NDT Advance Access originally published online on October 2, 2006
Nephrology Dialysis Transplantation 2007 22(2):666-667; doi:10.1093/ndt/gfl571
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Urokinase for restoration of patency of occluded permanent central venous access in haemodialysis patients—a new protocol
Email: jps{at}szmc.org.ilSir,
Tunnelled central vein catheters (TCVCs) are widely used for haemodialysis either as permanent dialysis access in elderly patients with severe peripheral vascular disease or transiently during the maturation period of an arteriovenous fistula. Their use is associated with a relatively high incidence of complications including infection and dysfunction. The most frequently occurring complication is catheter dysfunction or poor flow. Catheter dysfunction may be classified as early, which occurs immediately after insertion and is related to malposition or technical problems with placement, and late, usually induced by partial or complete thrombosis. Catheter thrombosis frequently results in catheter loss and should be addressed immediately. Local instillation or infusion of lytic enzymes such as urokinase or tissue plasminogen activator (tPa) is widely used for clot dissolution and to restore catheter patency. Both have good success rates and safety profiles. In 1998, Twardowski [1] used intradialytic infusion of high dose urokinase (total dose of 250 000 units) for late catheter dysfunction with an 81% restoration of patency and 13% improvement in flow. Urokinase was infused over 3 h. Since dialysis treatment runs on a strict schedule, it is imperative that occluded catheters be restored in a timely, convenient and cost effective manner. After review of the literature, we developed a new shortened protocol: high dose (250 000 units) urokinase infused simultaneously through both lumens over 90 min in patients who developed complete (no blood flow) catheter occlusion.
We prospectively collected data on 15 chronic haemodialysis patients, who had received urokinase for complete catheter thrombosis during the period June 2004 to June 2006. Patients were eligible for inclusion in this study if blood could no longer be withdrawn from the catheter after a prior period of normal function of at least 7 days. We determined the average time from catheter placement to first clot event (primary patency PP), recurrent clot event after urokinase treatment (secondary patency SP), catheter salvage rate, overall catheter life, catheter related infections and cause for removal. All patients received 125 000 units urokinase in 50 cc of 0.9% saline infused simultaneously through each catheter lumen (total dose of 250 000 units urokinase) over 90 min. Haemodialysis was performed immediately after urokinase administration. Blood flow was initially set at a pump speed of 250 ml/min and was increased during the session to a maximum of 300 ml/min. A technical success of urokinase was defined as restoring catheter blood flow rate in both ports to at least 250 ml/min.
From June 2004 to June 2006, 88 TCVCs were inserted for our haemodialysis service. All these catheters were placed in our angiographic unit by the same radiologists. 19 of these catheters (in 15 patients) developed total thrombosis during this time and urokinase was used to restore patency one or more times—total 27 treatments. A high percentage of our patients suffered from diabetes, hypercholesterolaemia (53% each) and hypertension (70%). Of the total patients, 53% were receiving aspirin and 27% were on chronic anticoagulation with warfarin or low molecular weight heparin (LMWH). The average time of PP was 141 ± 43 days (7–784 days). Eight patients (57%) developed recurrent occlusion and were treated with urokinase more than once: six patients received urokinase twice and three patients received urokinase three times. The average time of SP was 90 ± 33 days (7–364 days). Catheter salvage rate was 100%. Nine catheters were removed over this period of time, but no catheters were removed because of dysfunction due to thrombosis. Catheters were removed due to infection (21%), fistula maturation (19%) or fell out spontaneously (10%). Regular haemodialysis was performed immediately after treatment with blood flow rates of 250 ml/min or more in all patients maximal blood flow rate was 300 ml/min. Overall catheter life (determined as the period of time from catheter placement to removal or to the time of writing) was 508 ± 327 days. No complications were reported during or after urokinase administration even with its recurrent use, except for one patient who developed gastrointestinal bleeding and required a blood transfusion. This patient was on long-term therapy with aspirin and warfarin for chronic atrial fibrillation and required urokinase administrations on three repeated occasions over the 67 days period. This low complication rate is comparable with that reported by Twardowski [1] using high dose urokinase to restore the patency of occluded haemodialysis catheters. Indeed, the total dose of urokinase infused is similar in our protocol, thus bleeding complications are very rare and likely to occur only in high-risk patients requiring recurrent intervention.
In contrast to previous protocols, our study demonstrated 100% efficacy and it is of interest to consider why. The experience gained with the use of thrombolytic agents to dissolve an occlusive coronary artery thrombus indicates that the ability of a thrombolytic agent to dissolve a thrombus is determined by several factors. In basic terms, the agent must be delivered to, bathe, and ultimately infiltrate the thrombus while concomitantly being provided with an adequate amount of substrate (plasminogen) and the appropriate metabolic environment for an enzymatic reaction (conversion of plasminogen to plasmin). The intrinsic composition or ultrastructure of the thrombus itself also affects its lysability. In our protocol, a relatively large dose of the thrombolytic agent is infused simultaneously through both lumens of the catheter allowing thrombus infiltration with higher amounts of urokinase than in other protocols.
During the last few years, since urokinase was removed from the market in the USA, tPa has been widely used in a similar manner. Meta-analysis of randomized comparisons of urokinase and tPa as full-dose thrombolytic agents, suggested that 1 mg of tPa is likely equivalent in thrombolytic potency to 36 000 units of urokinase, and likely to be more effective for catheter instillation and equally effective for infusion [2]. For practical reasons, it does seem that every dialysis facility should have a protocol in place for the use of thrombolytic therapy to open dysfunctional catheters. Use of our protocol can be accomplished with minimal disruption to the patient's dialysis schedule, and it is highly effective and is associated with a minimal complication rate even with repeated urokinase administration.
Conflict of interest statement. None declared.
1Nephrology Unit
Shaare Zedek Medical Center
Jerusalem
Israel
2University of Texas Health Science
Center at San Antonio
San Antonio
Texas
USA
References
- Twardowski ZJ. (1998) High-dose intradialytic urokinase to restore the patency of permanent central vein hemodialysis catheters. Am J Kidney Dis 31:841–847.[Web of Science][Medline]
- Clase CM, Crowther MA, Ingram AJ, Cina CS. (2001) Thrombolysis for restoration of patency to haemodialysis central venous catheters: a systematic review. J Thromb Thrombolysis 11:127.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||