Long-term Central Venous Access Devices Research Articles

Impact of insertion site on complications in central venous access devices.

There is still debate over the safest route for the placement of long-term central venous access devices. The aim of this study was to review a large, single-institution experience to determine the impact of access location on peri-operative complications. The records of patients undergoing subcutaneous port (SQP) and tunneled catheter insertion over a seven-year period were reviewed. Vein cannulated (subclavian (SCV) versus internal jugular (IJ) vein), and 30-day complications were assessed. Surgical complications included pneumothorax, hemothorax, infections, arrhythmia or malpositioning requiring intervention. A total of 1,309 patients were included (618 SQP, 691 tunneled catheters). The location for insertion was SCV (909, 69.4%) and IJ (400, 30.6%). There were 69 complications (5.2%) (41, 4.5% SCV, 28, 7.0% IJV) including: malpositioning/malfunctioning (SCV 13, 1.4% and IJV 14, 3.0%), pneumothorax (SCV 4, 0.4% and IJV 1, 0.3%), hemothorax (SCV 0 and IJV 1, 0.3%), arrhythmia (SCV 1, 0.1%, and IJV 0), and infection within 30days of placement (SCV 20, 2.2% and IJ 11, 2.8%). The complication rates were not significantly different based on site (p = 0.080). There was no significant difference in complication rates when using the subclavian versus the internal jugular vein as the site for long-term central venous access. III, retrospective comparative study.

Providing Hemostasis for Long-Term Central Venous Access Device (LTCVAD) Placement in Patients with Factor VIII (FVIII) Inhibitors

Introduction and Objectives: Inhibitors against FVIII can occur in the haemophilic and non-haemophilic patients. Venous access is critical to the treatment of the patients with FVIII inhibitors and the prevention of complications due to bleeding. However, there is no guide to the selection of the most appropriate LTCVADs in these patients. The aim of this study was to investigate the providing hemostasis and the results of the placement of LTVADs in patients with FVIII inhibitors.Patients and Methods: The results of the LTCVADs placement were investigated in 8 patients (7 males, 1 female) with FVIII inhibitors (a median age of 45 years, range 25-73). FVIII inhibitors were revealed in 6 patients with congenital haemophilia A, in the woman with von Willebrand disease and in the patient with acquired idiopathic haemophilia A. In all patients plasma FVIII activity was below 1%, and inhibitor titers were from 120 to 450 BU/ml. Indications, early and delayed complications, hemostatic therapy and implanted period were evaluated. All LTCVADs were monitored from insertion to removal.Results. In total, thirteen LTCVADs were placed. The indications for placement of LTCVADs were Immune tolerance therapy (5 patients), hemostatic therapy (2 patients) and chemotherapy in woman with von Willebrand disease and mammary cancer. Central Venous Port System (Bard Access System) was implanted in hemophilia A patient simultaneously wiht the hip replacement surgery. The hemostasis in this patient was provided by recombinant activated coagulation factor VII (rFVIIa) (Coagil VII, Generium, Russia) 120 mcg/kg every 2 hours for 2 weeks. However, when rFVIIa therapy after surgery was stopped and antibiotic therapy continued extensive hematoma on the breast developed and the port system was removed. In 7 patients 12 peripherally inserted central catheters (PICCs) (GROSHONG PICC CATHETER, Bard Access System) were placed. PICCs were inserted into brachial veins. All patients received rFVIIa (120 mcg/kg) before the procedure, and experienced no bleeding complications. After the procedure, one patient had some bleeding and required repeated administration of rFVIIa (90 mcg/kg). Overall mean PICC dwell time was 176 days (median 120 days; range 5-463). One patient died due to gastrointestinal bleed in 5 days. Occlusions occurred in 3 cases on 30, 120 and 300 days after PICC insertion in two patients. Accidental withdrawals occurred in one patient. At all three patients PICCs have been placed repeatedly. The obstruction rate was 30% (1.9 per 1000 PICC-days). No infection or thrombotic complications were observed. Six patients are still using a catheter without apparent problems for more than 4 months. There were no specific problems in using PICC with immune tolerance therapy and chemotherapy.Conclusion. PICCs appear safe to use in the patients with FVIII inhibitors, with acceptably low rates of infectious or thrombotic complications. Catheter occlusion was the most common complication.Single administration of the rFVIIa provides safe implantation of the PICCs in patients with FVIII inhibitors. PiCCs placement provides significant economic savings (decrease in rFVIIa requirements). DisclosuresNo relevant conflicts of interest to declare.

