Use of a novel immediate access dialysis graft designed to prevent needle-related complications: A first-in-man case report

Abstract

Currently, there is no vascular access that possesses all ideal qualities for hemodialysis access, but attributes particularly lacking include: ease of identification (cannulation zone), ease of access, resistance to stenosis, durable to repetitive cannulation, resistance to infection, resistance to acute needle-related injuries, and instant hemostasis. The overall value of these attributes could be appreciated in the reduction of complications (patient burden and suffering, which can also result in increased healthcare costs), and improved safety and durability. In this case report, we present a novel hemodialysis access graft that has the potential to provide the following benefits: it is designed to be self-sealing and immediately usable post implant, easy to identify, easy to access, has more durable cannulation zones, and protects from needle-related injuries. This case report describes the first-in-man use of this novel graft technology to replace a giant, thrombotic, and difficult-to-access arteriovenous fistula to provide the patient with a potentially safer and more durable access that does not require placement of a bridging dialysis catheter. This single-patient experience suggests that implantation and function of this novel graft as a hemodialysis access is feasible in a human subject with end-stage renal disease, and it suggests that the novel properties (i.e. immediate use, easy identification, easy use, cannulation zone durability, and protection from needle-related injuries) of this graft seem to function as intended.

Introduction

The ideal hemodialysis (HD) access is one that provides adequate flow, has cannulation zones that are easy to identify by the cannulators, reliably provides access to the blood, is resistant to stenosis, durable to repetitive needle puncture, is resistant to infection, resistant to acute needle-related injuries (NRI; e.g. backwall punctures or sidewall lacerations), is self-sealing (hemostatic), and thus, is immediately usable. To date, there is no vascular access that adequately provides all of these qualities. In this article, we report on a novel HD graft (InnAVasc Medical, Inc., Durham, NC, USA) that is designed to address many of these unmet needs (i.e. is easy to identify, easy to access, durable to repetitive puncture, resistant to acute NRI, and is immediately usable).¹

The potential realized benefit of these properties for patients could be significant in terms of safety, reduced morbidity, and reduction of overall patient burden; and for the healthcare system could be significant in terms of reduced resource utilization and cost related to cannulation injury. For example, an access that is easy to identify and easy to use could lower the skill and training required for the cannulators (dialysis technicians, nurses, patients, or family members) to safely puncture the vascular access. This in turn could translate to fewer overall NRI complications related to human error, and result in lower cost to the healthcare system and reduced morbidity for patients. Van Loon et al.² reported that 37% of patients with arteriovenous fistula (AVF) and 19% of patients with arteriovenous graft (AVG) suffered between 1 and 10 miscannulations in a period of approximalty 1 year, and some patients endured more than 30 miscannulations during their study period. Furthermore, an access that is easy to identify and easy to use could help to encourage and facilitate the transition to home HD (an arena where patients or family members are responsible for access cannulation) which has been shown to improve outcomes and provide better renal replacement therapy.³ However, cannulation fear has been one of the known barriers to the home HD movement.⁴

An access that protects from acute NRI may help patients avoid unnecessary complications that frequently require them to seek medical attention, lead to lengthy hospital admissions, and often require additional surgical procedures.⁵ Furthermore, NRI complications can be painful (infiltration injury-related large hematomas), dangerous (uncontrolled hemorrhage), or lethal (exsanguination, which is often due to pseudoaneurysms with poor skin integrity, especially if outflow stenosis is present) for patients and can cause undue suffering.^6,7 An access that resists material degradation from repetitive needle punctures would be beneficial in reducing potential for pseudoaneurysm formation, which can lead to graft thrombosis, or hemorrhage.^8–10

A truly self-sealing HD access could prevent unnecessary or dangerous bleeding from puncture sites, a feature especially useful in the hands of novice technicians, self-cannulators, or family members. Furthermore, a self-sealing access could promote early (<2 weeks) or immediate (within 24 h) needle access to the circulation obviating the requirement for tissue incorporation and scarring prior to use for HD, and therefor reduce catheter time. An access that can reduce the prolonged catheter contact time or possibly eliminate the need for a catheter altogether, could have a tremendously positive impact on patients by decreasing the probability of costly and dangerous blood stream infections and decreasing the incidence of central venous obstructive complications;¹¹ the latter of which, can lead to the rapid development of end-stage access situations (i.e. no remaining conventional AV access options), terminal loss of access, or death.¹² Currently available early cannulation grafts have shown promise to reduce catheter time but there is yet to be a strong culture shift toward operationalizing expedited catheter removal in the United States.¹³

