A prospective double-blind randomized trial of urokinase flushes to prevent bacteremia resulting from luminal colonization of subcutaneous central venous catheters. Prophylactic urokinase in the management of long-term venous access devices in children: a Children's Oncology Group study. What really affects the incidence of central venous catheter-related infections for short-term catheterization? Prevention of indwelling central venous catheter sepsis. Routine changing of intravenous administration sets does not reduce colonization or infection in 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. Comparison of central venous catheter dressings in bone marrow transplant recipients. A randomized, controlled trial of the efficacy of a heparin and vancomycin solution in preventing central venous catheter infections in children. Central venous catheterization: a prospective, randomized, double-blind study.
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. 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. Central venous catheterization is one of the important sepsis reasons in surgical patients. In this randomized controlled study, the effect of the frequency and type of catheter site care, as well as age, coexisting malignancy or diabetes mellitus, total parenteral nutrition administration and antibiotics use, on central venous catheter infection was investigated. Seventy-two single-lumen polyurethane catheters were included. In group I (n: 33), a transparent occlusive dressing was applied to the insertion site and not removed for 7 days unless there were signs of local infection. In group II (n: 39), daily site care was done with povidone-iodine 10% solution and a new sterile gauze was applied. Chi-square, linear correlation and multiple regression tests were used for statistical analysis. Mean duration of catheters was 8 +/- 4 days. There was no catheter-related sepsis. Ten (13.9%) patients had positive catheter tip cultures of whom three had site infection as well. The incidence of site and tip infections were not significantly different in group I and II (p > 0.05). Site infection and age younger than 60 years significantly increased the rate of tip infection (p: 0.004 and p: 0.02 respectively). Total parenteral nutrition administration was associated with higher rate of tip infection (p: 0.06). Coexisting malignancy or diabetes mellitus, duration of catheter and antibiotics use did not have any significant effect on the rate of central venous catheter infections (p > 0.05). In conclusion, we observed that the frequency of insertion site care and the type of dressing applied to the site had no significant effect on the rate of CVC infection. Insertion site infection was the most significant factor increasing the incidence of catheter tip infection. The use of the CVC for total parenteral nutrition facilitated tip infection as well. In an attempt to decrease the incidence of central venous catheter sepsis in children with cancer, we conducted a study to evaluate the benefit of adding broad-spectrum antibiotics to the catheter "flush solution." In a prospective, placebo-controlled, double-blinded, randomized trial, 69 children with different types of malignancies were studied. The central venous catheters in these children were flushed with either the standard solution (normal saline + 100 U/ml of heparin) or the study solution (25 microgram/ml of both amikacin and vancomycin added to the standard solution). At the conclusion of the study, 64 children with a total of 67 indwelling central venous lines were assessable. The total catheter days on study were 20,700 days, with a median of 323 catheter days per patient. We documented 10 events of catheter-related infections (0.49 events/1,000 catheter days at risk). Five of these events were catheter-related sepsis (0.24 sepses/1,000 catheter days): two were fungal and three were bacterial. Due to the low incidence of catheter-related sepsis in this study, no statement regarding the prophylactic use of antibiotics could be made. The extremely low rate of catheter-related sepsis reported herein may be retrospectively attributed to continuous staff education regarding aseptic techniques in handling these catheters. Staff education is essential, and probably the most effective factor in preventing catheter-related sepsis. To determine the effect of routine intravenous (IV) administration set changes on central venous catheter (CVC) colonization and catheter-related bacteremia.
                Prospective, randomized, controlled trial.
                Eighteen-bed intensive care unit (ICU) in a large metropolitan hospital.
                Two hundred fifty-one patients with 404 chlorhexidine gluconate and silver sulfadiazine-coated multi-lumen CVCs.
                CVCs inserted in the ICU and in situ on day 4 were randomized to have their IV administration sets changed on day 4 (n = 203) or not at all (n = 201). Use of fluid containers and blood product administration sets was limited to 24 hours. CVCs were removed when not required, infection was suspected, or in place on day 7. Catheter cultures were performed on removal by blinded laboratory staff. Catheter-related bacteremia was diagnosed by a blinded intensivist using strict definitions. Data were collected regarding catheter duration, site, Acute Physiology and Chronic Health Evaluation (APACHE) II score, patient age, diagnosis, hyperglycemia, hypoalbuminemia, immune status, number of fluid containers and IV injections, and administration of propofol, blood, total parenteral nutrition, or lipid infusion.
                There were 10 colonized CVCs in the group receiving a set change and 19 in the group not receiving one. This difference was not statistically significant on Kaplan-Meier survival analysis. There were 3 cases of catheter-related bacteremia per group. Logistic regression found that burns diagnosis and increased ICU stay significantly predicted colonization.
