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.     

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.     

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.     

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.     

Local infusion of urokinase for the lysis of thrombosis associated with permanent central venous catheters in cancer patients

We assessed the efficacy of local fibrinolytic therapy in 35 axillary-subclavian vein thromboses (SVT) that occurred in cancer patients with percutaneous central venous catheters (CVC). These catheters were indwelling for a median of 1 month (range, one day to 10 months) before thrombosis developed. Urokinase was administered at a dose of 500 to 2,000 U/kg/h. Complete lysis occurred in 25 of 30 thrombi that were directly infused, after a median of four days. Complete lysis occurred in one of 12 thrombi that could not be directly infused with urokinase and in two of six with associated phlebitis. Eighty-one percent of the thrombi that were symptomatic for less than 1 week before treatment resolved, compared with 56% present for longer than 1 week. Sixteen patients who had complete (12) or partial (four) thrombolysis did not have their CVCs removed. All four patients with partial thrombolysis had recurrent thrombosis at a median of eight days (range, one to 90). Only two patients who had complete thrombolysis had recurrent thrombosis, at 8 and 16 months. Only minor hemorrhagic toxicity was seen.     

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.     

Ultrasound (US) guided central venous catheterization of internal jugular vein on over 65-year-old patients versus blind technique

BACKGROUND AND OBJECTIVES: Performing a central venous catheterization (CVC) on older patients for long-term central intravenous therapy could be a very important procedure. It could be associated with a high incidence of related complications, especially on over 65-year-old, high risk, selected patients. METHODS: The authors analyzed the results of 72 central venous CVC of internal jugular vein performed on over 65-year-old patients with ultrasound (US) guide from January 1998 to April 2003. RESULTS: The average performing time was 4 min, with 98.7% of success, 0% of major complications, and 4.1% of minor complications (one mild vagal hypotension and two catheter dislocation). CONCLUSIONS: The US guided technique is a safer procedure especially in older patients; it affords an easier and more rapid cannulation of a central vein, drastically reducing major and minor complications.     

Management of cutaneous reactions and mechanical complications of central venous access devices in pediatric patients with cancer: algorithms for decision making

Surgically placed central venous catheters (CVCs) facilitate the delivery of medication and nutrition support for patients with malignant disease. There is little information regarding allergic reactions to materials used for standard CVC care or about mechanical complications associated with CVC use. This study describes allergic and mechanical complications that occurred in a series of 288 CVCs implanted in 238 pediatric patients with malignant disease. There were 20 episodes of cutaneous reactions to standard central line dressing care (alcohol/povidone-iodine/TegadermTM), 13 incidents of catheter exit site infections, and 14 experiences of mechanical breakage in external CVCs. Complications were managed from algorithms that provided a systematic sequence of nursing interventions for alternative catheter dressing techniques and line repair. Only two CVCs were removed because of progressive infection, and one catheter was removed because of occlusion after repair.     

Safety and efficacy of alteplase for restoring function in occluded central venous catheters: results of the cardiovascular thrombolytic to open occluded lines trial.

PURPOSE: To evaluate the safety and efficacy of alteplase (TPA) for restoring function to occluded central venous catheters (CVCs). PATIENTS AND METHODS: The study design was a phase III, open-label, single-arm multicenter trial. Subjects with occluded, nondialysis CVCs were enrolled. All subjects received a 2-mg dose of TPA within the dysfunctional catheter lumen that was allowed to dwell for 30 to 120 minutes. Functionality was tested at 30 and 120 minutes. If the CVC remained obstructed at 120 minutes, a second 2-mg TPA dose was allowed to dwell for 30 to 120 minutes. The primary safety end point was the rate of intracranial hemorrhage (ICH) within 5 days of treatment, and serious adverse events were recorded up to 30 days. RESULTS: Nine hundred ninety-five patients received treatment (female, 562; male, 433; mean age, 50.7 years; range, 2 to 91 years). CVCs treated were as follows: single (26%), double (39%), or triple (6%) lumen catheters or ports (29%). The primary end point was 0% ICH within 5 days. There were no cases of death, major bleeding episodes, or embolic events attributable to treatment. Flow was successfully restored in 52% and 78% of CVCs at 30 and 120 minutes after one dose, and 84% and 87% at 30 and 120 minutes after a second dose, respectively. Restoration of flow was 86%, 93%, 90%, and 79%, for single, double, and triple lumen catheters and ports, respectively. Estimated 30-day catheter patency was 74%. CONCLUSION: A regimen of up to two 2-mg doses of TPA is safe and effective for the restoration of flow to occluded central venous catheters.     

