Control of purge recovery using tissue plasminogen activator (TPA)

Abstract

A method of controlled purging of a blood pump and a blood pump assembly for carrying out the method are provided. The blood pump is in fluid communication with a purge device. The purge device includes a purge reservoir and an auxiliary reservoir configured to be fluidly connected to the blood pump. The purge reservoir is configured to contain a purge fluid and the auxiliary reservoir is configured to contain an auxiliary purge fluid. At least a portion of the blood pump is inserted into a patient and operated. A flow of purge fluid is provided from the purge reservoir to the blood pump. A purge flow parameter in the blood pump is measured using a measurement device, and a repair protocol is identified when the controller determines that the purge flow parameter meets a predetermined threshold.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 273,424, filed October 29, 2021, the entirety of which is incorporated herein by reference.

[0002] Technical Field

[0002] The present invention relates to a blood pump assembly including a blood pump, in particular an intravascular blood pump, for supporting blood flow within a patient's blood vessels, and a method for purging such a blood pump while it is in operation while inserted into a patient. [Background technology]

[0003] background

[0003] Various types of blood pumps are known, such as axial blood pumps, centrifugal blood pumps, or mixed blood pumps in which blood flow is driven by both axial and radial forces. One example of a blood pump is the Impella® line of blood pumps (e.g., Impella 2.5®, Impella CP®, Impella 5.5®, etc.) manufactured by Abiomed of Danvers, MA. Intravascular blood pumps are inserted into a patient's blood vessel, such as the aorta, by a catheter.

[0004]

[0004] In some pump designs, a purge fluid is placed to prevent blood from entering the pump mechanism and to mitigate the effects of blood and biological deposits buildup on the pump mechanism. For example, an anticoagulant such as heparin (typically a sodium salt of heparin) is used to maintain the patency of the pump components. Heparin is believed to prevent blood from clotting in the gaps between pump components such as the impeller shaft and the housing. Heparin is a commonly used anticoagulant that is typically administered in controlled doses. Summary of the Invention [Means for solving the problem]

[0005] overview

[0005] Described herein is a method of controlled purging of a blood pump and a blood pump assembly for carrying out the method. According to the described method, a blood pump is provided in fluid communication with a purging device. The purging device includes a purging reservoir and an auxiliary reservoir configured to be fluidly connected to the blood pump. The purging reservoir is configured to contain a purging fluid, and the auxiliary reservoir is configured to contain an auxiliary purging fluid. At least a portion of the blood pump is inserted into a patient. The method also includes operating the blood pump, providing a flow of purging fluid from the purging reservoir to the blood pump, measuring a purge flow parameter at the blood pump with a measuring device, and identifying a repair protocol when the controller determines that the purge flow parameter at the blood pump meets a predetermined threshold purge flow parameter.

[0006] Another aspect of the present disclosure relates to a blood pump assembly including a blood pump, a purge device in fluid communication with the blood pump, a measurement device configured to measure purge flow parameters in the blood pump, and a controller. The purge device includes a purge reservoir and an auxiliary reservoir configured to be fluidly connected to the blood pump. The purge reservoir is configured to contain a purge fluid, and the auxiliary reservoir is configured to contain an auxiliary purge fluid. The controller is configured to monitor the purge flow parameters in the blood pump and identify a repair protocol upon determining that the purge flow parameters in the blood pump meet a predetermined threshold purge flow parameter.

[0007]

[0007] In some embodiments, the blood pump includes a motor portion and a pump portion, and the purge fluid and the auxiliary purge fluid are supplied to the motor portion.

[0008]

[0008] The repair protocol includes stopping the flow of purge fluid from the purge reservoir to the blood pump and starting the flow of auxiliary purge fluid from the auxiliary reservoir to the blood pump, measuring an auxiliary purge measurement at the blood pump with a measuring device, and when the controller determines that the auxiliary purge flow parameter at the blood pump has fallen below or exceeded a predetermined threshold purge flow parameter indicating that auxiliary purge fluid is no longer needed, stopping the flow of auxiliary purge fluid from the auxiliary reservoir to the blood pump and resuming the flow of purge fluid from the purge reservoir to the blood pump.

[0009] In some embodiments, the flow of the auxiliary purge fluid is stopped and the flow of the purge fluid is resumed when the controller determines that the auxiliary purge flow parameter at the blood pump exceeds a predetermined threshold purge flow parameter. In some embodiments, the flow of the auxiliary purge fluid is stopped and the flow of the purge fluid is resumed when the controller determines that the auxiliary purge flow parameter at the blood pump exceeds the predetermined threshold purge flow parameter by a predetermined amount, the predetermined amount being at least 30% in 24 hours or at least 20% in 12 hours.

[0010] In other embodiments, the flow of the auxiliary purge fluid is stopped and the flow of the purge fluid is resumed when the controller determines that the auxiliary purge flow parameter at the blood pump falls below a predetermined threshold purge flow parameter. In some embodiments, the flow of the auxiliary purge fluid is stopped and the flow of the purge fluid is resumed when the controller determines that the auxiliary purge flow parameter at the blood pump falls below the predetermined threshold purge flow parameter by a predetermined amount, the predetermined amount being at least 30% in 24 hours or at least 20% in 12 hours.

[0011] In some embodiments, the purge flow parameter is a purge flow rate and the predetermined threshold purge flow parameter is a decrease in the purge flow rate by a predetermined amount, the predetermined amount being at least 30% within 24 hours or at least 20% within 12 hours. In some embodiments, the purge flow parameter is a purge flow rate and the predetermined threshold purge flow parameter is a decrease in the purge flow rate to less than 3 mL / hr within 6 hours. In some embodiments, the purge flow parameter is a purge pressure and the predetermined threshold purge flow parameter is an increase in the purge pressure by a predetermined amount, the predetermined amount being at least 30% within 24 hours or at least 20% within 12 hours. In some embodiments, the purge flow parameter is a purge pressure and the predetermined threshold purge flow parameter is an increase in the purge pressure to more than 700 mmHg within 24 hours.

[0012]

[0012] In some embodiments, the method further includes degassing the auxiliary purge fluid prior to supplying the auxiliary purge fluid to the blood pump.

[0013] In some embodiments, the supplemental purge fluid includes tissue plasminogen activator (tPA). The supplemental purge fluid may also include glucose. In some embodiments, the concentration of tPA is 2 mg / 50 mL. The tPA may be lyophilized before being combined with the purge fluid.

[0014]

[0014] In some embodiments, the purge fluid includes aqueous glucose. For example, the purge fluid may include a 5% glucose solution in water. In some embodiments, the purge fluid may also include an anticoagulant, a pH adjusting and buffering agent, or a combination thereof. In some embodiments, the anticoagulant is warfarin, coumarin, heparin, or a direct thrombin inhibitor. In some embodiments, the direct thrombin inhibitor is lepirudin, desirudin, argatroban, bivalirudin, or a mixture thereof. In some embodiments, the pH adjusting and buffering agent is sodium bicarbonate, sodium citrate, sodium lactate, sodium gluconate, sodium acetate, or sodium pyruvate.

[0015] BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The present invention will now be described, by way of example only, with reference to the accompanying drawings, which are not intended to be drawn to scale and in the interest of clarity not every component is numbered in every drawing, in which: [Brief description of the drawings]

[0016] [Figure 1]

[0016] FIG. 1 illustrates blood flow and purge flow through the gap between the shaft and housing of a blood pump. [Diagram 2]

[0017] FIG. 1 is a schematic diagram of an intravascular blood pump inserted in front of the left ventricle with its inflow cannula positioned within the left ventricle. [Diagram 3]

[0018] 1 is a schematic longitudinal cross-sectional view of an exemplary prior art blood pump. [Figure 4]

[0019] FIG. 4 is an enlarged view of a portion of the blood pump of FIG. [Diagram 5]

[0020] 1 is a schematic diagram of a prior art blood pump assembly. [Figure 6]

[0021] 1 is an embodiment of a purge cassette of the present invention. [Figure 7]1 is an embodiment of a purging cassette of the present invention during performance of a repair protocol. [Figure 8]

[0022] 1 is a plot illustrating an example of a relationship between purge pressure and purge flow rate. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Detailed Description

[0023] The embodiments of the present disclosure will be described in detail with reference to the drawings in which similar reference numerals identify similar or identical elements. It should be understood that the disclosed embodiments are merely examples of the present disclosure, which may be embodied in various forms. Well-known functions or structures are not described in detail to avoid obscuring the present disclosure with unnecessary details. Therefore, the specific structural and functional details disclosed herein should not be interpreted as limiting, but merely as a basis for claims and as a representative basis for teaching those skilled in the art to variously adopt the present disclosure into virtually any suitable detailed structure.

[0018]

[0024] Blood pumps are applied to patients who require critical life-saving treatment. It is therefore important to repair any aspect of the device that may adversely affect the operation of the pump. Disclosed herein is the automation of one aspect of the operation of a blood pump. In particular, the purge conditions are monitored by a controller, and the need to replace the purge fluid with a supplemental purge fluid, such as a purge fluid containing tissue plasminogen activator (tPA), is detected.

