Infectious complications of central venous catheters increase the risk of catheter-related thrombosis in hematology patients: a prospective study.

PURPOSE: We studied whether the risk of central venous catheter (CVC) -related thrombosis increased after an episode of CVC-related infection in patients undergoing intensive chemotherapy. Secondly, we determined whether thrombosis can be predicted or excluded by CVC lock fluid surveillance cultures. PATIENTS AND METHODS: In a prospective setting, 105 consecutive patients were carefully examined for CVC-related infection and thrombosis. In all patients, microbial surveillance cultures of CVC lock fluid were taken every other day. All patients with clinical suspicion of CVC-related thrombosis underwent Doppler ultrasound or additional venography. RESULTS: The cumulative incidence of CVC-related infection was 24% (25 of 105 patients). Clinically manifest thrombosis occurred in 13 (12%) of 105 patients. In patients with CVC-related infection, the risk of thrombosis increased markedly in comparison to those without infection (relative risk, 17.6; 95% CI, 4.1 to 74.1). In patients having two or more positive subsequent CVC lock fluid cultures with identical micro-organisms, 71.4% developed thrombosis, as compared with 3.3% in patients with negative or a single positive culture. CONCLUSION: The risk of clinically manifest thrombosis is increased after an episode of CVC-related infection in patients undergoing intensive chemotherapy. Surveillance culturing of CVC lock fluid may be clinically useful in estimating the risk for thrombosis and the instigation of focused early intervention.     

Therapy Insight: venous-catheter-related thrombosis in cancer patients

Central venous catheters (CVCs) have improved the management of patients with cancer substantially, by facilitating chemotherapy and supportive therapy. The use of CVCs is associated with complications such as infection and upper-limb deep vein thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related to the use of CVCs ranges between 2% and 4%. In the most recent study, the incidence of CVC-related thrombosis, as screened by venography, was approximately 18% in the absence of prophylaxis. In cancer patients with CVC-related UL-DVT, the incidence of clinically overt pulmonary embolism was between 15% and 25%, and the incidence of autopsy-proven pulmonary embolism was up to 50%. Pathogenic factors for CVC-related thrombosis include vessel injury caused by the CVC insertion procedure, venous stasis because of the indwelling CVC, and hypercoagulability associated with cancer. Recent studies have not confirmed a benefit for prophylaxis with antithrombotic agents for CVC-related thrombosis. The recommended treatment for CVC-related thrombosis is based on long-term anticoagulant therapy, with or without catheter removal.     

Thrombotic complications of central venous catheters in cancer patients

Central venous catheters (CVCs), such as the tunneled catheters and the totally implanted ports, play a major role in general medicine and oncology. Aside from the complications (pneumothorax, hemorrhage) associated with their initial insertion, all of these CVCs are associated with the long-term risks of infection and thrombosis. Despite routine flushing with heparin or saline, 41% of CVCs result in thrombosis of the blood vessel, and this markedly increases the risk of infection. Only one-third of these clots are symptomatic. Within days of insertion, almost all CVCs are coated with a fibrin sheath, and within 30 days, most CVC-related thrombi arise. Aside from reducing the function of the catheter, these CVC-related thrombi can cause postphlebitic syndrome in 15%-30% of cases and pulmonary embolism in 11% (only half of which are symptomatic). Risk factors for CVC thrombosis include the type of malignancy, type of chemotherapy, type of CVC, and locations of insertion site and catheter tip, but not inherited thrombophilic risk factors. Efforts to reduce CVC thrombosis with systemic prophylactic anticoagulation with low-molecular-weight heparin have failed. Low-dose warfarin prophylaxis remains controversial; all studies are flawed, with older studies, but not newer ones, showing benefit. Currently, less than 10% of patients with CVCs receive any systemic prophylaxis. Although its general use cannot be recommended, low-dose warfarin may be a low-risk treatment in patients with good nutrition and adequate hepatic function. Clearly, additional studies are required to substantiate the prophylactic use of low-dose warfarin. Newer anticoagulant treatments, such as pentasaccharide and direct thrombin inhibitors, need to be explored to address this major medical problem.     

