Arora, R. S., Roberts, R., Eden, T. O., & Pizer, B. (2010). Interventions other than anticoagulants and systemic antibiotics for prevention of central venous catheter-related infections in children with cancer. Cochrane Database of Systematic Reviews, 12, CD007785.

The primary objective was to find which interventions, if any, were effective in preventing central venous catheter (CVC)-related infections in children with cancer. The secondary objective was to examine the effectiveness of each intervention in the subgroups of (a) implanted venous external catheters, (b) hematologic versus nonhematologic malignancies, and (c) in those receiving hematopoietic stem cell transplantation (HSCT) versus no HSCT.

Databases searched were the Cochrane Central Register of Controlled Trials (2008), MEDLINE (January 1950–January 2009), EMBASE (January 1980–January 2009), and CINAHL (January 1982–March 2009), as were reference lists from relevant articles and international conference proceedings (2004–2008).

Reviews examined were randomized, controlled trials and quasi-randomized, controlled trials of children (younger than 18 years) with cancer who had long-term tunneled CVCs with a CVC infection-prevention intervention other than anticoagulants, systemic antibiotics, and antibiotic lock techniques versus no intervention, placebo, or other intervention to prevent CVC-related infections.

Studies with interventions to treat other catheter-related complications were excluded.

Twenty-eight total references were retrieved.

For dichotomous outcomes, risk ratio and 95% confidence interval (CI) were used to express the estimate of effect; for continuous outcomes, weighted mean differences, standard deviation (SD), and 95% CI were used to summarize the data for each group; and for rare events, rate ratio as a summary statistic and meta-analysis of rate ratios via a generic inverse-variance approach were used.  

The initial total search yielded 876 citations, 216 of which were duplicates. From this, 28 full-text articles were reviewed and three were kept for final analysis. The overall study quality was low.

• After all exclusions, three studies (with 793 participants) were examined.
• Sample range across studies was 103 to 577 patients.
• Patients younger than 22 years with hematologic and nonhematologic malignancies, and one study with HSCT recipients, who had long-term internal or external CVCs were included. Interventions were monthly flushes of 3 mL of prophylactic urokinase-heparin (total doses of 5,000 IU of urokinase) versus heparin alone (total doses of 300 units of heparin); two weekly catheter flushes with urokinase alone (5,000 IU/mL) versus heparin alone (100 units per mL); and transparent catheter dressing changes every 15 days versus every four days (HSCT study).

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for pediatrics.

Meta-analysis for the comparison of catheter flushing with urokinase (with or without heparin) versus heparin alone demonstrated an effect on the catheter-associated infection (CAI) rate with the rate ratio of CAI rate = 0.72 (95% CI [0.12, 4.41]) with use of urokinase in adults. One study reviewed reported an incidence of CAI of 2.6 per 1,000 CVC days with urokinase and 3.9 per 1,000 CVC days with heparin (p = 0.04). Studies involving different frequencies of dressing changes were difficult to analyze because adherence to every 14-day change was very low.

There were fewer CAIs with urokinase flushes, with or without heparin versus heparin alone, suggesting that urokinase use in catheter flushes may be beneficial. These findings are limited by the wide CI in findings and the fact that how CAI was defined for this systematic review was not described. No firm conclusions can be drawn from this review regarding urokinase, but the results suggest that further research in this area is warranted, although the difference between the groups was not statistically significant. There were no differences between groups who received dressing changes every 15 days versus every four days regarding the premature removal of the catheter due to infection. Catheter-related infections were not evaluated in the dressing change study, and adherence to the dressing change intervention was poor.

The results highlight need for clear and consistent outcomes definitions to further the research in this area.