Ethanol Lock Research Articles

Prevention of catheter-related blood stream infections in children with intestinal failure

Catheter-related bloodstream infections (CRBSIs) account for a major source of morbidity in children with intestinal failure. Many of these patients require long-term central venous access, placing them at significant risk for these infections. The purpose of this review is to highlight the most current strategies and interventions for minimizing CRBSIs in this population. Strategies for the prevention of CRBSIs continue to evolve, although most have not been specifically evaluated in children with intestinal failure. Some of the more recent interventions that are likely to be effective in this population include creating standardized protocols for catheter insertion and maintenance, ethanol lock therapy, and occasional use of antimicrobial catheters and dressings. Every effort must be made to prevent CRBSIs in infants and children with intestinal failure. Disease specific risk factors must be considered when determining the best approach for infection prevention. Because of their long-term access needs, checklists and protocols to maintain strict sterile technique at the time of catheter insertion are useful. Additionally, these children often have some degree of intestinal bacterial overgrowth secondary to dilation and dysmotility. Therefore, the use of antimicrobial locks, catheters and dressings likely provide benefit for some patients.

Evaluation of Ethanol Lock Therapy in Pediatric Patients on Long‐Term Parenteral Nutrition

Pediatric home parenteral nutrition (PN) patients present a unique challenge with risks of catheter-associated bloodstream infections (CABSIs), sometimes requiring subsequent catheter removal. Recurrent infections can lead to line removal and potential loss of venous access in the future. Demonstrate that weekly ethanol lock therapy decreases CABSIs in long-term home PN patients and decreases line removals due to infections. Beginning August 2007, patients receiving PN with a history of multiple previous CABSIs were started on ethanol lock therapy. Seventy percent ethanol solution was instilled into the central venous catheter (CVC) for 2 hours weekly. Episodes of CABSIs and catheter removal due to infection were documented in patients prior to and after ethanol lock therapy. Fourteen patients were followed for an average of 690 days after ethanol lock therapy was initiated. These patients were found to average 9.8 CABSIs per 1000 catheter days prior to starting ethanol lock therapy and only 2.7 CABSIs per 1000 catheter days after ethanol lock therapy (P < .001). Prior to ethanol lock therapy, the group averaged 4.3 catheter removals per 1000 catheter days but only 1.0 catheter removal per 1000 catheter days after ethanol lock therapy. Our group of patients showed a 73% reduction in CABSIs and a 77% reduction in catheter removal due to infection after ethanol lock therapy. In our patient population, weekly ethanol lock therapy for 2 hours is an effective technique to reduce CABSIs and catheter removal in long-term home PN patients.

A randomised controlled trial of Heparin versus EthAnol Lock THerapY for the prevention of Catheter Associated infecTion in Haemodialysis patients – the HEALTHY-CATH trial

BackgroundTunnelled central venous dialysis catheter use is significantly limited by the occurrence of catheter-related infections. This randomised controlled trial assessed the efficacy of a 48 hour 70% ethanol lock vs heparin locks in prolonging the time to the first episode of catheter related blood stream infection (CRBSI).MethodsPatients undergoing haemodialysis (HD) via a tunnelled catheter were randomised 1:1 to once per week ethanol locks (with two heparin locks between other dialysis sessions) vs thrice per week heparin locks.ResultsObserved catheter days in the heparin (n=24) and ethanol (n=25) groups were 1814 and 3614 respectively. CRBSI occurred at a rate of 0.85 vs. 0.28 per 1000 catheter days in the heparin vs ethanol group by intention to treat analysis (incident rate ratio (IRR) for ethanol vs. heparin 0.17; 95%CI 0.02-1.63; p=0.12). Flow issues requiring catheter removal occurred at a rate of 1.6 vs 1.4 per 1000 catheter days in the heparin and ethanol groups respectively (IRR 0.85; 95% CI 0.20-3.5 p =0.82 (for ethanol vs heparin).ConclusionsCatheter survival and catheter-related blood stream infection were not significantly different but there was a trend towards a reduced rate of infection in the ethanol group. This study establishes proof of concept and will inform an adequately powered multicentre trial to definitively examine the efficacy and safety of ethanol locks as an alternative to current therapies used in the prevention of catheter-associated blood stream infections in patients dialysing with tunnelled catheters.Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12609000493246

