap are disposed within a lumen of a tubular member.

[0015] In some embodiments, the bicarbonate may be sodium bicarbonate. In some embodiments, the fluid may contain 12.5 mEq / L to 100 mEq / L sodium bicarbonate, e.g., 25 mEq / L to 50 mEq / L sodium bicarbonate. In some embodiments, the fluid may contain a pharmaceutical therapeutic or prophylactic agent, such as an anticoagulant or a patient-specific pharmaceutical treatment (e.g., a small molecule drug). In some embodiments, the fluid may further contain aqueous dextrose.

[0016] In some embodiments, the method may include controlling a flow rate of the liquid such that the concentration of the liquid containing the bicarbonate in a volume of space defined by the first gap is at least 50% of the total liquid in the first gap.

[0017] In some embodiments, flowing the liquid through a first gap may comprise flowing the liquid through a second gap after passing through the first gap, wherein the second gap is located between the bearing and a surface of the impeller facing the bearing. In some embodiments, the method may comprise controlling a flow rate of the liquid such that the concentration of the liquid containing the bicarbonate in a volume defined by the second gap is no more than 40% of the total liquid in the second gap.

[0018] In some embodiments, the method may include automatically adjusting a flow rate of the fluid based on an operating characteristic of the pump.

[0019] In various aspects, a medical device may be provided. The medical device may include a tubular body having a distal end and a proximal end, and a lumen may extend therethrough. The lumen may have a central axis. The medical device may include an outer sheath disposed around the tubular body. The medical device may have a first gap formed radially between an outer surface of the tubular body and the inner surface of the outer sheath. The medical device may have a second gap formed axially between the tubular body and the outer sheath. A liquid containing a bicarbonate may be configured to flow through the first and second gaps to flush the first and second gaps.In some embodiments, the first gap may be 4-9 µm. In some embodiments, the second gap may be 90-110 µm.

[0020] In some embodiments, the bicarbonate may be sodium bicarbonate. In some embodiments, the fluid may contain 12.5 mEq / L to 100 mEq / L sodium bicarbonate, e.g., 25 mEq / L to 50 mEq / L sodium bicarbonate. In some embodiments, the fluid may contain a pharmaceutical therapeutic or prophylactic agent, such as an anticoagulant or a patient-specific pharmaceutical treatment (e.g., a small molecule drug). In some embodiments, the fluid may further contain aqueous dextrose.

[0021] In some embodiments, the concentration of the bicarbonate-containing liquid in a volume defined by the first gap may be at least 50% of the total liquid in the first gap. In some embodiments, the first gap may be filled with the bicarbonate-containing liquid. In some embodiments, the concentration of the bicarbonate-containing liquid in a volume defined by the second gap may be no more than 40% of the total liquid in the second gap. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The invention is explained below by way of example with reference to the accompanying drawings. The accompanying drawings are not drawn to scale. In the drawings, each identical or nearly identical component shown in the various figures is designated by the same number. For reasons of clarity, not every component is labeled in every drawing. In the drawings: Fig. 1 shows the blood flow and the flushing flow through the gap between the shaft and the housing of the pump; Fig. Figure 2 is a schematic representation of an intravascular blood pump inserted in front of the left ventricle with its inflow cannula positioned in the left ventricle; Fig. 3 is a schematic longitudinal section through an exemplary prior art blood pump; Fig. 4 is an enlarged view of part of the Fig. 3 illustrated blood pump according to a second embodiment; Fig. 5 is an enlarged view of a portion of a blood pump according to other embodiments; Fig. Figure 6A illustrates the reduced coagulability of blood by bicarbonate in the presence of heparin in a simulated state of part of a blood pump, where the coagulation parameters include the clot initiation time (“R-time”) and the clot formation time (“K-time”) in Fig. 6A and the coagulation rates (α-angle) in Fig. 6B; Fig. Figure 6C shows TEG-ACT data illustrating a synergistic effect on coagulation in the presence of heparin and bicarbonate; In Fig. 7 shows a kit according to some embodiments; Fig. 8 is a flowchart of one embodiment of a method; Fig. 9 is an illustration of an embodiment of a system; and Fig. 10 is a schematic diagram of a medical device according to some embodiments. DETAILED DESCRIPTION

[0023] Blood pumps are used on patients requiring critical, life-saving care. Therefore, it is important to address any aspects of the device that could affect pump operation. For example, some pump designs may incorporate a flushing fluid to prevent blood from entering the pump mechanism and to mitigate the effects of the blood on the pump mechanism. Typically, the flushing fluid contains an anticoagulant such as heparin (e.g., the sodium salt of heparin). Without wishing to be bound by theory, it is believed that heparin prevents blood from clotting in the gap between pump sections, such as an impeller shaft and the housing. Heparin is a commonly used anticoagulant, usually administered in controlled doses.

[0024] However, in some cases, physicians do not want heparin delivered to the patient's blood via the lavage fluid. For example, administering heparin during surgery can be counterproductive because it prevents blood clotting and thus prevents healing or hemostasis. Furthermore, the amount of heparin administered to the patient's blood, along with heparin in the lavage fluid, is difficult to control for several reasons. In some cases, the amount of heparin may be higher than physicians desire, and the amount of heparin administered to the patient may be difficult to precisely control. Accordingly, physicians may prefer to administer heparin to the patient when needed (and only in the amount needed), regardless of blood pump operation. Furthermore, some patients are heparin intolerant because they are prone to heparin-induced thrombocytopenia (HIT).For these patients, a heparin-based flush is therefore completely unsuitable. Furthermore, heparin salts can cause undesirable wear on pump bearings made of metal. Therefore, there is a need for an intravascular blood pump that can be operated, if desired, with a flushing fluid that contains no or at least a reduced amount of heparin.

