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

Abstract

Background. 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. Methods. 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. Results. 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. Conclusions. These findings suggest the potential benefit of short-dwell ELT combined with systemic antimicrobials in CLABSI treatment. Randomized controlled trials are needed.

Keywords

ethanol lock bloodstream infection intravascular device central line–associated bloodstream infection (CLABSI)children pediatrics

Background

Central lines are permanent and semipermanent foreign bodies inserted into the vasculature of patients for a variety of important functions, including infusion of antibiotics, chemotherapy, total parenteral nutrition, and blood products. In pediatrics, their use has increased to lessen the need for multiple peripheral catheter placements and the pain suffered from ongoing needle stick.^1,2 A major known complication of central line use is central line–associated bloodstream infection (CLABSI).^3-5

The management of CLABSI usually consists of removal of the infected central line and systemic antimicrobial therapy for most pathogens.³ Removal of the central line may not always be possible, especially in critically ill pediatric patients with limited vascular access. Therefore, attempts to salvage infected central lines without catheter removal by various methods with continued systemic antimicrobial therapy have been used with varying success (˜50%).^2,6-10 Antibiotic lock therapy, along with systemic antimicrobials, has been used in the salvage of infected central lines in pediatric patients.^9,11 This is done by infusing concentrated antibiotic solution, to which the causative organism is susceptible, into the lumen of the infected central line to dwell, but success rates vary from 67% to 83%.^8,9,11

Ethanol has been found to have broad-spectrum antimicrobial activity based on denaturization of biofilms (organized microorganisms adherent to living and nonliving environmental surfaces¹²) instead of a specific microbial target, making the risk of development of drug resistance low.^13-16 Exposure to 70% ethanol and water has been shown to kill organisms in biofilms that include gram-positive and gram-negative bacteria, and Candida sp. in as little as 2 hours.¹⁷ Studies have shown that 70% ethanol is the preferred concentration to disinfect catheter lumens and surfaces.^18,19

Two previous studies have reported successful use of ethanol lock therapy (ELT) in pediatric patients with CLABSI. A solution of 70% ethanol and water with dwell times ranging from 12 to 24 hours for 3 to 5 consecutive days was instilled into the infected central line in combination with systemic antimicrobial therapy.^1,2 A retrospective study on ELT use with dwell times of 20 to 24 hours for 3 consecutive days to treat bloodstream infection (BSI) in pediatric oncology patients with Broviac catheters was performed by Dannenberg et al.² A total of 67% of 28 children (2-18 years) treated with ELT and systemic antimicrobials cleared the infection and had no relapse of their infection within 4 weeks compared with only 47% in those treated with systemic antimicrobial therapy alone.² Onland et al¹ reported 88% (n = 51) successful sterilization of infected central lines using ELT in addition to systemic antimicrobial therapy without recurrence in pediatric patients (1-14 years) with hematologic and oncologic disorders, bone marrow and small bowel transplants, metabolic disorders, and gastrointestinal disorders. Ethanol lock with 12- to 24-hour dwell times per day for 5 consecutive days for each catheter lumen was done.¹ In both studies ELT was well tolerated.

A review of the medical literature^1,2 on the use of ELT for treatment of pediatric CLABSI revealed varying durations of ELT from 3 to 5 days. However, no data were available on the use of short dwell ELT (≤4 hours to 25 hours for ≤3 days) in addition to systemic antimicrobials for sterilization and retention of central lines in pediatric patients with CLABSI. Reports on the use of ELT in other types of catheters such as peripherally inserted central catheter lines and tunneled and implanted central lines are lacking. Limited information in the medical literature regarding ethanol lock use in pediatric patients suggests that the addition of short-dwell ELT to standard care with systemic antimicrobial therapy may be associated with increased rates of CLABSI clearance above the clearance rate using only systemic antimicrobial therapy alone.^1,2 The purpose of our study was to test this hypothesis by comparing the clearance rate calculated with data from a retrospective review of the use of ELT with systemic antimicrobials for treatment of CLABSI in a tertiary care children’s hospital and an estimated clearance rate of 50% from the use of systemic intravenous antibiotics alone based on the medical literature.^2,6,7,9,10

Methods

Procedures

Ethanol lock therapy of infected central lines was performed by interventional radiology nurses under sterile conditions. After central line cleansing with alcohol, the intraluminal (dead) space of the line was determined (measured at time of insertion or measured at bedside). The catheter was then flushed with 5 mL of normal saline and followed by instillation of 70% ethanol and water at a calculated volume (catheter dead space + 0.1 mL). The line was then clamped and this volume was allowed to dwell in the catheter for a planned duration of time (4-47 hours). At the completion of the ELT, 5 mL of normal saline was flushed through the line (ethanol flushed to patient) and a 5 mL aspirate of blood was discarded via a 3-way stopcock. Up to 10 mL of blood was then obtained for post-ELT blood culture. Sterile tubing was connected if continued intravenous (IV) support was required or a heparin lock was used if no further infusions were needed.