Venous thromboembolism associated with long-term use of central venous catheters in cancer patients.

Long-term central venous catheters (CVCs) have considerably improved the management of cancer patients because they facilitate chemotherapy, transfusions, parenteral nutrition, and blood sampling. However, the use of long-term CVCs, especially for chemotherapy, has been associated with the occurrence of upper-limb deep venous thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related to CVCs has been reported to vary between 0.3% and 28.3%. The incidence of CVC-related UL-DVT screened by venography reportedly varies between 27% and 66%. The incidence of clinically overt pulmonary embolism (PE) in patients with CVC-related UL-DVT ranges from 15% to 25%, but an autopsy-proven PE rate of up to 50% has been reported. Vessel injury caused by the procedure of CVC insertion, venous stasis caused by the indwelling CVC, and cancer-related hypercoagulability are the main pathogenetic factors for CVC-related venous thromboembolism (VTE). Several studies have assessed the benefit of the prophylaxis of UL-DVT after CVC insertion in cancer patients. According to the results of these studies, prophylaxis with low molecular weight heparin or a low fixed dose of warfarin has been recently proposed. However, the limitations of the experimental design of the prophylactic studies do not allow definitive recommendations. The recommended therapy for UL-DVT associated with CVC is based on anticoagulant therapy with or without catheter removal. This review focuses on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of VTE in cancer patients with long-term CVC.     

Thrombotic and infectious complications of central venous catheters in patients with hematological malignancies.

Central venous catheters (CVCs) have considerably improved the management of patients with hematological malignancies, by facilitating chemotherapy, supportive therapy and blood sampling. Complications of insertion of CVCs include mechanical (arterial puncture, pneumothorax), thrombotic and infectious complications. CVC-related thrombosis and infections are frequently occurring complications and may cause significant morbidity in patients with hematological malignancies. CVC-related thrombosis and infections are related and can therefore not be seen as separate entities. The incidence of symptomatic CVC-related thrombosis had been reported to vary between 1.2 and 13.0% of patients with hematological malignancy. The incidence of CVC-related bloodstream infections varies between 0.0 and 20.8%. There is need for a specific approach regarding diagnosis and treatment of CVC-related thrombosis and infection with specific attention to the preservation of the catheter. Since data on CVC-related infections and thrombosis in hematological patients have been obtained mainly from retrospective studies of small sample size, prospective, randomized studies of prophylactic measures concerning CVC-related thrombosis and infection are warranted.     

Catheter-related thrombosis: risks, diagnosis, and management

Symptomatic thromboembolic complications of central venous catheters (CVCs) occur in 5% or less of general oncology patients. Asymptomatic CVC-related thrombi are more common, but their clinical significance is unclear. Thrombotic risk may be increased by primary thrombophilic disorders, especially the factor V G1691A (Leiden) mutation, thrombogenic catheter material, larger catheter diameter and greater number of lumens, catheter tip malposition, left-sided placement, percutaneous or multiple insertion attempts, a previous CVC or preexisting venous obstruction, prothrombotic therapeutic agents, catheter-associated infections, and fibrinous catheter lumen occlusion. Three recent randomized, prospective, placebo-controlled trials observed no benefit of routine low-dose warfarin or low-molecular-weight heparin in preventing catheter-associated thrombosis. Nevertheless, thromboprophylaxis may be appropriate and safe for selected high-risk patients. Duplex ultrasound can accurately detect CVC-related thrombi involving the jugular, axillary, distal subclavian, and arm veins. Contrast venographic imaging is required for indeterminate duplex findings and to evaluate the deep central veins and pulmonary arteries. Therapeutic anticoagulation, with or without catheter removal, is indicated for patients with acute deep vein thrombosis (DVT) or pulmonary embolism who have no contraindications. Catheter removal alone, with close follow-up, may be sufficient when bleeding risk precludes safe anticoagulation. Approaches to managing catheter-associated thrombosis, including the use of thrombolytic agents, are guided by limited published experience and extrapolation from practices used for lower-extremity DVT. Prospective, randomized, controlled trials are needed to identify the safest and most effective anticoagulant agents, treatment durations, and alternative venous access strategies for cancer patients who develop catheter-associated thrombosis.     

Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer

BACKGROUND:

The use of central venous catheters (CVCs) has greatly improved the quality of care in children with cancer, yet these catheters may cause serious infectious and thrombotic complications. The aim of this prospective registry study was to assess the host and CVC‐related risk factors for CVC‐created thrombotic complications.

METHODS:

Patients undergoing CVC insertion for chemotherapy were followed prospectively for CVC complications. At the time of enrollment, demographic, clinical, and CVC‐related data, and family history of thrombosis were collected. Survival and Cox regression analyses were performed.

RESULTS:

A total of 423 CVCs were inserted into 262 patients for a total of 76,540 catheter days. The incidence of CVC‐related deep‐vein thrombosis (DVT) was 0.13 per 1000 catheter‐days (95% confidence interval [CI], 0.06‐0.24). Insertion of peripherally inserted central catheters (PICCs) and insertion in an angiography suite significantly increased the risk of symptomatic CVC‐related DVT. The incidence of CVC occlusion was 1.35 per 1000 catheter‐days (95% CI, 1.1‐1.63). Positive family history of thrombosis significantly increased the risk of CVC occlusion (hazard ratio [HR], 2.16; 95% CI, 1.2‐3.8). The CVC‐related risk factors were insertion of Hickman catheters, insertion in angiography suite, and proximal‐tip location. Patients developing at least 1 episode of both CVC occlusion and infection had an increased risk for developing symptomatic CVC‐related DVT (HR, 4.15; 95% CI, 1.2‐14.4).

CONCLUSIONS:

Both patient‐related and CVC‐related factors are associated with higher risk of symptomatic thrombotic complications. These risk factors could be used in the clinical setting and in developing future studies for CVC thromboprophylaxis. Cancer 2010. © 2010 American Cancer Society.     

Anticoagulation prophylaxis for central venous catheter-associated thrombosis in cancer patients: An Australian perspective

Background: The use of indwelling central venous catheters (CVC) for chemotherapy delivery is essential for people receiving therapies by protracted venous infusion and for patients with difficult venous access. Complications include infection and catheter‐related thrombosis. Strategies have been suggested to prevent catheter‐related thrombosis, however, there is no clear consensus on how to proceed. Guidelines recommend against the use of prophylactic anticoagulation in adult patients with solid organ malignancies and an indwelling CVC. We investigated the practice of Australian medical oncologists. Methods: A written questionnaire was mailed to all members of the Medical Oncology Group of Australia assessing practices of prophylactic anticoagulation in adult patients with solid organ malignancies and CVC. Results: Responses were obtained from 141 (55%) medical oncologists and from 40 advanced trainees. Ten percent (n = 4) of oncology trainees and 18.4% (n = 26) of medical oncologists routinely administered anticoagulants to patients with a CVC without a previous history of line‐related thrombus. The most common strategy employed (73% of those using anticoagulation) was to recommend 1 mg of warfarin. Conclusions: The results demonstrate that a significant number of patients in Australia receive routine anticoagulation, the most popular strategy being the use of low‐dose warfarin. Based on our results there is a clear need for further education regarding the lack of supporting data and the potential harm that may ensue.     