The graft discussed here, first used in man in January 2019, encompasses many of the benefits described above. Some of these features are similar to early cannulation grafts on the market, but with the additive benefit of posterior and sidewall needle protection, improved tactile identification of the cannulation area, and increased durability of the puncture zone. The InnAVasc Graft (IAVG) combines a standard expanded polytetrafluoroethylene (ePTFE) vascular graft with a novel graft modification technology engineered with materials that provide durable, self-sealing cannulation chambers with puncture-resistant posterior and sidewall surfaces. The penetration-resistant cannulation chambers are externally molded and bonded circumferentially to one contiguous segment of ePTFE, and provides protection against expansion, deformation, and injury to the posterior and sidewalls of the graft. A dense, light-weight polymer extends along the length of the chamber on the posterior aspect to function as a needle-stopping back plate. The raised oval on the top of each chamber provides an easily identifiable cannulation zone, which when punctured in this area, ensures safe needle access to the graft lumen.¹ This feature is novel to HD access and has the potential to reduce acute NRI due to technical error during cannulation and a feature that, hypothetically, could encourage patients and family members to consider home HD. The proprietary multi-layered construction of the graft is intended to result in a self-sealing puncture zone designed to allow immediate use for HD (Figure 1).

Figure 1.

Rendering of the InnAVasc Graft (Gen. 1.0) “straight” configuration. The chambers are designed with a raised cannulation zone indicator on top to denote the safe cannulation zone. If the dialysis needle is placed in this zone it cannot penetrate through the back or sidewall of the graft and the needle tip will remain in the flow lumen. Note the flattened bottom of the chamber to provide orientation and to prevent rotation in the tunnel. The chambers are closer together in the “straight” configuration so as to allow for placement in a straight or soft “C” geometry in the upper arm (consistent with the configuration in this case report). The chambers are arranged further apart in the looped configuration (not shown) to allow for adequate placement in a looped geometry in the upper or lower arm.

In a previous report, the self-sealing properties were demonstrated in a pre-clinical model with an average time to hemostasis of <30 s (essentially, this was the bleeding from skin capillaries).¹ In terms of durability potential, previous data from the pre-clinical studies have demonstrated that the IAVG can maintain pressurized flow after 468 cannulations (equivalent to 3 years of dialysis cannulations), whereas the current standard ePTFE grafts can only maintain pressurized flow up to 130 cannulations (or <1 year (9 months) of dialysis needle punctures). On gross evaluation, there was no evidence of delamination or dissection of any layers of the cannulation chamber. The relevance of this data translates to the potential for the IAVG to offer extended use as a HD conduit before succumbing to the complications of NRI such as bleeding, hematoma, pseudoaneurysm, and infection, all of which can result in pre-mature access loss.

In this case report, we document the first-in-man implant of a novel, immediate use HD graft designed to prevent needle-related complications. This case highlights the novel features of the IAVG including easily identifiable cannulation zones, protection from inadvertent NRI, and self-sealing material with properties designed to allow for immediate cannulation in the acute phase, as well as improved durability in the long-term phase (longest follow-up is measured out to 12 months at this point).

Case description

We describe a 48-year-old male with a 3-year history of end-stage renal disease (ESRD). He has had only one previous surgically created access, an AVF created in the left upper arm approximately 3 years ago. Over time, the fistula became extremely large and aneurysmal throughout. The combination of tortuosity and burden of mural thrombus throughout the fistula made it extremely difficult for the dialysis technicians to reliably access for HD. Following several referrals to the surgical clinic and growing frustration from the patient, the team developed a plan to salvage the current access site. After informed consent to participate in the clinial investigation was obtained, the decision was made to replace the fistula using the IAVG as an interposition replacement. This strategy would allow the patient to avoid the need for a bridging central venous dialysis catheter given the self-sealing and immediate use potential of the novel graft.

The proximal and distal aspects of the AVF were exposed and dissected free from the surrounding tissue. A standard tunneler with a 10-mm tunneling tip was used for the first pass in the subcutaneous space and the IAVG was delivered into place in the standard fashion. Due to the discrepant outer diameter profile between the cannulation chambers and the diameter of the base graft (13.5 vs 7.2 mm), there was a slight increase in the force required to pull the IAVG into place in the subcutaneous tissue, although this was not prohibitive for placement and did not alter the standard process for graft delivery. The AVF was clamped and transected with a bevel, and the IAVG was placed as an interposition replacement in an end-to-end fashion using the stumps of the existing fistula for inflow and outflow. The remaining portion of aneurysmal AVF was excised to avoid subsequent hematoma or bleeding complications.

The IAVG was cannulated immediately post implant while the patient was still on the operating room table to conduct completion angiography for confirmation of proper placement and to rule out kinks or other geometric and anastomotic abnormalities. Two 16ga dialysis needles were used to access the IAVG cannulation chambers simultaneously (one arterial and one venous). The angiogram evaluated the arterial inflow, chamber and arterial anastomosis followed by the venous chamber, anastomosis, and outflow. There were no kinks or twists identified and inflow and outflow were of good quality (Figure 2).

Figure 2.

(a) InnAVasc Graft immediately post implant. 16ga dialysis needles have been placed into each cannulation chamber during the operation to perform a completion angiogram. (b) Completion angiogram performed while in the operating room to verify proper placement of the graft and to, rule out any technical graft abnormalities such as kinking or twisting.

