Lack of efficacy of twice-weekly urokinase in the prevention of complications associated with Hickman catheters: a multicentre randomised comparison of urokinase versus heparin

Abstract

Hickman catheters (HC) are associated with complications, in particular infection, occlusion and thrombosis. We tested the hypothesis that regular flushing of catheters with urokinase would reduce the frequency of these complications. Patients who required a double-lumen HC for (1) bone marrow or peripheral blood progenitor cell transplantation or (2) intensive combination chemotherapy for haematological malignancies were randomised to receive twice-weekly flushes of either urokinase (5000 units) or heparin (50 units). HC-survival analysis was determined by Cox regression. 100 patients were enrolled (urokinase=52; heparin=48) and treated for a mean of 8.5 weeks. No significant difference was observed in the incidence of HC-associated septicaemic events, which occurred in 8/52 in the urokinase group and 9/48 in the heparin group (actuarial incidence 20% versus 25%, P=0.50). Similarly, there was no differences in the incidence of exit site infections (urokinase=27/52 and heparin=28/48, P=0.122); HC-septic thromboses (urokinase=2/52 and heparin=4/48, P=0.34); lumen occlusion (urokinase=30/52 and heparin=30/48, P=0.681); or venous thrombosis (urokinase=8/52 and heparin=6/48, P=0.726). Overall, a high incidence of HC-related complications was seen in both groups; 40/52 in the urokinase group and 40/48 in the heparin group (actuarial incidence 80% versus 90%, P=0.367). Despite this only 18% of HC required early removal due to complications (urokinase=8, heparin=10). There was no difference in the incidence of complications in patients undergoing transplantation (n=68) compared with chemotherapy alone (n=32). Patients with haematological malignancies were more likely to have HC-related infective complications (P=0.006), and patients with solid tumours more likely to have venous thrombosis (P=0.027). The cumulative incidence of HC-related complications in this prospective study was higher than in previously reported series. Urokinase did not appear effective in reducing the frequency of these complications.