Safety and Comfort of Domestic Bortezomib Injection in Real-Life Experience

BackgroundSubcutaneous bortezomib administration has huge advantages to treat patients with poor venous accesses and, generally, it is convenient for both patients and physicians because it overcomes problems related to a prolonged intravenous infusion or the insertion of a long-term central venous access device. Moreover, overall incidence of peripheral neuropathy is lower with the subcutaneous administration in comparison with the intravenous route, reducing the possibility of a therapy discontinuation related to this adverse event. In recent years, for some non-histotoxic anti-cancer drugs, such as rituximab, trastuzumab or cladribine, the subcutaneous route, as alternative to the intravenous one, has been successfully compared and the possibility of a self-administration modality for adequately informed patients or adult care-givers was also demonstrated. Previous randomized trials proved that subcutaneous bortezomib administration is pharmacologically and clinically equivalent to the intravenous one, with an equal safety profile.AimsWe focused our retrospective study on a population of elderly patients not eligible for high-dose therapy with autologous hematopoietic stem-cell transplantation (HDT-HSCT) as frontline therapy, but treated with VMP regimen, that was demonstrated to be highly effective in this setting.MethodsSince 2009, in our Hematology Unit, 63 patients requiring bortezomib for the treatment of MM, in association with orally administered prednisone and melphalan (VMP), performed subcutaneous injection of bortezomib at home for personal or logistic reasons. Initially, the drug was administered by qualified personnel; subsequently, the patient or an adult care-giver learned to inject it in the deltoid muscle. Patient were supplied with bortezomib in ready-to-use plastic syringes, where the drug was appropriately constituted in saline solution, under hood in sterile conditions by qualified personnel.Patients received 4-weeks cycles of melphalan (9 mg/m2) and prednisone (60 mg/m2) on days 1 to 4, bortezomib (1.0 mg/m2) on days 1, 8, 15 and 22 (mean number of cycles 9, r. 3-12), according to a schedule adapted for frail patients [4,9,10]. The first cycle was usually administered at hospital to assess and confirm the safety of this route.ResultsData about efficacy and safety were similar to those observed in major clinical trials. We evaluated the overall response rate (ORR): 45 patients (72%) achieved a response; in particular, 20 patients (32%) achieved a complete response (CR), 25 patients (40%) achieved a partial response (PR) and 6 patients (9%) achieved a minimal response (MR) after four cycles of therapy and the adverse events rate (Table 1). Moreover, results showed the equal incidence of adverse events (AEs) for domestic administration (Table 1). There were no severe AEs requiring hospitalization or access to Emergency Unit.ConclusionsThese results confirm the effectiveness and safety of subcutaneous bortezomib, in a real-life-experience, and define a new possibility of safe auto-administration in a comfortable domestic setting. We believe that domestic treatment can significantly improve the quality of life of the patients, avoiding unnecessary transfer to the hospital without reducing treatment efficacy. [Display omitted] DisclosuresPane:Novartis: Honoraria, Speakers Bureau.

Bacteremia due to Ralstonia mannitolilytica: A report of the first case in Peru.

The first report of Ralstonia mannitolilytica bacteremia in Peru is presented. The patient was a pediatric cancer patient with a long-term central venous access device. For the diagnosis, the MicroScan Walk Away 96 automated system was used. 16S rDNA was amplified by conventional PCR, and the bacterial genus and species were identified by genetic sequencing. In addition, the bacterial resistance profile to major antimicrobials was determined. The article discusses the need to actively monitor Ralstonia mannitolilytica, especially in hospital areas of immunocompromised patients.