[0025] It has been shown that a specific fluid, alone or in combination with heparin (e.g., in systemic heparin treatment), can provide significant benefit when present in specific spaces within an intravascular blood pump.

[0026] As disclosed herein, the inventors have recognized the benefit of a lavage solution containing sodium bicarbonate. The inventors have also recognized the benefit of using such a lavage solution with systemically anticoagulated blood. For example, as described herein, the inventors have recognized a synergistic or adjunctive role for sodium bicarbonate in the lavage solution when used in conjunction with systemic anticoagulation as part of an overall anticoagulation strategy. In some embodiments, the sodium bicarbonate lavage fluid can create environmental conditions that delay the onset of clotting and suppress fibrin formation. This, in turn, can lead to an overall lower clotting rate when lavage fluid and systemically anticoagulated blood mix in the axial gap.

[0027] In some embodiments, the rinsing fluid may contain aqueous dextrose. In some embodiments, the rinsing fluid may contain, for example, a 5% dextrose-water solution. In some embodiments, the rinsing fluid may contain 12.5 mEq / L to 100 mEq / L of sodium bicarbonate. In some embodiments, the rinsing fluid may contain 25 mEq / L to 50 mEq / L of sodium bicarbonate.

[0028] In some cases, the lavage fluid may also contain a pharmaceutical therapeutic or prophylactic agent. In some cases, the pharmaceutical therapeutic or prophylactic agent may be an anticoagulant (e.g., heparin). In some cases, the pharmaceutical therapeutic or prophylactic agent may contain one or more small molecule drugs that can be used to treat a patient, such as blood thinners, anti-inflammatories, etc.

[0029] Fig. 1 shows a pump 100 comprising a tubular member having a drive section 110 and a pump section 130, a catheter 115 attached to a proximal end 120 of the drive section 110 (e.g., the end of the drive section closer to the physician or "back end" of the drive section) through which lines extend for supplying power to the drive section 110, and the pump section 130 attached to the distal end 125 of the drive section. The drive section 110 may include a motor housing 150 with an electric motor 151 disposed therein, with the motor shaft 160 of the electric motor extending distally from the drive section 110 and into the pump section 130. The pump section 130 may in turn comprise a tubular pump housing 165 with an impeller 170 rotating therein, which is seated on the end of the motor shaft 160 protruding from the motor housing 150.The motor shaft 160 can be mounted in the motor housing in two bearings 171, 172, which are spaced apart as far as possible to ensure precise, centered guidance of the impeller 170 in the motor housing 150. Different bearing types can be used for different pump designs. As shown in . Fig. 1, the bearing 171 may be a radial ball bearing and the bearing 172 may be an axial-radial plain bearing. As shown in Fig. 1, the blood 140 can escape from the drain cage of the pump housing 165. Blood that would otherwise enter the motor housing 150 can also be contained by a flushing fluid 135 that is directed through the motor housing and the impeller-side shaft seal bearing. Accordingly, the flushing fluid can be directed through the gap of the impeller-side radial journal bearing to prevent blood from entering the housing. This is achieved by maintaining a flushing fluid pressure that is higher than the prevailing blood pressure.

[0030] As in Fig. 1, the flushing fluid 135 can fill the motor housing 150 of the pump to form a lubricating film in the bearings 171, 172 of the pump. As described in US Patent Publication No. 2015 / 0051436, the flushing fluid 135 can, for example, form a lubricating film in a bearing gap 180 of the thrust bearing of a pump. It is described that flushing fluids are supplied through a flushing fluid line and flow through the radial bearing gap 173 at the distal end of the motor housing 150 and then also through the bearing gap 180 of the thrust bearing. The flushing fluids supplied in this manner can be responsible for hemodilution and reduce the residence time of blood under the impeller 170.

[0031] To ensure that the flushing fluid 135 reaches the distal radial bearing 172 at a higher pressure than the existing blood pressure, in some embodiments a channel is provided in at least one of the surfaces forming the bearing gap of the axial plain bearing, which channel penetrates the bearing gap 180 from radially outside to radially inside, so that the flushing fluid can flow through this channel to the distal radial bearing. This channel does not necessarily have to be located in a bearing gap surface, but can also be designed as a separate channel or as a bore. In some embodiments, however, the arrangement of the channel in one of the bearing gap surfaces can have the advantage that the lubricating film in the bearing gap heats up less because part of the lubricating film is constantly replaced by inflowing flushing fluid. In some embodiments, the channel is located in the stationary bearing gap surface in order to minimize the radial flow rate.

[0032] Fig. Figure 2 shows the use of a blood pump to assist, in this particular example, the left ventricle. As shown in this figure, the blood pump may comprise a catheter 14 and a pumping device 10 attached to the catheter 14. The pumping device 10 may comprise a motor section 11 and a pumping section 12 arranged coaxially one behind the other to form a rod-shaped configuration. The pumping section 12 may have an extension in the form of a flexible suction hose 13, a tubular element often referred to as a "cannula." An impeller may be provided in the pumping section 12 to effect blood flow from a blood flow inlet to a blood flow outlet, and the rotation of the impeller is effected by an electric motor arranged in the motor section 11. The blood pump may be placed so that it lies primarily in the ascending aorta 15b, which leads to the aortic arch 15a.When closed, the aortic valve 18 rests against the outside of the pump section 12 or its suction tube 13, which is located essentially in the left ventricle 17. The blood pump, with the suction tube 13 in front of it, can be moved into the position shown by advancing the catheter 14, if necessary using a guidewire. The suction tube 13 can then pass retrograde through the aortic valve 18, so that the blood is sucked through the suction tube 13 and pumped into the aorta 16.

[0033] As you can imagine, the use of the blood pump does not have to be limited to the Fig. 2, which represents only a typical application example. The pump can also be inserted through other peripheral vessels, such as the subclavian artery. Alternatively, reverse applications for the right ventricle are also conceivable. As will be seen, other suitable pump arrangements can also be used in other embodiments.