Drug Shortage–Associated Increase in Catheter-Related Blood Stream Infection in Children

Ethanol lock therapy (ELT) has been shown to reduce the incidence of catheter-related blood stream infections (CRBSI) in intestinal failure (IF) patients. Dosing and frequency remains undefined. Scrutiny of pharmaceutical facilities by the Food and Drug Administration led to the voluntary shutdown of the sole supplier of ethanol, resulting in a nationwide shortage. To conserve supply, we reduced ELT frequency from a daily regimen. We examined the impact that reduction in ELT frequency had on CRBSI in pediatric IF patients. We retrospectively reviewed our parenteral nutrition-dependent IF children. Primary outcome measure was CRBSI per 1000 catheter days after ELT frequency reduction. Data were compared (paired t test) to the same group over 1 year before ethanol shortage and to historical controls. During the shortage 13 outpatients received ELT. Eight met study criteria. Mean ± SD age was 9.1 ± 7.8 years. Mean CRBSI rate per 1000 catheter days was 0.7 ± 1.3 before ELT shortage. This increased to 6.2 ± 2.5 after frequency reduction (P < .001). This CRBSI rate was similar to historical IF children not on ELT (8.0 ± 5.4). Seven children developed CRBSI after frequency reduction, 6 requiring hospitalization, 2 to the ICU. Mean length of stay (15.5 days) averaged $104,783(± 111,034) in hospital charges. Organisms included Gram-negatives (6), methicillin-resistant Staphylococcus aureus (1), and Candida spp (1). ELT frequency reduction resulted in complete failure in CRBSI prophylaxis. The nationwide shortage of this drug has been costly both financially and in patient morbidity.

Activity of ethanol and daptomycin lock on biofilm generated by an in vitro dynamic model using real subcutaneous injection ports

Vancomycin lock solution (LS) is recommended for the conservative treatment of subcutaneous injection port (SIP)-related infections, but may be associated with failure. We used an in vitro dynamic model of biofilm formation in an SIP, based on a continuous flow circulating via a real SIP, to assess the effectiveness of vancomycin (5 mg/ml), daptomycin (5 mg/ml) and ethanol 40 % LS in eradicating a pre-established Staphylococcus epidermidis biofilm. Heparin, Ringer's lactate and enoxaparin sodium LS were used as controls. The logarithmic reductions of colony-forming units (CFU) were compared by Student's t-test. After 24 h of exposure, the vancomycin LS did not exert a greater bactericidal effect than the heparin LS control (mean logarithmic reduction: 2.27 ± 0.58 vs. 1.34 ± 0.22, respectively, p = 0.3). The mean logarithmic reduction was greater with daptomycin LS (5.45 ± 0.14 vs. 0.39 ± 0.12, p < 0.01) and ethanol LS (6.79 ± 1.03 vs. 1.43 ± 0.54, p = 0.02). Bacterial revival after exposure to 24 h of LS was assessed. The mean viable bacteria count was significantly higher for vancomycin LS (9.36 ± 0.10 log(10)CFU) and daptomycin LS (9.16 ± 0.02 log(10)CFU) than for ethanol LS (2.95 ± 1.65 log(10)CFU). Ethanol appeared to be the most attractive option to treat SIP-related infection, but its poor ability to entirely disrupt the biofilm structure may require its use in association with a dispersal agent to avoid renewal of the biofilm.

2012 PPAG Fellows

2012 PPAG Fellows

Ethanol lock therapy in pediatric hematology and oncology

Central venous catheters are essential for treatment of cancer and hematologic disorders in children. Central line-associated bloodstream infection (CLABSI) is the most common important complication and can lead to serious sequelae. Conventional antibiotic treatment is often unsuccessful. Ethanol lock therapy (ELT) has been shown to prevent CLABSI in various patient groups and might also be beneficial as adjunctive treatment for active infection. Efficacy and safety have not been adequately studied in the pediatric hematology/oncology population. Catheter occlusion and intraluminal clots have been reported. Routine use of ELT should not be recommended in this population until more data are available.