GAVeCeLT-WoCoVA Consensus on subcutaneously anchored securement devices for the securement of venous catheters: Current evidence and recommendations for future research.

Subcutaneously anchored securement devices (or subcutaneous engineered securement devices) have been introduced recently into the clinical practice, but the number of published studies is still scarce. The Italian Group of Long-Term Central Venous Access Devices (GAVeCeLT)-in collaboration with WoCoVA (World Congress on Vascular Access)-has developed a Consensus about the effectiveness, safety, and cost-effectiveness of such devices. After the definition of a panel of experts, a systematic collection and review of the literature on subcutaneously anchored securement devices was performed. The panel has been divided in two working groups, one focusing on adult patients and the other on children and neonates. Although the quality of evidence is generally poor, since it is based mainly on non-controlled prospective studies, the panel has concluded that subcutaneously anchored securement devices are overall effective in reducing the risk of dislodgment and they appear to be safe in all categories of patients, being associated only with rare and negligible local adverse effects; cost-effectiveness is demonstrated-or highly likely-in specific populations of patients with long-term venous access and/or at high risk of dislodgment. Subcutaneously anchored securement is a very promising strategy for avoiding dislodgment. Further studies are warranted, in particular for the purpose of defining (a) the best management of the anchoring device so to avoid local problems, (b) the patient populations in which it may be considered highly cost-effective and even mandatory, (c) the possible benefit in terms of reduction of other catheter-related complications such as venous thrombosis and/or infection, and-last but not least-(d) their impact on the workload and stress level of nurses taking care of the devices.

Vascular Access in Children With Blood Disorders or Cancer.

* Abbreviations: CVAD — : central venous access device miniMAGIC — : Michigan Appropriateness Guide for Intravenous Catheters in Pediatrics PICC — : peripherally inserted central catheter Children with disorders of blood and cancer frequently require long-term central venous access devices (CVADs) for recurrent blood draws, blood transfusions, and infusion of caustic medications, such as chemotherapy, immunotherapy, and biological agents. Their diagnosis puts them at increased risk for other comorbidities, such as systemic infection from neutropenia, along with thrombosis secondary to malignancy, immobility, chemotherapeutic agents (eg, steroids and asparaginase), or the underlying thrombogenic state of sickle cell disease.1–3 Therefore, careful consideration is needed when choosing a CVAD that is best for these patients. The guidelines/recommendations in this article are not American Academy of Pediatrics policy, and publication herein does not imply … Address correspondence to Julie Jaffray, MD, Division of Hematology, Oncology, and Bone Marrow Transplant, Department of Pediatrics, Children’s Hospital Los Angeles, 4650 Sunset Blvd, Mailstop #54, Los Angeles, CA 90027. E-mail: jjaffray{at}chla.usc.edu

Utility of Blood Cultures and Empiric Antibiotics in Febrile Pediatric Hemophilia Patients With Central Venous Access Devices.

Children with hemophilia frequently require long-term central venous access devices (CVADs) for regular infusion of factor products. Hemophilia patients are not immunocompromised, but the presence and use of CVADs are associated with infections including bacteremia. Currently, the utility of blood cultures in evaluation of the febrile hemophilia patient with an indwelling CVAD is unknown, nor is optimal empiric antibiotic use. We performed a retrospective cross-sectional study of febrile immunocompetent hemophilia patients with CVADs presenting to a large academic urban pediatric emergency department from 1995 to 2017. We used a natural language processing electronic search, followed by manual chart review to construct the cohort. We analyzed rate of pathogen recovery from cultures of blood in subgroups of hemophilia patients, the pathogen profile, and the reported pathogen susceptibilities to ceftriaxone. Natural language processing electronic search identified 181 visits for fever among hemophilia patients with indwelling CVADs of which 147 cases from 44 unique patients met study criteria. Cultures of blood were positive in 56 (38%) of 147 patients (95% confidence interval, 30%-47%). Seventeen different organisms were isolated (10 pathogens and 7 possible pathogens) with Staphylococcus aureus and coagulase-negative Staphylococcus species as the most common. Thirty-four percent of isolates were reported as susceptible to ceftriaxone. Positive blood cultures were more common in cases involving patients with inhibitors (n = 71) versus those without (n = 76), odds ratio, 7.4 (95% confidence interval, 3.5-15.9). This was observed irrespective of hemophilia type. Febrile immunocompetent hemophilia patients with indwelling CVADs have high rates of bacteremia. Empiric antimicrobial therapy should be targeted to anticipated pathogens and take into consideration local susceptibility patterns for Staphylococcus aureus.

