Central Venous Access Devices Occlusion Research Articles

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Pediatric Central Venous Access Device Lock Solutions: A Network Meta-analysis.

Central venous access device (CVAD) locks are routine interventions used to prevent and treat complications, such as infection, thrombosis, and catheter occlusion. To compare and rank lock-solutions for prevention or treatment of complications in pediatrics. Design Systematic review and network meta-analysis. Five databases and 2 clinical trial registries were searched. Published and unpublished randomized controlled trials that enrolled pediatric patients with a CVAD and compared the effectiveness of lock-solutions. Data extraction was conducted by 2 reviewers. Odds ratio (OR) for prevention or treatment of CVAD-associated bloodstream infection (BSI), thrombosis, occlusion, CVAD-failure, and mortality were calculated, with point estimates ranking lock-solutions. Twenty-nine studies were included. Chelating agents and antibiotic locks given as prevention were associated with lower odds (OR: 0.11; 95% confidence interval [CI]: 0.02-0.67; moderate-quality; OR: 0.19; 95% CI: 0.05-0.79, high-quality, respectively) of CVAD-associated BSI compared with heparinized saline (reference). Preventative thrombolytic agents had lower odds (OR: 0.64, 95% CI: 0.44-0.93; low-quality) of CVAD occlusion, whereas ethanol had higher odds (OR: 2.84, 95% CI: 1.31-6.16; high-quality) compared with heparinized saline (reference). No lock solution had effects on thrombosis prevention or treatment, CVAD-failure, CVAD-associated BSI treatment failure, or mortality. There was substantial uncertainty around the point estimates because of the limited number of studies for outcomes and study heterogeneity. More high-quality studies are needed to confirm the efficacy of lock solutions. Chelating agents and antibiotic locks may be effective for CVAD-associated BSI prevention in pediatrics. Thrombolytic agents can be an option for CVAD occlusion prevention, whereas ethanol may not be recommended.

Routine Catheter Lock Solutions in Pediatric Cancer Care: A Pilot Randomized Controlled Trial of Heparin vs Saline.

BackgroundCentral venous access devices (CVADs) are integral to cancer care provision. Despite the high prevalence of CVAD complications in children with cancer, preventative strategies are understudied.ObjectiveThe aim of this study was to assess study feasibility, occlusive events, thrombolytic use, adverse events, and direct costs of catheter lock solutions.MethodsA single-center, parallel-group, pilot randomized controlled trial was undertaken at a tertiary-referral pediatric hospital in Australia. Children 18 years or younger with an oncological or malignant hematological condition and a CVAD were eligible. Participants were 1:1 randomized to (1) normal or (2) heparinized (10–100 U/mL; CVAD-type dependent) saline lock solutions.ResultsOf 217 children assessed for eligibility, 61 were recruited and randomized to normal (n = 30; 3850 CVAD days) or heparinized (n = 31; 4036 CVAD days) saline. Eligibility (52%) and recruitment (54%) feasibility targets were not met. Protocol adherence was high (95% assessments), with no attrition. Parent/clinician satisfaction of interventions was high (median, 10/10 clinicians/parents). Complete CVAD occlusion occurred in heparin only (n = 2, 6.7% CVADs; incidence rate [IR], 0.49/1000 CVAD days [0.06–1.78]). Central venous access device partial occlusion was detected in 23.3% of CVADs in heparin (n = 7; IR, 2.73/1000 CVAD days [1.36–4.87]) and 13.8% of CVADs in normal saline (n = 4; IR, 2.59/1000 CVAD days [1.24–4.77]). Thrombolytic agents were used in 16.7% heparin (5 CVADs) and 3.5% normal saline (1 CVAD). Adverse events did not differ between groups.ConclusionMultisite randomized controlled trials examining CVAD locks are safe, but strategies and resources to increase recruitment and eligibility are required.Implications for PracticeBoth routine CVAD lock solutions seem safe but may not prevent all forms of CVAD-associated harm.