Preoperative duplex venous imaging in the assessment of patients with venous access

Occult or clinically apparent central venous thrombosis frequently complicates central venous catheter placemnt in patients requiring long-term vascular access. Thirty-three patients, aged 12-83 years, underwent duplex scanning of the internal jugular, axillary, and brachial veins prior to placement of long-term venous access catheters. Twenty-seven patients underwent duplex scanning because of a prior history of either long-term or short-term central venous access. Of 12 patients with a history of long-term central venous access, without complications, 42% (5/12) had an abnormal duplex scan demonstrating thrombosis. Duplex scans on 15 patents having complications associated with central venous access demonstrated thrombosis of one or more of the central veins, 46% (7/15). Five patients who underwent duplex scanning without a history of a previous central venous catheter or other indication were found to have normal normal central veins. In 13 patients found to have thrombosis or obstruction by duplex scan, the surgeon was directed to successful venous access in all cases. Normal findings were very helpful in confirming that the venous system was normal in selected patients. In approximately 40% of patients with a history of venous access, catheters were found to have evidence of thrombosis of one or more of the central veins. In 13 patients found to have thrombosis or obstruction by duplex scan, the surgeon was directed to a successful site for venous access in all cases. © 1993 Wiley-Liss, Inc.     

(Mis)placed central venous catheter in the left superior intercostal vein

BACKGROUND: Chest X-ray is routinely performed to check the position of the central venous catheter (CVC) inserted through the internal jugular or subclavian vein, while the further evaluation of CVC malfunction is usually performed by contrast venography. In patients with superior vena cava obstruction, the tip of the catheter is often seen in collateral mediastinal venous pathways, rather than in the superior vena cava. In such cases detailed knowledge of thoracic vessel anatomy is necessary to identify the exact location of the catheter. CASE REPORT.: We report a case of 32-year-old female patient with relapsing mediastinal lymphoma and previous superior vena cava obstruction with collateral azygos-hemiazygos venous pathways. The patient had CVC inserted through the left subclavian vein and its position was detected by CT to be in the dilated left superior intercostal vein and accessory hemiazygos vein. Considering that dilated accessory hemiazygos vein can tolerate infusion, the CVC was left in place and the patient had no complaints related to CVC (mal)position. Furthermore, we present anatomical and radiological observations on the azygos-hemiazygos venous system with the special emphasis on the left superior intercostal vein. CONCLUSIONS: Non-contrast CT scans can be a valuable imaging tool in the detection of the CVC position, especially in patients with renal insufficiency and contrast media hypersensitivity.     

Central venous catheter-related complications in children with oncological/hematological diseases: an observational study of 418 devices.

