WO2009012492A1

WO2009012492A1 - Shape memory polymer hemodialysis needle adapter

Info

Publication number: WO2009012492A1
Application number: PCT/US2008/070646
Authority: WO
Inventors: Jason M. Ortega; Anthony J. Makarewicz; James E. Trebes; Duncan J. Maitland; William J. Benett; Iv Ward Small; Thomas S. Wilson; Jennifer N. Rodriguez; Patrick R. Buckley
Original assignee: Lawrence Livermore National Security, Llc
Priority date: 2007-07-19
Filing date: 2008-07-21
Publication date: 2009-01-22

Abstract

A deployable, shape memory polymer (SMP) hemodialysis adapter for reducing the hemodynamic stress caused by dialysis needle flow impingement within an arteriovenous graft. The SMP adapter has a unibody tubular construction with a radially expandable portion that is expandable in situ via either electromagnetic or thermal energy. In the expanded state, the SMP adapter geometry is changed, such as into a flared funnel shape, to control exit flow velocity.

Description

SHAPE MEMORY POLYMER HEMODIALYSIS NEEDLE ADAPTER

I. CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of provisional Application No. 60/961,560 filed July 19, 2007, incorporated by reference herein.

II. FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] The United States Government has rights in this invention pursuant to Contract No. DE-AC52-07NA27344 between the United States Department of Energy and Lawrence Livermore National Security, LLC for the operation of Lawrence Livermore National Laboratory.

III. FIELD OF THE INVENTION

[0003] The present invention relates to dialysis needles, cannulas, and catheters and more particularly to a shape memory polymer (SMP) expandable cannula, needle adapter, and improved dialysis needle, for controlling the turbulence of fluid flow out from a needle and into an arteriovenous (AV) body, such as a polytetrafluoroethylene (PTFE) graft, and for reducing the hemodynamic stresses on the arteriovenous body.

IV. BACKGROUND OF THE INVENTION

[0004] Each year in the United States alone, over two-hundred thousand end stage renal disease patients receive PTFE grafts for use in hemodialysis. However, vascular access complications resulting from AV graft failures are one of the most challenging and costly aspects in the care of these patients. For example, vascular access complications resulting from PTFE graft failure account for over 20% of hospitalizations and consume more than 10% of the total cost of health care of dialysis patients in the US, or about $1.5 billion per year. [0005] The primary mode of failure of arteriovenous fistulas (AVF' s) and PTFE grafts is the development of intimal hyperplasia (IH) and the subsequent formation of stenotic lesions, resulting in a graft flow decline. When the flow falls below about 600 mL/min, the risk of thrombosis increases dramatically and the graft can no longer be used for hemodialysis treatment. [0006] Hemodynamic stresses arising within AVF's and PTFE grafts play an important role in the pathogenesis of IH. Studies have shown that vascular damage and/ or graft failure can occur in regions of hemodynamic turbulence from arteriovenous needle flow by producing extreme values of wall shear stress (WSS). For example, in "Turbulent floxv evaluation of the arteriovenous needle during hemodialysis," by S. Unnikrishnan et al. (Journal of Biomechanical Engineering, vol. 127, no. 7, 1141-1146, 2005), flow visualization and laser Doppler velocimetry was used to show that the arteriovenous needle flow behaves like a turbulent jet co-flowing with the AV blood flow, and that the disparity in velocities between jet and the graft flow causes hemodynamic instabilities to occur and subsequent high frequency flow unsteadiness. In particular, Unnikrishnan et al. found that turbulence intensities are 5-6 times greater in the AV graft when arteriovenous needle flow was present and that increased levels of turbulence exist for approximately 7-8 cm downstream of the needle. Figures 1 and 2 illustrate the turbulence 13 created by jet impingement from a needle 11 in a PTFE graft 12. Since the AV or PTFE graft is exposed to these high levels of turbulence and hemodynamic stress several hours each week during dialysis sessions, it is quite possible that turbulent arteriovenous needle flow is an important contributor to lesion formation and vascular access occlusion. Furthermore, in "Physical effects in red blood cell trauma," by C. G. Nevaril et al (Am. Inst. Chem. Eng. ]., vol. 15, pp. 707-11, 1969), it was shown that exposure of red blood cells to WSS' s on the order of 1500 dynes/ cm² can result in hemolysis.