[0019]

[0025] A blood pump of the aforementioned type is known, for example from EP 0961621 (B1), which is incorporated herein by reference. With reference to FIG. 1, a pump 100 is shown having a drive 110, a catheter 115 attached to a proximal end 120 of the drive 110 (the end of the drive closer to the clinician or the "rear end" of the drive) and having a line extending therethrough for power supply to the drive 110, and a pump section 130 fastened to a distal end 125 of the drive. The drive 110 includes a motor housing 150 in which an electric motor 151 is disposed, the motor shaft 160 of the electric motor projecting distally from the drive 110 to the pump section 130. The pump section 130 further includes a tubular pump housing 165 having an impeller 170 rotating therein, the impeller 170 being seated on the end of the motor shaft 160 projecting from the motor housing 150. The motor shaft 160 is mounted in the motor housing on two bearings 171, 172, which are maximally spaced apart from each other to ensure a true, precisely centered guidance of the impeller 170 in the pump housing 150. Different bearing types are used for different pump designs. As shown in FIG. 1, the bearing 171 is a radial ball bearing and the bearing 172 is an axial radial plain bearing. As shown in FIG. 1, the blood 140 leaves the outflow cage of the pump housing 165. The blood that would otherwise enter the motor housing 150 is further impeded by the purge fluid 135 passing through the motor housing and the impeller-side shaft seal bearing. The purge fluid therefore passes through the gap of the impeller-side radial plain bearing to prevent the blood from entering the housing. This is done at a purge pressure higher than the pressure present in the blood.

[0020]

[0026] As shown in FIG. 1, the purge fluid 135 fills the motor housing 150 of the pump to form a lubricating film on the bearings 171, 172 of the pump. As described in U.S. Patent Application Publication No. 20150051436, which is incorporated herein by reference, the purge fluid 135 can form a lubricating film in the bearing gap 180 of the axial slide bearing of the pump. The purge fluid is described as being supplied through a purge fluid supply line and flowing through the radial bearing 171 located at the distal end of the motor housing 150, and then also flowing through the bearing gap 180 of the axial slide bearing. The purge fluid supplied in this manner is responsible for hemodilution and reduces blood residence time under the impeller 170.

[0021]

[0027] To ensure that the purge fluid 135 reaches the distal radial bearing 172 at a pressure higher than the existing blood pressure, at least one of the surfaces forming the bearing gap of the axial plain bearing is provided with a channel penetrating the bearing gap 180 from the radial outside to the radial inside, so that the purge fluid can flow through this channel to the distal radial bearing. This channel does not necessarily have to be in the bearing gap surface, but can also be realized as a separate channel or bore. However, providing a channel in one of the bearing gap surfaces has the advantage that the lubricant film in the bearing gap is not heated much, because part of it is constantly replaced by the purge fluid that enters later. Preferably, the channel is located in a stationary bearing gap surface in order to minimize the radial transport capacity.

[0022]

[0028] Typically, such purge fluids contain heparin. However, clinicians often do not want to administer heparin to the patient's blood via the purge fluid. For example, administering heparin during some surgical procedures can be counterproductive, as it can prevent blood clotting and thus prevent healing or hemostasis. Also, the amount of heparin administered to the patient's blood with the purge fluid is difficult to control for various reasons. In particular, the amount of heparin often exceeds the amount the clinician desires, and the amount of heparin administered to the patient is difficult to precisely control. Therefore, clinicians often prefer to supply heparin to the patient on demand (and therefore only in the amount required) separately from the operation of the blood pump. Furthermore, some patients are heparin intolerant due to their susceptibility to heparin-induced thrombocytopenia (HIT). Therefore, a purge containing heparin is completely unsuitable for these patients. Therefore, an intravascular blood pump may be operated, as needed, with a purge fluid that is free of heparin or that contains at least a reduced amount of heparin.

[0023]

[0029] Another common problem arises with respect to the heparin typically mixed into the purge fluid. Although the purge fluid flows through the gap formed between the shaft and the opening of the housing, thereby pushing back any blood that may tend to enter the housing through such gap, it cannot completely prevent blood from entering the gap. In particular, some blood or blood components may always enter at least the distal portion of such gap. The heparin helps to prevent blood from clotting in the gap or sticking to surfaces, thus preventing the shaft from being blocked from rotating.

[0024]

[0030] EP 3542837 A2, incorporated herein by reference, describes a pump that at least intermittently limits the use of purge fluid to mitigate the consequences of administering heparin to the patient via the blood pump purge fluid. To achieve this, EP 3542837 A2 proposes using a material for at least one surface of the plain bearing that has a relatively high thermal conductivity relative to the gap surface. An example of such a material is silicon carbide. The opposing surface may be made of a ceramic material with a lower thermal conductivity (e.g., alumina-reinforced zirconia). As described, the shaft is made of alumina-reinforced zirconia and the sleeve in which the shaft is journaled is made of silicon carbide. Thus, using special materials for the pump components is one solution to limit or even eliminate the use of heparin-containing purge fluid.

[0025]

[0031] FIG. 2 illustrates the use of a blood pump to support the left ventricle in this particular example. The blood pump includes a catheter 14 and a pumping device 10 attached to the catheter 14. The pumping device 10 has a motor portion 11 and a pump portion 12 arranged coaxially in series to provide a rod-like structural form. The pump portion 12 has an extension in the form of a flexible suction hose 13, often referred to as a "cannula." An impeller is provided in the pump portion 12 to generate blood flow from a blood flow inlet to a blood flow outlet, the rotation of the impeller being generated by an electric motor arranged in the motor portion 11. The blood pump is arranged to be located primarily within the ascending aorta 15b. In the closed state, the aortic valve 18 is arranged to be located outside the pump portion 12 or its suction hose 13, which is adjacent to the left ventricle 17 when the pump is arranged. The blood pump, with suction hose 13 forward, is advanced to the position shown by advancing catheter 14, optionally using a guidewire, as suction hose 13 passes retrograde through aortic valve 18 so that blood is drawn through suction hose 13 and pumped into aorta 16 via aortic arch 15a.

[0026]

[0032] The use of the blood pump is not limited to the application shown in Fig. 2, which is merely a representative application example. The pump can therefore also be inserted through other peripheral blood vessels, such as the subclavian artery. Alternatively, a reverse application to the right ventricle can also be envisaged.

[0027]

[0033] FIG. 3 shows an exemplary embodiment of a blood pump as described in US Patent Application Publication No. 2015 / 0051436 A1, which is also suitable for use in the context of the present invention, except that the encircled front end marked with an "I" may be modified (such modification is shown in FIG. 4), which is incorporated herein by reference. The motor portion 11 thus has an elongated housing 20 in which an electric motor 21 may be housed. The stator 24 of the electric motor 21 may have, in the usual manner, a number of windings distributed circumferentially and a longitudinal magnetic return 28. The magnetic return 28 may form an outer cylindrical sleeve of the elongated housing 20. The stator 24 is connected to a motor shaft 25 and may surround a rotor 26 consisting of permanent magnets magnetized in an active direction. The motor shaft 25 may extend over the entire length of the motor housing 20 and may protrude distally from the motor housing 20 through an opening 35. An impeller 34 is carried therein, the impeller 34 having pump vanes 36 projecting therefrom, which may rotate within a tubular pump housing 32 which may be rigidly connected to the motor housing 20 .

[0028]

[0034] The proximal end of the motor housing 20 has a flexible catheter 14 sealingly attached thereto. An electrical cable 23 for powering and controlling the electric motor 21 may extend through the catheter 14. Additionally, a purge fluid line 29 may extend through the catheter 14 and penetrate the proximal end wall 22 of the motor housing 20. Purge fluid may be supplied to the interior of the motor housing 20 through the purge fluid line 29 and exit through an end wall 30 at the distal end of the motor housing 20. The purging pressure is selected to be higher than the existing blood pressure, between 300 and 1400 mmHg depending on the application, thereby preventing blood from entering the motor housing.

[0029]

[0035] As previously mentioned, the purge seal may be combined with a pump driven by a flexible drive shaft and a remote motor.

[0030]

[0036] As the impeller 34 rotates, blood is drawn in through a distal opening 37 in the pump housing 32 and transported axially rearward within the pump housing 32. The blood exits the pump section 12 through a radial outlet opening 38 in the pump housing 32 and flows further along the motor housing 20. This ensures that heat generated within the motor is removed. It is also possible to operate the pump section in the reverse transport direction, where blood is drawn along the motor housing 20 and exits through the distal opening 37 in the pump housing 32.

[0031]

[0037] The motor shaft 25 is 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 hand. The radial bearings, in particular the radial bearing 31, in the opening 35 at the distal end of the motor housing are configured as plain bearings. Furthermore, the motor shaft 25 is also mounted axially in the motor housing 20, and the axial bearing 40 is likewise configured as a plain bearing. The axial plain bearing 40 serves to receive the axial force of the motor shaft 25 acting in the distal direction when the impeller 34 transports blood from distal to proximal. If the blood pump is used to transport blood also or only in the reverse direction, a corresponding axial plain bearing 40 (also or only the corresponding axial plain bearing 40) may be provided in a corresponding manner at the proximal end of the motor housing 20.