BACKGROUND: The use of indwelling central venous catheters (CVCs) has become commonplace in the management of children undergoing anticancer treatment. Several types of CVC are available, while information on complications observed in children is scarce. We describe the experience of two tertiary care centers in Italy that prospectively followed up three types of CVC used at both institutions over a 30-month period. PATIENTS AND METHODS: Between January 2000 and May 2002, double-lumen (DL) or single-lumen (SL) Hickman-Broviac (HB) catheters, and single-lumen pressure-activated safety valve (PASV) catheters were used and prospectively evaluated. Four types of possible complication were defined a priori: mechanical, thrombotic, malfunctioning and infectious. RESULTS: Four hundred and eighteen CVCs (180 SL-HB, 162 DL-HB and 76 PASV) were inserted in 368 children, for a total of 107 012 catheter days at risk of complication. At least one complication occurred while using 169 of the devices (40%): 46% of the DL-HB, 46% of the PASV and 33% of the SL-HB (P=0.02) catheters. Subjects with hematological malignancies or non-malignant diseases had significantly more complications than those with solid tumors (P <0.0001). Overall, 234 complications were documented: 93 infectious [complication rate per 1000 catheter days at risk (CR)=0.87], 84 malfunctioning (CR=0.78), 48 mechanical (CR=0.45) and nine thrombotic (CR=0.08). SL-HB had statistically fewer infectious complications, while PASV had more mechanical complications. In a multivariate regression model, the most significant risk factors for having a CVC complication were hematological disease [relative risk (RR)=3.0; 95% confidence interval (CI) 1.8-4.8] and age <6 years at CVC insertion (RR=2.5; 95% CI 1.5-4.1). As for the type of CVC, compared with SL-HB, the DL-HB catheter had a statistically significant two-fold increased risk of any complication (RR=2.1; 95% CI 1.2-3.6), while the PASV catheter had a borderline RR of 1.8 (95% CI 1.0-3.6). Analysis by tumor type showed a higher risk of any kind of complication in patients with solid malignancies who had received a DL-HB catheter as compared with an SL-HB catheter (RR=7.2; 95% CI 2.8-18.7). CONCLUSIONS: CVCs may cause complications in up to 40% of patients, with type of CVC, underlying disease and patient age being the three main factors that affect the incidence of CVC-related complications. SL-HB catheters have the best performance.     

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。     

Prophylaxis of central venous catheter-related thrombosis with minidose warfarin: analysis of its use in 427 cancer patients

BACKGROUND: In the past few years, several studies have been performed to evaluate thrombosis prophylaxis with warfarin in cancer patients with central venous catheters (CVC), but the analysis of these studies does not allow firm conclusions to be drawn. PATIENTS AND METHODS: Four hundred and twenty-seven cancer patients were evaluated. Each received warfarin at a dose of 1 mg/daily as prophylaxis, starting the day after CVC positioning until its removal. RESULTS: The catheters were monitored for a mean of 168 days (range 22-706). There were 9 thrombotic events (1.8%). Overall, International Normalised Ratio (INR) elevation occurred in 55 (12.8%) patients. Bleeding was observed in 15 (3.5%) patients, 10 of whom had elevated INR levels. Of these, all were treated with continuous-infusion 5-Fluorouracil (5-FU)-based regimens. CONCLUSION: Minidose warfarin can protect from clinical thrombosis, but can induce an alteration in INR values and/or haemorrhagic symptoms in patients being treated with 5-FU-based regimens.     

The Hohn catheter in the management of haemopoietic stem cell transplant recipients

Patients undergoing bone marrow transplantation require a reliable venous access. The authors have tested the feasibility and safety of a new, silicone, open-ended, non-tunnelled central venous catheter (CVC), the Hohn catheter (Bard Access System, USA). From January 1994 to December 1996, 58 Hohn were inserted into 56 bone marrow transplant (BMT) patients (26 women : 30 men; mean age 38 years, range 19–62 years). The CVC was inserted percutaneously at the bedside by puncture of the subclavian or the internal jugular vein. No early complications were observed. Significant late complications were infection (documented only in 14%) and accidental removal (11%). The median life of the CVC was 30 days (range 15–180 days). Major causes of removal were end of use (25 patients) and fever (19 patients; but infection was documented only in eight patients). In spite of the relatively small gauge (5 Fr), the Hohn catheter was adequate for rapid or high density infusion. In our experience, the unique features of the Hohn CVC (versatility, optimal biocompatibility, bedside management, low cost) may contribute to making the BMT procedure safer and less expensive.     

Clinical and economic effects of central venous catheters on oncology patient care

Central Venous Catheters (CVC) and ports are essential devices to the medical care of cancer patients. Every year about one million CVCs are inserted in cancer patients. The field of oncohematology is making a great contribution to the development of new models of catheters and to the use of innovative materials. New therapeutic protocols, based on continuous administration and higher doses of anticancer drugs with relative phlebitis problems, have raised the issue of long CVC in situ permanence. Different complications are related to the intravascular catheters such as those associated with insertion (pneumothorax, damages to arteries and nerves), or with the duration of catheterization (thrombosis and infections). Furthermore, Catheter-Related Bloodstream Infections (CRBSI), in particular, cause significant mortality and excessive hospital costs. The aim of this prospective study was to analyze the costs related to the use of polyurethane (PU) CVC. 44 patients with a non tunneled double lumen PU CVC in place were followed for 6 months, and for each patient, time of permanence, possible antibiotic prophylaxis, blood parameters, adverse events and medical treatments were monitored. Our results suggest that physicians should pay greater attention to the correlation between new medical devices and the real benefit for the patient, and economic consequences.     