大肠癌术后中心静脉导管真菌感染相关因素分析

目的：探讨大肠癌患者术后中心静脉导管（CVC）真菌感染的相关因素,寻求有效的预防改进措施。方法：回顾性分析100例住院的大肠癌手术患者（手术组）留置CVC的感染情况,并分析感染的相关因素。与同时期62例术后化疗患者（化疗组）留置CVC的感染情况进行比较。结果：手术组中7例（7．00％）发生CVC相关性真菌感染,其中6例单纯CVC感染,1例同时合并真菌血症。7例患者均为念珠菌感染,主要为近平滑念珠菌57．1％（4／7）。其感染与术后并发吻合口瘘有关,而与患者年龄、性别、手术方式、肿瘤大小、分期、导管留置时间和置管位置无关。6例患者拔除CVC后感染自愈,1例真菌血症患者抗真菌治疗后痊愈。化疗组没有患者发生导管相关真菌感染,与手术组感染率相比差异有统计学意义,P〈10．05。结论：大肠癌手术后CVC相关真菌感染的主要病原菌是近平滑念珠菌,吻合口瘘可能是其高危因素,及时拔除感染的CVC,可有效地防治导管相关的血行感染。     

Catheter-related infection and thrombosis of the internal jugular vein in hematologic-oncologic patients undergoing chemotherapy: a prospective comparison of silver-coated and uncoated catheters

BACKGROUND: Catheter-related venous thrombosis is one of the most frequent complications of central venous catheters (CVCs). This complication occurs in 4- 40% of patients with hematologic malignancies receiving conventional chemotherapy after placement of CVCs. METHODS: The objective of this prospective study was to assess whether a silver-coated CVC poses an additional risk in the development of catheter-related thrombosis in hematologic-oncologic patients. Patients were randomized to receive either silver-coated polyurethane catheters (BactiGuard; Metacot, Stockholm, Sweden) or uncoated standard polyurethane catheters (Cavatheter, Fresenius AG, Bad Homburg, Germany) for central venous access. Silver-coated catheters (n = 120) and standard catheters (n = 113) were inserted into the jugular vein in 233 consecutive patients. Variables that may be significant for the development of thrombosis were comparable in the two groups. After removal of the CVC, the patency of both jugularian veins internal as well as external was assessed with real-time ultrasound (Sonolayer-SAL-35A; Toshiba, Tokyo, Japan). RESULTS: Four of 233 patients (1.5%) were found to have venous thrombosis. Incomplete occlusion of the internal jugular vein occurred in 2 patients (0.75%, parietal thrombosis), and complete thrombosis, although clinically silent, was found in 2 patients (0.75%). There was no difference between patients with silver-coated and uncoated CVCs. CONCLUSIONS: The authors concluded that this novel silver-coated CVC does not cause a higher rate of central venous thrombosis compared with standard CVCs. The low overall incidence of central venous thrombosis might be attributed to the routine application of low-dose heparin in our patients during chemotherapeutic treatment.     

Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized study in cancer patients.

PURPOSE: The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. PATIENTS AND METHODS: In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. RESULTS: Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. CONCLUSION: In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.     

Central venous catheter placement by an interventional radiology unit: An Australian experience

The aim of this retrospective study was to analyse the outcomes of central venous catheter (CVC) placement carried out by an interventional radiology unit. A review of our hospital records identified 331 consecutive patients who underwent insertion of a tunnelled or non‐tunnelled CVC between January 2000 and December 2004. Key outcome measures included the technical success rate of CVC insertion and the percentage of immediate (<24 h), early (24 h–30 days) and late (>30 days) complications. A total of 462 CVCs were placed under radiological guidance, with an overall success rate of 98.9%. Immediate complications included one pneumothorax, which was diagnosed 7 days after subclavian CVC insertion, and eight episodes of significant haematoma or bleeding within 24 h of CVC insertion. No cases were complicated by arterial puncture or air embolus. Catheter‐related sepsis occurred in 2% of non‐tunnelled CVC and 8.9% of tunnelled CVC. The overall incidence of catheter‐related sepsis was 0.17 per 100 catheter days. As the demand for chemotherapy and haemodialysis grows with our ageing population, interventional radiology suites are well placed to provide a safe and reliable service for the placement of central venous access devices.     

