The Scourges of the Hemodialysis Catheter

Hemodialysis (HD) sustains life for those with ESRD. Currently, nearly 400,000 individuals in the United States receive HD as management of ESRD (1). Sustainable vascular access that provides high-volume blood flow rates (Qb) above 300 mL/min is essential, whether through arteriovenous autologous fistulas, synthetic grafts, or tunneled dialysis catheters (TDCs) (2). Unfortunately, the overwhelming majority of incident patients begin HD treatments with a TDC: 82 percent, according to the most recent data from the U.S. Renal Data System (1). More than 20 percent of prevalent patients become or remain dependent on long-term TDC use, spanning months to years (35). Other nations, such as Brazil and some in Europe and the Far East, appear to be able to reduce their use of TDCs more quickly and to reduce dependence on long-term TDC use to less than 5–10 percent.

Because of the widespread use of TDCs, research efforts are focused on identifying strategies to prevent and minimize the risk of the most common catheter-related complications—thrombotic occlusion, infection, and central vein occlusion—the three catheter scourges. Proper catheter management to preserve patency and maintain high blood flow rates, reduce the risk of infection, and avoid stenosis is vital in improving patient outcomes.

The first scourge: maintaining patency

The standard procedure for maintaining patency between dialysis treatments, the instillation of heparin into the lumens in a volume sufficient to fill to the lumen tip (the lock) is being replaced by the substitution of a trisodium citrate (TSC) 4 percent lock at many centers. One large Canadian study (6) showed a lower rate of TDC exchange and tissue plasminogen activator (tPA) use without a change in hospitalization for TSC 4 percent versus heparin. On the basis of available evidence, the American Society of Diagnostic and Interventional Nephrology Clinical Practice Committee (7) recommends using a locking solution of heparin 1000 U/mL or TSC 4 percent to maintain TDC patency.

Although a larger-bore catheter design allows an initial rate of blood flow above 400 mL/min to be achieved, virtually all catheters show eventual flow dysfunction manifested as progressive blood flow reductions at prepump pressures considered safe: 200–250 mm Hg.

Prospective monitoring for blood flow dysfunction through systematic monitoring of blood flow and prepump negative arterial pressure (Pa) during HD should be a routine part of the management of patients using TDCs (8) but in many centers it is not. Most large-gauge catheters have a conductance (Qb/Pa) of 2 mL/min/mm Hg. When prescribed blood flow rate (e.g., 350–400 mL/min) is examined serially over time, an increasing negative prepump pressure over time to achieve the prescribed flow reflects alterations in inlet orifice and suggests impending access dysfunction, which may warrant intervention.

Dysfunction manifests as thrombus formation within or at the tip of an HD catheter or by its entrapment within a fibrin sleeve. Systemic anticoagulants and antiplatelet agents have proved to be ineffective in preventing such dysfunction while adding a risk of bleeding. Noninvasive pharmacotherapy with thrombolytic agents has proved to be effective in restoring catheter patency over the short term. All too often, however, adequate flow function can be restored only by catheter replacement with balloon disruption of the fibrin sheath (9), an invasive and costly procedure.

Various protocols for thrombolytic dwells are used by dialysis centers to restore TDC blood flow, usually when the situation is urgent. I favor the slow advancement of the thrombolytic by the injection of saline solution 0.2 mL/lumen behind it every 10–15 minutes to advance the lytic to the catheter tip during a 1-hour dwell, because this strategy decreases the need for repeat lytic dwells by 81 percent (10). Two alternative strategies attempt to improve flow before the development of an “emergency” TDC flow problem: so-called preemptive postdialysis thrombolytic lock or intradialysis lytic infusions. I favor the use of a thrombolytic agent as a prolonged lock of 44–68 hours, both to restore flow and to prevent flow dysfunction. Regular once-weekly use of a tPA agent as a catheter lock solution may be the most effective technique to reduce the risk of vessel occlusion between HD sessions, avoid bleeding risk, and may incur the additional benefit of lower catheter-related bloodstream infection (CRBSI) (11). However, there have been no comparative efficacy or cost studies of the various strategies.

The second scourge: CBRSI

TDCs are responsible for almost half of all infections in HD patients. The infection rates of TDC are 15- and 25-fold higher than those for grafts and native fistulas, respectively. Infection is the leading cause of catheter removal, and CRBSI is a major reason for the loss of anatomic sites for vascular access. CRBSI is associated with substantial morbidity, including metastatic infection. One can estimate from the U.S. Renal Data System and Medicare reimbursement data that there are approximately 100,000 episodes of CRBSI per year in the United States at an average cost of $22,000 per episode (1). CRBSI usually requires catheter removal and 3 weeks of appropriate antibiotics. In some circumstances, catheter removal may be avoided by adding an antibiotic lock to the systemic antibiotic therapy.