The effectiveness of chlorhexidine-silver sulfadiazine impregnated central venous catheters in patients receiving high-dose chemotherapy followed by peripheral stem cell transplantation

Immuno-compromised patients are at high risk for all kind of infections. Unfortunately, they need central venous catheters (CVCs), which are associated with infectious complications. In this study we examined the effectiveness of chlorhexidine-silver sulfadiazine impregnated CVCs to prevent catheter-related infections in patients receiving high-dose chemotherapy followed by peripheral stem cell transplantation. This historical cohort study evaluated 139 patients of whom 70 patients were provided with non-impregnated CVCs and 69 patients with impregnated CVCs. Patients were treated for different diagnoses. The median number of days a CVC stayed in situ was 18 in the non-impregnated group and 16 in the impregnated group. The median duration of neutropenia of patients with non-impregnated CVCs was 9 days compared with 7 days of patients with impregnated CVCs. We found less catheter colonization (CC) in patients with chlorhexidine-silver sulfadiazine CVCs (RR 0.63, 95% CI 0.41–0.96; P  = 0.03). Catheter-related blood stream infections (CR-BSI) were also diminished, but this result was not statistically significant (RR 0.15, 95% CI 0.02–1.15; P  = 0.06). The reduction in CC and CR-BSI did not diminish the incidence of fever. We conclude that the use of chlorhexidine–silver sulfadiazine impregnated CVCs provide an important improvement in the attempt to reduce CC and CR-BSI.     

Catheter-related thrombosis in cancer patients: pathophysiology, diagnosis, and management

Central venous catheters (CVCs) are commonly used in oncology patients. Up to 50% of CVCs are complicated by thrombosis within the catheter or the blood vessel. These thrombi are the result of local tissue damage, the catheter itself, and the thrombophilia of cancer. Frequent flushes with saline or heparin may reduce the frequency of catheter dysfunction but do not reduce the rate of deep venous thrombosis (DVT) in the catheterized blood vessel. Efforts to use prophylactic heparin or warfarin to reduce catheter-related DVT have not been rewarding.     

Managing peripherally inserted central catheter‐related venous thrombosis: How I do it

Imaging‐guided insertion of central venous catheters, either in the form of a peripherally inserted central catheter (PICC) or through a subclavian or a jugular approach, is becoming the preferred method of acquiring long‐term venous access for a variety of therapeutic purposes. The most significant complication from central venous catheters is thrombosis of the catheterized vein. Venous thrombosis related to the insertion of PICC lines is conventionally treated with line removal followed by anticoagulation. Direct thrombolysis with urokinase, using the lumen of the PICC line to facilitate the insertion of the infusion catheter is a simple, safe and effective treatment option. In this article, we describe our experience with this procedure and the technique used.     

Complications des sites veineux implantés pour chimiothérapie

Introduction

Implantable venous catheters have become indispensable tools in the management of patients requiring long-term intravenous treatment. The objective of this work is to evaluate the implantable venous catheter technique, and incidents and complications that may arise during installation or during use.

Methods

Retrospective study over six years covering all implantable venous catheters laid between January 2003 and December 2008 in order to establish chemotherapy for cancer.

Results

A total of 580 implantable venous catheters were placed in 412 men and 168 women. The average age of the patients was 43 years, with ages ranging from 16 to 76 years. Ninety percent of the catheters were placed on the right and 10% on the left, of which half were due to failure of insertion on the right. The sites of the insertion were 42% cephalic, 31% external jugular, 17% internal jugular, and 10% subclavicular. The average duration of catheter use was 7 months, with duration ranging from 10 days to 36 months. Seventeen percent of the patients presented at least a complication dominated by infection or thrombosis. In our series, there was no mortality due to the insertion.

Conclusion

Comparing our results with that of the literature, we recommend the use of polyurethane catheter, to prefer the jugular route, and the insertion be done by an experienced operator.