恶性肿瘤中心静脉置管并发血栓22例分析

目的：探讨中心静脉置管肿瘤患者发生血栓的原因及治疗对策。方法：对2003年-2006年808例中心静脉置管的恶性肿瘤患者发生深静脉血栓的病例进行回顾性分析。结果：22例发生深静脉血栓,4例腋静脉,18例股静脉。结论：术后及下肢静脉置管的肿瘤患者易发生血栓。贵要和锁骨下静脉穿刺置管可减少血栓发生。     

Identifying Risk Factors for Anthracycline Chemotherapy-induced Phlebitis in Women with Breast Cancer: An Observational Study

AimsAnthracycline chemotherapy administered via a peripheral cannula results in severe anthracycline chemotherapy-induced phlebitis (ACIP) in about 20–30% of patients. Administering chemotherapy via a central venous catheter (CVC) prevents ACIP. However, CVCs are associated with an increased risk of thrombosis and sepsis. Our aim was to identify risk factors associated with severe ACIP and to provide evidence about the individual risk of developing symptoms.Materials and methodsA prospective observational study of 263 women with breast cancer receiving peripheral administration of anthracycline chemotherapy at a UK cancer centre was conducted between May 2016 and January 2018. Data were collected at baseline and every 3 weeks following each chemotherapy treatment, using both healthcare professional- and participant-reported symptom assessments.ResultsAfter three cycles of chemotherapy, 27% of participants experienced severe ACIP. Factors associated with symptom severity were identified as: arm used for chemotherapy administration, epirubicin dose, age, pre-existing hypertension, comorbidity, ethnic group and pain during chemotherapy administration. The sequence of arm used for chemotherapy administration was the single most significant factor (P < 0.001). When alternating arms were used no other risk factor was influential. Where alternating arms were not used, younger age and higher dose were associated with higher-grade symptoms, with age being more influential than dose. The cumulative effect of increasing symptom severity with repeated cycles was also identified (P < 0.001).ConclusionIt is recommended that a CVC is not routinely required for women with breast cancer who have not undergone an axillary node clearance and receive chemotherapy in alternate arms. The need for a CVC for women who are planned to receive all anthracycline chemotherapy cycles in the same arm should be assessed in the light of peripheral venous access assessment and the key risk factors of age, dose and number of cycles.     

Enoxaparin can be used safely in patients with severe thrombocytopenia due to intensive chemotherapy regimens

Treatment with intensive chemotherapy regimens is frequently complicated by severe thrombocytopenia. During the period of severe thrombocytopenia, anticoagulant treatment is not uncommonly indicated for thromboembolic events or thromboprophylaxis in these patients. We report 10 hematological patients treated with intensive chemotherapy protocols that were anticoagulated with enoxaparin for catheter related central venous thrombosis and thromboprophylaxis. During the period of severe thrombocytopenia the dosages of enoxaparin were reduced and no major bleeding occurred. Based on our experience we suggest that reduced dosages of low molecular weight heparins may be used relatively safely during transient severe thrombocytopenia.     

Primary thromboprophylaxis for cancer patients with central venous catheters--a reappraisal of the evidence

Venous thromboembolism (VTE) is responsible for an estimated 25 000 deaths per annum in UK hospital practice. It is well established that many of these deaths could be prevented through the use of appropriate thromboprophylaxis. This issue is of particular relevance in oncology practice, where the risks of VTE and bleeding are both significantly higher than those observed in general medical patients. Cancer patients with in-dwelling central venous catheters (CVCs) are at particularly high risk of developing thrombotic complications. However, the literature has produced conflicting conclusions regarding the efficacy of using routine primary thromboprophylaxis in these patients. Indeed such is the level of confusion around this topic, that the most recent version of the American College of Chest Physicians (ACCP) guidelines published in 2004 actually reversed their previous recommendation (published in 2001). Nevertheless, minidose warfarin continues to be routinely used in many oncology centres in the UK. In this article, we have performed a systematic review of the published literature regarding the efficacy and the risks, associated with using thromboprophylaxis (either minidose warfarin or low-dose LMWH) in cancer patients with CVC. On the basis of this evidence, we conclude that there is no proven role for using such thromboprophylaxis. However, asymptomatic CVC-related venous thrombosis remains common, and further more highly powered studies of better design are needed in order to define whether specific subgroups of cancer patients might benefit from receiving thromboprophylaxis.     