[0032]

[0038] FIG. 4 shows in more detail the part marked "I" in FIG. 3, but which has been structurally modified. In particular the radial plain bearing 31 and the axial plain bearing 40 can be seen. The bearing gap of the radial plain bearing 31 is formed on the one hand by the peripheral surface 25A of the motor shaft 25 and on the other hand by the surface 33A of the through bore in the bush or sleeve 33 of the end wall 30 of the motor housing 20, and defines a gap outer diameter of about 1 mm, but the gap outer 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 over its entire length, and not just at the front end or impeller side of the gap. Preferably, the gap width is between 1 μm and 2 μm. The length of the bearing gap may be in the range of 1 mm to 2 mm, preferably between 1.3 mm and 1.7 mm, for example 1.5 mm. The surfaces forming the gap of the radial plain bearing 31 have a surface roughness of 0.1 μm or less. These dimensions vary by pump type and are given by way of example and not limitation.

[0033]

[0039] The bearing gap of the axial plain bearing 40 is formed on the one hand by the axially inner surface 41 of the end wall 30 and the opposing surface 42. This opposing surface 42 is part of a ceramic disk 44 which sits on the motor shaft 25 on the distal side of the rotor 26 and rotates with it. A channel 43 in the bearing gap surface 41 of the end wall 30 ensures that the purge fluid can pass between the bearing gap surface 41 and the bearing gap surface 42 of the axial plain bearing 40 to the radial plain bearing 31 and exit distally from the motor housing 20. The axial plain bearing 40 shown in FIG. 3 is a normal plain bearing. Contrary to this representation, the axial gap of the axial plain bearing 40 is very small, a few μm.

[0034]

[0040] Instead of the axial plain bearing 40 and the radial plain bearing 31, a combined radial-axial plain bearing 40 can also be realized, which has a concave bearing shell, into which a convex bearing surface extends. Such a variant is shown in FIG. 4 by a spherical plain bearing 40. The bearing gap surface 41 is of spherical-concave design, and the opposing bearing gap surface 42 is of corresponding spherical-convex design. The channel 43 is again 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 of convex configuration, and the opposing bearing gap surface 42 can be of concave configuration. The surfaces 42, 43 can also be conical instead of spherical. Preferably, corresponding radial-axial plain bearings are provided on both sides of the motor housing 20, so as not to allow a radial offset during the axial movement of the shaft 25. The advantage of a combined axial-radial plain bearing is a higher load capacity. However, the disadvantage is a larger friction diameter.

[0035]

[0041] In some embodiments, the blood pump is inserted into the patient's blood vessel through a sheath. In some embodiments, a sheath is not used. In other embodiments, the blood pump is inserted using a guidewire.

[0036]

[0042] As shown in FIG. 5, the blood pump assembly 200 may include a blood pump 210 fluidly connected to a purging device 250. The blood pump assembly 200 also includes a controller 230 (e.g., Automated Impella Controller® by Abiomed, Inc., Danvers, MA), a display 240, a connector cable 260, a plug 270, and a position conversion unit 280. As shown, the controller 230 includes the display 240. The controller 230 monitors and controls the blood pump 210. During operation, the purging device 250 delivers a purging fluid to the blood pump 210 through the catheter tube 217 to prevent blood from entering the motor (not shown) within the motor housing 216. In some embodiments, the purging fluid includes a glucose solution (e.g., a 5% glucose solution in water with 25 or 50 IU / mL of heparin). The connector cable 260 provides an electrical connection between the blood pump 210 and the controller 230. A plug 270 connects the catheter tube 217, the purge device 250, and the connector cable 260. In some embodiments, the plug 270 includes memory to store operating parameters in case the patient needs to be transferred to another controller. A position conversion unit 280 can be used to convert the blood pump 210 to a different position.

[0037]

[0043] As shown, the purge device 250 includes a reservoir 251, a purge fluid supply line 252, a purge cassette 253, a purge disk 254, a purge tube 255, a check valve 256, a pressure reservoir 257, an infusion filter 258, and a side arm 259. The reservoir 251 can be, for example, a bag or a bottle. A purge fluid is contained within the reservoir 251. A purge fluid spike at the end of the purge fluid supply line 252 can be used to puncture the reservoir 251 and connect the purge fluid in the reservoir 251 to the purge fluid supply line 252. The purge fluid supply line 252 transports the purge fluid from the reservoir 251 to the purge cassette 253. The purge tube 255 transports the purge fluid from the purge cassette 253 to the blood pump 210.

[0038]

[0044] The purge cassette 253 controls how the purge fluid in the reservoir 251 is delivered to the blood pump 210 and the flow path of the purge fluid from the reservoir 251 to the blood pump 210. For example, the purge cassette 253 may include one or more valves (e.g., purge path diverters) for controlling the pressure and / or flow rate of the purge fluid. In addition to including components for delivering the purge fluid, the purge cassette 253 also maintains a pressure barrier between the blood and the motor of the blood pump 210 to prevent blood from entering the motor. The purge cassette 253 may include a rack and pinion attached to a piston. The purge disk 254 includes one or more measurement devices, such as a pressure sensor (e.g., a pressure-sensing diaphragm) for measuring the purge pressure of the purge fluid in the blood pump 210. The controller 230 is connected to the purge cassette 253 and the purge disk 254. The purge disk 254 communicates pressure to the controller 230 based on the purge pressure in the purge tube 255. A sensor in the controller 230 measures this pressure and can be displayed on the screen 240. The controller 230 can include a stepper motor. A tick (or step) represents the position of the stepper motor in microsteps, also called a pulse. In some embodiments, a purge pressure / purge flow rate curve algorithm is applied by the controller 230 along with the number of steps / minute of the stepper motor and the pressure measurement by the purge disk 254 to calculate the corresponding purge flow rate.

[0039]

[0045] As mentioned above, the purge tube 255 provides a fluid connection through the purge cassette 253 to the blood pump 210. In some embodiments, a Y-connector and / or a yellow luer connector is also provided to facilitate a continuous or purge fluid path. The Y-connector is an adapter that connects the purge tube 255 to the blood pump 210. The yellow luer connector connects the purge tube 255 to a check valve (yellow luer lock) of the blood pump 210. The pressure reservoir 257 provides additional fill volume during purge fluid exchange. In some embodiments, the pressure reservoir 257 includes a flexible rubber diaphragm that provides additional fill volume through an expansion chamber. The infusion filter 258 helps prevent bacterial contamination and air ingress into the catheter tube 217. A side arm 259 provides a fluid connection between the infusion filter 258 and the plug 270.

[0040]

[0046] In operation, the controller 230 receives measurements from the purge disk 254 and controls the stepper motor ticks to control the purge pressure. In some embodiments, in operation, the purge cassette 253 is disposed in the controller 230 and connected to the blood pump 210. As described above, the controller 230 controls and measures the purge pressure and calculates the purge flow rate through the purge cassette 253 and / or the purge disk 254. The controller 230 may also control the purge fluid supply. In operation, after exiting the purge device 250 through the side arm 259, the purge fluid is directed through the catheter tube 217 and a purge lumen (not shown) in the plug 270. The catheter tube 217, the connector cable 260, and the sensor cable (not shown) in the plug 270 provide electrical connections between the purge disk 254 and the controller 230. The catheter tube 217, connector cable 260, and motor cable (not shown) in plug 270 provide electrical connections between the motor in the motor housing 216 and the controller 230. In operation, the controller 230 receives measurements from the purge disk 254 via the sensor cable and controls the power provided to the motor in the motor housing 216 via the motor cable. By controlling the power provided to the motor in the motor housing 216, the controller 230 can control the speed of the motor in the motor housing 216. In some embodiments, the controller 230 includes a safety feature to prevent air from entering the purge tube 255. The controller 230 may include circuitry to monitor a drop in motor current, which indicates that there is air in the line. The controller 230 may include an alarm sound, light, or indicator to notify the operator of a break or break in the purge tube 255 that could result in the introduction of air into the line.

[0041]

[0047] Various modifications may be made to the blood pump assembly 200 and one or more of its components. For example, as detailed in Abiomed, Impella® Ventricular Support Systems for Use During Cardiogenic Shock and High-Risk PCI: Instructions for Use and Clinical Reference Manual, Document No. 0042-9028 rG (Apr. 2020), which is incorporated herein by reference, the blood pump assembly 200 may be modified to accommodate other types of blood pumps, such as Impella 2.5®, Impella LD®, and Impella CP® catheters. As another example, one or more additional measurement devices may be added to the blood pump 210. For example, a signal generator may be added to the blood pump 210 for generating a signal indicative of the rotational speed of the motor in the motor housing 216, as described in U.S. Patent Application Publication No. 2020 / 0288988 (A1), which is incorporated herein by reference. As another example, a second measurement device, a pressure sensor configured to measure left ventricular blood pressure, may be added to blood pump 210 near inlet region 212. In such an embodiment, an additional sensor cable may be disposed within catheter tube 217, connector cable 260, and plug 270 to provide an electrical connection between one or more additional measurement devices and controller 230. As yet another example, one or more components of blood pump assembly 200 may be separate. For example, display 240 may be incorporated into a separate device that communicates with controller 230 (e.g., wirelessly or via one or more electrical cables).