[0007] In U.S. patent publication No. 2005/0107817 to White et al, a dynamic cannula is disclosed capable of expanding to a larger diameter at an outlet end so as to reduce turbulence in the vessel. The dynamic cannula has a two component construction, with the first component being a tube-shaped wire structure that is capable of expansion/ contraction due to the interlocking/ interwoven construction; and the second component being an optional cover or coating which may be selectively or partially permeable. In one embodiment, reversible radial expansion and contraction memory properties are conferred by the wire structure, and a silicone covering dictates the final expanded diameter and the rate of force of expansion.

[0008] There is therefore a need for a dialysis needle adapter and cannula having a simpler one piece (unibody) construction, that has the advantages of shape memory expansion and contraction for use especially in hemodialysis applications to reduce and or minimize WSS, turbulence, and graft damage and failure,

V. SUMMARY OF THE INVENTION

[0009] One aspect of the present invention includes an expandable cannula comprising: a shape memory polymer unibody tube having a proximal end, a distal end, and at least a portion of its length that is radially expandable in situ. [0010] Another aspect of the present invention includes an arteriovenous needle adapter comprising: an expandable cannula capable of being retractably extended from the needle, and having a shape memory polymer unibody tube construction with a proximal end, a distal end, and at least a portion of its length that is radially expandable in situ. [0011] And another aspect of the present invention includes an improved dialysis needle for injecting fluid into an arteriovenous body with reduced flow turbulence and wall shear stress on the arteriovenous body, said improvement comprising: an elongated catheter tube extending through the needle and having a leading end section with a radially expandable portion thereof that is capable of being retractably extended from the needle, said radially expandable portion of the leading end section having a shape memory polymer unibody tube construction that is radially expandable in situ.

VI. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The accompanying drawings, which are incorporated into and form a part of the disclosure, are as follows:

[0013] Figure 1 shows a schematic perspective view of turbulent jet flow from a conventional dialysis arteriovenous needle.

[0014] Figure 2 shows a computer simulation of the turbulent jet flow (shown as time averaged velocity streamlines) from the conventional dialysis arteriovenous needle of Figure 1.

[0015] Figure 3 shows a side schematic view of an exemplary embodiment of the present invention, shown with the radially expandable portion in the contracted stated.

[0016] Figure 4 shows a schematic side view of the exemplary embodiment of Figure 3, shown with the radially expandable portion in the expanded state. [0017] Figure 5 shows a schematic perspective view of the exemplary embodiment of Figure 4, shown with the radially expandable portion in the expanded state so that the increased cross-sectional area of the adapter results in a reduction of the exit blood velocity and turbulence production. [0018] Figure 6 shows a computer simulation of the substantially laminar jet flow (shown as time averaged velocity streamlines) from the exemplary embodiment of Figure 5.

[0019] Figure 7 shows another exemplary embodiment of the present invention constructed of porous SMP material which provides the permeability and outflow in both transverse and longitudinal directions.

[0020] Figure 8 shows another exemplary embodiment of the present invention having perforations which provide the permeability and outflow in both transverse and longitudinal directions.

[0021] Figure 9 shows another exemplary embodiment of the present invention having a radially expandable section between non-expandable narrower sections, for delivering blood to the AV graft in both a radial and an axial manner. [0022] Figure 10 shows another exemplary embodiment of the present invention with pleats for device compaction and expansion, and a mesh at the distal end. [0023] Figure 11 shows another exemplary embodiment of the present invention with perforations on the radially expandable portion that are elongated, longitudinally oriented, open slots.

VIL DETAILED DESCRIPTION

[0024] Generally, the present invention pertains to an expandable cannula alone, as used as an arteriovenous needle adapter, and as used as part of an improved dialysis needle, and having a deployable shape memory polymer unibody tube to tailor the fluid dynamics of the arteriovenous needle flow as it enters into the AV graft, for substantially reducing needle turbulence and hemodynamic stress in an AV graft. Because the present invention utilizes expandable SMP material to adapt to existing graft flow conditions, the present invention is hereinafter referenced as "SMP adapter." In particular, the SMP adapter has a radially expandable portion made of SMP material that is deployed (extended/ retracted) through the arteriovenous needle into the graft, after which the radially expandable portion of the SMP adapter is caused to expand into the expanded shape using electromagnetic or thermal energy. When the dialysis session is completed, the radially expandable portion of the SMP adapter is retracted through the needle. In one embodiment, the SMP adapter has a funnel shape when in the radially expanded state, with a distal end (i.e. tip end) having a larger cross-sectional area than that of the needle. And in another embodiment, the radially expandable portion is permeable, such as by using a porous wall material, or having perforations on the wall. Generally, however, the radially expandable portion of the cannula (as well as the SMP adapter) has a unibody tube construction, i.e. it is made from a single monolithic piece that is not interwoven from multiple pieces, or otherwise assembled from multiple pieces to enable the expansion/ contraction capability. It is appreciated that the term "cannula" refers to a tube which can be inserted into the body, for delivery or removal of fluid. And it is appreciated that the term "permeable" refers to having pores or other openings, such as perforations, that permit fluids to pass through.

