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NIHR Signal Ethanol locks in catheters for dialysis may prevent sepsis

Published on 25 September 2018

doi: 10.3310/signal-000648

In patients with tunnelled central venous catheters used for dialysis, ethanol locks may reduce catheter-related bloodstream infections when compared with other locks, mainly saline. There was no increase in the risk of catheter blockage with ethanol locks in this study.

Long-term catheters carry a risk of bloodstream infection. ‘Locks’ are the small amount of fluid left inside a long intravenous catheter between uses to reduce the risk of blockage with clotted blood and ideally also to reduce infections. Ethanol locks may offer an alternative to saline, but there were only a few studies comparing them with heparin locks. None of the studies compared ethanol locks to the commonly-used antibiotic locks.

The review had a broad scope, covering adults and children on haemodialysis, and other conditions such as cancer or gastrointestinal conditions requiring intravenous nutrition. So, it seems that further work needs to be done before making specific recommendations on type and context for using ethanol locks.

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Why was this study needed?

Central venous catheters are used for patients requiring chemotherapy, haemodialysis or long-term total parenteral nutrition. Blockage necessitates removal and re-siting of the catheter, so heparin is often used as a lock to prevent clots. Catheter infection often spreads through the bloodstream and can be fatal if untreated. Estimated occurrence of catheter-related infection is between 2.5-18 cases per 1,000 catheter days. The risk increases for catheters that are left in for a long time.

To prevent catheter-related infection, lock solutions are placed in the catheter to kill bacteria in the line. Ethanol is one option; others in common use include antibiotics, citrate and saline.

A Cochrane review of this topic already exists but in the light of recent trials, a new systematic review of ethanol locks was needed to combine the results of smaller studies and bring the evidence up to date.

What did this study do?

This was a meta-analysis of seven randomised controlled trials of 2,575 patients comparing ethanol lock with another solution lock: mostly heparinised saline or saline only in the two larger trials.

Most used 70% ethanol solution while one used 60% ethanol; flushed in four studies but not three. Ethanol lock volume ranged from 1.5 to 3.0ml and dwell time ranged from 2 minutes to 2 hours.

The main outcome was catheter-related bloodstream infection, usually defined as finding bacteria in more than one blood culture. The trials were carried out in high-income countries comparable to the UK, so findings should be applicable.

What did it find?

  • Ethanol lock almost halved the risk of catheter-related bloodstream infections (41/1,735 catheters), compared with heparinised saline or saline only (73/1,639 catheters), (risk ratio [RR] 0.54; 95% confidence interval [CI] 0.38–0.78). The number needed to treat to prevent one infection was 48. This benefit was observed in patients with tunnelled catheters but not in studies with untunnelled catheters.
  • Thrombosis can be a concern with the use of ethanol lock compared with heparinised saline, but this study found no difference in the incidence of thrombosis between ethanol and control groups (RR 1.05; 95% CI 0.91–1.22). However, one study, contributing almost 90% of the weight to this comparison, used saline only as a control and had a very high thrombosis rate in both groups, so the effect of ethanol over heparin was not properly assessed.
  • There was significant variability between studies by population characteristics, ethanol protocols and definitions of infection. Therefore, the results need to be treated with caution.

What does current guidance say on this issue?

There is little current national guidance on this issue. The NICE guideline on Healthcare-associated infections: prevention and control in primary and community care (2012, updated 2017) does not make any recommendations on the use of ethanol flush and lock solutions. Instead, it recommends using sterile 0.9% saline to flush and lock the catheter. It recommends against routinely using antibiotic lock solutions to prevent catheter-related bloodstream infections.

A UK Renal Association guideline (2015) suggests that antibiotic or antimicrobial locking solutions should be used. It does not mention using ethanol as a lock.

What are the implications?

Evidence is increasing on the advantages of ethanol locks compared with heparinised saline or saline alone.

The use of citrate, ethanol, antibiotic or other locks is currently based on local hospital policy as few trials exist. For now, the findings give us some evidence about the value of ethanol locks.

If concerns regarding antibiotic resistance escalate, it is possible that more research into this issue could directly compare the variety of locks in current practice.

Citation and Funding

Zhao T, Liu H, Han J. Ethanol lock is effective on reducing the incidence of tunneled catheter-related bloodstream infections in hemodialysis patients: a systematic review and meta-analysis. Int Urol Nephrol. 2018;50(9):1643-52.

No funding information was provided for this study.

Bibliography

Arechabala MC, Catoni MI, Claro JC, et al. Antimicrobial lock solutions for preventing catheter-related infections in haemodialysis. Cochrane Database Syst Rev. 2018;4:CD010597.