Multivariate analysis on complications of central venous access devices in children with cancer and severe disease influenced by catheter tip position and vessel insertion site (A STROBE-compliant study)

ContextReliable long-term central venous access device (CVAD) is essential for the management of pediatric patients with cancer or chronic diseases. However, there is no general consensus for optimal catheter tip location and vessel insertion site in children. ObjectiveThis single center study analyzes the risk of complications associated with long-term upper body CVAD and evaluates them with respect to catheter tip location as well as vessel insertion site. DesignPediatric patients who received long-term upper body CVAD from January 2008 through April 2017 and underwent radiographic documentation of the tip location were retrospectively included in the study. Data on demographics, catheter tip location on chest x-ray, intraoperative vessel insertion sites and postoperative complications were analyzed. Catheter tip location was categorized as “high” (above the right mainstem bronchus), “medium” (at the level of the bronchus), and “low” (below the right mainstem bronchus). Distance to the carina was measured as well. ResultsA total of 396 patients, 74.7% suffering from cancer were included in our study (mean age 6.3 ± 0.3 years). Complications occurred in about one fourth of all patients. Catheter-related blood stream infections (BSI) (n = 40, 36.4%) were most prevalent, but catheter tip position or vessel insertion site had no impact on the risk of infections. Dislodgement (n = 27, 24.6%) and occlusion (n = 11, 10.0%) were more frequent in “high” positioned catheter tips.While there was one patient who developed arrhythmia, no case of cardiac perforation, and in particular, no catheter-related death was recorded in our series. The vessel insertion site seemed to have no influence on the complication frequency of CAVDs. ConclusionThe catheter tip position seems to have an impact on the catheter-related complication profile in children. To avoid complications, we recommend avoiding a “high” localization of the catheter tip above the right main bronchus. “Low” catheter tip placement was associated with the lowest dislocation rate.Given the overall low complication rate, insertion and use of CVADs in children can generally be considered as safe.

A prospective audit evaluating use of urokinase in oncology patients with occluded central venous access devices.

This article reports the results of a single-site prospective audit evaluating the safety and effectiveness of urokinase (Syner-Kinase®) to restore patency in central venous access devices (CVADs) for cancer patients. CVADs are routinely inserted to allow the safe and timely administration of systemic anti-cancer therapies; therefore, catheter dysfunction can interrupt the treatment schedule and adversely affect patient outcome. The aim was to contribute to the development of evidence-based, standardised, best practice guidelines. Prospective data were collected from all patients (n=22) identified with an occluded CVAD, requiring use of Syner-Kinase to manage a persistent withdrawal occlusion or total occlusion, over a 6-month period. Findings revealed a single administration of Syner-Kinase for catheter occlusion clearance to be effective in 92% of cases. Results suggest that use of the thrombolytic agent is well-tolerated and an effective means of restoring patency for long-term CVADs in cancer patients.

Fungal biofilm associated with long-term central venous access device: Complications and therapeutic difficulties

Las infecciones fungicas asociadas a biofilms en dispositivos biomedicos son refractarias al tratamiento antifungico y habitualmente se requiere del retiro oportuno del dispositivo, asi como la administracion de antifungicos sistemicos. Presentamos el caso de una paciente mujer de 36 anos que recibe terapia para el dolor administrada por dispositivo intravascular de larga permanencia, cateter Port-A-Cath, y que desarrollo candidemia y endocarditis por Candida parapsilosis asociada al cateter; el cual tuvo que ser retirado mediante toracotomia por persistencia de la infeccion a pesar de la terapia antifungica sistemica. Se evidencio extenso biofilm rodeando al cateter, con aislamiento de Candida parapsilosis y se completaron seis semanas de tratamiento antifungico con evolucion clinica favorable.