Several approaches have been used to decrease the incidence of CRBSI: the use of intravenous antibiotics around the time of catheter implantation; the use of exit-site antimicrobial agents such as honey, mupirocin, and povidone-iodine combined with nasal mupirocin; and the use of antimicrobial-impregnated catheters and antimicrobial locks (AMLs) instilled into the catheter lumen.

Of these, only AMLs and exit-site antimicrobial agents significantly reduce the risk and rate of catheter-related infection and the risk of catheter loss from any complication (12). In a metaanalysis, the use of AMLs resulted in a 75 percent reduction in the risk of CRBSI (12) and only one published study showed the emergence of resistant organisms. Despite the demonstrated effectiveness of AMLs in reducing CRBSI, there is obvious reluctance to their use because of the potential for the development of bacterial drug resistance. Given that the U.S. Food and Drug Administration is unlikely to approve an antibiotic lock, current research focuses on the use of antimicrobial agents, usually combinations of several agents that prevent biofilm formation (13).

The third scourge: central vein stenosis and occlusion

The insertion of a large-bore catheter into a central vein is all too frequently associated with the development of stenosis within that vein. Central vein stenosis is catastrophic when it develops on the side of an established or maturing permanent access, graft, or native fistula, and it all too often precludes the placement of permanent access in the ipsilateral upper extremity. When such catheters are placed in the inferior vena cava, stenosis of the iliac vein can compromise the placement of a kidney graft. Strategies considered to reduce such stenosis include self-centering catheters and catheters configured to support themselves at opposite points of the superior vena cava. Inasmuch as longer catheter dwell times increase the development of central vein abnormalities, and catheter-related infection appears to promote stenosis, it is imperative to keep a TDC as short as possible and prevent infection.

Although catheters offer several advantages in the acute setting, acting as a bridge to more permanent vascular access, continued improvement in the design and performance of catheters is needed. Future studies should focus on better defining the prophylactic use of thrombolytic agents as locking solutions and the appropriate use of AMLs. Clearly, we need improvements in the process of care to reduce the fraction of patients in whom HD is begun with a TDC.

Notes

[1] Anatole Besarab, MD, is affiliated with the Henry Ford Hospital, Detroit.

References

1.U.S. Renal Data System. USRDS 2011 Annual Data Report: Atlas of chronic kidney disease and end-stage renal disease in the United States. Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2011.

2.National Kidney Foundation. Clinical practice guidelines for vascular access, 2006 update. Am J Kidney Dis 2006; 48(Suppl 1):S176–S285.

3.Pisoni RL, et al. Vascular access use in Europe and the United States: Results from the DOPPS. Kidney Int 2002; 61:305–316.

4.Mendelssohn DC, Ethier J. Hemodialysis vascular access problems in Canada: Results from the Dialysis Outcomes and Practice Patterns Study (DOPPS II). Nephrol Dial Transplant 2006; 21:721–728.

5.Moist LM, et al. Increased hemodialysis catheter use in Canada and associated mortality risk: Data from the Canadian Organ Replacement Registry 2001–2004. Clin J Am Soc Nephrol 2008; 3:1726–1732.

6.Lok CE, et al. Trisodium citrate 4%: an alternative to heparin capping of haemodialysis catheters. Nephrol Dial Transplant 2007; 22:477–483.

7.Moran JE, Ash SR, for the ASDIN Clinical Practice Committee. Locking solutions for hemodialysis catheters; heparin and citrate: A position paper by ASDIN. Semin Dial 2008; 21:490–492.

8.Besarab A, Pandey R. Catheter management in hemodialysis patients: Delivering adequate flow. Clin J Am Soc Nephrol 2011; 6:227–234.

9.Janne d’Othée B, Tham JC, Sjeiman RG. Restoration of patency in failing tunneled hemodialysis catheters: A comparison of catheter exchange, exchange and balloon disruption of the fibrin sheath, and femoral stripping. J Vasc Interv Radiol 2006; 17:1011–1015.

10.Seddon PA, et al. Effectiveness of low dose urokinase on dialysis catheter thrombolysis. ASAIO J 1998; 44:M559–M561.

11.Hemmelgarn BR, et al. Canadian Hemodialysis Catheter Working Group: Prevention of catheter lumen occlusion with rTPA versus heparin (Pre-CLOT): N Engl J Med 2011; 364:303–312.

12.Rabindranath KS, et al. Systematic review of antimicrobials for the prevention of haemodialysis catheter-related infections. Nephrol Dial Transplant 2009; 24:3763–3774.

13.Steczko J, et al. Microbial inactivation properties of a new antimicrobial/antithrombotic catheter lock solution (citrate/methylene blue/parabens). Nephrol Dial Transplant 2009; 24:1937–1945.