[0042]

[0048] The display 240 can provide useful information to a user of the blood pump assembly 200. For example, U.S. Patent Application Publication No. 2020 / 0376183(A1), incorporated herein by reference, describes and illustrates several types of information that can be displayed that can relate to the characteristics of the blood pump assembly (e.g., blood pump type, serial number, software version, etc.) as well as the operation of the blood pump assembly (e.g., current blood pump speed (performance) setting, blood pump flow measurements, purge device measurements, status indicators, etc.). Some of this information can be obtained from the purge disk 254 described above. The display 240 can also provide notifications to the user. For example, the notifications can function as alerts and can include text that describes the cause of the alert. In some embodiments, the display 240 can be a touch screen and the user can switch between screens by tapping button labels on the display 240. In some embodiments, the user can use a separate input device, such as a mouse or keyboard, to switch between screens.

[0043]

[0049] A system for monitoring and / or controlling multiple medical device controllers, such as controller 230, is described and illustrated in US Patent Application Publication No. 2020 / 0376183(A1). The system may include medical device controllers, a computer network, a local area network (LAN), a remote link module, a router, a wireless access point, a base station, a server, a data store, an OCR engine, and / or a monitoring station. The computer network may include wired and / or wireless segments and / or networks. The medical device controllers may be connected to the computer network using various known technologies. For example, the medical device controllers may be connected to the computer network directly, through a remote link module, or through a LAN, a router, and a wireless access point. The server may be configured to request status information from the medical device controllers via the computer network. In some embodiments, the server automatically and / or repeatedly requests the status information. The server may also be configured to process the received status information.

[0044]

[0050] The data store may be configured to store the raw and / or processed status information. The data store may also be configured to provide at least a portion of the raw and / or processed status information to the monitoring station upon request. The monitoring station may be, for example, a phone, a tablet, and / or a computer. In some embodiments, the monitoring station may use cloud-based technology to reliably and remotely display at least a portion of the raw and / or processed status information on a corresponding display. For example, the monitoring station may use an online device management system, such as Impella Connect® from Abiomed, Inc., Danvers, MA, to reliably and remotely display at least a portion of the raw and / or processed status information. In some embodiments, the server and / or monitoring station may also be configured to remotely send commands to one or more medical device controllers in the system. In some embodiments, one or more medical device controllers in the system may offload one or more calculations to the server and / or monitoring station. For example, if a controller 230 is added to the system, the controller 230 may offload complex calculations (e.g., machine learning algorithms) to the server and / or monitoring station. To reduce latency, the controller 230 may also offload such calculations to another computing device on the same LAN.

[0045]

[0051] During operation, the blood pump is attached to a purge fluid source (such as a purge fluid reservoir) and fluid enters the motor housing through a purge fluid line. The purge fluid then flows through the axial plain bearing and then through the distal radial bearing. In the axial plain bearing, the purge fluid forms a lubricating film in the bearing gap. The pressure at which the purge fluid flows through the motor housing, however, adversely affects the width of the bearing gap. Specifically, the higher the purge pressure, the smaller the bearing gap width required and the thinner the lubricating film between the sliding surfaces. The thinner the lubricating film, the higher the motor current required to drive the electric motor to overcome the frictional forces. This complicates the control of the blood pump, since the amount of current carrying is usually established by a stored characteristic curve based only on the motor current and rotation speed, both of which are known quantities. If the purge pressure also affects the motor current, this factor must also be taken into account. Considering that the same blood pump type can be operated in a wide variety of applications with different purge pressures ranging from 300 mmHg to 1400 mmHg, it is important to avoid a dependency of the motor current on the purge pressure.

[0046]

[0052] Such a dependency is avoided if a purge fluid is selected that has a viscosity significantly higher than that of water (η=0.75 mPas at 37° C.). For purge fluids that contain glucose, the viscosity of the purge fluid is controlled by the concentration of glucose in the purge fluid. Aqueous glucose solutions are widely administered to patients for a variety of reasons. The amount of glucose in the aqueous solution is about 5% to about 50%. In one embodiment, the purge fluid includes a 5% aqueous glucose solution (i.e., 278 mmol / liter). The viscosity can be increased by including an aqueous solution with a higher concentration of glucose (e.g., D20W, D40W, etc.). When a purge fluid with a high viscosity is used, the fluid film is maintained even at high pressures, and thus the friction of the axial plain bearing becomes independent of the purge pressure. In some embodiments, when the purge fluid has a viscosity of about 1.2 mPas or more at 37° C., the axial plain bearing can be configured as a simple plain bearing and does not need to be configured as a hydrodynamic plain bearing. Therefore, when purge fluids that are heparin-free or contain less heparin are considered, the viscosity of such purge fluids must still be considered.

[0047]

[0053] The pump impeller induces shear stresses in the blood passing through the pump. The shear stresses are primarily induced in the gap between the impeller and the outer surface of the ceramic bearing, and between the impeller shaft and the inner ring of the bearing (e.g., ceramic bearing, ball bearing, etc.). Due to the shear stresses experienced by the blood, blood proteins denature and polymerize as the blood passes through the pump. The deposition of denatured and aggregated proteins causes activation of the coagulation cascade, which in turn causes the accumulation of biological deposits in the pump mechanism (e.g., impeller, outflow cage, etc.). The accumulation of biological deposits increases the motor current required for the pump to operate. The increased motor current or biological deposits can reduce the performance of the pump or even cause the pump to stall.

[0048]

[0054] As mentioned above, the purge fluid used in purged blood pumps typically contains 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 or to mitigate the buildup of biological deposits due to blood debris collecting in the purge fluid path. The glucose concentration determines the viscosity of the purge fluid and therefore affects the purge flow rate. The lower the glucose concentration of the purge fluid, the less viscous it is and the faster it will flow through the purge system at lower pressures. The higher the glucose concentration of the purge fluid (the more viscous it is), the lower the purge flow rate and the greater the purge pressure required. Reducing the glucose concentration from 20% to 5% increases the purge flow rate by approximately 30% to 40%.

[0049]

[0055] The purge flow rate is typically in the range of about 2 mL / hr to about 30 mL / hr, as shown in FIG. 8. This results in a purge pressure of about 1,000 mmHg to about 300 mmHg. The typical purge flow rate of the blood pumps described herein, such as the Impella CP®, Impella 2.5®, Impella 5.0®, Impella LD®, and Impella RP®, is about 5 mL / hr to about 20 mL / hr. All of these pumps have ball bearing rotor / stator systems with similar tolerances that lead to similar purge operating ranges. The typical purge flow rate of the Impella 5.5® is about 2 mL / hr to about 10 mL / hr. This low flow rate is due to the placement 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. For surgical patients, surgeons prefer not to administer heparin during the first few days after surgery, therefore, for these patients, a heparin-free purge fluid is preferred.

[0050]

[0056] A constant purge flow is used to keep debris out of two critical areas: 1) the gap between the rotor shaft and the sleeve bearing, and 2) the gap between the sleeve bearing and the impeller. Due to diffusion and flow comixture, some blood components can reach these gaps. Heparin in the purge solution improves protection against ingress, adsorption, deposition, and coagulation of blood components. Heparin in the purge solution also improves the operating life of the bearings for at least the reasons described below.

[0051]

[0057] Specifically, the continuous and dynamic physical adsorption (physisorption) of heparin onto the surfaces surrounding the purge path reduces the adsorption of blood components and thus prevents the biological deposition of blood residues on the bearings and other pump components. Heparin also partially neutralizes the weakly acidic D5W solution, helping to maintain a physiological pH in the aforementioned gap, thus reducing the risk of denaturation of blood proteins. The localized high concentration of heparin both under the impeller and inside the sleeve-bearing gap may also reduce the risk of blood clotting in these areas. The addition of heparin increases the conductivity of the purge fluid, thus reducing the negative impact of electrostatic discharge on the operating life of the bearings.

[0052]

[0058] Thus, heparin is provided in the purge fluid to prevent shear-induced formation of biological material or biological deposits and the resulting undesirable deposition / accumulation of biological material within the pump, such as between the impeller shaft and the inner ring of the bearing in high shear regions. However, as noted above, there are challenges associated with the addition of heparin to the purge fluid. Specifically, heparin a) complicates the administration of systematic anticoagulants (i.e., the dose of heparin the patient receives via the purge fluid must be considered), b) heparin, as an anticoagulant, increases the patient's tendency to bleed, c) heparin makes it more difficult to control bleeding in such patients post-operatively, especially when surgical devices are used on the patient, and d) heparin cannot be used in patients with heparin-induced thrombocytopenia.