A narrative review of long-term central venous access devices for the intensivist.

Long-term central venous access devices are increasingly prevalent and consequently often encountered by intensivists. This review introduces the different types of long-term central venous access devices, outlines their potential utility, examines potential complications associated with their use and outlines an approach to the management of these complications.

Impact of a modified Broviac maintenance care bundle on bloodstream infections in paediatric cancer patients.

Background: During intensive chemotherapy, bloodstream infection (BSI) represents an important complication in paediatric cancer patients. Most patients carry a long-term central venous access device (CVAD). Improved maintenance care of these vascular catheters may decrease the risk of BSI.Methods: Intervention study (adapted CVAD prevention protocol) with two observation periods (P1: 09-2009 until 05-2011; P2: 09-2011 until 05-2013); prospective surveillance of all laboratory confirmed BSIs. In P2, ready to use sterile NaCl 0.9% syringes were used for CVAD flushing and octenidine/isopropanol for the disinfection of catheter hubs and 3-way stopcocks. Results: During P1, 84 patients were included versus 81 patients during P2. There were no significant differences between the two patient populations in terms of median age, gender, underlying malignancy or disease status (first illness or relapse). Nearly all CVADs were Broviac catheters. The median duration from implantation to removal of the CVAD was 192 days (Inter-quartile-range (IQR); 110–288 days) in P1 and 191 days (IQR; 103–270 days) in P2. 28 BSI were diagnosed in 22 patients in P1 (26% of all patients experienced at least one BSI) and 15 BSI in 12 patients in P2 (15% of all patients). The corresponding results for incidence density (ID) were 0.44 (CI95 0.29–0.62) for P1 vs. 0.34 (0.19–0.53) BSI per 100 inpatient days for P2 and for incidence rate (IR) 7.76 (5.16–10.86) in P1 vs. 4.75 (2.66–7.43) BSI per 1,000 inpatient CVAD utilization days. In P1, 9 BSI were caused by CoNS vs. only 2 in P2 (IR 2.49; CI95 0.17–4.17 vs. 0.63; CI95 0.08–1.72). In P1 two BSI (7%) lead to early removal of the device. During P2 one CVAD was prematurely removed due to a Broviac-related BSI (6.7%).Conclusion: The preventive protocol investigated in this study led to a reduction of BSI in paediatric cancer patients. This result was clinically relevant but – due to insufficient power in a single centre observation – the difference did not reach statistical significance. The most pronounced trend in BSI reduction was observed for CoNS infections. Thus, improving maintenance care of the CVAD may result in lower CVAD-linked infection rates. The higher acquisition cost of the ready to use NaCl 0.9% flushing syringes and octenidine/propanol hub disinfection were probably balanced by cost savings in the intervention period.

The ISP (Safe Insertion of PICCs) protocol: a bundle of 8 recommendations to minimize the complications related to the peripherally inserted central venous catheters (PICC)

The ISP (Safe Insertion of PICCs) protocol: a bundle of 8 recommendations to minimize the complications related to the peripherally inserted central venous catheters (PICC). The insertion of a peripherally inserted central venous catheter (PICC) is not without risks. The Italian Group for the Study of Long-Term Central Venous Access Devices (GAVeCeLT) has developed a protocol (SIP: Safe Implantation of PICCs) with the aim of minimizing the risks which may be associated with the placement of PICCs. The protocol is based on recommendations available in the literature and on the main clinical practice guidelines. The SIP protocol, a bundle of evidence-based recommendations, it is is easy to use, inexpensive, and cost-effective. If routinely used and carefully inplemented, it greatly reduces complications such as failure of venipuncture, accidental arterial puncture, damage of median nerve, infection and catheter related venous thrombosis.