Efficacy of 4% tetrasodium ethylenediaminetetraacetic acid (T-EDTA) catheter lock solution in home parenteral nutrition patients: A quality improvement evaluation.

A functioning and reliable central venous access device is fundamental for home parenteral nutrition patients to administer essential nutrition. Complications of central venous access devices including occlusion, microbial colonization, and biofilm formation are problematic and sometimes life-threatening. A novel lock solution, 4% tetrasodium ethylenediaminetetraacetic acid, has properties that may reduce such complications. The aim of this study was to determine the safety, efficacy, and cost implications of implementing 4% tetrasodium ethylenediaminetetraacetic acid to prevent catheter-related complications in home parenteral nutrition patients. A pre- and post-intervention study was carried over 36 months (12 months pre; 24 months post) by the British Columbia Home Parenteral Nutrition Program in Vancouver, Canada, where 4% tetrasodium ethylenediaminetetraacetic acid was implemented for patients at high risk for central venous access device occlusion and catheter-related infection. Patients were included in the study if they had previous central venous access device complications. The outcomes evaluated were central line-associated bloodstream infection, catheter occlusion requiring thrombolytic treatment, and catheter replacements. In total, 22 out of 105 patients met the inclusion criteria. Two patients were excluded from analyses due to non-adherence and concomitant use of other lock solutions. Post intervention, 20 home parenteral nutrition patients experienced significant reduction in the central line-associated bloodstream infection rate (pre = 1.918/1000 catheter days; post = 0.563/1000 catheter days; p = 0.04) There were no occlusion events reported post intervention. For home parenteral nutrition patients, 4% tetrasodium ethylenediaminetetraacetic acid lock solution effectively reduces the risk of central venous access device complications including occlusions and catheter-related infections.

Prevention of occlusion of cEnTral lInes for children with cancer: An implementation study.

Central venous access devices (CVADs) are vital medical devices to support the treatment of paediatric cancer; however, device occlusion is common, which disrupts treatment. This study aimed to improve the identification and management of CVAD occlusions in children with cancer, as well as to identify the demographic, clinical and device characteristics associated with increased risk for CVAD occlusion. A pre-post-implementation study was conducted at a metropolitan paediatric oncology facility in Australia, using the Theoretical Domains Framework. Patients with a CVAD for anti-cancer therapy were prospectively followed for occlusive events pre- and post- the implementation of clinical resources to support the identification and management of CVAD occlusive events. CVAD occlusion and management data were collected and compared pre- and post-implementation. Risk factors for CVAD occlusion were described by mixed-effects Poisson regression and incident rate ratios (IRR). A total of 133 CVADs were inserted into 131 patients for a total of 6784 catheter days. The incidence of CVAD-related occlusion pre-implementation was 59.7 (95% confidence interval (CI) 51.4-69.0, per 1000 catheter days); compared to 31.6 (95% CI 26.4-37.6); P < 0.01) post-implementation of clinical resources. In multivariate models, other than post-implementation phases (IRR 0.51 (95% CI 0.32-0.81)), only neutropaenia significantly increased the risk of CVAD occlusion (IRR 2.14 (95% CI 1.15-3.97)). CVAD occlusions in paediatric oncology are common. The development and implementation of CVAD occlusion resources to guide the identification and management of occlusive episodes led to a significant decrease in occlusive events.

Use of alteplase to manage central venous access device occlusion

This paper is a clinical review of the management of central venous access device (CVAD) occlusion. Steve Titmarsh explore the causes and consequences of CVAD occlusion, and evaluate the use of thrombolytic therapies to restore catheter function, with a focus on alteplase.