                IV administration sets can be used for 7 days in patients with short-term, antiseptic-coated 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. To determine the effect of two central venous catheter (CVC) dressing protocols on catheter-related infections in hospitalized patients with long-term tunneled catheters undergoing an autologous bone marrow transplant (BMT), to determine the prevalence of long-term CVC-related infections in this population, and to identify other factors in the study sample related to long-term CVC infection.
                Experimental.
                BMT unit of a regional oncology center in a tertiary care hospital.
                The sample consisted of 101 adult patients with cancer with long-term, tunneled CVCs inserted in the operating room on admission for autologous BMT.
                Patients randomly were assigned to one of two dressing-change procedure groups. The control group received the current standard of care for patients receiving BMT--a dry, sterile gauze dressing (DSGD) changed every 24 hours. The experimental group received Opsite 3000TM (Smith + Nephew Ltd., Massilon, OH) transparent moisture vapor permeable dressings (MVPD) changed weekly.
                CVC infection rates, frequency of IV tubing changes, immune status, duration of catheter use, occurrence and outcome of catheter occlusion, and use of a catheter for total parenteral nutrition.
                Researchers determined the difference in CVC-related infections between the two groups and the impact of select variables on CVC-related infection. When all categories of CVC-related infection (i.e., suspected, sepsis, tunnel) were considered, no statistical difference was found in the likelihood of the groups remaining infection-free (p = 0.76) over time. CVC sepsis occurred in one patient in the DSGD group and five patients in the MVPD group; however, this difference was not statistically significant over time (p = 0.067).
                Development of CVC sepsis or tunnel infection in close proximity to the time of CVC surgical placement suggests that factors other than the assigned dressing were associated with the occurrence of CVC-related infection in three cases. Although the MVPD group required dressing changes more frequently than every seven days (as specified by the protocol) because of exit-site drainage and nonocclusiveness, transparent dressings were more cost-effective than daily gauze dressings in this population.
                For adults undergoing autologous BMT, either DSGD or transparent CVC dressing can be used safely based on patient preference and skin tolerance to the dressing material. To determine whether adding vancomycin to central venous catheter (CVC) flush solution would significantly reduce the incidence of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms.
                Fifty-five children with cancer and eight children given total parenteral nutrition by the surgery or nutrition support services were randomly assigned to receive a heparin CVC flush solution (n = 31) or a heparin-vancomycin CVC flush solution (n = 32).
                During 9158 catheter days, 6.5% of the patients in the heparin group and 15.6% of the patients in the heparin-vancomycin group had bacteremia attributable to luminal colonization with vancomycin-susceptible organisms (p = 0.43). The mean rates of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms were 0.6/1000 catheter days in the heparin group and 1.4/1000 catheter days in the heparin-vancomycin group (p = 0.25). There was no significant difference between the groups when the time to the first episode of bacteremia attributable to luminal colonization with a vancomycin-susceptible organism was compared by means of Kaplan-Meier survival estimates. Streptococcus viridans infection was not attributable to luminal colonization.
                The addition of vancomycin to heparin CVC flush solution did not reduce bacteremia with vancomycin-susceptible organisms. Bacteremia with Streptococcus viridans was not related to the use of a CVC. Central venous catheters (CVCs) are extensively used worldwide. Mechanical, infectious and thrombotic complications are well described with their use and may be associated with prolonged hospitalization, increased medical costs and mortality. CVCs account for an estimated 90% of all catheter-related bloodstream infections (CRBSI) and a host of risk factors for CVC-related infections have been documented. The duration of use of CVCs remains controversial and the length of time such devices can safely be left in place has not been fully and objectively addressed in the critically ill patient. Antimicrobial-impregnated catheters have been introduced in an attempt to limit catheter-related infection (CRI) and increase the time that CVCs can safely be left in situ. Recent meta-analyses concluded that antimicrobial-impregnated CVCs appear to be effective in reducing CRI. The authors conducted a prospective, randomized, double-blind study at Johannesburg Hospital over a 4-year period. The study entailed a comparison of standard triple-lumen versus antimicrobial impregnated CVCs on the rate of CRI. Our aim was to determine whether we could safely increase the duration of catheter insertion time from our standard practice of seven days to 14 days, to assess the influence of the antimicrobial impregnated catheter on the incidence of CRI, and to elucidate the epidemiology and risks of CRI. One hundred and eighteen critically ill patients were included in the study which spanned 34 951.5 catheter hours (3.99 catheter years). It was found that antimicrobial catheters did not provide any significant benefit over standard catheters, which the authors feel can safely be left in place for up to 14 days with appropriate infection control measures. The most common source of CRI was the skin. The administration of parenteral nutrition and the site of catheter insertion (internal jugular vein vs subclavian vein) were not noted to be risk factors for CRI. There was no clinical evidence of thrombotic complication in either of the study groups. This study offers direction for the use of CVCs in critically ill patients and addresses many of the controversies that exist.
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.