A Single Center's Experience with Candida parapsilosis Related Long-Term Central Venous Access Device Infections: The Port Removal Decision and Its Outcomes

Pediatric cancer patients have an increased risk of potentially life-threatening fungal infections such as Candida parapsilosis, associated with long-term CVADs. The Infectious Diseases Society of America (IDSA) guidelines on Candida catheter-related bloodstream infections recommend systemic antifungal therapy and catheter removal. In this study, we focused on our experience with antifungal failure due to totally implanted catheter-associated C. parapsilosis bloodstream infections. We investigated cases leading to port removal in pediatric malignancy patients and the associated patient outcomes. In the first phase of the study, a retrospective chart review was performed to collect patient information, including primary disease; time from hospitalization to port-related candidemia; antifungal drug choice; and the time at which port removal occurred. During the second phase, antifungal susceptibility tests for C. parapsilosis were performed in our microbiology laboratory. All patients had fevers and were neutropenic at the time of candidemia diagnosis. The mean duration between the first isolation of Candida parapsilosis from the port samples to the port removal was 9.75 ± 5.29 days for 11 patients. Patient fevers lasted for a mean time of 16.22 ± 6.51 days. The median recovery duration from fever after CVC removal was four days (range 2–12 days). The median duration for achieving negative blood cultures, following antifungal treatment was 18 days (range 10–27 days). Our data favored the removal of catheters in the presence of ongoing fever, as suggested by the guidelines, independent of the chosen antifungal treatment. Future studies with large samples are needed to evaluate the effects of catheter removal on mortality rates and patient outcomes.

Pain and discomfort management during central venous catheter insertion

Pain and discomfort management during central venous catheter insertion

Central Venous Access: Evolving Roles of Radiology and Other Specialties Nationally Over Two Decades

The aim of this study was to evaluate national trends in central venous access (CVA) procedures over 2 decades with regard to changing specialty group roles and places of service. Aggregated claims data for temporary central venous catheter and long-term CVA device (CVAD) procedures were extracted from Medicare Physician/Supplier Procedure Summary Master Files from 1992 through 2011. Central venous catheter and CVAD procedure volumes by specialty group and place of service were studied. Between 1992 and 2011, temporary and long-term CVA placement procedures increased from 638,703 to 808,071 (+27%) and from 76,444 to 316,042 (+313%), respectively. For temporary central venous catheters, radiology (from 0.4% in 1992 to 32.6% in 2011) now exceeds anesthesiology (from 37% to 22%) and surgery (from 30.4% to 11.7%) as the dominant provider group. Surgery continues to dominate in placement and explantation of long-term CVADs (from 80.7% to 50.4% and from 81.6% to 47.7%, respectively), but radiology's share has grown enormously (from 0.7% to 37.6% and from 0.2% to 28.6%). Although volumes remain small (<10% of all procedures), midlevel practitioners have experienced >100-fold growth for most services. The inpatient hospital remains the dominant site for temporary CVA procedures (90.0% in 1992 and 81.2% in 2011), but the placement of long-term CVADs has shifted from the inpatient (from 68.9% to 45.2%) to hospital outpatient (from 26.9% to 44.3%) setting. In all hospital settings combined, radiologists place approximately half of all tunneled catheters and three-quarters all peripherally inserted central catheters. Over the past 2 decades, CVA procedures on Medicare beneficiaries have increased considerably. Radiology is now the dominant overall provider.

The Intracavitary ECG Method for Positioning the Tip of Central Venous Catheters: Results of an Italian Multicenter Study

The aim of this multicenter study was to assess the feasibility, safety, and accuracy of the intracavitary ECG method for real-time positioning of the tip of different types of central venous catheters. A total of 1444 catheter insertions in adult patients were studied in eight Italian centers (539 ports, 245 PICCs, 325 tunneled CVCs, 335 non-tunneled CVCs). Patients with no visible P wave at the standard baseline ECG were excluded. Depending on the type of catheter and its purpose, the target was to position the tip either (a) at the cavo-atrial junction, or (b) in the lower third of the superior vena cava, or (c) in the upper part of the atrium. The final position was verified by a post-procedural chest x-ray. The method was feasible in 99.3% of all cases. There were no complications potentially related to the method itself. At the final x-ray control, 83% of all tips were positioned exactly at the target; 12.4% were positioned within 1-2 cm from the target, but still in a correct central position; only 3.8% were malpositioned. The mismatch between intra-procedural ECG method and post-procedural x-ray was significantly lower when the x-ray was taken in supine position. Our multicenter study confirms that the intracavitary ECG method for real time verification of tip position is accurate, safe, feasible in all adult patients and applicable to any type of short-term or long-term central venous access device.

