Recombinant tissue plasminogen activator may reduce frequency of central venous access device infection in hemophilia patients undergoing immune tolerance therapy

Many patients with hemophilia, particularly those with inhibitory antibodies, utilize central venous access devices (CVADs) to facilitate frequent infusions. Infection of these devices is a common complication of factor replacement therapy. This communication reports our center's experience with CVAD infection in three patients with severe hemophilia A undergoing immune tolerance therapy (ITT) in whom intermittent infusions of recombinant tissue plasminogen activator (rTPA, Cathflo Activase) were utilized. In this small experience, patients experienced a decreased frequency of gram-positive infections when receiving routine rTPA treatments. Larger randomized trial should be performed in this patient population at high risk of CVAD infection.     

Hematopoietic growth factors in prophylaxis and therapy of infections complications in children with neutropenia

Hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures to reduce infectious complications associated with congenital or acquired neutropenia. Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications. In the course of evaluating the corpus of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors. To prevent serious infection, the use of G-CSF or GM-CSF is recommended in a subset of pediatric cancer patients shortly after having received chemotherapy or a form of a marrow transplant. Children with highly intensive chemotherapy (e.g., children with high risk ALL or NHL) seem to benefit from hematopoietic growth factors whereas this is still unclear for children undergoing therapy for solid tumors. An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells for autologous or allogeneic transplantation. In pediatric patients with hematological diseases, there are only few data on the use of hematopoietic growth factors in children with myelodysplastic syndrome. Experts recommend the early administration of G-CSF in children with very severe aplastic anemia. The use of G-CSF is also recommended in children with severe chronic neutropenia, but these patients have to be monitored regularly for cytogenetic abnormalities. No larger study has shown a clinical benefit of hematopoietic growth factor in preterm or term infants. Future studies in pediatric patients are clearly warranted to address several issues. Prospective clinical trials are still needed to define specific treatment groups who can benefit from growth factor support. In this regard, efforts must be directed at better defining the endpoints and in particular assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs. In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups of patients. In addition, combinations of different growth factors have to be tested, particularly if ex vivo expansion and the storage of hematopoietic stem cells are to be utilized in a wider spectrum of patients.     

Endocarditis with a large thrombus complicating a central venous access device

A 12-month-old child on total parenteral nutrition via a central venous access device developed an infected thrombus and endocarditis. The vegetation disappeared on conservative management. The device was left in place.     

Experience with a totally implantable venous device in children

Venous access was attained in 15 children by use of a totally implantable central venous catheter and reservoir. Catheters were in place from 28 to 581 days, giving a cumulative experience of 4,094 days. Although they were well accepted by physicians, parents, and the children, they were not without major complications. These included extravasation of a chemotherapeutic agent in one, migration of the catheter tip to an unacceptable location in another, and catheter thrombosis and catheter-related sepsis in two each. The malpositioned catheter, one of the thrombosed catheters, and both infected catheters were removed. Ease of care, freedom from protruding tubing, and compatibility with normal activities are major positive features of the implantable devices that should be considered when deciding on the type of prolonged central venous access for use in children being treated with cancer.     

Central venous totally implantable access for high dose chemotherapy in children]

BACKGROUND: The feasibility and complication rate of central venous totally implantable access ports (TIAP), used for delivering high-dose chemotherapy (HDC) with autologous stem cell transplantation, have not been fully investigated to date, due to the almost exclusive use of external catheters (EC) in this clinical setting. PATIENTS AND METHODS: We retrospectively studied infectious and mechanical complications of 45 TIAP and 19 EC, in 64 children receiving HDC and autologous stem cell transplantation at the Centre Leon-Berard (Lyon) or at the oncology unit of Toulouse children hospital between January 1999 and December 2003. RESULTS: From the beginning of intensification to 60 days after bone marrow transplantation, 7 catheter-related bloodstream infections (3/19 EC or 15.8% corresponding to 2.69 infections for 1000 days of observation; 4/45 TIAP or 8.9% corresponding to 1.38 infections for 1000 days of observation) and 2 local infections (1/45 TIAP; 1/19 EC) were reported. Seven cases of reversible obstruction (6/7 with TIAP) and no deep venous thrombosis were detected. In 7 cases, another venous access was required either for accidental removal (2 EC), catheter infection (2 TIAP), or admission to intensive care (2 TIAP, 1 EC). TIAP complication rate does not seem to be influenced by factors such as low weight, massive blood product transfusion or prolonged parenteral nutrition. In 8 children, TIAP were used for collection of hematopoietic progenitor cells. CONCLUSIONS: The use of TIAPs appears as a safe and effective option for HDC. We found more mechanical complications but less infectious complications with TIAP than with EC. Nevertheless, results need to be validated prospectively in a larger study cohort.     