Patients with single-lumen central lines had a peripheral IV line placed for infusion of intravenous antimicrobials through the duration of ELT. For patients with double-lumen central lines, ELT was placed in one lumen while the other lumen was used for infusions including systemic antimicrobials. After the completion of the ELT dwell time, the lumen with ethanol was flushed, repeat blood cultures were obtained and the central line was re-accessed as needed. The same procedure was then performed on the other lumen. In patients with limited or no peripheral IV access, the ELT dwell time was shortened to accommodate the required infusions and repeated 2 – 4 times (total duration ≤ 72 hours).

Participants

All patients with CLABSI that were treated with clinically indicated ELT 1/1/07 - 7/15/09 at Children’s Hospital of Michigan were identified. Medical records of eligible patients were reviewed. The Wayne State University Institutional Review Board approved the study.

All episodes included in the study met the National Healthcare Safety Network (NHSN)/Centers for Diseases Control and Prevention’s (CDC) definition of central line–associated bloodstream infections.^3,4,20 CDC defines a CLABSI as recovery of a pathogen from a blood culture (a single blood culture for organisms not commonly present on the skin and 2 or more blood cultures for organisms commonly present on the skin) in a symptomatic patient who had a central line at the time of infection or within the 48-hour period before development of infection. The infection cannot be related to any other infection the patient might have^3,4,20. Subset analysis was also performed on those episodes with positive paired cultures (positive peripheral and central blood cultures for at least one pathogen) and meeting CLABSI criteria.

Patients were excluded if they had another indwelling foreign body (ie, left ventricular assist device) communicating with the bloodstream of which infection or colonization could not be excluded or a diagnosis of endocarditis or presumed endovascular infection (Figure 1). Individual CLABSI episodes in the same patient were defined as distinct if separated by >30 days from prior ELT and if caused by a different organism than the prior infection. All types of central lines were included.

Measurements

The primary outcome was sterilization of the infected central line after ELT, defined as a negative blood culture obtained within 25 hours from the infected catheter post-ELT (short-term sterilization). Secondary outcomes included CLABSI recurrence as defined by a positive blood culture with the same organism obtained from the central line after initial clearance of infection within 30 days of ELT; central line retention; resolution of signs and symptoms of infection (fever, tachypnea, and tachycardia) 48 hours post-ELT; and safety and tolerability of ELT.

Definitions

Short-term sterilization of the infected central line was defined as a negative blood culture obtained from the infected catheter after initial ELT. If the central line was retained for further clinical use, long-term sterilization was defined as negative blood culture(s) obtained from the catheter post-ELT and sustained negative blood cultures for at least 30 days from the initial ELT. Central line retention was defined as successful if retained for at least 30 days post-ELT.

Statistics

Statistical analysis was performed using SAS 9.2 (SAS Institute, Cary, NC). Descriptive statistics (including means, standard deviations, rates, and ratios) were used to summarize the results. Rate of CLABSI clearance (plus 95% confidence interval [CI]) was computed as the ratio of the episodes with CLABSI eradication over the total episodes. Z test was used to compare the observed clearance rate of this study (with ethanol lock and systemic antimicrobials) with a clearance rate of 50%, which is the conservatively estimated rate of CLABSI eradication using systemic antimicrobials alone, based on existing pediatric and adult literature.^2,6,7,9,10 Significant differences in the clearance rate between the two at P < .05 level (2-sided) was used as evidence supporting the study hypothesis that the addition of ELT to standard care (systemic antimicrobials) is associated with increased likelihood of CLABSI eradication.

Results

Patient Characteristics

The mean age was 6.5 years (SD = 6.1). Males comprised 32 of 59 patients. Patient characteristics, types of central lines, risk factors for CLABSI, and CLABSI rates are shown in Table 1.

Table 1.

