Prophylactic urokinase in the management of long-term venous access devices in children: a Children's Oncology Group study. A prospective double-blind randomized trial of urokinase flushes to prevent bacteremia resulting from luminal colonization of subcutaneous central venous catheters. Less frequent catheter dressing changes decrease local cutaneous toxicity of high-dose chemotherapy in children, without increasing the rate of catheter-related infections: results of a randomised trial.
Infection and thrombosis are serious complications of long-term vascular access devices in children undergoing chemotherapy. Since routine fibrinolytic therapy may decrease these complications, the purpose of this study was to compare the efficacy of an every-2-week administration of urokinase with standard heparin flushes in reducing the incidence of device-related infections and occlusions.
                This study was a prospective, randomized phase III multicenter trial conducted by the Children's Cancer Group, in which patients with implantable ports or tunneled catheters received either urokinase or heparin every 2 weeks for 12 months. Study end points were time to first occlusion or time to first device-related infection.
                Five hundred seventy-seven patients from 29 institutions were enrolled, of whom 51% had external catheters and 49% had ports. Urokinase administration resulted in fewer occlusive events than heparin (23% v 31%; P =.02), a longer time to first occlusive event (log-rank analysis, P =.006), and a 1.6-fold difference in the rate of occlusive events (Poisson regression, P =.003). Similar results were noted when comparing ports and tunneled catheters. The urokinase group also had a 1.4-fold difference in the rate of infection (Poisson regression, P =.05) and longer time to first infection (log-rank, P =.07), but the difference was significant only in tunneled catheters.
                Urokinase administration every 2 weeks significantly affects the rate of occlusive events in ports and tunneled catheters and of infectious events in external catheters compared with heparin administration. This study was undertaken to determine if central venous catheter (CVC)-related infection in children with cancer could be prevented by monthly flushing of the catheter with urokinase.
                Between August 1994 and July 1998, 103 patients with cancer were randomized at the time of subcutaneous CVC placement to receive monthly flushing of their catheters with either 5000 IU of urokinase-heparin or heparin alone. Patients subsequently had blood cultures taken from their CVCs during an episode of fever.
                Seventy-four of the 103 patients (72%) enrolled in the study received at least 6 catheter flushes: 40 with urokinase-heparin and 34 with heparin. The median number of flushes was 9.5 in the urokinase-heparin group and 10.2 in the heparin-only group (P = 0.62). There were 5 positive blood cultures in the urokinase-heparin group and seven in patients receiving heparin alone (P = 0.27). Staphylococcus epidermidis was isolated from the blood of 3 patients receiving urokinase-heparin and 6 in those receiving heparin alone (P = 0.17).
                Prophylactic monthly catheter flushes with 5000 IU urokinase did not significantly decrease the number of documented bacteremic events in children with cancer who have CVCs. Cutaneous lesions caused by catheter dressing changes can be serious and generate local pain in children undergoing high-dose chemotherapy followed by bone marrow transplantation. One hundred and thirteen children entered a randomised trial to compare two catheter dressing change frequencies (15 days vs 4 days). Skin toxicity was classified according to the following scale: grade 0: healthy skin, to grade 4: severe skin toxicity. A qualitative culture of the skin at the catheter entry site was taken whenever the dressing was changed. Of the 112 evaluable children (56 in each group) 32 developed grade > or = 2 local skin toxicity (eight in the 15-day group and 24 in the 4-day group; P = 0.001). Although higher in the 4-day group, the proportions of children experiencing pain during and between dressing changes were not statistically different between the two groups. The proportion of patients with one or more positive skin culture(s) at the catheter entry site during hospitalisation were similar in the two groups (27% in the 15-day group and 23% in the 4-day group) as were the proportions of documented nosocomial bloodstream infections (11% and 13%; NS). Whereas the planned frequency was maintained in the 4-day group (mean = 4 days, s.d. = 1), it was usually shortened in the 15-day group (mean = 8 days, s.d. = 4), mainly because dressings had loosened. Decreasing the catheter dressing change frequency proved efficient in reducing cutaneous toxicity without increasing the risk of local and systemic infection. In our unit, catheter dressings are changed every 8 days since this analysis.
Three RCTs for only two types of interventions to prevent CVC-related infections in children with cancer have been identified. Flushing CVC with urokinase (with or without heparin) compared to heparin alone possibly leads to decrease in CAI rates. Changing catheter dressings every 15 days versus every 4 days does not lead to more premature catheter removals due to infection although data were insufficient to assess if catheter-related infection rates were changed.