植入性中心静脉通道装置(Port)在肿瘤患儿中的应用

目的 探讨植入性中心静脉通道装置(Port)在肿瘤患儿中应用的疗效.方法 通过对176例安装化疗泵的恶性肿瘤患儿的观察,分析其置管的途径、导管放置的长度、并发症发生的原因及处理.结果本组176例患儿经颈外静脉切开123例,锁骨下静脉穿刺插管38例,经颈内静脉穿刺插管15例.导管应用期间共有46例出现相应的并发症,占26.1%.其中导管相关性感染占15.3%,导管的阻塞占16.8%.结论 化疗泵在肿瘤患儿中有良好的应用价值.导管相关性感染是化疗泵使用过程中最常见的并发症,导管的阻塞多因放置的位置或者长度不当而引起.操作医师的专业化对减少并发症的发生具有相当重要的作用.     

Totally implantable central venous access devices in children with hemato-oncologic malignancies: evaluation of complications and comparison of incidence of febrile episodes with similar patients without central venous access devices

The incidence of mechanical and infectious complications of totally implantable central venous access devices (TIDs) must be related to underlying disease, intensity of the chemotherapy, and frequency of manipulations. Records of the patients hospitalized from January 2002 to May 2005 were evaluated. Patients with TIDs were matched with patients without TIDs having the same malignancy and the same anti-neoplastic chemotherapy. Catheter-related complications were documented and corresponding phases of the chemotherapy in matched pairs were compared with regard to infections. TIDs were inserted in 31 patients with a median age of 4.3 years (22 acute leukemia, 1 NHL, and 8 solid tumors). Total number of catheter days was 5268, with a median catheter life of 174 days (range 9-493 days). Nine catheters (29%) were removed due to mechanical and infectious complications. There was 13 catheter-related infections with a rate of 2.46/1000 catheter days. Total number of mechanical complications was 5 and overall rate of complications was 3.41/1000 catheter days. The rate of febrile episodes was 54 and 41 in the TID and no TID group, respectively (p: .11). Duration of neutropenia was 9.6 and 7.4 days and duration of fever per febrile attack was 5.6 and 4.4 days in the TID and no TID group, respectively (p: .047 and .56). Although most of the patients in this study had hematological malignancy and required frequent manipulation, the results were similar to those in developed countries. TIDs are essential for management of chemotherapy in pediatric malignancies with acceptable complications.     

Primary prophylaxis of venous thromboembolism in children

Venous thromboembolism (VTE) is rare in children and young adolescents, and occurs predominantly in those with congenital heart disease in whom guidelines exist for VTE prophylaxis. For other paediatric patients, the rarity of the event makes writing an evidence‐based clinical practice guideline difficult because each of the known risk factors contributes only a small increase in risk. Thrombophilia screening is controversial because few results assist with prediction of likely thrombosis and may not alter recommendations for prophylaxis. Recent publications highlight the importance of non‐pharmacological prevention of VTE in children and adolescents undergoing surgery and the importance of liaison among surgeon, anaesthetist and haematologist. This annotation was written with the aim of collating current evidence for VTE prophylaxis and emphasising the need for further research in vulnerable subgroups.     

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??We reviewed some relevant literatures at home and abroad in recent years?? and summarized the developmental status of family therapy and nursing care of children with hemophilia.During more than 40 years of practice?? their life expectancy and their quality of life have significantly been improved after the hemophilia patients received treatment from the Hemophilia Treatment Center in Europe and the United States. Comprehensive hemophilia care and family therapy and care started late in China?? and large domestic Hemophilia Centers played greater roles in improvement of the life quality of the patients??but there were still many problems. Family therapy and nursing care can improve the quality of life of children with hemophilia?? and save the cost of health care. Family therapy and nursing care for children with hemophilia should be strengthened in Hemophilia Treatment Centers.     