[0034] Fig. Figure 3 shows an exemplary embodiment of a blood pump as described in US Patent Publication No. 2015 / 0051436 A1, which may also be suitable for use in the present disclosure, except that the circled front end marked “I” may be modified, such modification being disclosed in Fig. 4. Accordingly, the motor section 11 may include an elongated housing 20 in which an electric motor 21 may be housed. A stator 24 of the electric motor 21 may, in the usual manner, include numerous circumferentially distributed windings and a longitudinal magnetic return 28. The magnetic return 28 may form an outer cylindrical sleeve of the elongated housing 20. The stator 24 may surround a rotor 26 connected to the motor shaft 25, which rotor 26 is made of permanent magnets magnetized in the effective direction. The motor shaft 25 may extend the entire length of the motor housing 20 and protrude distally therefrom through an opening 35. There, it may carry an impeller 34 with pump blades 36 projecting therefrom, which impeller may rotate in a tubular pump housing 32, which may be rigidly connected to the motor housing 20.

[0035] The flexible catheter 14 can be sealingly attached to the proximal end of the motor housing 20. Electrical cables 23 for supplying power and controlling the electric motor 21 can extend through the catheter 14. Furthermore, a flushing fluid line 29 can extend through the catheter 14 and penetrate a proximal end wall 22 of the motor housing 20. The flushing fluid can be directed through the flushing fluid line 29 into the interior of the motor housing 20 and exit through the end wall 30 at the distal end of the motor housing 20. The flushing pressure can be selected to be higher than the prevailing blood pressure to thereby prevent blood from entering the motor housing. In some embodiments, the flushing pressure can be between 300 and 1400 mmHg, for example, depending on the application.

[0036] In some embodiments, the same flushed seal may be combined with a pump driven by a flexible drive shaft and an external motor.

[0037] When the impeller 34 rotates, blood can be sucked in through the distal opening 37 of the pump housing 32 and conveyed rearward within the pump housing 32 in the axial direction. The blood flows out of the pump section 12 through radial outlet openings 38 in the pump housing 32 and further along the motor housing 20. In some embodiments, this ensures that the heat generated in the motor can be dissipated. It is also possible to operate the pump section in the opposite direction, with the blood being sucked in along the motor housing 20 and exiting through the distal opening 37 of the pump housing 32.

[0038] The motor shaft 25 can be mounted in radial bearings 27, 31 at the proximal end of the motor housing 20 on the one hand and at the distal end of the motor housing 20 on the other. The radial bearings, in particular the radial bearing 31 in the opening 35 at the distal end of the motor housing, are designed as plain bearings. Furthermore, the motor shaft 25 can also be mounted axially in the motor housing 20, with the axial bearing 40 also being designed as a plain bearing. The axial plain bearing 40 serves to absorb axial forces of the motor shaft 25 that act in the distal direction when the impeller 34 pumps blood from distal to proximal. If the blood pump is also used or only used in the opposite direction to pump blood, a corresponding axial plain bearing 40 can be provided (also or only) at the proximal end of the motor housing 20 in a corresponding manner.

[0039] Fig. 4 shows the Fig. 3 in greater detail, but structurally modified according to an embodiment of the present disclosure. The radial plain bearing 31 and the axial plain bearing 40 are particularly visible. The bearing gap of the radial plain bearing 31 is formed, on the one hand, by the circumferential surface 25A of the motor shaft 25 and, on the other hand, by the surface 33A of a through-bore in a bushing or sleeve 33 of the end wall 30 of the motor housing 20, which defines an outer gap diameter of approximately 1 mm, although the outer gap diameter may also be larger than this. In one example, the bearing gap of the radial plain bearing 31 has a gap width of 2 µm or less, not only at the front end or on the impeller side of the gap, but over its entire length. In some embodiments, the gap width is between 1 µm and 2 µm.The length of the bearing gap can be between 1 mm and 2 mm, preferably between 1.3 mm and 1.7 mm, e.g., 1.5 mm. The surfaces forming the gap of the radial plain bearing 31 can have a surface roughness of 0.1 µm or less. These dimensions vary depending on the pump type and are presented as an example and not as a limitation.

[0040] The bearing gap of the axial plain bearing 40 can be formed by the axially inner surface 41 of the end wall 30 and a surface 42 opposite it. This counter surface 42 can be part of a ceramic disk 44, which is located distally of the rotor 26 on the motor shaft 25 and rotates with the rotor 26. A channel 43 in the bearing gap surface 41 of the end wall 30 ensures that flushing fluid can flow between the bearing gap surfaces 41 and 42 of the axial plain bearing 40 to the radial plain bearing 31 and exit distally from the motor housing 20. The Fig. The thrust bearing 40 shown in Figure 3 is a standard plain bearing. Contrary to the illustration, the axial gap of the thrust bearing 40 is very small, amounting to only a few micrometers (e.g., 10 µm or less).

[0041] Instead of the axial plain bearing 40 and the radial plain bearing 31, a combined radial-axial plain bearing 40 with a concave bearing shell in which a convex bearing surface runs can also be realized. Such a variant is shown in Fig. 4 is represented by a spherical plain bearing 40. The bearing gap surface 41 can be spherically concave, and the opposite bearing gap surface 42 is correspondingly spherically convex. The channel 43 can in turn be located in the stationary bearing gap surface 41 of the end wall 30. Alternatively, the stationary bearing gap surface 41 of the end wall 30 can be convex and the opposite bearing gap surface 42 can be concave. The surfaces 42, 43 can also be conical instead of spherical. In some embodiments, a corresponding radial-axial plain bearing is provided on both sides of the motor housing 20 in order to prevent radial misalignment during the axial movement of the shaft 25. The advantage of a combined axial-radial plain bearing can be the higher load-bearing capacity.