Lean Six Sigma for Intravenous Therapy Optimization: A Hospital Use of Lean Thinking to Improve Occlusion Management

BackgroundContinual improvement is a necessary part of hospital culture. This occurs by identifying opportunities for improvement that influence efficiency while saving money. MethodologyAn investigation of intravenous device-related practices was performed by the nurses of the intravenous access team, pharmacy, and hospital operations at Hartford Hospital using Lean Six Sigma methodology. Central venous access device occlusion and tissue plasminogen activator variability was identified. Using observation, measurement of performance, and root cause analysis, the hospital's practices, policies, and equipment were evaluated for the process of occlusion management. The team utilized a Six Sigma strategy employing the elements define, measure, analyze, improve, and control, which is a disciplined, data-driven methodology that focuses on eliminating defects (waste). Interventions initiated based on the assessment performed by the team using the define, measure, analyze, improve, and control approach included replacement of negative displacement needleless connectors with antireflux needleless connectors and specialty team assessment before tissue plasminogen activator use. ResultsOver the course of the 26-month study, Hartford Hospital experienced a 69% total reduction in tissue plasminogen activator use representing a total 26-month savings of $107,315. Other cost savings were reflected in areas of flushing, flushing disposables, and in a decrease in needleless connector consumption. Central line-associated bloodstream rates fell 36% following the intervention as an unexpected secondary gain, resulting in further savings related to treating this nonreimbursable hospital-acquired condition. ConclusionsThis study examined the influence of using Lean Thinking and Six Sigma methodology as a tool in saving hospital money, resulting in better patient outcomes.

Complications of Central Venous Access Devices: A Systematic Review.

The failure and complications of central venous access devices (CVADs) result in interrupted medical treatment, morbidity, and mortality for the patient. The resulting insertion of a new CVAD further contributes to risk and consumes extra resources. To systematically review existing evidence of the incidence of CVAD failure and complications across CVAD types within pediatrics. Central Register of Controlled Trials, PubMed, and Cumulative Index to Nursing and Allied Health databases were systematically searched up to January 2015. Included studies were of cohort design and examined the incidence of CVAD failure and complications across CVAD type in pediatrics within the last 10 years. CVAD failure was defined as CVAD loss of function before the completion of necessary treatment, and complications were defined as CVAD-associated bloodstream infection, CVAD local infection, dislodgement, occlusion, thrombosis, and breakage. Data were independently extracted and critiqued for quality by 2 authors. Seventy-four cohort studies met the inclusion criteria, with mixed quality of reporting and methods. Overall, 25% of CVADs failed before completion of therapy (95% confidence interval [CI] 20.9%-29.2%) at a rate of 1.97 per 1000 catheter days (95% CI 1.71-2.23). The failure per CVAD device was highest proportionally in hemodialysis catheters (46.4% [95% CI 29.6%-63.6%]) and per 1000 catheter days in umbilical catheters (28.6 per 1000 catheter days [95% CI 17.4-39.8]). Totally implanted devices had the lowest rate of failure per 1000 catheter days (0.15 [95% CI 0.09-0.20]). The inclusion of nonrandomized and noncomparator studies may have affected the robustness of the research. CVAD failure and complications in pediatrics are a significant burden on the health care system internationally.

Comparison of complication rates of Hickman® catheters versus peripherally inserted central catheters in patients with acute myeloid leukemia undergoing induction chemotherapy

Central venous access devices (CVADs) are used for intravenous therapy in patients with hematological malignancies. There are limited data comparing catheter outcomes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy. A retrospective review comparing the incidence of early and late CVAD-associated complications and their effect on CVAD removal was performed in patients with AML undergoing induction chemotherapy between 2007 and 2011. Overall, 64 Hickman® catheters and 84 peripherally inserted central catheters (PICCs) were inserted. There was a trend toward increasing use of PICCs. The rate of CVAD occlusion was higher in PICCs compared to Hickman catheters (48.2% vs. 3.2%), for a rate of 20.43 vs. 1.25 per 1000 CVAD-days (p = 0.0001). There was no significant difference in the rates of CVAD-associated thrombosis, premature removal, blood stream infection (BSI) and CVAD-related BSI. Importantly, there was no significant difference in the rate of CVAD removal between Hickman catheters and PICCs for the duration that the CVADs were in place. The choice of type of CVAD inserted into patients with newly diagnosed AML will depend on ease of catheter placement, cost, perception of frequency and severity of complications, and clinician preference.