Broom JK, Krishnasamy R, Hawley CM, et al. A randomized controlled trial of heparin versus ethanol lock therapy for the prevention of catheter-associated infection in haemodialysis patients–the healthy-cath trial. BMC Nephrol. 2012;13:146.

Kumwenda M, Mitra S, Reid C. Clinical practice guideline. Vascular access for haemodialysis. 6th edition. Glasgow: UK Renal Association; 2015.

NICE. Healthcare-associated infections: prevention and control in primary and community care. CG139. London: National Institute for Health and Care Excellence; 2012, updated March 2017.

NICE. Infection: A summary of selected new evidence relevant to NICE clinical guideline 139. Evidence Update 64. London: National Institute for Health and Care Excellence; 2014.

Sanders J, Pithie A, Ganly P, et al. A prospective double-blind randomized trial comparing intraluminal ethanol with heparinized saline for the prevention of catheter-associated bloodstream infection in immunosuppressed haematology patients. J Antimicrob Chemother. 2008;62(4):809-15.

Schoot RA, van Dalen EC, van Ommen CH, van de Wetering MD. Antibiotic and other lock treatments for tunnelled central venous catheter-related infections in children with cancer. Cochrane Database Syst Rev. 2013;(6):CD008975.

Worth LJ, Slavin MA, Heath S, et al. Ethanol versus heparin locks for the prevention of central venous catheter-associated bloodstream infections: a randomized trial in adult haematology patients with Hickman devices. J Hosp Infect. 2014;88(1):48-51.

Why was this study needed?

Central venous catheters are used for patients requiring chemotherapy, haemodialysis or long-term total parenteral nutrition. Blockage necessitates removal and re-siting of the catheter, so heparin is often used as a lock to prevent clots. Catheter infection often spreads through the bloodstream and can be fatal if untreated. Estimated occurrence of catheter-related infection is between 2.5-18 cases per 1,000 catheter days. The risk increases for catheters that are left in for a long time.

To prevent catheter-related infection, lock solutions are placed in the catheter to kill bacteria in the line. Ethanol is one option; others in common use include antibiotics, citrate and saline.

A Cochrane review of this topic already exists but in the light of recent trials, a new systematic review of ethanol locks was needed to combine the results of smaller studies and bring the evidence up to date.

What did this study do?

This was a meta-analysis of seven randomised controlled trials of 2,575 patients comparing ethanol lock with another solution lock: mostly heparinised saline or saline only in the two larger trials.

Most used 70% ethanol solution while one used 60% ethanol; flushed in four studies but not three. Ethanol lock volume ranged from 1.5 to 3.0ml and dwell time ranged from 2 minutes to 2 hours.

The main outcome was catheter-related bloodstream infection, usually defined as finding bacteria in more than one blood culture. The trials were carried out in high-income countries comparable to the UK, so findings should be applicable.

What did it find?

  • Ethanol lock almost halved the risk of catheter-related bloodstream infections (41/1,735 catheters), compared with heparinised saline or saline only (73/1,639 catheters), (risk ratio [RR] 0.54; 95% confidence interval [CI] 0.38–0.78). The number needed to treat to prevent one infection was 48. This benefit was observed in patients with tunnelled catheters but not in studies with untunnelled catheters.
  • Thrombosis can be a concern with the use of ethanol lock compared with heparinised saline, but this study found no difference in the incidence of thrombosis between ethanol and control groups (RR 1.05; 95% CI 0.91–1.22). However, one study, contributing almost 90% of the weight to this comparison, used saline only as a control and had a very high thrombosis rate in both groups, so the effect of ethanol over heparin was not properly assessed.
  • There was significant variability between studies by population characteristics, ethanol protocols and definitions of infection. Therefore, the results need to be treated with caution.

What does current guidance say on this issue?

There is little current national guidance on this issue. The NICE guideline on Healthcare-associated infections: prevention and control in primary and community care (2012, updated 2017) does not make any recommendations on the use of ethanol flush and lock solutions. Instead, it recommends using sterile 0.9% saline to flush and lock the catheter. It recommends against routinely using antibiotic lock solutions to prevent catheter-related bloodstream infections.

A UK Renal Association guideline (2015) suggests that antibiotic or antimicrobial locking solutions should be used. It does not mention using ethanol as a lock.

What are the implications?

Evidence is increasing on the advantages of ethanol locks compared with heparinised saline or saline alone.

The use of citrate, ethanol, antibiotic or other locks is currently based on local hospital policy as few trials exist. For now, the findings give us some evidence about the value of ethanol locks.

If concerns regarding antibiotic resistance escalate, it is possible that more research into this issue could directly compare the variety of locks in current practice.