Central venous catheter-related infection due to Candida membranaefaciens, a new opportunistic azole-resistant yeast in a cancer patient: a case report and a review of literature

An unusual central venous catheter (CVC)-related infection caused by Candida membranaefaciens in a patient with non-Hodgkin's lymphoma is described. Clinical signs and microbiological results observed in this case may support the hypothesis of an emerging CVC-related fungaemia, because of new azole-resistant yeast, successfully treated with liposomal amphotericin B. To date C. membranaefaciens (the teleomorph of Pichia membranaefaciens) has traditionally been considered non-pathogenic and this report seems to be the first case of systemic fungal infection. We believe that another fungus can be added to the list of opportunistic strains.     

胃癌合并门静脉癌栓的CT表现

为了提高对胃癌合并门静脉癌栓CT表现的认识,回顾性分析1990年5月23日~2005年9月18日7例经胃镜、手术病理及临床确诊的胃癌合并门静脉癌栓患者的资料。7例患者均行CT平扫加增强检查。CT检查均显示胃病变区胃壁明显不规则增厚,3例患者出现肝转移灶。门脉癌栓栓子发生的部位主要位于门脉主干段(7例),其中2例累及左、右分支;1例累及肠系膜上静脉;1例同时累及肠系膜上静脉和脾静脉。7例患者中有5例癌栓未见明显强化,2例患者增强后癌栓轻度强化。5例患者癌栓的所在门脉主干明显扩张,门脉血流阻断,5例患者扩张的门脉主干周围可见明显强化迂曲的侧枝血管影,其中2例出现大量腹水。研究结果显示,虽然绝大部分门静脉癌栓由原发性肝癌引起,但门静脉癌栓也可以是由进展期胃癌形成,密切结合临床资料,两者鉴别诊断并不困难。     

Prevention and management of long-term catheter related infections in cancer patients

Long-term central venous catheters (CVC) are necessary in the care of cancer patients. However, catheter-related bloodstream infection (CRBSI) is commonly associated with serious complications resulting in considerable morbidity and mortality. The diagnosis of CRBSI frequently requires catheter removal to confirm the diagnosis by either quantitative or semiquantitative catheter culture method. Differential time to positivity, whereby a nonquantitative blood culture drawn from the CVC that becomes positive at least 2 hr earlier than the peripheral blood culture, is a new method for the diagnosis of CRBSI without removing the catheter. Prevention of CRBSI may be accomplished with the use of strict infection control measures, antimicrobial-impregnated catheters; and antibiotic-lock technique, as well as other methods. Once infection develops, management of long-term CRBSI is dictated by the type of organism, the severity of the infection, and availability of other venous access sites. If the infection is caused by Staphylococcus aureus, gram-negative bacilli, or Candida, the catheter should be removed and systemic antimicrobial therapy given for 10-14 days or longer in cases of complicated or deep-seated infection. In some cases, where there is no other venous access site, the catheter can remain in place, but a combination of systemic antimicrobials and antibiotic-lock therapy should be used.     

Central venous catheters in acute blood malignancies

A one-year prospective study to evaluate the use of central venous catheters in intensive treatment of patients with acute blood malignancies was performed. Forty-seven catheters in 29 patients were studied. In spite of thrombocytopenia in several patients, no severe bleeding episodes were observed. Five patients with agranulocytosis had episodes of bacterial growth in the blood. Four patients had a clinical infection in the subcutaneous tunnel of the catheter. Bacterial growths on the tips of the catheters were found in three cases. Six patients died during the observation period, none of these was in remission. One of these patients had a growth of coagulase negative staphylococci in the blood, and another on the tip of the catheter, without any other known source of infection. The use of central venous catheters facilitates patient care and minimizes discomfort. It is associated with acceptable complications, necessitating meticulous insertion techniques, and careful daily care on the ward or at home.