Patient and CLABSI Episode Characteristics

Characteristic	n (%)
Age; n = 59; range (mean ± SD; median)	2 mo to 19 y (6.5 ± 6.1y; 3.8 y)
Gender (n = 59)
Male	32/59 (54)
Female	27/59 (46)
Race/ethnicity (n = 59)
African American	33 (56)
Caucasian	22 (37)
Hispanic	2 (3)
Asian	2 (3)
Primary diagnosis (n = 59)
Hematologic malignancy/solid tumor	18 (31)
Short bowel syndrome	7 (12)
Bone marrow/stem cell transplant	8 (14)
Infection/prolonged IV antimicrobials	5 (8)
Hematologic disorders	5 (8)
Genetic and congenital syndromes	6 (10)
Other^a	11 (19)
Catheter types (n = 80)
Broviac	29 (36)
Port-A-Cath	19 (24)
PICC line	15 (19)
Tunneled PICC/PowerLine	12 (15)
Hickman	3 (2)
Pheresis	1 (1)
Hemodialysis	1 (1)
Catheter type not documented	1 (1)
Immunosuppressed	38/80 (48)
ANC < 500/mm³ (neutropenic)	15/80 (19)
TPN use	25/80 (31)
Total catheter-days before BSI	10 815 d
BSI/1000 catheter-days in study population	7.3

Abbreviations: SD, standard deviation; ANC, absolute neutrophil count; TPN, total parenteral nutrition; CLABSI, central line–associated bloodstream infection; BSI, bloodstream infection; PICC, peripherally inserted central catheter.

Other diagnoses (number): nephrotic syndrome (3), lung disease (2), inflammatory bowel disease (2), kidney disease (1), cardiac surgery (1), central nervous system disease (1), nonaccidental trauma (1).

Clinical and Laboratory Data

A total of 59 patients had 80 episodes of CLABSI (Figure 1). All episodes fulfilled CDC’s definition of CLABSI with no other known source of infection and with either one positive blood culture of a pathogen (criterion 1) or 2 or more positive blood cultures of skin contaminant with fever (≥38.0°C), hypotension, or chills (criterion 2).^3,4,20 Fever was present in 67 (84%) episodes. In all episodes, the average time from first positive blood culture to ELT was 4 days with an average of 3 persistent positive blood cultures before ELT was ordered at the discretion of the treating clinician.

Because of difficult peripheral IV access, only 57 of 80 episodes had at least one paired blood culture (both peripheral blood culture drawn in addition to blood culture obtained from the central line) available and 36 of these 57 episodes had at least one positive result which are included in subset analysis.

Of the total 80 episodes of CLABSI, 36 distinct pathogens were isolated (Table 2). The most common gram-positive and gram-negative pathogens isolated were Staphylococcus epidermidis and Pseudomonas aeruginosa, respectively. Fungal pathogens were also isolated, including Candida spp. and Cryptococcus neoformans. Polymicrobial infections occurred in 27 (34%) episodes.

Table 2.

Isolated Pathogens

Gram-Positive Organisms, n = 66	Gram-Negative Organisms, n = 44
Staphylococcus epidermidis, 26	Pseudomonas aeruginosa, 7
Coagulase-negative Staphylococcus, 3	Enterobacter cloacae, 6
Staphylococcus aureus, 9 (MRSA, 5 of 9)	Klebsiella pneumoniae, 6
Enterococcus faecalis, 5	Escherichia coli, 5
Staphylococcus hominis, 5	Acinetobacter baumannii, 3
Enterococcus faecium, 4 (VRE, 3 of 4)	Acinetobacter junii, 3
Viridans group Streptococci, 2	Pseudomonas agglomerans, 3
Corynebacterium sp., 2	Stenotrophomonas sp., 3
Staphylococcus auricularis, 1	Klebsiella oxytoca, 2
Actinomyces sp., 1	Serratia marscesens, 1
Staphylococcus capitus, 1	Citrobacter freundii, 1
Bacillus sp., 1	Enterobacter aerogenes, 1
Streptococcus constellatus, 1	Methylbacterium sp., 1
Streptococcus salivarius, 1	Pseudomonas stuteri, 1
Streptococcus mitus, 1	Chryseobacterium sp., 1
Micrococcus sp., 1
Rothia sp., 1
Lactobacillus sp., 1
	Fungal isolates, n = 7
	Candida parapsilosis, 3
	Candida albicans, 2
	Candida lusitaniae, 1
	Cryptococcus neoformans, 1

Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; VRE, vancomycin resistant Enterococcus.