[0042] During operation, the blood pump can be connected to a flushing fluid source, and the fluid enters the motor housing through the flushing fluid line. The flushing fluid then flows through the thrust bearing and further through the distal radial bearing. In the thrust bearing, the flushing fluid can form the lubricating film in the bearing gap. However, the pressure at which the flushing fluid flows through the motor housing adversely affects the width of the bearing gap. In particular, higher flushing fluid pressure may require a narrower bearing gap width, resulting in a thinner lubricating film between the sliding surfaces. The thinner the lubricating film, the greater the motor current required to drive the electric motor to overcome frictional forces.This complicates blood pump control, as the current flow rate is usually determined by stored characteristic curves based solely on the motor current and speed (both known variables). If the irrigation fluid pressure also influences the motor current, this factor must also be taken into account. Since the same blood pump type can be operated for a variety of applications with different irrigation fluid pressures between 300 and 1400 mmHg, it is important to avoid a dependence of the motor current on the irrigation fluid pressure.

[0043] Such dependence is avoided if an irrigation fluid with a viscosity significantly higher than that of water is selected (η=0.75 mPas at 37°C). The viscosity of the irrigation fluid can be controlled by the concentration of dextrose in the irrigation fluid. Aqueous glucose solutions are frequently administered to patients for various reasons. The amount of dextrose in the aqueous solution can range from about 5% to about 50%. In one embodiment, the irrigation fluid can contain 5% dextrose in water (D5W, i.e., 278 mmol / liter). The viscosity can be increased by using solutions with a higher concentration of dextrose in water (e.g., D20W, D40W, etc.). If a highly viscous irrigation fluid is used, the fluid film can be maintained even at high pressures, and the friction of the axial sliding bearing is accordingly independent of the pressure of the irrigation fluid.In some embodiments, the axial plain bearing may be designed as a simple plain bearing and need not be designed as a hydrodynamic plain bearing if a flushing fluid has a viscosity at 37°C of about 1.2 mPas or higher.

[0044] In some embodiments, the pump impeller can exert shear stress on the blood flowing through the pump. The shear stress can occur in the gap between the impeller and the outer surface of the ceramic bearing, as well as between the impeller shaft and the inner race of the bearing (e.g., ceramic bearing, ball bearing, etc.). Due to the shear stresses the blood is subjected to, the blood proteins denature and polymerize as the blood flows through the pump. The deposition of the denatured and agglomerated protein leads to the activation of the coagulation cascade, which in turn can lead to the formation of biodeposits on the pump mechanisms (e.g., the impeller, the outflow cage, etc.). Small gaps between components (e.g., flush gaps) are particularly susceptible to clogging by biodeposits. The accumulation of biodeposits leads to an increase in the motor current required to operate the pump.The increased motor current or biological deposits can impair pump performance or even cause the pump to stop.

[0045] Fig. 5 shows another embodiment of flushing fluid flowing through flushing gaps. As shown in this illustration, the pump may include a first gap 290 and a second gap 292. In some embodiments, the first gap 290 may include a small radial gap 291 between an outer surface of a shaft 25 and an inner surface of a journal bearing 289, which may control the flow rate of flushing fluid 288 as it flows through the flushing gaps. In some embodiments, the small radial gap 291 may extend in a radial direction between 4 µm and 9 µm, e.g., between 5 and 6 µm for some pumps and between 7 and 8 µm for other pumps. In some embodiments, the first gap may contain mostly flushing fluid.In some embodiments, the concentration of the rinsing fluid in a fluid filling the volume defined by the first gap may be at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% of the total fluid in the first gap. In some embodiments, the first gap is completely filled with rinsing fluid. In some embodiments, some blood components may reach the distal end of this gap due to mixing of the flow. Due to the small size, heat, and high shear forces, the biological material accumulating at this location may contain denatured protein, which may lead to an increase in rinsing pressure and increased friction, causing a high motor current. In some embodiments, the most likely mechanism of action for bicarbonate is with an exemplary pump (e.g.,the Impella. ® Pump) in the first gap is to neutralize the acidic pH of the D5 carrier solution in order to reduce the denaturation and adsorption of blood proteins in the radial gap.

[0046] In some embodiments, the second gap 292 may include an axial gap 293 between the impeller 34 and a journal bearing 289. In some embodiments, the axial gap 293 may extend in an axial direction (e.g., at a distance parallel to the impeller shaft axis 299) between about 90 and 110 µm, e.g., about 100 µm. In some embodiments, the second gap may be the location where irrigating fluid and blood initially mix. The irrigating fluid may flow along the back of the appeal, drawing the system's blood into the gap, forming a clockwise flow pattern in this microenvironment. In some embodiments, the volume of blood drawn into the second gap may be between about 0.75 and 1.1 cubic mm, depending on the pump. In some embodiments, the irrigating fluid and blood do not completely mix in the axial gap.The mixing ratio of blood and rinsing fluid in the second gap can vary with the rinsing flow. For example, at higher rinsing flows (e.g., 30 ml / hr), the ratio can be approximately 60% blood, while at lower rinsing flows (e.g., approximately 0 ml / hr), the ratio is approximately 100% blood. This means that in some embodiments, the concentration of the rinsing fluid in a fluid filling the volume defined by the second gap can be at least 40%, at most 40%, at most 30%, at most 20%, or at most 10% of the total fluid in the first gap, depending on the flow rate of the rinsing fluid.