[0025] Expansion of the radially expandable portion of the SMP adapter may be performed in situ by various methods including electromagnetic energy or thermal energy. For example, optical energy may be delivered (e.g. up to 8W of power) through a diffusing fiber element inserted down the center of the adapter so as to generate thermal energy. Using a SMP with a lower glass transition temperature (Tg) will reduce the amount of thermal energy needed to achieve actuation and, hence, reduce the risk of thermal damage. In the alternative, if the Tg is lowered to near body temperature (-37⁰C), the need for external energy delivery may be eliminated. In this case, when the SMP adapter is deployed through the dialysis needle and warmed by the vascular access blood flow, it will expand to its primary shape. Because the modulus of elasticity of the SMP remains relatively low when the SMP temperature is near Tg, the adapter can easily be retracted through the needle when the dialysis session is completed. (0026) Turning now to the drawings, Figures 3-6 show a first exemplary embodiment of the SMP adapter, having an expandable cannula 20 capable of extending/ retracting from an arteriovenous needle 11, and shown inserted in a graft 12. Direction of blood flow is shown by arrows at the graft inlet. Figure 3 in particular shows the radially expandable portion of the cannula in a non- expanded (contracted) state 20, while Figure 4 shows the radially expandable portion of the cannula in an expanded state 20'. As can be seen in Figure 4, the expanded cannula has a flared, funnel shape of a flared diffuser. In particular, the diameter of the expanded cannula increases toward the distal end, such that the distal end of the cannula has a larger cross-sectional area than that of the arteriovenous needle 11. With this increase in cross-sectional area, the blood velocity flowing through the adapter is proportionately reduced, minimizing the disparity in velocities between the graft flow and the SMP adapter outflow. It is appreciated that the expandable cannula may also be characterized as being part of a catheter which extends through the needle. In particular, the radially expandable portion of the SMP adapter may be characterized as being a part of a leading end section of the catheter, and the distal end of the cannula may be characterized as the tip end of the leading end section of the catheter. And Figures 5 and 6 show the substantially laminar flow produced by the larger cross-section of the opening at the distal end. And while not shown in the drawings, the open distal end of the SMP adapter may also have a permeable SMP plug (such as an SMP foam plug) connected to it in order to eliminate any velocity gradients within the arteriovenous needle flow as it enters into the AV graft.

[0027] Figure 7 shows an exemplary embodiment of the SMP adapter 30 that may be used as an alternative to a permeable SMP plug at the open distal end. In this embodiment, the distal end (and tip end) is closed (shown with a hemispherical cap), and the entire unibody cannula (and leading end section) of the SMP adapter is constructed of expandable SMP foam and therefore operates as the radially expandable portion. As such, blood may flow both in the transverse as well as longitudinal directions out from the SMP adapter. And Figure 8 shows a similar unibody tube construction of the SMP adapter 40 as that shown in Figure 7, but having perforations along the sides as well as at the closed distal end which enable outflow in both transverse and longitudinal directions.

[0028] Another embodiment of the SMP dialysis needle adapter 50 is shown in Figure 9, where the radially expandable portion docs not include the distal end (i.e. tip end). As such, in the expanded stated shown, the radially expanded portion forms a radially wider section between two radially narrower sections. As the blood enters the wider section from the upstream narrower section, the wider section fills with blood due to the back pressure provided by the subsequent re-narrowing of the SMP adapter at the downstream narrower section, and the velocity decreases in the wider section relative to the upstream narrower section. Pores, perforations or other openings in the wall of the wider section allow some blood to escape in a transverse direction into the AV graft. The remainder of the blood will exit from the downstream narrower section and the distal end, where the velocity is also reduced due to the reduced blood volume relative to the upstream narrow section. Lengths and diameters of the wider section and the two narrower sections, and pore size/ distribution in the wider section can be chosen to achieve the most desirable flow characteristics. [0029] And in Figure 10, another embodiment of the SMP adapter 60 is shown having pleats for the radially expandable portion (i.e. shown as the flared portion), which allows the SMP adapter to be more easily retracted back into the dialysis needle. Furthermore, a mesh is also shown located at the distal end to close the distal end but also to smooth the outflow as it enters the AV graft. [0030] And Figure 11 shows another exemplary embodiment of the SMP adapter 70, and having perforations that are in the form of elongated, longitudinally directed open slots 71, which may improve transverse fluid flow dynamics out to the AV graft.

