A pig model of tunneled dialysis catheter (TDC) infection and dysfunction: Opportunities for therapeutic innovation

Abstract

Background: Although tunneled dialysis catheters (TDC) are far from ideal, they still represent the main form of vascular access for most patients beginning dialysis. Catheters are easy to place and allow patients instant access to dialysis, but regardless of these benefits, catheters are associated with a high incidence of significant complications like bloodstream infections, central venous stenosis, thrombosis, and dysfunction. In the present study, we aim to describe and characterize a swine model of catheter dysfunction and bloodstream infection, that recreates the clinical scenario, to help to serve as a platform to develop therapeutic innovations for this important clinical problem. Methods: Six Yorkshire cross pigs were used in this study. Non-coated commercial catheters were implanted in the external jugular recreating the main features of common clinical practice. Catheters were aseptically accessed twice a week for a mock dialysis procedure (flushing in and out) to assess for and identify catheter dysfunction. Animals were monitored daily for infections; once detected, blood samples were collected for bacterial culture and antibiograms. Study animals were euthanized when nonresponsive to treatment. Tissue samples were collected in a standardized fashion for macroscopic inspection and histological analysis. Results: The data analysis revealed an early onset of infection with a median time to infection of 9 days, 40% of the isolates were polymicrobial, and the average time to euthanasia was 20.16 ± 7.3 days. Median time to catheter dysfunction onset was 6 days post-implantation. Postmortem dissection revealed external fibrin sheath and internal thrombosis as the main causes of catheter dysfunction. There was also evidence of central venous stenosis with positive cells for αSMA, CD68, Ki67, Smoothelin, and Vimentin within the venous neointima. Conclusions: The described model represents a reliable and reproducible large animal model of catheter dysfunction and bloodstream infection, which recreates all the main complications of TDC’s and so could be used as a validated large animal model to develop new therapies for TDC related infection, thrombosis/dysfunction and central venous stenosis.

Nitric Oxide-Releasing Hemodialysis Catheter Lock Solutions

“…In pigs, a bloodstream infection is denoted by a sustained body temperature of >103.5 °F coupled with either a decrease in appetite or activity. Such infections occur readily in this model of catheter use, with a median time to infection reported as 9 d . Notably, the time to infection was increased from 11.3 ± 8.4 d (control) to 22.7 ± 5.3 d upon using the NO-releasing lock solutions, a 100% relative improvement (Figure C).…”

“…Catheter placement was performed to mimic placement in human patients . Following placement, blood was flushed in and out of the catheters twice weekly to simulate a dialysis event. , In between events, catheters were locked using either the heparin control or NO-releasing lock solution as would be done during the interdialytic period in patients. The study was maintained for 28 d unless pigs developed a nonresponsive CRBSI.…”

“…Hickman dual-lumen hemodialysis catheters were implanted in all six study animals. The protocol closely replicates the most commonly used clinical technique used to place these same catheters in patients with kidney failure …”

“…The protocol closely replicates the most commonly used clinical technique used to place these same catheters in patients with kidney failure. 57 In brief, the vein was localized with ultrasound, a Seldinger technique was used to facilitate percutaneous access, and a guidewire was then advanced followed by vessel dilators and a peel-away sheath. An exit point for the tunnel was then carefully selected over the back of the neck to have the catheter exit from a point that was not continuously moving.…”

Pathology of catheter-related complications: what we need to know and what should be discovered

“…Our research in a pig model identified cells in the venous neointima that were positive for a-smooth muscle actin, CD68, Ki67, smoothelin, and vimentin. 70 Movement of the catheter with respiration, head movements, changes in position, increased flow and turbulence during maturation of the arteriovenous access, and changes in shear stress lead to deposition of platelets and venous wall remodeling. 71 Meanwhile, trauma to the vessel wall contributes to generation of thrombin, activation of platelets, and expression of P-selectin with an inflammatory response and activation of leukocytes, all of which cause release of myeloperoxidase and development of platelet aggregates, which deposit into thrombi inside the vascular lumen.…”