[0047] As previously mentioned, the flushing fluids used in blood pumps typically contain the anticoagulant heparin (e.g., 50 units / ml) in 5% dextrose (D5W) to mitigate the adverse effects of shear on the blood flowing through the pump. In some embodiments, heparin is included in the flushing fluid to prevent the formation of shear-induced biomaterial or biodeposits and the resulting undesirable deposition / accumulation of biological material within the pump, e.g., between the impeller shaft and the inner race of the bearings in high shear areas. However, as previously mentioned, the addition of heparin to the flushing fluid can be associated with problems. In particular, heparin can: a) complicate systematic anticoagulant management (i.e.,the dose of heparin the patient receives via the lavage fluid must be taken into account); b) as an anticoagulant, heparin may increase a patient's bleeding tendency; c) complicate the control of bleeding in postoperative patients, particularly when surgical devices are used in these patients; and d) should not be used in patients with heparin-induced thrombocytopenia (HIT). In addition, heparin may also be administered systemically in some patients, making it difficult to manage the administration of heparin from two sources.

[0048] As described here, the dextrose concentration can determine the viscosity of the irrigation fluid and thus influence the flow rate. Irrigation fluids with lower dextrose concentrations are less viscous and flow faster through the irrigation system with less pressure. Irrigation fluids with higher dextrose concentrations (more viscous) result in a lower flow rate and require higher irrigation pressure. For example, a reduction in dextrose concentration from 20% to 5% can result in an increase in flow rate of approximately 30 to 40%.

[0049] Flow rates typically range from approximately 2 mL / hour to approximately 30 mL / hour. This results in a purge pressure of approximately 1100 mmHg to approximately 300 mmHg. Typical purge flows for the blood pumps described here, e.g., Impella CP, Impella 2.5, Impella 5.0 / LD, and RP, are approximately 5 mL / hour to approximately 20 mL / hour. These pumps all use a ball-bearing rotor / stator system with similar tolerances, resulting in similar purge operating ranges. Typical purge flows for the Impella 5.5 are approximately 2 to 10 mL / hour. This lower flow rate results from the use of a ceramic-bearing rotor / stator system designed with a reduced purge gap (radial) to reduce or eliminate the amount of heparin delivered to the patient. In surgical patients, surgeons prefer not to administer heparin during the first few days after surgery. Therefore, heparin-free lavage fluids are preferred for these patients.

[0050] Therefore, a rinsing fluid additive is still required to mitigate the pump performance issues caused by pump operation. It has been observed that denatured proteins tend to agglomerate because unfolding exposes hydrophobic regions of the protein. This leads to unwanted biological deposits. Without denaturation and agglomeration, the hydrophobic segments are shielded, and the protein molecules are repelled by the electrostatically charged groups of the protein.

[0051] Soluble calcium ions are known to mediate blood clotting. Human serum albumin in the blood controls calcium ions. At higher pH values, albumin retains calcium ions more strongly. This mechanism reduces the effective concentration of calcium available for clotting. Therefore, adding an additive to the irrigant that raises the pH of the irrigant reduces the amount of calcium that supports clotting in the highly stressed areas. This document describes relatively high-pH buffers for use in an irrigant that raise the blood pH and thus attenuate clotting.

[0052] Proposed are pH control and buffering agents added to the lavage fluid that avoid the problems of heparin while fulfilling the other objectives of the lavage fluid (reduction of biological deposits, reduction of bearing wear, higher pressure than blood pressure, etc.). One example of a suitable pH-regulating and buffering agent is sodium bicarbonate. However, pH control and buffering agents other than sodium bicarbonate are also considered. These pH control and buffering agents include, for example, salts of small organic acids, such as citrate, lactate, gluconate, acetate, pyruvate, etc. In one example, the pH of sodium bicarbonate is about 7.4 to about 9.1. In one example, the pH of the lavage fluid with bicarbonate is about 8.4.Other ranges are contemplated, including but not limited to about 7.5 to about 9.1, 7.6 to about 9.1, 7.7 to about 9.1, 7.8 to about 9.1, 7.9 to about 9.1, 8.0 to about 9.1, 8.1 to about 9.1, 8.2 to about 9.1, 8.3 to about 9.1, 8.4 to about 9.1, 8.5 to about 9.1, 8.6 to about 9.1, 8.7 to about 9.1, 8.8 to about 9.1, 8.9 to about 9.1, and 9.0 to about 9.1. The pH of blood is about 7.3 to about 7.4. The addition of sodium bicarbonate to the irrigating fluid raises the pH of the blood that comes into contact with the irrigating fluid. The increased pH in these rinsing columns (e.g. first and second columns 290, 292, as shown in . Fig. 5) reduces biodeposits caused by blood clotting due to the high shear forces in the pump. Due to this effect, the presence of sodium bicarbonate can reduce the formation of insoluble biodeposits, even when clotting results in the formation of individual fibrin molecules.

[0053] In one embodiment, adding a bicarbonate-containing solution mixed with a dextrose solution such as 5% dextrose in water (D5W), 20% dextrose in water (D20W), 40% dextrose in water (D40W), etc., to the blood can increase the local pH of the blood at the crevices (higher shear area) and prevent protein agglomeration by increasing the electrostatic charge of the serum protein, thus reducing the formation of biodeposits. The amount of bicarbonate in the bicarbonate solution mixed with the dextrose solution can be from about 1.5 milliequivalents per liter (mEq / L) to about 50 mEq / L. In some embodiments, the amount of sodium bicarbonate can be from 12.5 mEq / L to 100 mEq / L, e.g., between 25 mEq / L and 50 mEq / L. In such embodiments, the rinsing solution may not contain heparin.In such embodiments, the pH value in the columns can be adjusted to ensure optimal presentation of the positively charged key amino acids of the heparin targets.

[0054] Described herein are systems and methods that use sodium bicarbonate as an alternative to heparin in a flushing fluid used to maintain the patency of a flushing system for a blood pump, e.g., at the first and second gaps. The sodium bicarbonate may be introduced into the flushing system and is not used for systemic anticoagulation of the patient in whom the pump is deployed. Instead, systemic anticoagulation with heparin, bivalirudin, and / or argatroban may be used to prevent thromboembolic events, even when sodium bicarbonate is used in the flush. As will be appreciated, other suitable anticoagulants may also be used in other embodiments.