Mean duration of concomitant systemic antimicrobial use was 10 days (range 3-25 days) with the most common therapies being intravenous vancomycin and cefepime. Effective empiric therapy was given in 71 (89%) of the episodes followed by appropriate therapy switch, when culture susceptibilities were known, in 79 (99%) of 80 episodes.

Ethanol Lock Data

Information on ELT dwell times and results are shown in Tables 3 and 4, respectively. The majority of CLABSI episodes were treated with a single ethanol lock with a dwell time of 24 to 25 hours. For patients requiring more than one ELT, the most common reason was limited IV access and the need for continued infusion (total parenteral nutrition) through the central line. The mean volume of ethanol used was 0.5 mL (range 0.3-1.0 mL).

Table 3.

Ethanol Lock Therapy Dwell Times (n = 80 Episodes)

Lock(s) per Lumen	Number of Episodes (%)	Dwell Time in Hours; n (%)
1	80 (100)	24-25; 66 (83)
		22-23; 7 (9)
		18-20; 2 (3)
		4-10; 5 (7)
		Dwell Time; Range (Hours)
2	10 (13)	18^a; 4-47
3	7 (9)	14^a; 4-24
4	1 (1)	20

Average dwell time.

Table 4.

Ethanol Lock Therapy (ELT) Results (n = 80 Episodes)

	Result; n (%)	95% Confidence Interval	Z Score, PValue
Primary outcome measure
Short-term sterilization^a (negative blood culture obtained from central line approximately 25 hours after initial ELT placed)	69/80 (86)	79%, 94%	2.35, <.05
Other outcome measures
Overall short-term sterilization (negative blood cultures obtained from central line after ≤4 ethanol locks)	76/80 (95)	90%, 100%	Not applicable
Long-term sterilization (short-term sterilization and negative repeat blood cultures obtained ≥30 days post-ELT)	59/79^b (75)	65%, 84%	Not applicable
Number with recurrence of prior infection after initial ELT (a positive blood culture with prior pathogen obtained from the central line after initial clearance of infection, within 30 days of initial ELT)	7/79^b (9)	3%, 15%	Not applicable
Central line retention after initial ELT	61/79^c (77)	68%, 86%	Not applicable
Central line retention after second ELT	61/79^c (77)	68%, 86%	Not applicable
Central line retention after third or fourth ELT	60/77^d (78)	69%, 87%	Not applicable

Z test comparing bloodstream infection eradication rate of short-dwell ELT with systemic antimicrobials with 50%, the estimated clearance rate of bloodstream infection eradication from the standard therapy of systemic antimicrobials alone based on pediatric and adult literature.

n = 79; central line out <30 days, 1.

n = 79; no information, 1.

n = 77; central line out <30 days, 1; no information, 2.

Of 80 episodes, CLABSI was eradicated in 69 (86%; 95% CI 79%, 94%) after one ELT along with systemic antimicrobials (standard care). This rate of 86% was significantly greater than the 50% estimated clearance rate of CLABSI eradication from the standard therapy using systemic antimicrobials alone, based on pediatric and adult literature (Z = 2.35, P < .05).^2,6,7,9,10 Overall, 60 central lines (60/77; 78%; 95% CI 69%, 87%) were retained during the study after up to 4 ethanol locks (Table 4).

Of the 20 central lines removed, 7 were removed specifically for the reason of “failure of ELT.” Three of 7 catheter tips were sent for culture. Only one grew Enterococcus faecium (vancomycin-resistant Enterococcus), the same isolate recovered from the initial central line blood culture. The other 13 central lines were removed for various reasons, including catheter malfunction (5/13), no further use (3/13), elective removal (4/13), and one patient with multiple congenital anomalies with an existing central line expired because of complications of underlying illness.

There were 9 bacterial CLABSI episodes with persistent positive blood cultures obtained after the first ELT. Six of 9 episodes eventually cleared after a second or third ethanol lock. Two of 9 episodes had no repeat blood culture obtained after the first ELT and were considered primary outcome failures, but repeat blood cultures obtained after the third ethanol lock were negative in both cases. Therefore, documented persistent CLABSI, after up to 3 ethanol locks, occurred in only 3 of these 9 episodes: one patient with short bowel syndrome (SBS; S aureus; MRSA), one solid tumor patient (S aureus), and one genetic syndrome patient (Micrococcus sp. and S epidermidis). All these 3 episodes were treated with appropriate systemic antimicrobials and the central lines were eventually removed.