[0053]

[0059] To alleviate pump performance issues when the purge fluid has no heparin or a low concentration of heparin, the use of different purge fluids / purge fluid additives has been previously proposed. For example, U.S. Provisional Patent Application No. 63 / 017,445, filed April 29, 2020, incorporated herein by reference, proposes using a purge fluid that includes a pH adjusting and buffering agent. Non-limiting examples of suitable pH adjusting and buffering agents include, for example, sodium bicarbonate, sodium citrate, sodium lactate, sodium gluconate, sodium acetate, or sodium pyruvate. In some embodiments, the pH adjusting and buffering agent is sodium bicarbonate. In one example, the pH of sodium bicarbonate is about 7.4 to about 9.1. Other ranges include, but are not limited to, from 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.

[0054]

[0060] A pH adjusting and buffering agent is added to the purge fluid containing glucose alone or in combination with a reduced amount of heparin. The concentration of the pH adjusting and buffering agent in the aqueous glucose solution is selected to provide a solution having a pH within the ranges specified above. In one embodiment, a solution containing bicarbonate is mixed with a glucose solution such as a 5% aqueous glucose solution (D5W), a 20% aqueous glucose solution (D20W), a 40% aqueous glucose solution (D40W), and the like. The amount of bicarbonate in the combined glucose and bicarbonate solution is about 1.5 milliequivalents per liter (mEq / L) to about 50 mEq / L. In some embodiments, the purge fluid solution may include a reduced amount of heparin along with the pH adjusting and buffering agents mentioned above. In some embodiments, a reduced concentration of heparin of about 12.5 units / mL or less is contemplated. In some embodiments, a reduced concentration of about 6.25 units / mL or less is also contemplated. In some embodiments, reduced concentrations ranging from about 1 unit / mL to about 6.25 units / mL are also contemplated.

[0055]

[0061] If a patient is heparin intolerant due to heparin-induced thrombocytopenia (HIT), but still requires the addition of an anticoagulant to the purge solution that combines pH adjustment and buffering agents with aqueous glucose, a direct thrombin inhibitor (DTI) may be added to the solution. If a DTI is added to the purge solution, the concentration of the DTI in the purge solution should be a dose equivalent of about 0.01 mg / kg / hour to about 0.012 mg / kg / hour. The dose equivalent is selected to provide a partial thromboplastin test (PTT) time of about 40 to 50 seconds. Non-limiting examples of suitable DTIs include, for example, lepirudin, desirudin, argatroban, bivalirudin, or mixtures thereof. The concentration of the DTI in the purge solution is about 20 mg / 500 mL to about 60 mg / 500 mL.

[0056]

[0062] Another solution previously proposed to mitigate pump performance challenges due to undesirable deposition / accumulation of biological material within the pump includes the use of an auxiliary purge fluid containing tissue plasminogen activator (tPA). See, e.g., Sorensen, E. et al., “Use of Tissue Plasminogen Activator to Resolve High Purge System Pressure in a Catheter-based Ventricular-assist Device,” The J. of Heart & Lung Transplantation, 33(4): 457-8 (Apr. 2014) (hereinafter “Sorensen”); Oetken H. et al., “Use of Tissue Plasminogen Activator Via Purge System in a Catheter-based Ventricular Assist Device,” Proceedings of the 48th Critical Care Congress, San Diego, CA (Feb. 17-20, 2019), Critical Care Medicine, Abstract No. 159 (Jan. 2019) (hereinafter “Oetken”). tPA is a protein involved in the breakdown of blood clots. tPA is a serine protease present in endothelial cells, the cells that line blood vessels. As an enzyme, tPA catalyzes the conversion of plasminogen to plasmin, the main enzyme responsible for clot breakdown. Sorensen discloses that in a patient with a blood pump inserted into the left ventricle, 2 mg of tPA diluted in 50 mL of saline was used in place of the heparinized purge solution when the purge pressure rose above 700 mmHg. This helped to resolve the high purge pressure. Oetken discloses that in a patient with a blood pump inserted into the heart, 4 mg of tPA diluted in 100 mL of 5% dextrose in sterile water was used in place of the heparinized purge solution when the purge pressure rose above 900 mmHg and the purge flow rate decreased to 1-3 mL / hr. This helped to resolve the high purge pressure and low purge flow rate.The Sorensen authors believe that tPA initiates local fibrinolysis by binding to fibrin in the clot and converting plasminogen to plasmin. The alternative to the timely use of tPA in Sorensen and Oetken would have been emergency surgery to replace the inserted blood pump with a new one.

[0057]

[0063] Sorensen and Oetken demonstrate that when biological material accumulation in the pump reduces the purge flow rate or increases the purge pressure compared to normal values, administration of tPA may help solve the problem. However, tPA must be administered in a timely manner to be effective. Currently, blood pump users must manually monitor the purge flow rate and / or purge pressure, and if they appear abnormal, the user must make a judgment call about when to administer tPA. However, the challenge is determining when to deliver tPA. If administration of tPA is delayed when the purge pressure is too high, the likelihood of purge recovery is reduced due to an insufficient concentration of tPA being delivered to the site of biological material accumulation or clot. The current procedure in which the user first obtains tPA and then replaces the purge fluid with a purge fluid containing tPA may also lead to undesirable delays in administration of tPA.

[0058]

[0064] The present disclosure provides a method and blood pump assembly that allows for controlled purge recovery in a timely and convenient manner. One aspect of the present disclosure relates to an automated process that monitors certain purge flow parameters that may indicate potential mechanical challenges of the pump motor due to biological material accumulation, and identifies the timely administration of tPA to maximize the likelihood of purge recovery. Another aspect of the present disclosure relates to a blood pump assembly for conveniently administering tPA without delay.

[0059]

[0065] Blood pump assembly 300 may include a blood pump 210 fluidly connected to a purging device 350. Blood pump assembly 300 also includes a controller 230 (e.g., an Automated Impella Controller® from Abiomed, Inc., Danvers, Mass.), a display 240, a connector cable 260, a plug 270, and a position conversion unit 280, all of which may be substituted for blood pump assembly 200 shown in FIG.

[0060]

[0066] The purge device 350 includes a purge fluid reservoir 351, a purge fluid supply line 352, a purge cassette 353, a purge disk 354, a purge tube 355, and a check valve 356, all of which may be substituted for the purge device 250 shown in FIG. 5. FIGS. 6 and 7 show an exemplary purge cassette 353 of one embodiment of the present disclosure. However, the purge cassette 353 also includes an auxiliary purge fluid reservoir 380, an auxiliary purge fluid supply line 385, a first purge path diverter 371, and a second purge path diverter 372. The reservoir 351 (similar to the reservoir 251 in FIG. 5) may be, for example, a bag or a bottle. The purge fluid is contained in the reservoir 251. The purge fluid supply line 352 provides a fluid connection between the reservoir 351 and the purge cassette 353. In some embodiments, a piston and cylinder 374 is used to drive the flow of purge fluid from the reservoir 351 through the purge fluid supply line 352 to the purge cassette 353. The purge cassette 353 controls how the purge fluid in the reservoir 351 is supplied to the blood pump 210 and the flow path of the purge fluid from the reservoir 351 to the blood pump 210. For example, the purge cassette 353 includes a first purge path diverter 371 and a second purge path diverter 372 (e.g., one or more valves) for controlling the pressure and / or flow rate of the purge fluid, as shown. Referring again to FIG. 5, the purge disk 254 includes one or more measurement devices, such as a pressure sensor (e.g., a pressure-sensing diaphragm) for measuring the purge pressure. The controller 230 is connected to the purge cassette 353 and the purge disk 254. The purge cassette 353 may include an actuator that is a rack and pinion attached to a piston. Purge disk 254 sends a pressure to controller 230 based on the purge pressure in purge tube 255. A sensor in controller 230 measures this pressure and can be displayed on screen 240. Controller 230 can include a stepper motor. A tick (or step) represents the position of the stepper motor in microsteps, also called a pulse.In some embodiments, the controller deploys a purge pressure / purge flow rate curve algorithm along with the number of steps per minute of the stepper motor and the pressure measurement by the purge disk 254 to calculate the corresponding purge flow rate.

[0061]

[0067] As shown, the purge tube 355 provides a fluid connection through the purge cassette 353 to the blood pump 210. The purge fluid enters the blood pump 210 through tube 373. In some embodiments, a Y-connector and / or a yellow luer connector is also provided. The Y-connector is an adapter that connects the purge tube 255 to the blood pump 210. The yellow luer connector connects the purge tube 255 to a check valve (yellow luer lock) of the blood pump 210. The pressure reservoir 257 provides additional fill volume during purge fluid exchange. In some embodiments, the pressure reservoir 257 includes a flexible rubber diaphragm that provides additional fill volume through an expansion chamber. The infusion filter 258 helps prevent bacterial contamination and air ingress into the catheter tube 217. A side arm 259 provides a fluid connection between the infusion filter 258 and the plug 270.