Remifentanil for the insertion and removal of long-term central venous access during monitored anesthesia care

Study Objective To determine the analgesic efficacy of three different rates of remifentanil infusion in patients undergoing insertion or removal of long-term central venous access devices during monitored anesthesia care and local anesthetic field infiltration. Design Double-blinded, randomized, controlled study. Setting Operating theatre of an University hospital. Patients 44 unpremedicated, ASA physical status 1 and 2 patients, aged 18-65 years, undergoing insertion or removal of a Port-a-Cath or Hickman catheter. Interventions Patients sedated with a propofol target-controlled infusion were randomly allocated to three groups: Group R25 (n = 14), Group R50 (n = 15), and Group R75 (n = 15), to receive remifentanil 0.025, 0.05, and 0.075 μg/kg/min, respectively. Rescue remifentanil 0.5 μg/kg was administered for pain scores > 3. The remifentanil infusion rate was maintained constant unless respiratory and/or cardiovascular unwanted events occurred, whereupon the rate was adjusted in 0.01 μg/kg/min decrements as necessary. Measurements Pain scores (primary outcome), sedation, and movement scores (secondary outcomes) were assessed during local anesthetic infiltration of the anterior chest wall and 5 other procedural steps. Main Results All infusion rates had equal analgesic efficacy, as shown by comparable pain scores, number of rescue boluses, and number of patients requiring rescue analgesia. Excessive sedation was associated with the highest remifentanil rate such that Group R75 patients were significantly more sedated than Groups R25 or R50 at selective procedural steps ( P < 0.05). More Group R75 patients (6/15) required remifentanil rate reduction than did patients from Group R50 (1/15) or Group R25 (0/14), P < 0.01, most commonly because of respiratory depression. Conclusions For the insertion or removal of long-term central venous access devices, all three remifentanil infusion rates proved to be equally analgesic-efficient. However, the excessive sedation and tendency to respiratory and cardiovascular events associated with the highest remifentanil infusion rate renders such a rate less desirable for this purpose.

A Phase 3 Prospective Randomized International Study (MMY-3021) Comparing Subcutaneous and Intravenous Administration of Bortezomib In Patients with Relapsed Multiple Myeloma