Citation and Funding

Zhao T, Liu H, Han J. Ethanol lock is effective on reducing the incidence of tunneled catheter-related bloodstream infections in hemodialysis patients: a systematic review and meta-analysis. Int Urol Nephrol. 2018;50(9):1643-52.

No funding information was provided for this study.

Bibliography

Arechabala MC, Catoni MI, Claro JC, et al. Antimicrobial lock solutions for preventing catheter-related infections in haemodialysis. Cochrane Database Syst Rev. 2018;4:CD010597.

Broom JK, Krishnasamy R, Hawley CM, et al. A randomized controlled trial of heparin versus ethanol lock therapy for the prevention of catheter-associated infection in haemodialysis patients–the healthy-cath trial. BMC Nephrol. 2012;13:146.

Kumwenda M, Mitra S, Reid C. Clinical practice guideline. Vascular access for haemodialysis. 6th edition. Glasgow: UK Renal Association; 2015.

NICE. Healthcare-associated infections: prevention and control in primary and community care. CG139. London: National Institute for Health and Care Excellence; 2012, updated March 2017.

NICE. Infection: A summary of selected new evidence relevant to NICE clinical guideline 139. Evidence Update 64. London: National Institute for Health and Care Excellence; 2014.

Sanders J, Pithie A, Ganly P, et al. A prospective double-blind randomized trial comparing intraluminal ethanol with heparinized saline for the prevention of catheter-associated bloodstream infection in immunosuppressed haematology patients. J Antimicrob Chemother. 2008;62(4):809-15.

Schoot RA, van Dalen EC, van Ommen CH, van de Wetering MD. Antibiotic and other lock treatments for tunnelled central venous catheter-related infections in children with cancer. Cochrane Database Syst Rev. 2013;(6):CD008975.

Worth LJ, Slavin MA, Heath S, et al. Ethanol versus heparin locks for the prevention of central venous catheter-associated bloodstream infections: a randomized trial in adult haematology patients with Hickman devices. J Hosp Infect. 2014;88(1):48-51.

Ethanol lock is effective on reducing the incidence of tunneled catheter-related bloodstream infections in hemodialysis patients: a systematic review and meta-analysis

Published on 19 April 2018

Zhao, T.,Liu, H.,Han, J.

Int Urol Nephrol , 2018

PURPOSE: The purpose of this meta-analysis is to evaluate the effect of ethanol lock on the incidence of catheter-related bloodstream infection (CRBSI) in patients with central venous catheters. METHODS: RCTs comparing ethanol lock with another solution lock for prevention of CRBSI were obtained by searching databases of PubMed, Embase, Web of Science and Cochrane Central Register of clinical trials for eligible randomized controlled trials (inception to December 2017). Two researchers separately selected the RCTs and assessed their quality. Data on patient characteristics and ethanol protocols were collected. The primary outcome was the incidence of CRBSI, and the secondary outcomes were catheter colonization, exit infection and thrombosis. RESULTS: A total of 2575 patients with 3375 catheters from 7 eligible RCTs were included. Overall, ethanol lock significantly decreased the risk of CRBSI, with RR 0.54 (95% CI 0.38-0.78; I(2) = 0%; p = 0.001); no obvious heterogeneity was observed in the fixed-effects model (I(2) = 0%). Of note, subgroup analysis demonstrated that ethanol lock conferred significant benefit in studies with tunneled catheters (RR 0.46; 95% CI 0.30-0.72) but not in studies with untunneled catheters. Only two studies provided data regarding catheter colonization, and no significant difference was found (RR, 1.09; 95% CI, 0.87-1.38; I(2) = 41%; p = 0.45). Moreover, pooled data did not show significant differences between ethanol and control groups with regard to the incidence of thrombosis (RR 1.05; 95% CI 0.91-1.22; I(2) = 0%; p = 0.48). CONCLUSIONS: Our meta-analysis suggests that ethanol lock is effective on reducing the incidence of CRBSI in hemodialysis patients with tunneled central venous catheters.

Expert commentary

Patients with kidney failure sometimes have central venous catheters inserted in order to undertake dialysis. This analysis shows that using ethanol as a catheter ‘lock’ can significantly reduce infection risks. This is very important as such infections can be life-threatening. 

However, the two largest trials in this study used poor controls (saline solution only), and it is, therefore, possible this meta-analysis has overestimated the benefits of ethanol. Alternatives include antibiotic containing or citrate containing locks, both of which have shown benefits in some circumstances and are widely available. 

This research adds another possible treatment to prevent dialysis catheter-related infections, but should not be used first line, and reinforces the importance of using fistulas in dialysis patients to avoid the need for catheters at all.

Jeremy Levy, Professor of Practice (Medicine), Director of Clinical Academic, Imperial College London; Consultant Nephrologist, Imperial College Healthcare NHS Trust