[0055] According to some embodiments, systemic anticoagulation (e.g., using heparin) with a sodium bicarbonate lavage fluid may limit biomaterial deposition and the risk of embolism. For example, the sodium bicarbonate lavage fluid may maintain a slightly higher neutral pH in blood and lavage fluid mixtures at the lavage gaps (e.g., the first and second gaps 290 and 292). This may result in environmental conditions that 1) support protein stability in the radial gap to maintain patency of the lavage flow, and 2) delay the onset of clotting, suppressing fibrin formation, with an overall reduced rate of clot formation when lavage fluid and systemically anticoagulated blood mix in the second gap (e.g., the axial gap).

[0056] As in the Fig. 6A, Fig. 6B and Fig. As shown in Figure 6C, the effects of sodium bicarbonate in the irrigant environment were simulated by in vitro coagulability experiments using thromboelastography (TEG). As can be seen from the figures, systematically anticoagulated blood in the presence of sodium bicarbonate can exhibit a delayed onset of clot formation and a reduced clotting rate compared to the baseline blood (R and K (Figure 6A), angle parameters (Figure 6B), and TEG-ACT (Figure 6C)). In such embodiments, the effects of sodium bicarbonate in the irrigant gap environment were simulated with 60% blood and 40% irrigant fluid (e.g., to illustrate the irrigant fluid concentrations in a given irrigant gap environment at the high irrigant flow rate of 30 ml / hr). Although the irrigant fluid concentration in the local microenvironment may be 40%, the total irrigant fluid concentration in the patient's bloodstream will be substantially lower.For example, the total dose of bicarbonate administered to a patient may be 12 mEq (or less) over 8 hours. In some embodiments, the pH in the Impella columns, with a lavage fluid containing sodium bicarbonate mixed with blood, can maintain an optimal presentation pattern of the positively charged key amino acids of the heparin targets, and conditions are optimal for systemic heparin action.

[0057] As in Fig. As shown in Figure 6C, TEG-ACT was used to evaluate the interaction of the lavage fluid with systemically heparinized blood in gap 2 (e.g., the axial gap). Again, the simulation was performed with 60% blood and 40% lavage fluid (e.g., to represent the lavage fluid at the high lavage fluid flow rate of 30 ml / h). As shown in Fig. As shown in Figure 6C, a synergistic effect on blood coagulability was observed in the presence of bicarbonate and heparin.

[0058] Fig. 7 shows a kit according to some embodiments of the present disclosure. As shown in this view, in some embodiments, the kit 700 includes a pump 100, such as a pump having one or more features described herein. In some embodiments, the pump may include an inlet portion, a cannula, one or more sensors, an outlet portion, a motor housing, and a catheter. In some embodiments, as shown in this view, the kit may include a flushing cassette 702 configured to deliver a flushing fluid to and through the catheter and pump, for example, to prevent blood from entering the motor. As can be seen, the flushing cassette is configured to be connected to a flushing fluid, such as the flush bag 704. In some embodiments, the flush bag contains a premixed solution including sodium bicarbonate.In some embodiments, the rinsing fluid may, for example, contain a 5% dextrose-water solution with a sodium bicarbonate content between 12.5 and 100 mEq / L, e.g., between 25 mEq / L and 50 mEq / L. In some cases, the amount of sodium bicarbonate is 25 mEq / L.

[0059] With reference to Fig. 8, a method may be provided. The method may include providing 810 the required components. This may include providing 812 a pump, as described herein, and providing 814 a rinsing fluid, as described herein. Further components are described in Fig. 9 can be seen.

[0060] As in Fig. 9, a blood pump assembly 900 may include a blood pump 910 connected via a flushing device 953 to a container 951 (e.g., a flushing bag) containing a flushing fluid disclosed herein. The blood pump assembly 900 may also include a controller 930 (e.g., an Automated Impella Controller® from Abiomed, Inc., Danvers, MA), a display 940, a connecting cable 960, a connector 970, and a repositioning unit 980. As shown, the controller 930 may include a display 940. The controller 930 may monitor and control the blood pump 910. During operation, the flushing device 953 of the blood pump 910 can supply a flushing fluid described herein via a first line 950, 955 (e.g., a hose), via one or more components 956, 957, 958, 959, and via a catheter tube 917 to prevent blood from entering the motor (not shown) in a motor housing of the pump.The connecting cable 960 can establish an electrical connection between the blood pump 910 and the control unit 930. The connector 970 connects the catheter tube 917, the flushing device 953, and the connecting cable 960. In some embodiments, the connector 970 can include a memory for storing operating parameters in case the patient needs to be transferred to another control unit. The repositioning unit 980 can be used to reposition the blood pump 910. As shown in this view, the fluid line 950, 955 can be separated from the connecting cable 960 with one or more electrical lines.

[0061] The method may include operating the pump 820, which may include rotating 822 the impeller of the pump. The method may also include injecting 824 the flushing fluid into the exposed gaps of the pump. This may be accomplished by controlling the flushing device 953 (which may, for example, comprise a positive displacement pump). This may include flowing the fluid through a first gap between a bearing and an outer surface of a rotatable shaft connected to the impeller, wherein the bearing and gap are disposed in a lumen of a tubular member. In some embodiments, this may include flowing the fluid through a second gap after passing through the first gap, wherein the second gap is between the bearing and a surface of the impeller facing the bearing.

[0062] In some embodiments, the method may include controlling 830 a flow rate of the liquid into the pump during operation. In some embodiments, this may include controlling the flow rate such that the concentration of the liquid containing the bicarbonate in a volume of space defined by the first gap is at least 50% of the total liquid in the first gap. In some embodiments, this may include controlling the flow rate of the liquid such that the concentration of the liquid containing the bicarbonate in a volume of space defined by the second gap is no more than 40% of the total liquid in the second gap.