Example Fabrication

[0031] The following is an illustrative example construction and fabrication method of the SMP adapter of the present invention. In this example, fabrication begins by dipcoating a solution of MM-5520 SMP (available from DiAPLEX Company, Ltd., a subsidiary of Mitsubishi Heavy Industries Ltd.) about an aluminum mandrel, which defines the inner surface of the adapter shape. Depending on the coating number, the SMP is dried at 50⁰C under nitrogen for 15 to 60 min. The mandrel and SMP coating are then vacuum dried for 24 hours at 50⁰C. To release the adapter from the mandrel, the entire assembly is immersed in acetone, which plasticizes and swells the soft phase of the SMP. The adapter is then vacuum dried at 50⁰C and 1 Torr for 24 hours. The resulting glass transition temperature, Tg, and wall thickness of the SMP adapter are 75°C and approximately 0.015-0.025 cm, respectively. Using UV-cured epoxy (such as EPO-TEK OG603, available from Epoxy Technology, Inc.), the SMP adapter is bonded to a 3F catheter (such as Fastracker - 18MX, available from Target Therapeutics, Inc.), which is attached to a syringe pump (such as model PHD 2000, available from Harvard Apparatus) that simulates the blood flow from a dialysis machine. The SMP adapter is compressed using a balloon wrapping/ stent crimping machine (Interface Associates) from an initial maximum diameter of 0.27cm to 015 cm, allowing the adapter to fit through the dialysis needle (such as available from Medisy stems).

[0032] Furthermore, in order to facilitate directing the flow in the downstream direction, a longer SMP adapter may be cast about a mandrel that has an inherently curved shape. Given the ease of machining and molding the SMP material, this and other modifications can readily be incorporated into alternate adapter designs.

Computer Simulation

[0033] Computational fluid dynamics (CFD) simulations were performed by Applicants at the Lawrence Livermore National Laboratory to assess the changes in the hemodynamic stress on a graft wall when the SMP adapter is utilized and not utilized as in the conventional case. A simplified computational setup is used for the CFD simulations, as shown in Figures 2 and 6. The graft is taken to be a straight, noncompliant, circular tube with an internal diameter of 0.60 cm, which is representative of typical PTFE grafts. A dialysis needle (0.16 cm inner diameter, 0.18 cm outer diameter) is positioned at an angle within the graft to account for percutaneous needle entry. The inlet boundary condition to the graft is a parabolic velocity profile with a physiological fiowrate of 1000 mL/min. A parabolic velocity profile is also applied to the inlet of the dialysis needle to provide a fiowrate of 400 mL/min, which is typical of a dialysis machine. A zero gradient boundary condition is applied to the outlet of the AV graft, such that all computed variables on the outlet nodes are extrapolated from interior nodes. The blood is assumed to behave like a Newtonian fluid with a constant viscosity, μ, of 0.035g/cm -s and density, p, of 1.0ό0g/cm\ The resulting Reynolds numbers, Ud /v , of the graft and needle flows are 1070 and 1609, respectively, where U is the mean inlet velocity within the graft or needle, d the inner diameter of the graft or needle, and v the kinematic viscosity, μ/p, of blood. Unstructured meshes with 4.5e6 and 3.2e6 cells are used to fill computational domain with and without the SMP adapter, respectively, and a time step of 1.0e-4s is chosen for these unsteady simulations. Using a finite-volume CFD code, the unsteady, Navier-Stokes equations were solved for dialysis sessions with and without the adapter.