Hospital Readmissions for Catheter‐Related Bloodstream Infection and Use of Ethanol Lock Therapy

Catheter-related bloodstream infection (CRBSI) is the most serious long-term infectious complication of long-term home parenteral nutrition (PN). Ethanol is being used more commonly as a catheter locking solution in the home PN setting for prevention of CRBSI; however, no current literature reports the use of ethanol lock (ETL) in skilled nursing facility (SNF) patients. The authors evaluated the number of hospital readmissions for CRBSI and length of stay between SNF (not receiving ETL) and home patients (receiving or not receiving ETL) receiving PN or intravenous fluid therapy. SNF patients had a significantly longer length of stay (LOS) for CRBSI hospital admissions compared with patients receiving PN at home with or without ETL (P < .001; 16 vs 8 vs 8 days). There was no LOS difference for CRBSI between home patients with or without ETL. Home PN patients not receiving ETL were more likely to have a CRBSI from Staphylococcus sp (48% vs 27%; P = .015), whereas SNF PN patients not receiving ETL were more likely to have a CRBSI from Enterococcus sp (16% vs 3%; P = .004). Despite different causative organisms and medical acuity likely affecting the differences observed in LOS, the SNF population is another setting ETL can be used to prevent CRBSI.

In Vitro Analyses of Ethanol Activity against Candida albicans Biofilms

Candida albicans is a common cause of catheter-related bloodstream infections (CR-BSI). Ethanol (EtOH) lock therapy has been attempted despite limited data on optimal dose and duration. Concentrations of 35% EtOH or higher for a minimum of 4 h demonstrated a >99% reduction in mature C. albicans biofilm metabolic activity and prevented regrowth. Concentrations of 10% EtOH or higher reduced C. albicans biofilm formation by >99%. Further investigation of EtOH lock therapy for treatment and prevention of C. albicans CR-BSI is warranted.

Ethanol Locks to Prevent Catheter-Related Bloodstream Infections in Parenteral Nutrition: A Meta-Analysis

Patients with pediatric intestinal failure (IF) depend on parenteral nutrition for growth and survival, but are at risk for complications, such as catheter-related bloodstream infections (CRBSIs). CRBSI prevention is crucial, as sepsis is an important cause of IF-associated liver disease and mortality. We aim to estimate the pooled effectiveness and safety of ethanol locks (ELs) in comparison with heparin locks (HLs) with regard to CRBSI rate and catheter replacements for pediatric IF patients with chronic parenteral nutrition dependence. A systematic review without language restriction was performed on Medline (1948-2010), Embase (1980-2010), and conference programs and trial registries up to December 2010. Search terms included "Catheter-Related Infections," "Catheter," "Catheters, Indwelling," "alcohol," "ethanol," and "lock." Two authors identified 4 retrospective studies for the pediatric IF population. Double, independent data extraction using predefined data fields and risk of bias assessment (Newcastle-Ottawa scale) was performed. In comparison with HLs, ELs reduced the CRBSI-rate per 1000 catheter days by 7.67 events and catheter replacements by 5.07. EL therapy decreased the CRBSI rate by 81% and replacements by 72%. One hundred eight to 150 catheter days of EL exposure were necessary to prevent 1 CRBSI and 122 to 689 days of exposure avoided 1 catheter replacement. Adverse events were rare and included thrombotic events. In pediatric patients with IF, EL is a more effective alternative to HL. Adverse events include thrombotic events.