[0063] In some embodiments, the controller may be configured to control the flow rate of fluid into the pump based on the impeller speed. For example, the fluid flow rate may be relatively low at low impeller speeds, and as the impeller speed increases, the fluid flow rate is automatically increased to compensate for the increased pressure of blood attempting to enter the gap(s) of the pump. In some embodiments, this blood flow is controlled to maintain a substantially constant ratio of blood to bicarbonate-containing fluid in each gap.For example, if the flow rate is initially selected to produce an 80% / 20% blood / fluid containing bicarbonate ratio, and then later the impeller speed increases (or decreases) (which would change the 80 / 20 ratio), the method may include controlling the flow rate of fluid into the pump to increase (or decrease) accordingly so that the ratios remain substantially the same. In some embodiments, this is accomplished via a correlation based on empirical data. In some embodiments, the controller is configured to trigger a predetermined function that relates the flow rate to, for example, the impeller speed.

[0064] Although the embodiments disclosed herein involve influencing the microenvironment of irrigation gaps (e.g., axial and radial gaps) within a blood pump (e.g., a percutaneous blood pump) via a sodium bicarbonate-containing irrigation fluid, it is recognized that such a sodium bicarbonate irrigation may also be used with other components of a blood pump system or even other medical devices (or other medical device components) with similar irrigation gaps. For example, in some embodiments, as shown in the schematic representation of Fig. 10, a sodium bicarbonate irrigation fluid 1030 may be used to create an axial gap 1026 and a radial irrigation gap 1024 between a tubular body 1010 (e.g., a catheter) having a distal end 1012 and a proximal end 1011 (and may include a lumen 1013 extending therethrough, the lumen having a central axis 1005), and an outer sheath 1020 (e.g., an accessory sheath, such as a sheath used to insert and / or retain the pump within the patient) disposed around the tubular body. The irrigation fluid may be configured to flow in a direction 1031 (e.g., generally axially when in the radial irrigation gap and radially in the axial gap) through the radial irrigation gap and the axial gap to flush these gaps. In an exemplary embodiment, this can be used to flush a side arm 1040 of a shell (which, for example,(may be connected to the radial flushing gap via an opening 1022 in the side of the outer shell 1020) to minimize clot formation. In some embodiments, as shown in FIG. Fig. As shown in Figure 10, the axial gap may be located near a first end of the outer shell. However, it should be understood that the axial gap may be located at any suitable portion along the length of the outer shell, e.g., near the side arm of the outer shell.

[0065] In some embodiments, the maximum distance D1 between a first edge of an axial gap and an end of the outer shell may be ≤ 10 cm. In some embodiments, D1 ≤ 5 cm. In some embodiments, D1 ≤ 4 cm. In some embodiments, D1 ≤ 3 cm. In some embodiments, D1 ≤ 2 cm. In some embodiments, D1 ≤ 1 cm. In some embodiments, the maximum distance D2 between a first edge of the axial gap and the center of an opening (e.g., opening 1022) in the outer shell may be ≤ 5 cm. In some embodiments, D2 ≤ 4 cm. In some embodiments, D2 ≤ 3 cm. In some embodiments, D2 ≤ 2 cm. In some embodiments, D2 ≤ 1 cm.

[0066] As can be seen and as shown in this view, the axial and radial gaps can be formed between the outer diameter of the catheter and the inner diameter of the sheath. In some embodiments, the ratio of blood to bicarbonate-containing fluid can be higher than the storage gaps shown and described (e.g., higher than 80% / 20% and increasing to 100% blood). Although not shown, a fluid line can be connected to the sheath so that the flushing fluid can be directed into the flushing gaps. As described above, a controller can be used to control the rate at which the flushing fluid is directed into the sheath.

[0067] Although specific embodiments of this technology have been described, it will be apparent to those skilled in the art that the present technology may be embodied in other specific forms without departing from its essential characteristics. The present embodiments and examples are therefore to be considered in all respects as illustrative and not restrictive. It is further understood that any reference to art-known subject matter does not constitute an admission that such subject matter is well known to those skilled in the art to which the present technology relates, unless otherwise stated. QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited patent literature

[0000] US Provisional Patent Application 63 / 312,277

[0001] 2015 / 0051436

[0030] 2015 / 0051436 A1

[0034]