[0062]

[0068] In operation, as described above with respect to FIG. 5, the controller 230 receives measurements from the purge disk 254, controls the stepper motor ticks, and controls the purge pressure. In some embodiments, in operation, the purge cassette 253 is disposed in the controller 230 and is connected to the blood pump 210. As described above, the controller 230 controls and measures the purge pressure and calculates the purge flow rate through the purge cassette 253 and / or the purge disk 254. The controller 230 may also control the purge fluid supply. In operation, after exiting the purge device 350 through the side arm 259, the purge fluid is directed through the catheter tube 217 and a purge lumen (not shown) in the plug 270. The catheter tube 217, the connector cable 260, and the sensor cable (not shown) in the plug 270 provide electrical connections between the purge disk 254 and the controller 230. The catheter tube 217, connector cable 260, and a motor cable (not shown) in plug 270 provide an electrical connection between the motor in the motor housing 216 and the controller 230. In operation, the controller 230 receives measurements from the purge disk 254 via the sensor cable and controls the power supplied to the motor in the motor housing 216 via the motor cable.

[0063]

[0069] Prior to operation of the blood pump assembly, a predetermined threshold purge flow parameter is determined and programmed into the controller 230. The predetermined threshold purge flow parameter is such that when this value is met, a repair protocol is identified. In some embodiments, the predetermined threshold purge flow parameter is set by the blood pump manufacturer. In some embodiments, the predetermined threshold purge flow parameter is set by a user of the blood pump assembly, such as a clinician. In some embodiments, the predetermined threshold purge flow parameter is set by the blood pump manufacturer and the user of the blood pump assembly is prompted to approve or change the value of the predetermined threshold purge flow parameter prior to operation of the blood pump.

[0064]

[0070] The predetermined threshold purge flow parameter can be a predetermined threshold purge flow rate and / or a predetermined threshold purge pressure. In some embodiments, the predetermined threshold purge flow parameter is a predetermined threshold purge flow rate. During operation of the blood pump, the normal purge flow rate in the blood pump (i.e., when there are no pump performance issues due to accumulation of biological material in the blood pump) ranges from about 2 mL / hour to about 30 mL / hour, depending on the type of blood pump used. For example, for the Impella 5.5® (Abiomed, Inc., Danvers, MA), the normal purge flow rate in the blood pump typically ranges from about 2 mL / hour to about 10 mL / hour. However, when there is accumulation of biological material in the blood pump, the purge flow rate in the blood pump is reduced. In one example, the predetermined threshold purge flow rate is a reduction in the purge flow rate in the blood pump of at least 30% within 24 hours. Other examples are contemplated, including, but not limited to, a reduction in the purge flow rate in the blood pump of at least 35%, at least 40%, or at least 45% within 24 hours. In yet another example, the predetermined threshold purge flow rate in the blood pump is a reduction in the purge flow rate in the blood pump to less than 2 mL / hr within 24 hours. Other examples are contemplated including, but not limited to, a reduction in the purge flow rate in the blood pump to less than 3 mL / hr within 6 hours, 8 hours, 12 hours, 16 hours, 18 hours, or 24 hours.

[0065]

[0071] In some embodiments, the predetermined threshold purge flow parameter is a predetermined threshold purge pressure. During operation of the blood pump, normal purge pressure in the blood pump (i.e., when there are no pump performance issues due to accumulation of biological material in the blood pump) typically ranges from about 300 mmHg to about 1,000 mmHg. However, if there is accumulation of biological material in the blood pump, the purge pressure in the blood pump increases. In one example, the predetermined threshold purge pressure is an increase in the purge pressure in the blood pump of at least 30% within 24 hours. Other examples are contemplated, including, but not limited to, an increase in the purge pressure in the blood pump of at least 35%, at least 40%, or at least 45% within 24 hours. In yet another example, the predetermined threshold purge pressure in the blood pump is an increase in the purge pressure in the blood pump to greater than 700 mmHg within 24 hours. Other examples are contemplated, including, but not limited to, increasing the purge pressure in the blood pump to greater than 700 mmHg within 6, 8, 12, 16, or 18 hours.

[0066]

[0072] FIG. 6 shows the direction of flow of purge fluid through the purge device to the blood pump without accumulation of biological material in the blood pump. As described above, the controller 230 receives, calculates, and monitors purge flow parameters, such as purge pressure and / or purge flow rate, from the purge disk 254. When the controller 230 detects that the purge flow parameters have reached a predetermined threshold purge flow parameter, it identifies a repair protocol to a user of the blood pump assembly, such as a clinician. As shown in FIG. 8, a purge flow alarm can be at a flow rate approaching below 2 ml / hr or above 30 ml / hr. If the flow rate exceeds 30 ml / hr, the pump is shut off. In some embodiments, a display associated with the blood pump 210 (e.g., display 140) can be configured to display a repair protocol so that a clinician can respond appropriately. In some embodiments, the display can show an alert and optionally include a message such as "Consider administering tPA." As yet another example, the message can be replaced with a different type of information, such as an explanatory text. For example, a notification can function as an alert and include a text explaining the cause of the alert. As noted above, in some embodiments, the monitoring station may use cloud-based technology to reliably and remotely display at least a portion of the recommendations on a corresponding display (e.g., display 140). For example, the monitoring station may use an online device management system, such as Impella Connect® from Abiomed, Inc., Danvers, MA, to reliably and remotely display at least a portion of the recommendations.

[0067]

[0073] Upon receiving the repair protocol message, the user decides whether to initiate the repair protocol. In some embodiments, the user may check to see if there are kinks in one or more tubes of the blood pump and purging device that may have caused line pressure or biological material accumulation that may have caused the purge flow parameter to reach a predetermined threshold purge flow parameter. In one embodiment, the user may perform the check before initiating the repair protocol. Once it is detected that there are no kinks in one or more tubes of the blood pump and purging device, the user may initiate the repair protocol. For example, the user may press a button on a display (e.g., display 140) that initiates the repair protocol.

[0068]

[0074] The repair protocol helps resolve the purging challenge and allows for controlled purging of the blood pump. The controller 230 stops the flow of purge fluid through the purge tube 355 to the blood pump 201 and diverts the flow of purge fluid to the blood pump 210 via the auxiliary reservoir 380. The controller 230 performs the diversion step by operating the first purge path diverter 371 to divert the flow of purge fluid (e.g., glucose solution) in the purge cassette 353 to the auxiliary purge line 385 and the auxiliary reservoir 380 where the purge fluid combines with the auxiliary purge additive (e.g., tPA) to form the auxiliary purge fluid. The amount of purge fluid entering the auxiliary reservoir 380 can be controlled such that the amount of tPA delivered to the blood pump 201 is regulated. Auxiliary purge fluid (e.g., carrying tPA) flows from an auxiliary reservoir 380 through an auxiliary purge fluid supply line 385 via a second purge path diverter 372 and tubing 373 to the blood pump 210. In some embodiments, the blood pump 210 includes a motor portion and a pump portion, and the purge fluid and auxiliary purge fluid are supplied to the motor portion. In some embodiments, the auxiliary purge fluid is degassed before being supplied to the blood pump. FIG. 7 illustrates the auxiliary purge fluid flow path described above, which is implemented only if the user decides to proceed with a repair protocol.

[0069]

[0075] In some embodiments, the auxiliary purge fluid includes tPA and glucose. The tPA is preferably freeze-dried before being mixed with the purge fluid. The freeze-dried tPA retains its activity for a significant amount of time, so the purge cassette 353 does not need to be used immediately after manufacture. In some embodiments, the glucose solution passes through the purge fluid supply line 352 to the auxiliary purge fluid supply line 385 and into the auxiliary reservoir 380, where it dissolves the freeze-dried tPA. For example, 4 mg of tPA can be dissolved in 100 mL of 5% glucose solution in water. The concentration of tPA in the auxiliary purge fluid is 2 mg / 50 mL to 4 mg / 50 mL. In some embodiments, the concentration of tPA in the auxiliary purge fluid is 2 mg / 50 mL. An upper limit for the concentration of the auxiliary purge fluid can also be set prior to operation of the blood pump. For example, the controller can be programmed to monitor the concentration of the auxiliary purge fluid, which is determined by the amount of material and the volume of the auxiliary reservoir. In some embodiments, when the concentration of the auxiliary purge fluid reaches a predetermined threshold, the controller may automatically stop the flow of the auxiliary purge fluid to the blood pump or may identify a fix to the user to stop the flow of the auxiliary purge fluid to the blood pump.

[0070]

[0076] Just like with the purge fluid, the controller 230 receives, calculates, and monitors auxiliary purge flow parameters, such as the pressure and / or flow rate of the auxiliary purge fluid in the blood pump, from the purge disk 254. If the controller 230 determines that the auxiliary purge flow parameters are below (in the case of purge flow rate) or above (in the case of purge pressure) a predetermined threshold purge flow parameter, in some embodiments, the controller 230 automatically stops the flow of auxiliary purge fluid from the auxiliary reservoir 380 to the blood pump 210 and resumes the normal flow of purge fluid from the purge cassette 353 to the blood pump 210 (i.e., the purge fluid path shown in FIG. 6 and described above before the repair protocol was implemented). In some other embodiments, instead of automatically stopping the flow of auxiliary purge fluid to the blood pump 210, the controller 230 identifies a recommended protocol for the user to initiate stopping the flow of auxiliary purge fluid to the blood pump 210. If the user decides to proceed with the recommendations, the controller 230 stops the flow of auxiliary purge fluid to the blood pump 210 and resumes the flow of normal purge fluid from the purge cassette 353 to the blood pump 210 .