Seven CLABSI episodes were due to fungal organisms (Table 2). The primary diagnosis among these patients included one patient with decubitus ulcers and osteomyelitis requiring prolonged IV antimicrobial therapy with subsequent fungal CLABSI (C parapsilosis) and one patient each with the following diagnosis: genetic syndrome (C parapsilosis), malignancy (Cryptococcus neoformans), end-stage renal disease patient on dialysis (C lusitanae), SBS (C albicans), inflammatory bowel disease (C albicans), and nephrotic syndrome (C albicans). There was one failure in this group, which occurred in the patient with underlying SBS who had polymicrobial infection due to C albicans, E faecalis and coagulase-negative Staphylococcus resulting in subsequent catheter removal. The remaining 6 fungal episodes achieved short-term sterilization post-ELT and 3 of 6 retained their central lines. Of 3 central lines removed, 1 malfunctioned post-ELT and 2 were removed electively.

A total of 48 episodes of ELT had laboratory data available that were collected 48 hours post-ELT. The laboratory data consisted of alanine aminotransferase, aspartate aminotransferase, total and direct bilirubin, prothrombin time, activated partial thromboplastin time, and international normalized ration. The majority, 36 of 48 episodes (75%), had normal post-ELT laboratory studies. The 12 episodes with abnormal post-ELT laboratory results all had the equivalent of a grade 1 toxicity level elevation²¹ (majority of these had mild transaminase elevation) and were reversible.

Of 74 episodes with evaluable systemic signs and symptoms 48 hours post-ELT, 62 episodes (84%) had resolution of signs and symptoms (fever >38°C, tachypnea, tachycardia).

No central line removals occurred as a result of ELT. Two of the 80 (3%) episodes post-ELT had transient difficult saline flush, both eventually resolved with one requiring tissue plasminogen activator infusion.

Additional Subset Analysis

A subset analysis for the main study objectives was conducted on 36 of 80 episodes who had paired blood culture data available (Table 5). Paired blood cultures from these patients were collected both peripherally and from central lines and both were positive for at least one organism. The majority of these episodes were treated with one ethanol lock (30/36; 83%) for 24 to 25 hours (28/36; 78%) along with systemic antimicrobials with overall short-term sterilization success rate of 86%.

Table 5.

Subset Analysis Results (n = 36 Episodes)

Outcome Measures	Result; n (%)	95% Confidence Interval
Short-term sterilization (negative blood culture obtained from central line approximately 25 hours after initial ethanol lock therapy [ELT] placed)	31/36 (86)	75%, 97%
Overall short-term sterilization (negative blood cultures obtained from central line after ≤4 ethanol locks)	35/35^a (100)	Not applicable
Long-term sterilization (short-term sterilization and negative repeat blood cultures obtained ≥30 days post-ELT)	26/35^a (74)	60%, 89%
Number with recurrence of prior infection after initial ELT (a positive blood culture with prior pathogen obtained from the central line after initial clearance of infection, within 30 days of initial ELT)	5/35^b (14)	3%, 26%
Central line retention after initial ELT	27/35^b (77)	63%, 91%
Central line retention after second ELT	27/35^b (77)	63%, 91%
Central line retention after third or fourth ELT	27/34^c (79)	66%, 93%

n = 35; central line out <30 days, 1.

n = 35; no information, 1.

n = 34; no information, 2.

Discussion

Biofilms are composed of organized microorganisms that adhere to living and nonliving environmental surfaces and secrete extracellular polysaccharides that further promote colonization. Formation of biofilms in central lines is universal and can occur with gram-positive and gram-negative bacteria and fungal species.¹² Potential complications are possible as a critical level of biofilm formation occurs above which portions of the biofilm itself may embolize, leading to clinical symptoms and BSI in patients with central lines.^3,12

There are several definitions of BSI caused in the presence of a central line.^3,4,20,22 O’Grady et al²² has a strict definition for catheter-related BSI that requires culture of the catheter tip on removal of the infected catheter, using differential time to positivity, or qualitative blood cultures along with positive central and peripheral blood cultures and clinical signs or symptoms of infection.²² This definition can be problematic in pediatric patients for 2 main reasons. First, repeated removal and replacement of central lines is difficult because of limited vascular access sites in young children.¹ Second, because of difficulties in obtaining peripheral blood cultures due to limited vascular access, peripheral blood cultures may not be drawn in some patients, with some studies specifically not including peripheral blood cultures.^23,24 Additionally, catheter segment/tip cultures may also be sterile as empiric antimicrobials are often started before central line removal.³ Although there is continued debate on CLABSI definitions,²⁵ we used the definition of CLABSI by the CDC/NHSN as described in Figure 1, which is widely used for surveillance and may be more applicable in pediatric patients.^3,4,20

