Efficacy, Safety, and Cost of Thrombolytic Agents for the Management of Dysfunctional Hemodialysis Catheters

A Systematic Review

Daniel Hilleman, Pharm.D., FCCP; Jennifer Campbell, Pharm.D.

Disclosures

Pharmacotherapy. 2011;31(10):1031-1040. 

In This Article

Abstract and Introduction

Abstract

Approximately 100,000 patients begin hemodialysis each year in the United States. Although an arteriovenous fistula or graft is the preferred method for long-term vascular access during hemodialysis, as these types of vascular access are the most reliable, approximately 30% of patients require the use of catheters to continue hemodialysis. Tunneled, cuffed hemodialysis catheters are discouraged for permanent vascular access because of their high rates of infection, morbidity and mortality, and thrombotic and technical complications. These catheters have a short functional life span and require medical intervention, often thrombolytic therapy, to treat the catheter malfunction. No thrombolytic agent is specifically indicated for the management of occluded hemodialysis catheters. Thus, we performed a systematic review to critically evaluate all available studies that examined the efficacy, safety, and cost of thrombolytic therapy for the management of dysfunctional hemodialysis catheters. Studies were included if they reported efficacy in a specific proportion of affected dysfunctional hemodialysis catheters; reported the proportion of patients experiencing an adverse outcome (especially bleeding); and described the type of catheter used, dose of thrombolytic agent, administration protocol, dwell time, definition of treatment success, time to follow-up for study end points, and sample size. Eighteen studies met the inclusion criteria. The mean ± SD success rate in clearing dysfunctional hemodialysis catheters was greatest with reteplase at 88 ± 4%, followed by alteplase at 81 ± 37% and tenecteplase at 41 ± 5%. Adverse effects associated with the use of these thrombolytic agents administered at low doses were extremely rare. No serious adverse bleeding events attributed to thrombolytic therapy were reported in any of the trials. Aliquotted reteplase from vials for intravenous use was the least costly thrombolytic agent. Thus, at centers that use high volumes of thrombolytics for dysfunctional hemodialysis catheters, reteplase is the thrombolytic agent of choice.

Introduction

Reliable vascular access is needed in order to provide long-term hemodialysis. In the United States, approximately 100,000 patients begin hemodialysis each year.[1] Of these patients, more than 80% require urgent initiation of hemodialysis with use of catheters.[1] An attempt is made in most of these patients to place an arteriovenous fistula or graft to provide permanent dialysis, as these types of vascular access are the most reliable approaches for long-term hemodialysis.[2,3] Tunneled, cuffed catheters are discouraged for permanent vascular access because of their high rates of infection, morbidity and mortality, and thrombotic and technical complications.[3,4] Despite these limitations, 30% of patients undergoing dialysis in the United States require the use of catheters to continue long-term hemodialysis.[5,6] Unfortunately, hemodialysis catheters have a short functional life span. At the end of a 1-year followup, at least 50% of catheters failed to perform as needed to achieve adequate hemodialysis.[7–10] This rate of failure highlights the importance of appropriate care of hemodialysis catheters.[3]

Management of catheter-related complications is an important challenge that must be dealt with in order to maintain timely and efficient hemodialysis. Since 1997, the National Kidney Foundation's Dialysis Outcomes Quality Initiative (KDOQI) has recommended thrombolytic therapy as the primary medical intervention to treat catheter malfunction.[11] Although urokinase was initially recommended as the thrombolytic drug of choice for catheter clearance, manufacturing problems led to its removal from the U.S. market.[12] Streptokinase has been used for catheter clearance, but repeated administration of the drug may lead to the development of allergic reactions.[13] Thus, the United States Food and Drug Administration (FDA) issued a warning that the use of streptokinase be avoided in the restoration of patency in intravenous catheters.[14]

Currently, alteplase is the only thrombolytic agent approved for central venous catheter clearance (Cathflo Activase; Genentech, Inc. South San Francisco, CA).[15] Although alteplase is not specifically indicated for use in hemodialysis catheters, several publications describe its use in relatively small numbers of patients requiring these catheters to deliver renal replacement therapy. One disadvantage associated with the use of alteplase for hemodialysis clearance is its cost. The wholesale acquisition cost of an alteplase 2-mg vial (Cathflo Activase) has increased 34% since 2006 ($66.39 in 2006 to $88.83 in 2010).[16] Because of the increased cost, some institutions have started using a thrombolytic agent not approved for catheter clearance (reteplase) as an alternative to alteplase. In addition, a new biologic application for the use of tenecteplase in catheter clearance has recently been submitted.[17] It is uncertain whether tenecteplase will be approved for hemodialysis catheter clearance. It is also unknown what tenecteplase will cost.

With limited exceptions, the numbers of patients included in each of the published studies of thrombolytics for the treatment of dysfunctional hemodialysis catheters have been small. In addition, no head-to-head trials have been conducted that compared the currently available thrombolytic agents for this indication. No thrombolytic agent is specifically indicated for the management of occluded hemodialysis catheters. Thus, our objective in this systematic review was to critically evaluate all available studies that examined the efficacy and safety of thrombolytic therapy for the management of dysfunctional hemodialysis catheters. In addition, cost was considered to make recommendations concerning drug product selection and formulary status.

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