Potential Alternative Locking Solutions

One strategy to improve catheter performance and reduce the risk of catheter-related bloodstream infections (CRBSI) is to use different locking solutions. Much research has been published about substitutes for heparin lock solutions, yet no alternative solutions are commercially available in the United States at the present. The locking solutions discussed below are only available from a compounding pharmacy.

Combinations of various antibiotics and heparin, known as antibiotic lock therapy (ALT), have been suggested as a means to treat existing CRBSI. Although this has been reported as a successful treatment for the salvage of infected catheters, the use of ALT as a routine prophylactic flushing or locking solution remains controversial. There is growing concern about the development of drug resistance when ALT is routinely used. Because these questions do not address the fundamental issue of alternatives to heparin, ALT is not included in this discussion.

The published literature contains two major trends—improving catheter flow rates in hemodialysis patients and reducing catheter-related bloodstream infection in all types of central venous catheters. The criteria for an alternative locking solution should focus on the following key points:

• The required length of time the solution must remain in the catheter lumen to be effective. An extended period (ie, 20-24 hours) would make the solution inappropriate for critical-care patients receiving frequent doses of medication
• The absence of adverse reactions when the locking solution is flushed through the catheter. It would be virtually impossible to ensure that every nurse would remember to aspirate and discard the locking solution rather than the current practice of flushing it into the bloodstream
• The effectiveness for ensuring catheter patency
• The effectiveness of reducing or preventing the development of intraluminal biofilm and subsequent CRBSI
• The impact of the locking solution on the integrity of the catheter material
• The compatibility of the locking solution with other fluids and medications infused through the catheter

Ethylenediaminetetraacetate (EDTA) was suggested as an alternative locking solution approximately 20 years ago because it has anticoagulant properties and kills Staphylococcus and Candida. Disodium EDTA combined with minocycline has been shown to reduce fresh and mature biofilm in animal, in vitro, and ex vivo studies.63-65 Tetrasodium EDTA is now the focus of research.66,67

Ethanol has been used for more than 20 years for the treatment of catheters occluded with fat emulsion, yet there has always been concern about the use of all alcohol solutions in catheters made of polyurethane. There are three types of polyurethane used in the manufacturer of catheters. The oldest is an organic compound in an open chain structure. This type has the potential for stress cracking. The catheter surface can feel tacky after exposure to alcohol because the material absorbs the alcohol and swells but does not return to its original size when dry. The second generation of polyurethane material is more chemically stable because of changes in the organic structure. The most recent formulation has the greatest chemical tolerance with the lowest risk of stress cracking. In vitro testing by exposing the second generation of polyurethane to 70% ethanol has demonstrated no changes in the force required to break a catheter segment or the maximum elongation and strain before breakage.68 It is imperative to know the catheter manufacturer’s instructions before exposing it to any form of alcohol, as these instructions would be based on the specific type of polyurethane being used.

Ethanol as a locking solution has been successfully used to treat catheter-related bloodstream infection. Ethanol concentrations in these studies ranged from 25% to 74%, and catheters were locked for 12, 20, and 24 hours. A randomized animal study locked tunneled catheters contaminated with Staphylococcus epidermis with either 70% ethanol or heparinized saline for one 3-hour treatment. Intraluminal and extraluminal catheter surfaces were then cultured with more catheters in the ethanol group, producing no growth.69 Another randomized study compared locking tunneled cuffed catheters in hematology patients. All catheter lumens were locked with heparin lock solution or 70% ethanol for 2 hours each day. The solution was then aspirated and all lumens were locked with heparin lock solution for the remainder of the day. Three patients in the ethanol group and 11 in the heparin group developed a bloodstream infection.70

Sodium citrate acts an anticoagulant by binding to calcium and removing it from the coagulation cascade. It is also antibacterial in hypertonic concentrations. Studies have included 4%, 10%, 30%, and 47% concentrations of sodium citrate.71-75

Taurolidine is a derivative of the amino acid taurine, which inhibits and kills a wide range of organisms. Randomized and nonrandomized studies of dialysis catheters have compared combinations of citrate and taurolidine with heparin and found favorable results.76

An in vitro study examined the effects of 4% citrate and 30% ethanol on the newest formulations of polyurethane. Although the force required to elongate and break the catheters was lower with citrate/ethanol than with catheters exposed to heparin, the authors thought this difference was not significant in clinical applications.77 Biofilm reduction was demonstrated in another in vitro study of hemodialysis catheters.78

Another in vitro study found that a combination of 7% sodium citrate, methylene blue, and parabens showed positive benefits as a locking solution compared with heparin plus preservative. This combination is effective against free-floating and attached biofilm.79

Tissue plasminogen activator as a catheter-locking solution has been compared with heparin locking in hemodialysis catheters and was shown to produce greater flow rates and fewer complications.80,81 A study comparing 3 mL of lepirudin 100 micrograms per mL with 3 mL of heparin 100 units per mL in catheters used for bone marrow transplantation showed lepirudin to be no more effective than heparin. There is also concern about anaphylactic reactions to lepirudin.82 A literature review of 5 randomized trials comparing heparin locking with urokinase locking found that the methodology of those trials prevented a recommendation of one solution versus the other.83