Fibrolase: Trials and Tribulations

Fibrolase is the fibrinolytic enzyme isolated from Agkistrodon contortrix contortrix (southern copperhead snake) venom. The enzyme was purified by a three-step HPLC procedure and was shown to be homogeneous by standard criteria including reverse phase HPLC, molecular sieve chromatography and SDS-PAGE. The purified enzyme is a zinc metalloproteinase containing one mole of zinc. It is composed of 203 amino acids with a blocked amino-terminus due to cyclization of the terminal Gln residue. Fibrolase shares a significant degree of homology with enzymes of the reprolysin sub-family of metalloproteinases including an active site homology of close to 100%; it is rapidly inhibited by chelating agents such as EDTA, and by alpha2-macroglobulin (α2Μ). The enzyme is a direct-acting thrombolytic agent and does not rely on plasminogen for clot dissolution. Fibrolase rapidly cleaves the A(α)-chain of fibrinogen and the B(β)-chain at a slower rate; it has no activity on the γ-chain. The enzyme exhibits the same specificity with fibrin, cleaving the α-chain more rapidly than the β-chain. Fibrolase was shown to have very effective thrombolytic activity in a reoccluding carotid arterial thrombosis model in the canine. A recombinant version of the enzyme was made in yeast by Amgen, Inc. (Thousand Oaks, CA, USA) and called alfimeprase. Alfimeprase is identical to fibrolase except for a two amino acid truncation at the amino-terminus and the insertion of a new amino-terminal amino acid in the truncated protein; these changes lead to a more stable enzyme for prolonged storage. Alfimeprase was taken into clinical trials by Nuvelo, Inc. (San Carlos, CA), which licensed the enzyme from Amgen. Alfimeprase was successful in Phase I and II clinical trials for peripheral arterial occlusion (PAO) and central venous access device (CVAD) occlusion. However, in Phase III trials alfimeprase did not meet the expected end points in either PAO or CVAD occlusion and in a Phaase II stroke trial, and Nuvelo dropped further development in 2008.

Safety and Efficacy of Alfimeprase in Subjects with Occluded Central Venous Access Devices: The SONOMA-2 Study.

Introduction: The infusion of chemotherapy and blood products is facilitated by central venous access devices (CVAD), and the occurrence of thrombotic CVAD occlusion results in delays in these crucial therapies. Alfimeprase is a direct-acting thrombolytic agent with the potential to rapidly re-establish catheter function.Methods: SONOMA-2 was a multicenter, multinational, randomized, double blind, placebo-controlled phase 3 study evaluating the efficacy and safety of alfimeprase in subjects with occluded CVADs. Subjects were randomized in a 2:1 ratio to receive either intra-luminal alfimeprase (A) at a dose of 3.0 mg or placebo (P). Study drug was delivered in a total volume of 2 mL. If re-establishment of catheter function was not established within 30 minutes, a second dose of the same study drug was instilled and allowed to dwell for an additional 30 minutes. Re-establishment of catheter function was assessed by an attempt to withdraw 3 mL of blood and infuse 5 mL of saline. The primary efficacy endpoint was re-establishment of a functional CVAD at 15 minutes post first infusion. The primary efficacy analysis prespecified a significance level of ≤ 0.00125.Results: A total of 303 patients (201 (A), 102 (P)) were randomized into the study. Treatment groups were well balanced at baseline with respect to overall demographics, catheter insertion site, and median days since last failed infusion or blood draw. The primary efficacy endpoint, re-establishment of a functional CVAD at 15 minutes post first infusion, was achieved in 34.3% (A) versus 21.6% (P) of subjects (p = 0.022). The cumulative proportion of subjects with re-establishment of a functional CVAD at 30 minutes post first or second infusions was 52.7% (A) versus 30.4% (P) (p = 0.0002). Rates of adverse events (65.8% (A), 59.4% (P)), serious adverse events (15.5% (A), 16.8% (P)), and hemorrhagic adverse events (3.6% (A), 10.9% (P)) were comparable between treatment groups. No intracranial hemorrhages were observed.Conclusions: Alfimeprase restored CVAD function in a numerically greater fraction of subjects than did placebo; however, the study did not achieve statistical significance for the primary endpoint at the prespecified p-value of ≤ 0.00125 necessary for demonstrating efficacy with a single pivotal study. Alfimeprase was well tolerated. Further clinical studies are underway that evaluate a higher and more concentrated alfimeprase dose which preclinical studies predict will result in greater efficacy. Alfimeprase remains a promising potential candidate for use in patients with CVAD occlusion.