[0071]

[0077] The controller 230 resumes normal purge fluid flow from the purge cassette 353 to the blood pump 210 by operating the first purge path diverter 371 and the second purge path diverter 372 to restore the flow of purge fluid through the purge tube 355. The direction of purge fluid flow to the blood pump 210 is as shown in FIG. 6. In some embodiments, the flow of the auxiliary purge fluid is stopped and the normal flow of purge fluid is resumed when the controller 230 determines that the auxiliary purge flow parameter in the blood pump exceeds the predetermined threshold purge flow parameter. In some embodiments, the flow of the auxiliary purge fluid is stopped and the normal flow of purge fluid is resumed when the controller 230 determines that the auxiliary purge flow parameter in the blood pump exceeds the predetermined threshold purge flow parameter by a predetermined amount, for example, at least 30% in 24 hours or at least 20% in 12 hours.

[0072]

[0078] In other embodiments, the flow of auxiliary purge fluid is stopped and the flow of purge fluid is resumed when the controller 230 determines that the auxiliary purge flow parameter at the blood pump 210 falls below a predetermined threshold purge flow parameter. In some embodiments, the flow of auxiliary purge fluid is stopped and the flow of purge fluid is resumed when the controller 230 determines that the auxiliary purge flow parameter at the blood pump 210 falls below the predetermined threshold purge flow parameter by a predetermined amount, for example, at least 30% in 24 hours or at least 20% in 12 hours. As mentioned above, if the flow rate rises above a threshold, for example, 30 ml / hr, the pump is deemed the cause of the problem and the pump may be replaced.

[0073]

[0079] In some embodiments, the purge fluid comprises aqueous dextrose. In some embodiments, the purge fluid further comprises an anticoagulant, a pH adjusting and buffering agent, or a combination thereof. In some embodiments, the anticoagulant is warfarin, coumarin, heparin, or a direct thrombin inhibitor. In some embodiments, the anticoagulant is heparin. In some embodiments, the direct thrombin inhibitor is lepirudin, desirudin, argatroban, bivalirudin, or a mixture thereof. In some embodiments, the pH adjusting and buffering agent is sodium bicarbonate, sodium citrate, sodium lactate, sodium gluconate, sodium acetate, or sodium pyruvate. In some embodiments, the pH adjusting and buffering agent is sodium bicarbonate.

[0074]

[0080] In some embodiments, the purge fluid also contains no heparin or a reduced amount of heparin. The amount of heparin in the purge fluid is about 0 to about 12.5 units / milliliter. In some embodiments, the amount of heparin in the purge fluid is about 0 to about 6.25 units / milliliter. In some embodiments, the amount of heparin in the purge fluid is about 1 unit / milliliter to about 6.25 units / milliliter.

[0075]

[0081] As noted above, the absence of heparin in the purge fluid (e.g., 5% dextrose only or 5% dextrose with DTI, etc.) or the presence of reduced concentrations of heparin in the purge fluid increases the likelihood of biological material accumulating in the blood pump motor, increasing purge pressure and motor current while decreasing purge flow rate, resulting in mechanical damage to the blood pump. The disclosed method and blood pump assembly allows for controlled purge recovery by monitoring purge flow parameters, such as purge flow rate and / or purge pressure, during operation of the blood pump and identifying a repair protocol for the user when a predefined threshold purge flow parameter is met. Administration of a supplemental purge fluid, such as a purge fluid containing tPA, dissolves the accumulation of biological material in the blood pump motor, thus resolving the high purge pressure and / or low purge flow rate, allowing the pump to operate as intended. As noted above, the timing of administration of tPA is important for it to be effective by reaching the affected area in the required concentration in a timely manner. By automating both the monitoring of conditions when intervention with tPA may be necessary and the identification of recommendations for initiating such intervention, a user, such as a clinician, is provided with the opportunity to intervene in a timely manner and appropriately mitigate the problem. Additionally, the modifications to the purge device disclosed herein provide a user with a quick and easy technique for replacing the purge fluid with a supplemental purge fluid, such as a purge fluid containing tPA, without undue delay.

[0076]

[0082] In one aspect, a method of purging a blood pump is described that includes: i) providing a blood pump in fluid communication with a purge device, the purge device including a purge reservoir fluidly connected to the blood pump and configured to contain a purge fluid, and an auxiliary reservoir fluidly connected to the blood pump and configured to contain an auxiliary purge fluid; ii) inserting at least a portion of the blood pump into a patient; iii) operating the blood pump; iv) providing a flow of purge fluid from the purge reservoir to the blood pump; v) measuring a purge flow parameter at the blood pump with a measurement device; and vi) identifying a repair protocol when a controller determines that the purge flow parameter at the blood pump meets a predetermined threshold purge flow parameter.

[0077]

[0083] In one aspect, the repair protocol includes: i) stopping the flow of purge fluid from the purge reservoir to the blood pump; ii) starting the flow of auxiliary purge fluid from the auxiliary reservoir to the blood pump; iii) measuring an auxiliary purge flow parameter at the blood pump with a measurement device; and iv) stopping the flow of auxiliary purge fluid from the auxiliary reservoir to the blood pump and resuming the flow of purge fluid from the purge reservoir to the blood pump when the controller determines that the auxiliary purge flow parameter at the blood pump has fallen below or exceeded a predetermined threshold purge flow parameter indicating that auxiliary purge fluid is no longer needed.

[0078]

[0084] In any of the above aspects, the flow of auxiliary purge fluid is stopped and the flow of purge fluid is resumed when the controller determines that the auxiliary purge flow parameter in the blood pump exceeds a predetermined threshold purge flow parameter.

[0079]

[0085] In any of the above aspects, the flow of auxiliary purge fluid is stopped and the flow of purge fluid is resumed when the controller determines that the auxiliary purge flow parameter in the blood pump exceeds a predetermined threshold purge flow parameter by a predetermined amount, the predetermined amount being at least 30% for 24 hours or at least 20% for 12 hours.

[0080]

[0086] In any of the above aspects, the purge flow parameter is a purge flow rate and the predetermined threshold purge flow parameter is a decrease in the purge flow rate by a predetermined amount, the predetermined amount being at least 30% within 24 hours or at least 20% within 12 hours.

[0081]

[0087] In any of the above embodiments, the purge flow parameter is a purge flow rate and the predetermined threshold purge flow parameter is a decrease in purge flow rate of less than 3 mL / hr within 6 hours.

[0082]

[0088] In any of the above embodiments, the purge flow parameter is purge pressure and the predetermined threshold purge flow parameter is a predetermined amount of increase in purge pressure, the predetermined amount being at least 30% within 24 hours or at least 20% within 12 hours.

[0083]

[0089] In any of the above embodiments, the purge flow parameter is purge pressure and the predetermined threshold purge flow parameter is an increase in purge pressure of more than 700 mmHg within a 24 hour period.

[0084]

[0090] In any of the above aspects, the method further includes degassing the auxiliary purge fluid prior to supplying the auxiliary purge fluid to the blood pump.

[0085]

[0091] In any of the above aspects, the method further includes detecting the absence of kinks in one or more tubes of the blood pump and the purging device.

[0086]

[0092] In any of the above aspects, the purge fluid comprises aqueous glucose.

[0087]

[0093] In any of the above embodiments, the purge fluid further comprises an anticoagulant, a pH adjusting and buffering agent, or a combination thereof.

[0088]

[0094] In any of the above aspects, the anticoagulant is warfarin, coumarin, heparin, or a direct thrombin inhibitor.

[0089]

[0095] In any of the above aspects, the anticoagulant is heparin.

[0090]

[0096] In any of the above embodiments, the direct thrombin inhibitor is lepirudin, desirudin, argatroban, bivalirudin, or a mixture thereof.

[0091]

[0097] In any of the above embodiments, the pH adjusting and buffering agent is sodium bicarbonate, sodium citrate, sodium lactate, sodium gluconate, sodium acetate, or sodium pyruvate.

[0092]

[0098] In any of the above embodiments, the pH adjusting and buffering agent is sodium bicarbonate.

[0093]

[0099] In any of the above embodiments, the supplemental purge fluid comprises tissue plasminogen activator (tPA).

[0094]

[0100] In any of the above aspects, the supplemental purge fluid further comprises glucose.

[0095]

[0101] In any of the above embodiments, the tPA is lyophilized tPA.

[0096]

[0102] In any of the above embodiments, the concentration of tPA is 2 mg / 50 mL to 4 mg / 50 mL.

[0097]

[0103] In any of the above aspects, the blood pump includes a motor portion and a pump portion, and the purge fluid and the auxiliary purge fluid are supplied to the motor portion.