Varicella in children with cancer: impact of antiviral therapy and prophylaxis

To estimate the impact of antiviral therapy and prophylaxis on the natural course of the infection, 288 cases of varicella in children with cancer were reviewed. Among 127 patients with untreated infections, the overall mortality rate was 7%. Varicella-zoster virus pneumonitis developed in 28% of the untreated patients and was associated with a 25% mortality rate. Pneumonitis was much more likely to develop in patients with acute leukemia than in those with other malignancies (32% v 19%). Similarly, deaths due to pneumonitis were restricted to patients with acute leukemia. Lymphopenia (absolute lymphocyte count less than 500/microL) was significantly associated with varicella-zoster virus pneumonitis and a higher fatality rate among patients with this complication. Both acyclovir and adenine arabinoside, administered to 18 and 28 patients, respectively, stopped the progression of skin lesions; however, pneumonitis developed in none of the acyclovir recipients after two days of treatment, compared with 29% of the adenine arabinoside recipients (P = .03). Passive immunization in 45 children who subsequently had varicella was associated with an 11% incidence of varicella-zoster virus pneumonitis. Despite passive immunization of approximately 150 children, the attack rate of varicella at our institution remains unchanged. Results of this study demonstrate the efficacy of antiviral therapy and passive immunization in patients with childhood cancer and varicella, but prevention of the infection will require a universal vaccine.     

Complications of central venous access in children

Central venous access has become a frequent requirement in the management of seriously ill or injured infants and children with a wide variety of conditions. This report evaluates the complications observed with the use of central venous catheters in 1,378 cases. Central venous catheters (n = 2,281) were placed in 1,378 children (728 boys:650 girls). There were 1,012 temporary catheters (noncuffed/percutaneously placed) while 1,268 were inserted operatively, including 37 portacaths and 1,231 with dacron cuffs (Hickman, Broviac) for long-term use. A single catheter was inserted in 542 cases and multiple catheters in 836. Indications for catheter insertion included emergency resuscitation or access (501), malignancy (462), and intestinal dysfunction (415). Catheter infection occurred in 430 cases (18.8%). Of 219 infected temporary access catheters, 123 were removed while 96 were changed over a guide wire. Of 211 infected permanent catheters, 18 were immediately removed while 193 were treated with i.v. (vancomycin, gentamicin) antibiotics. Forty-seven of 193 (24%) catheters were eventually removed because of persistent or recurrent infection (16 cases) or subsequent fungal sepsis due to Candida albicans (31 cases). Only 3 of 37 portacaths were removed because of infection. Bacterial isolates were single in 125 cases and multiple in 86. Organisms included Staphylococcus epidermidis in 104 cases, Staph. aureus in 65, Klebsiella pneumoniae in 51, Escherichia coli in 51, and others in 18. Catheter complications occurred in 107 (5%) cases, including symptomatic vessel thrombosis in 49, pneumothorax in 26, catheter migration in 25, vessel injury in 5, and catheter embolus in 2. Despite the relatively high complication rate there were no catheter-related deaths. Multiple-lumen catheters had twice the complication rate and infection rate of single lumen catheters (P < 0.05). Temporary percutaneous catheters had a complication/infection rate 1.5 times greater than permanent catheters (P < 0.05) that were operatively placed. Bacterial infection cleared with antibiotics in 76% of cases with catheter sepsis, however secondary fungal infection necessitated prompt catheter removal. These data indicate that percutaneously placed catheters and multilumen catheters are associated with significantly higher complication and infection rates. Surgeons should balance the risks of convenience vs. complications in their choice of catheters and methods of insertion.     

Septic arthritis in hemophilia with central venous catheter: a case report

A case is reported of septic arthritis in a child with human immunodeficiency virus-negative hemophilia A associated with a Staphylococcus aureus catheter-associated septicemia. The infection occurred in relation to the use of a totally implantable central venous catheter. The organism was eventually eradicated with antibiotics injected via the catheter. With increasing use of such catheters in the hemophilic population, clinicians should be alerted to the possibility of septic arthritis for prompt diagnosis and treatment.     