Central venous access device occlusions: part 2: nonthrombotic causes and treatment.

Home care nurses commonly care for patients with central venous access devices (CVAD) for administration of a variety of infusion therapies. Catheter occlusion is a potential complication. In the February 2002 issue of the etiology and treatment of thrombotic occlusions were described. This month, the focus is on nonthrombotic causes of CVAD occlusion.

Safe and cost effective use of alteplase for the clearance of occluded central venous access devices.

To determine whether cryopreserved solutions of the thrombolytic agent alteplase could be used as a safe, effective, and economically reasonable alternative to urokinase in patients presenting with occluded central venous access devices (CVADs). Alteplase has been reported as an efficacious alternative to urokinase for treatment of occluded CVADs. However, the practicality of using alteplase as the thrombolytic of choice for this indication remained conjectural. To make this approach economically feasible, alteplase was diluted to 1 mg/mL and 2.5-mL aliquots were stored at -20 degrees C until use. A need to confirm that the cryopreserving and thawing of the reconstituted solution did not compromise the safety and efficacy reported from prior trials was recognized. A quality assessment initiative was undertaken to concurrently monitor the safety and efficacy of this approach. Patients presenting with occluded CVADs received a sufficient volume of the thawed alteplase solution to fill the occluded catheter(s). Data, including efficacy, adverse reactions, dwell time, and catheter type, were collected over a 5-month period. One hundred twenty-one patients accounting for 168 attempted clearances were assessable for safety and efficacy. One hundred thirty-six (81%) of the 168 catheter clearance attempts resulted in successful catheter clearance (95% confidence interval, 74% to 86%). No adverse events were reported. Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVADs when stored at -20 degrees C for 30 days. The ability to cryopreserve alteplase aliquots makes it an economically reasonable alternative to urokinase in the setting of CVAD occlusion.

Recombinant tissue plasminogen activator for central venous access device occlusion

Maintaining and restoring the function of central venous access devices (CVAD) is an important component of pediatric oncology nursing care. Until 1999, Abbokinase Open Cath (urokinase; Abbott, Abbott Park, IL), a thrombolytic agent was the product primarily used to resolve thrombotic occlusions in intravascular devices. Changes in the manufacturing process mandated by the FDA have resulted in a lack of availability of Abbokinase Open Cath. Recombinant tissue plasminogen activator (TPA) has provided an alternative solution for clearing occluded intravascular devices. This article reviews the literature supporting the use of TPA for CVAD clearance and discusses the process of how to administer the medication. Future implications for research about the use of TPA, and its role in the care of CVADs are discussed.

Lock method using sodium hydroxide solution to clear occluded central venous access devices

Occlusion of central venous access devices (CVADs) is not an uncommon problem duringlong-term parenteral nutrition. A number of techniques have been developed to deal with obstructed CVADs. This study investigated the effectiveness of the sodium hydroxide (NaOH) lock method for gradual CVAD occlusion. When a progressively declining flow was noticed, 0.1 N NaOH solution was injected into the CVAD and locked. Nineteen CVAD occlusions in 11 home parenteral nutrition patients were treated Sixteen of 19 trials cleared the occlusions, whereas 3 of 19 failed. One of the failures was due to a mechanical occlusion and the other two were able to be restored by using ethanol. There were no significant complications. The benefits of this method are: (1) a shorter treatment time and a lower dose than NaOH infusion therapy, (2) it does not require hospital admission and (3) it does not result in bursting of the catheter.