Initial published literature on the use of antimicrobial therapy alone to clear CLABSI in pediatrics is limited and appears to have inflated positive results because of the exclusion of fungal BSIs, small sample sizes, and variable success definitions.^26,27 However, few published reports in the past 2 decades studied various catheter salvage interventions versus control groups receiving systemic antimicrobial therapy alone in both pediatric and adult patients.^6,7,9,10 These control group success rates varied from 32% to 66%, and, additionally in the report by Dannenburg et al,² infection cleared in 47% of CLABSI controls treated with antimicrobial therapy alone. Our estimated rate of successful BSI eradication from systemic antimicrobial therapy alone was 50% and was extrapolated from these 5 published studies.^2,6,7,9,10

Several studies, to date, have reviewed ELT for treatment of CLABSI^1,2,28,29 with reported success rates of 67% to 100% clearance when combined with systemic antimicrobials, although different success definitions were used. The short-term sterilization rate in our study was 86% after 1 ethanol lock, and 95% after up to 4 ethanol locks (total duration ≤72 hours) with concomitant antimicrobials. The results of the subset analysis among our patients with paired blood cultures were also similar at 86%, and 100%, respectively. In addition, this study is unique as our patient population is diverse with different underlying disorders and ELT was able to sterilize infected central lines in the presence of a wide variety of organisms, including fungal isolates. Failures of ELT were in CLABSI episodes associated with polymicrobial infections with Micrococcus sp. and S epidermidis; C albicans, E faecalis, and coagulase-negative Staphylococcus; and monomicrobial infections with S aureus.

Although cost savings was not specifically reviewed in this study, the estimated cost of treating one CLABSI ranges from $36 000 to $50 000 per episode.^30-33 Ethanol lock therapy has been reported to cost as little at $16 per patient.²⁸

Catheter material types were not frequently documented by interventional radiology. However, we estimate that the majority of our catheters are composed of silicone or polyurethane because of the fact that Broviacs are made of silicone and our peripherally inserted central catheters and Port-A-Caths are mainly polyurethane-based. There is some concern regarding a possible interaction between polyurethane and ethanol affecting catheter integrity,^34,35 but this is not supported in other studies. For instance, one study reported concentrations as high as 70% ethanol were not found to appreciably alter the catheter integrity of polyurethane or silicone catheters.³⁶ Furthermore, long-term ELT have also been used as prophylaxis to prevent CLABSI with no reported adverse effects to the catheters.^13,17,37-39 Similarly, in our study, we did not appreciate a significant interaction or increase in catheter malfunctions in the polyurethane catheters related to ethanol exposure.

Limitations of this study were related to its retrospective nature. Some clinical and laboratory data were missing in the medical records. We lack a control group because antibiotic locks with systemic antibiotics or systemic antimicrobials alone for treatment of CLABSI are not commonly used in our center. Post-ELT laboratory results were difficult to interpret in some patients because of their underlying diagnosis and treatments. Furthermore, assessment of signs and symptoms of infection based on retrospective chart review may not be accurate. Among the 12 patients who did not have resolution of clinical signs and symptoms after 48 hours of ELT, the majority had one respiratory rate recording above age-related norms which may have been because of interoperator variability in the methods used to obtain vital signs in children. Despite its limitations, this is the first study to demonstrate the positive association of short-dwell ELT and CLABSI clearance and central line retention in children and, thus, supports the need for further trials.

Conclusion

Short-dwell ELT for 4 to 25 hours with concomitant systemic antimicrobials was associated with a high rate (86%) of eradicating CLABSI caused by a broad variety of pathogens in a diverse pediatric population. The ELT appeared to be well tolerated and safe. ELT may have a role in the treatment of CLABSI obviating the need for catheter removal in patients requiring long-term venous access. Larger randomized, prospective trials are needed to confirm the efficacy of ELT with antimicrobials for treatment of CLABSI and salvage of infected central lines.

Footnotes

Acknowledgements

The authors thank Basim Asmar, MD, for his review of this article.

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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

Abstract

Keywords

Background

Methods

Procedures

Participants

Measurements

Definitions

Statistics

Results

Patient Characteristics

Clinical and Laboratory Data

Ethanol Lock Data

Additional Subset Analysis

Discussion

Conclusion

Footnotes

Acknowledgements

References