Impact of a National Shortage of Sterile Ethanol on a Home Parenteral Nutrition Practice

Catheter-related bloodstream infection (CRBSI) is a common and life-threatening infectious complication of home parenteral nutrition (PN). CRBSI is associated with hospital admissions, morbidity, mortality, loss of venous access, and healthcare costs. Ethanol has bactericidal and fungicidal properties, making it an ideal locking solution for preventing CRBSI. The authors report 6 patients with a recurrence of CRBSI when ethanol lock (ETL) was withheld due to a national shortage. This is the first known report of the ramifications of a national ethanol shortage on redevelopment of CRBSI in home PN patients with a history of CRBSIs. This series further supports the existing literature showing that ETL is a viable therapy for the prevention of CRBSIs, warranting prospective research. The impact of an ethanol shortage due to a sole-source manufacturer supports the need for the Food and Drug Administration to regulate pharmaceutical products to avoid shortages.

How to deal with dialysis catheters in the ICU setting

Acute kidney insufficiency (AKI) occurs frequently in intensive care units (ICU). In the management of vascular access for renal replacement therapy (RRT), several factors need to be taken into consideration to achieve an optimal RRT dose and to limit complications. In the medium and long term, some individuals may become chronic dialysis patients and so preserving the vascular network is of major importance. Few studies have focused on the use of dialysis catheters (DC) in ICUs, and clinical practice is driven by the knowledge and management of long-term dialysis catheter in chronic dialysis patients and of central venous catheter in ICU patients. This review describes the appropriate use and management of DCs required to obtain an accurate RRT dose and to reduce mechanical and infectious complications in the ICU setting. To deliver the best RRT dose, the length and diameter of the catheter need to be sufficient. In patients on intermittent hemodialysis, the right internal jugular insertion is associated with a higher delivered dialysis dose if the prescribed extracorporeal blood flow is higher than 200 ml/min. To prevent DC colonization, the physician has to be vigilant for the jugular position when BMI < 24 and the femoral position when BMI > 28. Subclavian sites should be excluded. Ultrasound guidance should be used especially in jugular sites. Antibiotic-impregnated dialysis catheters and antibiotic locks are not recommended in routine practice. The efficacy of ethanol and citrate locks has yet to be demonstrated. Hygiene procedures must be respected during DC insertion and manipulation.

Ethanol Lock Therapy in Reducing Catheter‐Related Bloodstream Infections in Adult Home Parenteral Nutrition Patients

Equivocal data demonstrate the efficacy of ethanol lock therapy (ELT) in preventing catheter-related bloodstream infections (CRBSIs) in home parenteral nutrition (HPN) patients, but it is not currently a standard of practice. The objective of this study is to investigate the efficacy of ELT in reducing the incidence of CRBSIs in HPN patients. Medical records from the Cleveland Clinic database of adult HPN patients with CRBSIs placed on prophylactic ELT were retrospectively studied from January 2006 to August 2009 (n = 31). Outcomes were compared pre- and post-ELT with the patients serving as their own controls. Medical-grade (70%) ethanol was instilled daily into each lumen of the central venous catheter (CVC) between PN infusion cycles. Comparative analysis was performed using McNemar's test and Wilcoxon ranked tests. Thirty-one patients had 273 CRBSI-related admissions prior to ELT in comparison to 47 CRBSI-related admissions post-ELT. Adjusted data for only tunneled CVC pre- and post-ELT showed a similar reduction of CRBSI-related admissions from 10.1 to 2.9 per 1000 catheter days (P < .001). There was also a statistically significant reduction in culture-positive CRBSIs and number of catheters changed pre- and post-ELT. There were no reported side effects or complications in any patient undergoing ELT. This study supports the efficacy and safety of ELT in reducing CRBSI-related admissions in HPN patients and potentially helps reduce the burden of CRBSI-related healthcare costs. This novel technique shows great promise as a standard prophylaxis for CRBSI in HPN patients and must be incorporated in routine practice.

Ethanol Locks Therapy for Resolution of Fungal Catheter Infections

Ethanol locks have been used to treat catheter infections and to decrease the rate at which they occur. Catheter-related infections caused by Candida spp. are especially difficult to manage medically and usually require catheter removal. We report 3 consecutive patients whose catheter infections caused by Candida were successfully treated with a combination of ethanol lock therapy and systemic antifungals.

