Urokinase lock or flush solution for prevention of bloodstream infections associated with central venous catheters for chemotherapy: a meta-analysis of prospective randomized trials.
BACKGROUND
Intravascular devices (IVDs) carry significant risk of device-associated bloodstream infection (BSI). Catheter thrombosis increases the likelihood of microbial colonization of the catheter and BSI. Urokinase has been studied for the prevention of BSI associated with IVDs. We undertook a systematic review to determine the efficacy of urokinase-heparin lock or flush solution compared with heparin alone in preventing IVD-associated BSI.


METHODS
Computerized databases were searched for relevant publications in English from January 1966 to 1 January 2007. We identified randomized controlled trials comparing a urokinase-heparin lock or flush solution with heparin alone for prevention of BSI associated with long-term IVDs. Summary effect sizes were calculated with assessment of heterogeneity.


RESULTS
Five randomized, controlled trials involving a total of 991 patients being treated with IVDs met the inclusion criteria; all five studies were conducted among patients with cancer; three of these studies were undertaken in children and two in adults. The summary risk ratio with a urokinase-heparin lock solution for IVD-associated BSI was 0.77 (95% confidence interval [CI], 0.60-0.98; p=0.01). Results of the test for heterogeneity were not statistically significant (p=0.53).


CONCLUSIONS
Use of a urokinase lock solution in high-risk patient populations being treated with long-term central IVDs may reduce the risk of BSI. However, there are few randomized trials and methodologic limitations of these preclude more robust recommendations regarding the use of urokinase to prevent BSI. Further adequately powered studies should seek to evaluate the efficacy of urokinase and optimize dosage and instillation regimen.
Kethireddy
S
S
Section of Infectious Diseases, Department of Medicine, University of Wisconsin Medical School, Madison, WI 53792, USA.
Safdar
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N
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001798:Blood Proteins / Q000627:therapeutic use*; D002405:Catheterization, Central Venous / Q000009:adverse effects* / Q000295:instrumentation; D002408:Catheters, Indwelling / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D009369:Neoplasms / Q000188:drug therapy; D011446:Prospective Studies; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D001798:Blood Proteins; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; C031220:urokinase inhibitor; D006493:Heparin; D014568:Urokinase-Type Plasminogen Activator