Antifungal therapy in children with invasive fungal infections: a systematic review

Invasive fungal infections are associated with significant morbidity and mortality. Differences between children and adults are reported, yet few trials of antifungal agents have been performed in pediatric populations. We performed a systematic review of the literature to guide appropriate pediatric treatment recommendations. From available trials that compared antifungal agents in either prolonged febrile neutropenia or invasive candidal or Aspergillus infection, no clear difference in treatment efficacy was demonstrated, although few trials were adequately powered. Differing antifungal pharmacokinetics between children and adults were demonstrated, requiring dose modification. Significant differences in toxicity, particularly nephrotoxicity, were identified between classes of antifungal agents. Therapy needs to be guided by the pathogen or suspected pathogens, the degree of immunosuppression, comorbidities (particularly renal dysfunction), concurrent nephrotoxins, and the expected length of therapy.     

Complications of central venous access devices in children with and without cancer

Objective: Complications of indwelling central venous access devices (CVAD) were assessed in 63 children with cancer and 35 without cancer.
Methodology: Central venous access devices placed surgically in 1991 were reviewed for complications.
Results: In cancer patients, the median CVAD duration was 211 days (range 9–924), compared to 37 days (range 3–339) in the non-cancer patients. Although significantly more CVAD, 41 of 72 (57%), were infected in the cancer patients compared to 14 of 40 (35%) CVAD in the non-cancer patients (OR = 2.46, 95% Cl 1.03–5.93), the rate of line infection in cancer patients was lower: 2.8 per 1000 catheter days compared with 7.6 per 1000 in non-cancer patients ( P = 0.0014). Infection was significantly more common in intensive chemotherapy cancer patients ( P = 0.0002).
Conclusions: Treating infected CVAD with antibiotics or hydrochloric acid (HCl), clearing occluded lines with streptokinase/HCl and repairing fractured lines, when successful, resulted in a considerable gain in the number of days of use for the CVAD.     

Cathlink 20: a subcutaneous implanted central venous access device used in children with sickle cell disease on long-term erythrocytapheresis--a report of low complication rates

BACKGROUND: Experience with the use of central venous access device (CVAD) in children with sickle cell disease (SCD) on hypertransfusion is limited and published studies report wide variability in the rates of CVAD-associated complications. PROCEDURE: In this study, a total of 18 Cathlink 20 ports (Bard Access systems, Salt Lake City, UT) were implanted in 15 patients aged 7-20 years with SCD for 19, 230 catheter patient days. RESULTS: No peri-operative complications were observed. Three episodes of catheter occlusion requiring replacement occurred in two patients for an observed rate of 0.16 per 1,000 catheter patient days for thrombotic occlusion. One patient required port replacement and another patient required replacement twice. In 13 out of 15 patients, the median duration of port use was 45 months. No episode of catheter-associated bacteremia or catheter tunnel infections was observed. CONCLUSIONS: Comparing our results with other reported studies of CVAD-associated complications in patients with SCD, we observed a lower rate of complications with the use of Cathlink 20 ports. These findings may be partly related to the design of the port and partly to a dedicated group of nurses accessing the ports in a controlled environment in an apheresis unit.     

Long-term results of central venous access devices in children with haemophilia

Aims  Central venous access devices (CVADs) are often used to provide reliable venous access for factor VIII administration in children with haemophilia. This study investigates their long-term outcome. Methods  A retrospective cohort study of 44 CVADs inserted into 31 children with haemophilia at a single centre between 1991 and 2006. Results  Eight (18%) CVADs are still in place and working well. Fourteen (31.8%) were removed when the child was able to return to peripheral vascular access. Twenty-two (50%) were removed because of complications, most of these children needing a replacement CVAD. The median duration that the first CVAD was in place was 51 months. There were no life-threatening complications. Conclusions  CVADs function well in children with haemophilia for a long time, with a relatively low complication rate, and can tide a child over a difficult period for vascular access.