Ethanol lock therapy for catheter-associated blood stream infections in a pediatric intensive care unit

Ethanol locks are being used to prevent and eradicate central venous catheter infections. This study describes the efficacy of ethanol locks in clearing central venous catheter infections in a pediatric intensive care unit. Retrospective chart review. Pediatric intensive care unit in a tertiary care children's hospital. All patients who received ethanol lock therapy for the treatment of catheter-associated bloodstream infections from January 2008 through December 2009. Ethanol locks of central venous catheters. The study period encompassed 26 catheter-associated bloodstream infections that were treated with ethanol lock therapy. Each catheter-associated bloodstream infection was defined by criteria set forth by the Centers for Disease Control/National Healthcare Safety Network 2008. Patients ranged in age from 77 days to 20 yrs. Of the 26 central venous catheters with associated bloodstream infections, 24 (92%) were sterilized as evidenced by negative repeat blood cultures obtained within 48 hrs of the initiation of the ethanol lock. Thirteen of the 26 treatment ethanol locks were single doses. The dwell times ranged between 4 and 48 hrs with a mean dwell time of 17 hrs. Twenty of the 26 catheters (77%) continued to be used, while six, which included the two treatment failures, were removed. Ethanol locks using 70% ethanol solution with dwell times as short as 4-6 hrs in conjunction with standard antibiotic therapy have 92% effective clearance of catheter-associated bloodstream infection and a 77% catheter salvage rate in our pediatric intensive care unit. The use of 70% ethanol locks appears to be well tolerated and represents a relatively inexpensive pharmacologic intervention that, along with systemic antibiotics, can help treat catheter-associated bloodstream infections and salvage central venous catheters.

Central Venous Catheter Thrombosis Associated With 70% Ethanol Locks in Pediatric Intestinal Failure Patients on Home Parenteral Nutrition

Central venous catheter (CVC) ethanol locks may reduce catheter-related bloodstream infection (CRBSI). Four children with intestinal failure on home parenteral nutrition (HPN) were selected for 70% ethanol locks because of their high rate of CRBSI. The 70% ethanol locks were instilled at a volume equal to the estimated internal volume of the CVC. Two children (aged 4 and 11 years) received 70% ethanol locks as CRBSI prophylaxis; another 2 children (aged 10 and 11 years) received 70% ethanol locks as adjunctive treatment for CRBSI. All 4 children developed either visible thrombosis in the CVC or CVC occlusion. To the authors' knowledge, this is the first report of CVC thrombosis associated with ethanol lock therapy in the pediatric HPN population. Although none of the CVCs were removed due to occlusion, these events raise serious concerns about the use of high-concentration ethanol locks.

Impact of short term use of interdialytic 60% ethanol lock solution on tunneled silicone catheter dysfunction

Ethanol lock (EL) is used to reduce catheter infections, but its impact on dialysis catheter dysfunction has not been studied. We analyzed the rate of dialysis silicone catheter dysfunction after an interdialytic 60% EL in an open prospective controlled non crossover cohort study, with each patient being his or her own control. The study was divided into three consecutive 2-week periods: the pre- and post-intervention periods, in which interdialytic standard locks (SL) were used, and the intervention period, in which one EL was instilled during the first week, and two consecutively in the second week. We analyzed the rate of catheter dysfunction (exchange, use of fibrinolytic, reversing the lines, difficulty in instilling or withdrawing fluid) after EL or SL. In 30 patients, 90 EL were instilled. The rate of catheter dysfunction increased during the EL period (2 - 13%, p < 0.001), and between the two consecutive dialysis sessions before and after EL (p < 0.05). It decreased between the two consecutive dialysis sessions after EL and the following dialysis session after an SL (p < 0.05). No catheter was removed. The urea reduction ratio did not differ in dialysis after an SL and after an EL (0.77 vs. 0.73, p = 0.17). Short term EL is associated with a transient increase in catheter dysfunction, without resulting in catheter removal or decreasing dialysis efficiency.