The patient did not have a central venous catheter in place at the time of surgery and presented to his dialysis center the next morning for continued renal replacement therapy via the novel graft. The IAVG was again successfully accessed with two 16ga dialysis needles (one per chamber, and needles were eventually stepped up to 15ga for ongoing treatment) without difficulty and he received his full dialysis treatment. Following dialysis, there was minimal skin bleeding from the puncture sites that ceased in less than 5 min. Despite excision of his previous fistula, the subject reported the development of a hematoma at the fistula excision site approximately 5 days post op. This did not require evacuation or further intervention and resolved without sequelae.

The subject has been able to use the IAVG for HD continuously from the day of implant through last available follow-up (month 12) without NRI or the need for additional vascular access modalities (e.g. dialysis catheter, etc.). Over the course of the first 6 months, the patient presented to his dialysis center for treatments 3 times per week (with the exception of 2 days) and there were no unsuccessful cannulation attempts during this period. His study-mandated ultrasound at the 6-month assessment confirmed no evidence of hematoma, seroma, or pseudoaneurysm at any point along the course of the graft or cannulation chambers. However, at month 6 the subject required angioplasty for a venous anastomosis stenosis and arterial chamber stenosis which required stent placement. At month 8, a venous anastomosis and venous chamber stenosis were treated with balloon angioplasty, and at month 10 the subject required angioplasty of the venous anastomosis, venous chamber, and cephalic arch stenosis. The subject has maintained primary assisted patency to date. Ultrasound and angiography of the IAVG at month 10 confirmed that there still was no evidence of graft degradation or pseudoaneurysm, no intragraft defects such as dissections, or delamination, and no perigraft hematoma or seroma. The subject continues to use the novel graft for HD 12 months post implantation and has not required a catheter since placement of the IAVG (Figure 3).

Figure 3.

(a) Case report subject with giant, aneurysmal, thrombogenic fistula prior to InnAVasc Graft placement. (b) Subject 3 weeks post InnAVasc Graft placement and use (approximately nine punctures per chamber). (c) Subject 10 months post InnAVasc Graft placement and use (approximately 120 punctures per chamber). (d) Angiogram of InnAVasc Graft after 10 months of use for hemodialysis (~120 punctures per chamber) without evidence of hematoma, seroma, intragraft defects, or pseudoaneurysm formation.

Conclusion

This case marks the first-in-man report on the use of a novel, self-sealing, immediate access HD graft designed to prevent NRI and their resulting complications. In this case report, we demonstrate that the tunneling and implant of the IAVG is safe and feasible in a human subject despite the slightly larger profile of the cannulation chambers. Furthermore, we confirm that immediate use of the graft (for both intra-operative angiography and for HD treatment within 24 h) is safe and feasible in this subject, and similarly to established early cannulation grafts, can be an option to avoid placement of a bridging catheter in cases of significant vascular access revision, reconstruction, or replacement. In this case, the patient was able to continue HD without the need for a catheter despite extensive AV access revision and “mega-fistula” excision. And finally, this case demonstrates that the cannulation zones of the chambers can be accessed for HD reliably at each dialysis session, and that they can be free of NRI complications and defects such as hematoma, bleeding, and pseudoaneurysm after 12 months of repetitive cannulation.

Although this is a single-case description, we believe this report is significant to document a novel dialysis access offering the potential to significantly reduce or eliminate complications and early graft loss from NRI. Early needle access has been reported with other early cannulation grafts currently on the market, but this is currently practiced with limited volume (relative to standard grafts) and varying success depending on the national or international region.¹³ Considering the extreme morbidity and cost associated with central venous catheters such as infection and central venous obstruction,^11,12 early or immediate access is not practiced to the degree that it should or could be for ESRD patients.

The ideal HD access has yet to be developed but we believe the novel features of the IAVG, such as improved cannulation zone durability, enhanced tactile identification of the cannulation zones, and protection from acute NRI are noteworthy advancements toward this goal. The overall value of these qualities could be appreciated in the reduction of complications (patient burden and suffering, and increased cost), improved safety profile, and improved early durability (prolonging the access lifecycle).^5,6,8 It is also conceivable that graft loss due to infection or severe bleeding could be reduced by a technology like the IAVG if freedom from pseudoaneurysm development (which could result in poor skin integrity or risk for infection) bears out over the life of the graft.

The IAVG has the potential to offer ESRD patients the first vascular access capable of providing both a reliable platform for immediate cannulation and one that provides protection from morbid and costly complications secondary to NRI. A HD graft with easy to identify cannulation zones and features described above could serve as an access that encourages and facilitates a larger subset of patients to pursue home HD, and in doing so has the potential to reduce some of the financial burden to the healthcare system, and potentially improve outcomes and comfort of our ESRD patients.^3,4