[0098]

[0104] In another aspect, a blood pump assembly is described that includes: i) a blood pump; ii) a purge device in fluid communication with the blood pump, the purge device including a purge reservoir fluidly connected to the blood pump and configured to contain a purge fluid, and an auxiliary reservoir fluidly connected to the blood pump and configured to contain an auxiliary purge fluid; iii) a measurement device configured to measure a purge flow parameter in the blood pump; and iv) a controller configured to monitor the purge flow parameter in the blood pump and identify a repair protocol upon determining that the purge flow parameter in the blood pump meets a predetermined threshold purge flow parameter.

[0099]

[0105] In another aspect, the controller is further configured to implement the repair protocol by controlling the purge device to i) stop the flow of purge fluid from the purge reservoir to the blood pump and start the flow of auxiliary purge fluid from the auxiliary reservoir to the blood pump, ii) measure an auxiliary purge flow parameter at the blood pump with the measuring device, and iii) stop the flow of auxiliary purge fluid from the auxiliary reservoir to the blood pump and resume the flow of purge fluid from the purge reservoir to the blood pump when it is determined that the auxiliary purge flow parameter at the blood pump has fallen below or exceeded a predetermined threshold purge flow parameter indicating that auxiliary purge fluid is no longer needed.

[0100]

[0106] In any of the above alternative aspects, the flow of auxiliary purge fluid is stopped and the flow of purge fluid is resumed when the controller determines that the auxiliary purge flow parameter in the blood pump exceeds a predetermined threshold purge flow parameter.

[0101]

[0107] In any of the above alternative aspects, when the controller determines that the auxiliary purge flow parameter in the blood pump exceeds a predetermined threshold purge flow parameter by a predetermined amount, the flow of auxiliary purge fluid is stopped and the flow of purge fluid is resumed, the predetermined amount being at least 30% in 24 hours or at least 20% in 12 hours.

[0102]

[0108] In any of the above alternative embodiments, the purge flow parameter is a purge flow rate and the predetermined threshold purge flow parameter is a decrease in the purge flow parameter by a predetermined amount, the predetermined amount being at least 30% within 24 hours or at least 20% within 12 hours.

[0103]

[0109] In any of the above alternative embodiments, the purge flow parameter is purge pressure and the predetermined threshold purge flow parameter is a predetermined amount of increase in purge pressure, the predetermined amount being at least 30% within 24 hours or at least 20% within 12 hours.

[0104]

[0110] In any of the above alternative aspects, the purge device further includes i) a purge fluid supply line fluidly connecting the purge reservoir to the blood pump, and ii) an auxiliary purge fluid supply line fluidly connecting the auxiliary reservoir to the purge fluid supply line.

[0105]

[0111] In any of the above alternative embodiments, the purge fluid comprises aqueous glucose.

[0106]

[0112] In any of the above alternative embodiments, the purge fluid further comprises an anticoagulant, a pH adjusting and buffering agent, or a combination thereof.

[0107]

[0113] In any of the above alternative embodiments, the anticoagulant is warfarin, coumarin, heparin, or a direct thrombin inhibitor.

[0108]

[0114] In any of the above alternative embodiments, the anticoagulant is heparin.

[0109]

[0115] In any of the above alternative embodiments, the direct thrombin inhibitor is lepirudin, desirudin, argatroban, bivalirudin, or a mixture thereof.

[0110]

[0116] In any of the above alternative embodiments, the pH adjusting and buffering agent is sodium bicarbonate, sodium citrate, sodium lactate, sodium gluconate, sodium acetate, or sodium pyruvate.

[0111]

[0117] In any of the above alternative embodiments, the pH adjusting and buffering agent is sodium bicarbonate.

[0112]

[0118] In any of the above alternative embodiments, the supplemental purge fluid comprises tissue plasminogen activator (tPA).

[0113]

[0119] In any of the above alternative aspects, the supplemental purge fluid further comprises glucose.

[0114]

[0120] In any of the above alternative embodiments, the tPA is lyophilized tPA.

[0115]

[0121] In any of the above other embodiments, the concentration of tPA is 2 mg / 50 mL to 4 mg / 50 mL.

[0116]

[0122] In any of the above alternative aspects, the blood pump includes a motor portion and a pump portion, and the purge fluid and the auxiliary purge fluid are supplied to the motor portion.

[0117]

[0123] In this specification, the word "comprising" is to be understood in its "open" meaning, i.e. "including", and therefore not limited to its "closed" meaning, i.e. "consisting only of". Where the corresponding words "comprise", "comprised" and "comprises" appear, the corresponding meanings are to be given.

[0118]

[0124] Although specific implementations of the present 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. Furthermore, it will be understood that reference herein to subject matter well known in the art is not an admission that such subject matter is generally known to those skilled in the art to which the present technology pertains, unless otherwise indicated to the contrary.

Claims

1. A blood pump and a purge device in fluid communication with the blood pump, the purge device comprising: a purge reservoir fluidly connected to the blood pump and configured to contain a purge fluid; an auxiliary reservoir fluidly connected to the blood pump and configured to contain an auxiliary purge fluid; a purge device including: a measuring device configured to measure a purge flow parameter in the blood pump; a controller, monitoring the purge flow parameters in the blood pump; Identifying a repair protocol upon determining that the purge flow parameters in the blood pump meet a predetermined threshold purge flow parameter. a controller configured to: A blood pump assembly comprising:

2. The controller further controls the purge device. stopping the flow of the purge fluid from the purge reservoir to the blood pump and starting the flow of the auxiliary purge fluid from the auxiliary reservoir to the blood pump; measuring an auxiliary purge flow parameter in the blood pump with the measuring device; stopping the flow of the auxiliary purge fluid from the auxiliary reservoir to the blood pump and resuming the flow of the purge fluid from the purge reservoir to the blood pump when it is determined that the auxiliary purge flow parameter at the blood pump has fallen below or exceeded the predetermined threshold purge flow parameter, indicating that the auxiliary purge fluid is no longer needed. and configured to implement the repair protocol by controlling the 10. The blood pump assembly of claim 1.

3. 3. The blood pump assembly of claim 2, wherein the flow of the auxiliary purge fluid is stopped and the flow of the purge fluid is resumed when the controller determines that the auxiliary purge flow parameter in the blood pump exceeds the predetermined threshold purge flow parameter.

4. 4. The blood pump assembly of claim 2, wherein the flow of the auxiliary purge fluid is stopped and the flow of the purge fluid is resumed when the controller determines that the auxiliary purge flow parameter in the blood pump exceeds the predetermined threshold purge flow parameter by a predetermined amount, the predetermined amount being at least 30% in 24 hours or at least 20% in 12 hours.

5. 4. The blood pump assembly of claim 2, wherein the purge flow parameter is a purge flow rate and the predetermined threshold purge flow parameter is a decrease in the purge flow parameter by a predetermined amount, the predetermined amount being at least 30% within 24 hours or at least 20% within 12 hours.

6. 4. The blood pump assembly of claim 2, wherein the purge flow parameter is a purge pressure and the predetermined threshold purge flow parameter is a predetermined amount increase in the purge pressure, the predetermined amount being at least 30% within 24 hours or at least 20% within 12 hours.

7. The purge device comprises: a purge fluid supply line fluidly connecting the purge reservoir to the blood pump; an auxiliary purge fluid supply line fluidly connecting the auxiliary reservoir to the purge fluid supply line; The blood pump assembly of claim 2 or 3, further comprising:

8. 4. The blood pump assembly of claim 2, wherein the purge fluid comprises aqueous glucose.

9. The blood pump assembly of claim 8 , wherein the purge fluid further comprises an anticoagulant, a pH adjusting and buffering agent, or a combination thereof.

10. 10. The blood pump assembly of claim 9, wherein the anticoagulant is warfarin, coumarin, heparin, or a direct thrombin inhibitor.

11. The blood pump assembly of claim 10, wherein the anticoagulant is heparin.

12. 11. The blood pump assembly of claim 10, wherein the direct thrombin inhibitor is lepirudin, desirudin, argatroban, bivalirudin, or a mixture thereof.

13. 11. The blood pump assembly of claim 10, wherein the pH adjusting and buffering agent is sodium bicarbonate, sodium citrate, sodium lactate, sodium gluconate, sodium acetate, or sodium pyruvate.

14. 14. The blood pump assembly of claim 13, wherein the pH adjusting and buffering agent is sodium bicarbonate.

15. 4. The blood pump assembly of claim 2, wherein the auxiliary purge fluid comprises tissue plasminogen activator (tPA).

16. The blood pump assembly of claim 15, wherein the auxiliary purge fluid further comprises glucose.

17. 16. The blood pump assembly of claim 15, wherein the tPA is lyophilized tPA.

18. 16. The blood pump assembly of claim 15, wherein the concentration of tPA is 2 mg / 50 mL to 4 mg / 50 mL.

19. 4. The blood pump assembly of claim 2, wherein the blood pump includes a motor portion and a pump portion, and the purge fluid and the auxiliary purge fluid are supplied to the motor portion.

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