Short-Dwell Ethanol Lock Therapy in Children Is Associated With Increased Clearance of Central Line–Associated Bloodstream Infections

Central line-associated bloodstream infection (CLABSI) is a known complication of central line use. Salvage of infected central lines with ethanol lock therapy (ELT) with systemic antimicrobials may be an alternative treatment option in children. Retrospective review was performed in children with CLASBI who underwent short-dwell ELT (70% ethanol, 4- to 25-hour dwell times ≤3 days) with systemic antimicrobials from January 1, 2007 to July 15, 2009. A total of 59 patients, aged 2 months to 19 years (mean ± SD = 6.3 ± 6.1 years) with 80 episodes of CLABSI were included. The CLABSI eradication rate was 86% (69/80 episodes; 95% confidence interval [CI] 78%, 94%), significantly greater than 50% (Z = 2.35, P < .05), the estimated clearance rate of CLABSI eradication using systemic antimicrobials alone. Overall central line retention was 78% (60/77 episodes, 95% CI 69%, 87%). ELT was well tolerated. These findings suggest the potential benefit of short-dwell ELT combined with systemic antimicrobials in CLABSI treatment. Randomized controlled trials are needed.

Ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients with intestinal failure: preliminary experience

BackgroundCatheter-related bloodstream infections (CRBSI) cause morbidity and mortality in patients with intestinal failure dependent on parenteral nutrition. Ethanol lock of central venous catheters may decrease CRBSI, but limited pediatric data are available. MethodsHome parenteral nutrition patients with at least one previous CRBSI were initiated on a 70% ethanol lock protocol for a minimum of 4 hours. Infection rates (per 1000 catheter days) before and after initiation of ethanol locks were compared using a paired t test. ResultsTen patients (4 girls; median age, 44 months [range, 31-129 months]) began ethanol lock therapy after a total of 91 CRBSIs (37 gram-positive, 30 gram-negative, and 24 fungal) with a mean of 10.2 ± 6.2 per 1000 catheter days. Patients received ethanol lock for an average of 227 ± 64 days with only 3 CRBSI occurring (CRBSI rate of 0.9 ± 1.8 per 1000 catheter days [P = .005]). Central venous catheter replacements decreased from 5.6 per 1000 days to 0.3 per 1000 days posttherapy (P = .038). Ethanol lock was discontinued in 2 of 10 patients because of catheter thrombosis. ConclusionPreliminary results demonstrate a significant decrease in CRBSI with a 70% ethanol lock protocol. Catheter thrombosis may be a limitation that needs to be addressed. With such a dramatic therapeutic effect, a randomized trial is feasible and should be performed.

Survival Outcomes of Pediatric Intestinal Failure Patients: Analysis of Factors Contributing to Improved Survival Over the Past Two Decades

Intestinal failure (IF) is associated with significant and life-threatening complications. Recent studies suggest that treatments for IF in the pediatric population are improving over time. Based on this, we examined whether pediatric IF survival rates have improved in our patient population over the past two decades, and secondarily examined which aspects of patient care contributed to changes in survival. We conducted a retrospective chart review of all pediatric patients with IF at our children's hospital from 1990 through 2009. Cox regression analyses were used to determine change in survival rates over time (5-y cohorts), and we examined multiple covariates to determine their potential influence on survival rates over time. A significant improvement in survival of 171 children with IF was noted over the past two decades. Children with an onset of IF in the 1990-1994 cohort had significantly decreased survival compared with children in all subsequent cohorts (P = 0.011). The only intervention that was identified between this time period and future periods was the establishment of a comprehensive intestinal failure clinical care team. While the latter three cohorts were not significantly different, progressively increased survival was noted. Ability to wean off parenteral nutrition (PN) and small bowel length greater than 10% of the expected length were significantly associated with improved survival over this time period (P < 0.01). Other tested covariates, including the more recent use of ethanol lock therapy (to prevent catheter sepsis) and lipid reduction strategies (to treat PN-associated cholestasis) failed to show a significant impact on improved survival. Despite a striking improvement in survival of children with IF over the past two decades, the only identified intervention that significantly impacted survival was establishment of a comprehensive care team. These findings emphasize the need for multi-disciplinary efforts to care for such complex and challenging children.