AbstractAbstract 312 Background:Bortezomib (VELCADE®) is approved in the US and Europe for the treatment of patients with multiple myeloma (MM) in both the frontline and the relapse settings. The recommended dose of bortezomib is 1.3 mg/m2 administered as a 3- to 5-second bolus intravenous (IV) injection. As an alternative to IV delivery, subcutaneous (SC) administration of bortezomib may be a good option for some patients, particularly those with poor venous access, since it would eliminate the need for repeated IV access or insertion of long-term central venous access devices, improving convenience for some patients and physicians. In a randomized phase 1 trial of SC versus IV bortezomib in 24 relapsed or refractory MM patients, both routes of administration demonstrated similar systemic drug exposure and proteasome inhibition, good local tolerability and, importantly, comparable response rates and safety profiles (Moreau et al. Haematologica 2008). A large, multicenter, international, randomized, phase 3 open-label trial was therefore undertaken to compare SC and IV administration in patients with previously treated MM to confirm these preliminary findings. Methods:Eligible patients were aged ≥18 years with measurable secretory MM who had relapsed or progressed following prior systemic therapy and had a Karnofsky performance status of ≥70%. Patients who had received prior bortezomib or >3 previous lines of therapy, or who had peripheral neuropathy or neuropathic pain of NCI CTCAE grade ≥2 were excluded. Patients were randomized 2:1 to receive SC or IV bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 every 21 days for a total of eight cycles. SC injection sites were the thighs or abdomen, and the injection site was rotated for subsequent injections within a cycle. IV injections were administered at a concentration of 1 mg/ml as a 3- to 5-second IV push, and SC injections were administered at 2.5 mg/ml. For cycles 1–4, patients received bortezomib monotherapy. After 4 cycles, if a patient had no change or partial response (PR) as the best response and had not progressed, oral dexamethasone 20 mg could be added on the day of and day after bortezomib dosing (days 1, 2, 4, 5, 8, 9 and 11, 12) in the next 4 cycles. At the end of 8 cycles, patients who had an unconfirmed PR or who were evolving steadily to a delayed PR could receive two additional cycles of study medication. The primary endpoint was overall response rate (ORR; complete response [CR + PR]) after 4 cycles. Response was evaluated using EBMT response criteria, modified with the addition of the response categories of near CR (nCR) and very good partial response (VGPR). Secondary endpoints were CR, nCR and VGPR rates after 4 cycles, ORR after 8 cycles including the effect of adding dexamethasone, duration of response (DOR), time to progression (TTP), progression-free survival, 1-year survival, and time to response. Safety and tolerability of the two administration routes, including local tolerability of SC administration, were also assessed. Pharmacokinetics (PK) and pharmacodynamics (PD) (via whole blood 20S proteasome inhibition assay) were evaluated in a subset of patients. Results:Between July 2008 and February 2010, 222 patients from 53 centers in 10 countries across Asia, Europe and South America were enrolled and randomized to SC or IV bortezomib (148 SC, 74 IV). 32 patients (18 SC, 14 IV) in 8 centers participated in the PK/PD substudy. The primary study analysis will occur in October 2010. Conclusion:Final data for all primary and secondary endpoints will be presented during the meeting, including time-to-event data for DOR, TTP and 1-year survival rate, as well as PK/PD data. Disclosures:Moreau:Jansen-Cilag: Honoraria; Millennium Pharmaceuticals, Inc.: Advisory board, Honoraria; Celgene: Honoraria. Off Label Use: Discussion of Velcade administered as an SC rather than an IV bolus is included. Leleu:Jansen-Cilag: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Co-Pharma: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Robak:Johnson & Johnson: Research Funding. Kropff:ORTHO BIOTECH: Honoraria; Celgene: Honoraria. Cavet:OrthoBiotech: Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Research Funding. Parasuraman:Millennium Pharmaceuticals, Inc.: Employment, Equity Ownership. Feng:Johnson & Johnson: Employment. Skee:Johnson & Johnson: Employment. van de Velde:Johnson & Johnson: Employment, Equity Ownership. Deraedt:Johnson & Johnson: Employment, Equity Ownership. Harousseau:Jansen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Removal of embedded central venous catheters

Background/Purpose Long-term central venous access devices (CVAD) play an integral role in the management of children who require nutritional support, chemotherapy, blood drawing, and transfusion of blood products. Infrequently, the CVAD may be difficult or impossible to remove with traction. Patient Population Four patients, with ages ranging from 6 to 13 years, had 4 CVAD in place for 431, 730, 2232, and 3285 days which could not be removed by manual traction and local exploration. Results With the use of technology developed for removal of embedded transvenous pacemaker catheters, each CVAD was successfully dislodged using a lead locking device (n = 3) or a lead locking device and an excimer laser (n = 1). There were no complications of the procedure in our series. Conclusions There is no consensus on optimal management of embedded CVADs. In this small series, devices used routinely to remove embedded transvenous pacemaker wires were used to extract 4 embedded CVADs without complication; however, use of this technology in pediatric surgical patients is controversial because a small percentage of adult cases have resulted in tamponade or hemothorax, potentially resulting in death. Selection of patients and use of the technology in the appropriate setting are important considerations in weighing the risks vs the benefits of extracting such catheters or leaving them in place.