[0034] Figure 2 shows the computer simulation of a conventional dialysis session and demonstrates that the basic flow features are a high speed jet (average u- component of 270 cm/s at the x-location of the needle tip) issuing from the needle and a slower background vascular access flow (average u-component of 60 cm/s at the x-location of the needle tip) within the graft. Downstream of the needle tip, the needle flow impinges upon the bottom of the graft wall and begins to sweep upwards along the sides to the top of the graft, forming two large-scale helical structures that persist down the length of the graft. Immersed within these helical structures are a host of small-scale, complex, three- dimensional flow structures that result in substantial flow unsteadiness downstream of the dialysis needle. The graft wall experiences increased hemodynamic stresses as a result of the impinging needle jet. This is evidenced by a sharp rise in the WSS field in the vicinity of the jet impingement region. Upstream of this region, the WSS was determined to be approximately 30 dynes/ cm², but downstream of it, the WSS rapidly was determined to undergo an eighty-fold increase to nearly 2400 dynes/ cm². [0035] Figure 6 shows the computer simulation of the fully deployed SMP adapter of Figures 3-5. The expandable cannula is represented by a thin tube that extends from the end of the dialysis needle. The adapter has a proximal diameter of 0.16 cm, a distal diameter of 0.25 cm, and a length of 1.28 cm from the needle tip. In contrast to the conventional case, when the fully deployed SMP adapter is present, the needle jet is oriented in the downstream direction and no longer impinges as severely upon the graft wall. As a result, the WSS is substantially reduced, In addition, the larger cross-sectional exit area of the adapter decelerates the needle flow. A comparison of the average u-component of velocity (130 cm/s) of the needle flow at the distal tip of the adapter with the average u-component of velocity (70 cm/s) of the background vascular access flow at the same x-location shows them to be closer in value, which could potentially reduce the strength of the shear layer instability that develops downstream of the adapter. In conclusion, the CFD simulations demonstrate that the SMP adapter significantly reduces the graft WSS, which could potentially reduce hemolysis and subsequent vascular access occlusion. [0036] While particular operational sequences, materials, temperatures, parameters, and particular embodiments have been described and or illustrated, such are not intended to be limiting. Modifications and changes may become apparent to those skilled in the art, and it is intended that the invention be limited only by the scope of the appended claims.

Claims

We Claim:

1. An ex pandable cannul a comprising: a shape memory polymer unibody tube having a proximal end, a distal end, and at least a portion of its length that is radially expandable in situ.

2. The expandable cannula of claim 1, wherein the radially expandable portion includes the distal end.

3. The expandable cannula of claim 2, wherein in the expanded state the diameter of the radially expandable portion increases toward the distal end.

4. The expandable cannula of claim 1, wherein the radially expandable portion is permeable.

5. The expandable cannula of claim 4, wherein the radially expandable portion does not include the proximal or distal ends so that in the expanded state the radially expandable portion forms a radially wider section between two radially narrower sections.

6. The expandable cannula of claim \, wherein the distal end is open.

7. The expandable cannula of claim 1, wherein the distal end is closed but permeable.

8. An arteriovenous needle adapter comprising: an expandable cannula capable of being retractably extended from the needle, and having a shape memory polymer unibody tube construction with a proximal end, a distal end, and at least a portion of its length that is radially expandable in situ.

9. The arteriovenous needle adapter of claim 8, wherein the radially expandable portion includes the distal end.

10. The arteriovenous needle adapter of claim 9, wherein in the expanded state the diameter of the radially expandable portion increases toward the distal end.

11. The arteriovenous needle adapter of claim 8, wherein the radially expandable portion is permeable.

12. The arteriovenous needle adapter of claim 11, wherein the radially expandable portion does not include the proximal or distal ends so that in the expanded state the radially expandable portion forms a radially wider section between two radially narrower sections.

13. The arteriovenous needle adapter of claim 8, wherein the distal end is open.

14. The arteriovenous needle adapter of claim 8, wherein the distal end is closed but permeable.

15. An improved dialysis needle for injecting fluid into an arteriovenous body with reduced flow turbulence and wall shear stress on the arteriovenous body, said improvement comprising: an elongated catheter tube extending through the needle and having a leading end section with a radially expandable portion thereof that is capable of being retractably extended from the needle, said radially expandable portion of the leading end section having a shape memory polymer unibody tube construction that is radially expandable in situ.

16. The improved dialysis needle of claim 15, wherein the radially expandable portion includes a tip end of the leading end section.

17. The improved dialysis needle of claim 16, wherein in the expanded state the diameter of the radially expandable portion increases toward the tip end.

18. The improved dialysis needle of claim 15, wherein the radially expandable portion is permeable.

19. The improved dialysis needle of claim 18, wherein the radially expandable portion does not include the tip end of the leading end section so that in the expanded state the radially expandable portion forms a radially wider section between two radially narrower sections.

20. The improved dialysis needle of claim 15, wherein a tip end of the leading end section is open.

21. The improved dialysis needle of claim 15, wherein a tip end of the leading end section is closed but permeable.