Claims

[1] Blood pump comprising: a tubular body having a distal end and a proximal end and a lumen extending therethrough, the lumen having a central axis; an impeller connected to a flexible shaft disposed at least partially within the lumen; and a bearing within the lumen, the bearing being disposed around a portion of the flexible shaft and being configured to form a first gap in the radial direction between an outer surface of the flexible shaft and an inner surface of the bearing, and forms a second gap in the axial direction between the bearing and a surface of the impeller facing the bearing; wherein the blood pump is configured such that a liquid containing a bicarbonate flows through the first gap and into the second gap. [2] The blood pump of claim 1, wherein the bicarbonate is sodium bicarbonate. [3] The blood pump of claim 2, wherein the fluid contains 12.5 mEq / L to 100 mEq / L sodium bicarbonate. [4] The blood pump of claim 1, wherein the fluid further contains a pharmaceutical therapeutic or prophylactic agent. [5] The blood pump of claim 4, wherein the pharmaceutical therapeutic or prophylactic agent is an anticoagulant. [6] The blood pump of claim 1, wherein the fluid further contains aqueous dextrose. [7] A blood pump according to claim 1, wherein the concentration of the liquid containing the bicarbonate in a volume defined by the first gap is at least 50% of the total liquid in the first gap. [8] A blood pump according to claim 7, wherein the first gap is filled with the liquid containing the bicarbonate. [9] A blood pump according to claim 8, wherein the concentration of the liquid containing the bicarbonate in a volume defined by the second gap is not more than 40% of the total liquid in the second gap. [10] The blood pump according to claim 1, wherein the first gap is 4 to 9 µm. [11] The blood pump according to claim 1, wherein the second gap is 90 to 110 µm. [12] System comprising: a pump comprising: a tubular body having a distal end and a proximal end and a lumen extending therethrough, the lumen having a central axis; an impeller connected to a flexible shaft disposed at least partially within the lumen; a bearing within the lumen, the bearing being disposed around a portion of the flexible shaft and being configured to form a first gap in the radial direction between an outer surface of the flexible shaft and an inner surface of the bearing, and forms a second gap in the axial direction between the bearing and a surface of the impeller facing the bearing; wherein the pump is configured such that a liquid containing a bicarbonate flows through the first gap and into the second gap; and an irrigation bag containing the fluid containing the bicarbonate, the irrigation bag being operatively connected to the pump. [13] The system of claim 12, wherein the bicarbonate is sodium bicarbonate. [14] The system of claim 13, wherein the liquid contains 12.5 mEq / L to 100 mEq / L sodium bicarbonate. [15] The system of claim 12, wherein the liquid further contains a pharmaceutical therapeutic or prophylactic agent. [16] The system of claim 15, wherein the pharmaceutical therapeutic or prophylactic agent is an anticoagulant. [17] The system of claim 12, wherein the liquid further contains aqueous dextrose. [18] The system of claim 12, wherein the concentration of the liquid containing the bicarbonate in a volume defined by the first gap is at least 50% of the total liquid in the first gap. [19] The system of claim 18, wherein the first gap is filled with the liquid containing the bicarbonate. [20] The system of claim 19, wherein the concentration of the liquid containing the bicarbonate in a volume defined by the second gap is not more than 40% of the total liquid in the second gap. [21] The system of claim 12, wherein the first gap is 4 to 9 µm. [22] The system of claim 12, wherein the second gap is 90 to 110 µm. [23] Kit comprising: a pump comprising: a tubular body having a distal end and a proximal end and a lumen extending therethrough, the lumen having a central axis; an impeller connected to a flexible shaft disposed at least partially within the lumen; a bearing within the lumen, the bearing being disposed around a portion of the flexible shaft and being configured to form a first gap in the radial direction between an outer surface of the flexible shaft and an inner surface of the bearing, and forms a second gap in the axial direction between the bearing and a surface of the impeller facing the bearing; wherein the pump is configured such that a liquid containing a bicarbonate flows through the first gap and into the second gap; a rinsing bag containing the liquid containing the bicarbonate; and a rinsing cassette designed to connect the rinsing bag to the pump. [24] A method for flushing a pump, the method comprising: Providing the pump with an impeller and a liquid containing bicarbonate; and Flowing the fluid through a first gap between a bearing and an outer surface of a rotatable shaft connected to the impeller, the bearing and the gap being arranged in a lumen of a tubular member. [25] The method of claim 24, wherein the bicarbonate is sodium bicarbonate. [26] The method of claim 25, wherein the liquid contains 12.5 mEq / L to 100 mEq / L sodium bicarbonate. [27] The method of claim 24, wherein the liquid further contains a pharmaceutical therapeutic or prophylactic agent. [28] The method of claim 27, wherein the pharmaceutical therapeutic or prophylactic agent is an anticoagulant. [29] The method of claim 24, wherein the liquid further contains aqueous dextrose. [30] The method of claim 24, further comprising controlling a flow rate of the liquid such that the concentration of the liquid containing the bicarbonate in a volume of space defined by the first gap is at least 50% of the total liquid in the first gap. [31] The method of claim 24, wherein the first gap is 4 to 9 µm. [32] The method of claim 24, wherein flowing the liquid through a first gap further comprises flowing the liquid through a second gap after passing through the first gap, the second gap being between the bearing and a surface of the impeller facing the bearing. [33] The method of claim 33, further comprising controlling a flow rate of the liquid such that the concentration of the liquid containing the bicarbonate in a volume of space defined by the second gap is no more than 40% of the total liquid in the second gap. [34] The method of claim 33, wherein the second gap is 90 to 110 µm. [35] The method of claim 24, further comprising automatically adjusting a flow rate of the liquid based on an operating characteristic of the pump. [36] Medical device comprising: a tubular body having a distal end and a proximal end and a lumen extending therethrough, the lumen having a central axis; an outer shell arranged around the tubular body; a first gap formed in the radial direction between an outer surface of the tubular body and the inner surface of the outer shell; a second gap formed in the axial direction between the tubular body and the outer shell; wherein a liquid containing a bicarbonate is configured to flow through the first and second gaps to flush the first and second gaps. [37] The medical device of claim 36, wherein the bicarbonate is sodium bicarbonate. [38] The medical device of claim 37, wherein the liquid contains 12.5 mEq / L to 100 mEq / L sodium bicarbonate. [39] The medical device of claim 36, wherein the fluid further contains a pharmaceutical therapeutic or prophylactic agent. [40] The medical device of claim 39, wherein the pharmaceutical therapeutic or prophylactic agent is an anticoagulant. [41] The medical device of claim 36, wherein the liquid further comprises aqueous dextrose. [42] The medical device of claim 36, wherein the concentration of the bicarbonate-containing liquid in a volume defined by the first gap is at least 50% of the total liquid in the first gap. [43] The medical device of claim 42, wherein the first gap is filled with the liquid containing the bicarbonate. [44] A medical device according to claim 43, wherein the concentration of the liquid containing the bicarbonate in a volume of space defined by the second gap is not more than 40% of the total liquid in the second gap. [45] The medical device of claim 36, wherein the first gap is 4 to 9 µm. [46] The medical device of claim 36, wherein the second gap is 90 to 110 µm.