Elsevier

European Journal of Cancer

Volume 51, Issue 14, September 2015, Pages 2031-2038
European Journal of Cancer

Prevention of central venous catheter-associated bloodstream infections in paediatric oncology patients using 70% ethanol locks: A randomised controlled multi-centre trial

https://doi.org/10.1016/j.ejca.2015.06.126Get rights and content

Abstract

Background

The prevention of central venous catheter (CVC) associated bloodstream infections (CABSIs) in paediatric oncology patients is essential. Ethanol locks can eliminate pathogens colonising CVCs and microbial resistance is rare. Aim of this study was to determine whether two hour 70% ethanol locks can reduce CABSI in paediatric oncology patients.

Methods

We conducted a randomised, double blind, multi-centre trial in paediatric oncology patients (1–18 years) with newly inserted CVCs. Patients were randomly assigned to receive two hour ethanol locks (1.5 or 3 ml 70%) or heparin locks (1.5 or 3 ml 100 IU/ml), whenever it was needed to use the CVC, maximum frequency once weekly. Primary outcomes were time to CABSI or death due to CABSI.

Results

We recruited 307 patients (ethanol, n = 153; heparin, n = 154). In the ethanol group, 16/153 (10%) patients developed a CABSI versus 29/154 (19%) in the heparin group. The incidence of CABSI was 0.77/1000 and 1.46/1000 catheter days respectively (p = 0.039). The number-needed-to-treat was 13. No patients died of CABSI. In particular, Gram-positive CABSIs were reduced (ethanol, n = 8; heparin, n = 21; p = 0.012). Fewer CVCs were removed because of CABSI in the ethanol group (p = 0.077). The ethanol lock patients experienced significantly more transient symptoms compared to the heparin lock patients (maximum grade 2) (nausea, p = 0.030; taste alteration, p < 0.001; dizziness, p = 0.001; blushing, p < 0.001), no suspected unexpected serious adverse reactions (SUSAR) occurred.

Conclusions

This is the first randomised controlled trial to show that ethanol locks can prevent CABSI in paediatric oncology patients, in particular CABSI caused by Gram-positive bacteria. Implementation of ethanol locks in clinical practice should be considered.

Introduction

The use of central venous catheters (CVC) is indispensable in the modern-day treatment of children with cancer. Despite improved international guidelines on CVC placement and catheter care, CVC colonisation is still an important problem in such patients [1]. Colonised CVCs can cause CVC-associated bloodstream infections (CABSI), with reported infection rates between 0.1 and 2.3 CABSIs per 1000 catheter days [2]. CABSIs are often difficult to treat. Pathogens become embedded in a self-made polymeric matrix, a biofilm and are difficult to eradicate with systemic antimicrobials: only 24–66% of CVCs are salvaged [2], [3]. Therefore CABSIs require prolonged treatment with extended hospital admissions, leading to increased healthcare costs [1]. The prophylactic flushing of CVCs with vancomycin/heparin locks has been reported to result in a significant reduction of Gram-positive CABSIs [4]. Nevertheless, such antibiotic locks may contribute to microbial resistance, and therefore alternative solutions need to be sought. Ethanol is a promising agent; it is easily available, cheap and bacterial resistance to ethanol is rare. Several studies in paediatric patients receiving parenteral nutrition have presented promising results with ethanol locks for the prevention of CABSI [5]. This is the first randomised controlled trial (RCT) investigating prophylactic ethanol locks in paediatric oncology patients. The primary aim of the study was to investigate the use of 70% ethanol locks for preventing CABSI. A secondary aim was to register (a)symptomatic thrombosis in paediatric oncology patients with tunnelled CVCs. These results will be published in a separate manuscript.

Section snippets

Setting

Five paediatric oncology centres in The Netherlands participated in this study and the protocol was approved by their respective institutional boards. The trial was registered in the Dutch trial register (http://www.trialregister.nl): NTR 1275. Written informed assent or consent was obtained from all parents and patients >12 years. The study medication was manufactured by a central pharmacy. The placement and care of the CVCs were performed in accordance with international guidelines [1]. In the

Patients

Between October 2007 and December 2012, 728 patients were screened for enrolment in the study, of which 134 were ineligible and 287 declined (Fig. 1). The remaining 307 patients were enrolled and 153 patients were allocated to the ethanol group and 154 to the heparin group. There were no significant differences in patient characteristics between the two groups (Table 1). The total number of catheter days was 40831 days (ethanol, 20916 days; heparin, 19915 days) and 60 study locks were administered

Discussion

This is the first multi-centre, RCT in paediatric oncology patients investigating the use of ethanol locks for the prevention of CVC associated bloodstream infections (CABSI). We found a statistically significant 50% reduction of predominantly Gram-positive CABSIs in patients receiving ethanol locks compared to patients receiving heparin locks.

Ethanol locks were safe: no SUSARs occurred. During the infusion of the ethanol solution patients reported symptoms of nausea, taste alteration,

Source of funding

This work was supported by Kika (children cancer free) [1561] and the Tom Voûte foundation [SKK-07-02]. Neither Kika nor the Tom Voûte foundation had any role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the article for publication.

Author contributions

Study concepts: Schoot, van Ommen, Stijnen, Heij, Lieverst, Spanjaard, Caron, van de Wetering.

Study design: Schoot, van Ommen, Stijnen, Heij, Lieverst, Spanjaard, Caron, van de Wetering.

Data acquisition: Schoot, Tissing, Michiels, Abbink, Raphael, Heij, Lieverst, Zwaan, van de Wetering.

Data analysis and interpretation: Schoot, van Ommen, Stijnen, Spanjaard, Zwaan, Caron, van de Wetering.

Statistical analyses: Schoot, van Ommen, Stijnen, Caron, van de Wetering.

Manuscript preparation: Schoot,

Conflict of interest statement

Dr. Huib Caron started working for F. Hoffman-La Roche Ltd, after the final version of this manuscript was drafted and there was no conflicting relationship with this current study. All authors reported no conflict of interest.

Acknowledgements

We thank the patients and their families for participating in this study. We thank the clinical research nurses and data managers from the participating centres for their tremendous efforts and dedication. We thank the trial managers of the Dutch Childhood Oncology Group, Marlies van Mierlo, Jacqueline Vreijling, Cindy Scholte and Hester de Groot-Kruseman in particular, for their support and central data collection. We thank the pharmacists of the participating centres, in particular Dr. E.M.

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