Catheter-related bloodstream infections (CRBSIs) are a serious complication associated with central venous catheters, frequently caused by microbial colonisation at the catheter site or migration of pathogens from distant sources. These infections can lead to life-threatening conditions, including sepsis, endocarditis, and abscess formation. Consequently, CRBSIs create challenges for both patients and healthcare providers. Various strategies have been developed to minimise the occurrence of CRBSIs, including the use of catheter-locking solutions. These solutions act as antimicrobial agents, and some can prevent the thrombus formation that can cause occlusion and/or biofilms to reduce microbial colonisation within the catheter lumen.
According to a study by Lemiech-Mirowska et al (2021), the prevalence of hospital-acquired or nosocomial infections exceeds 25% in developing countries and is up to 15% in developed countries, resulting in the death of approximately 40 000 hospitalised patients worldwide. It is well documented that up to 90% of inpatients have some form of vascular access device placed during the course of their hospital stay (Platt and Osenkarski, 2018). For most patients, this could be the most invasive procedure they would have experienced, so to reduce the risk of associated complications, it is vital that all measures are taken to protect the catheter in order to protect the patient.
Climo et al (2003) estimated that 80% to 90% of bloodstream infections seen in their surveillance of 2459 patients in six medical facilities were associated with central venous access devices (CVADs) and that, in most acute hospitals, surveillance and infection control efforts to reduce morbidity and mortality associated with bloodstream infections concentrate on the high-risk ICU patients with central venous catheters (CVCs). More focus outside of the ICU is needed, where longer-term devices, especially PICCs, are associated with lower rates of infections when compared with short acute CVC, and can be more easily managed with locking solutions.
Protecting the catheter and the patient
Any break in the skin is a breach of the body's first line of defence against infection. In relation to vascular access there are two key points of entry for infection entering into the body, these being the exit site of the vascular access device and the internal lumen of the catheter (Manjula, 2022) (Figure 1). The exit site can be managed with good care and maintenance practices, such as regular visual assessments of the exit site to detect phlebitis early on and specialist dressings to cover the exit site, containing products such as chlorhexidine (Eggimann et al, 2019). Alcohol-containing caps can also be used to protect the needle-free connector and internal lumen of the catheter when it is not in use. Alcohol-containing caps can act as a barrier for infection; however, this physical barrier to the external environment will not prevent bacteria already inside the catheter lumen forming biofilm nor will they prevent thrombosis. Recent studies have confirmed that up to 80% of blood stream infections are associated with the formation of biofilms (Arunan et al, 2023)
Organisms can still be introduced or migrate onto the inner surface of the lumen of the catheter via the needle-free connector when the catheter is in use, and this can start forming an adherent biofilm (Simmons et al, 2020). During infusion therapy, these organisms enter the circulation via flow from the catheter; when biofilm is present it can act as a medium for micro-organisms to develop and spread (Dutta and Bhattacharjee, 2022).
Catheter-locking solutions
Catheter locking refers to the practice of administering solutions into a vascular access device and leaving the solutions sitting or locked into the catheter. The locking solution is the last solution to be administered after the sodium chloride 0.9% flush.
The use of locking solutions is not a new phenomenon; historically, long-term vascular access devices have been locked with heparin solutions with little evidence of their efficacy, so much so that in recent years evidence has shown simple saline flushing to be more effective. The difference between a flush (pushing fluid through the catheter) and a lock (fluid dwelling in the catheter) makes a huge difference in maintaining a safe intraluminal environment. A 10ml saline flush should be used to confirm patency of the catheter and wash the intraluminal environment of any debris that could be a catalysts for biofilm. Locking the catheter should be the last action before the end of the catheter use for that episode of care in order to safeguard the intraluminal environment. The use of alternative locking solutions have only become more common place in the past few decades. Even though progress has been made in understanding the importance of intraluminal care and maintenance, it remains overlooked as a priority in many guidelines and protocols locally and nationally. A great deal of time and energy is spent on promoting extraluminal care and the maintenance of vascular access devices, that despite the risks associated with biofilms, thrombosis and bacteria most recommendations call for saline flushing only. However, it is as important to safeguard the intraluminal environment of catheters as it is for the extraluminal care. Practices in areas such as parenteral nutrition, renal dialysis, and cancer treatment have often included taurolidine catheter locking where long-term vascular access devices such as PICCs and tunnelled catheters or implanted ports are commonly used. The use of locking solutions in these types of catheters is included in most national and international guidelines and standards (Gorski et al, 2021).
Preparations for catheter-locking solutions have historically been limited to taurolidine citrate preparations, with or without heparin or urokinase. Ethanol locks and antibiotic solutions such as vancomycin have been used for many years to prevent CRBIs, and the addition of heparin or urokinase is aimed at preventing thrombus and maintaining patency (van den Bosch et al, 2022). There is mixed evidence about the efficacy of ethanol and some concerns about how the alcohol interacts with the catheter material. Heparin locking has been shown to be less effective at maintaining catheter patency than 10ml of saline when using a push-pause-flushing technique (Pérez-Granda et al, 2020; Santomauro et al, 2022). A pulsative flush (push pause method) is recommended when flushing an IV catheter to remove ‘debris’ from the catheter and confirm patency. This essentially means that the intraluminal debris is pushed into the patients' blood stream, which could have adverse outcomes if the debris contains bacteria or clots. It is, therefore, safer to lock the internal environment of the IV catheter with a solution that will prevent any debris such as biofilm, bacteria or thrombosis from accumulating in the first place. Antibiotic locking solutions are a concern due to antibiotic resistance and they do nothing to assist with occlusion or maintaining patency and can even interact with heparin to reduce the efficacy of the locking solution (Labriola, 2019). Until recently, locks containing taurolidine have been the most widely used and accepted as the most effective.
All patients with long-term VADs such as tunnelled, cuffed central venous catheters, PICCs and implanted ports are candidates for locking solution protection. Patients receiving parenteral nutrition are most familiar with using taurolidine citrate locks and this practice is supported by the European Society of Parenteral and Enteral Nutrition (ESPEN) (Pironi et al, 2020) in its guideline on home parenteral nutrition, recommendation 34. As an additional strategy to prevent CRBSIs, taurolidine locking should be used because of its favourable safety and cost profile. Patients rely on their long-term catheters in order to survive, often vascular access options are limited for these patients due to previous poor vessel health (Moureau, 2019) which means the preservation of their current VAD is essential. The risk of intraluminal contamination is high, especially when parenteral nutrition is being administered because bacteria can thrive on the nutritious solution.
The triple threat: thrombus, microorganisms and biofilm
Although CRBSI remains the most high-profile complication associated with vascular access, catheter occlusion is very common and equally as serious. Occlusions are often caused by blood clotting inside the catheter, also known as catheter thrombosis. This is often caused by a poor flushing technique or inadequate needle-free connectors (Steere, 2022). Disruptions in intravenous treatment can occur for several reasons. Catheter occlusion, suspected intraluminal catheter infection, the ability to withdraw blood prior to administering IV therapy to confirm catheter patency and tip location, especially with chemotherapy, are all disruptive complications that can be reduced by using catheter-locking solutions (Bering and DiBaise, 2023). Further delays in treatment occur when the occlusion becomes permanent, and catheter replacement becomes necessary. Replacing a PICC is relatively straightforward. However, replacing an occluded cuffed tunnelled catheter or implanted port is not straightforward and requires surgical intervention to remove and then to re-insert. Multiple placements will have a negative impact on vessel health and preservation while they also carry potential insertion complications each time. Eventually patients can lose vein availability in the upper body. This is a huge problem for patients relying on long-term parental nutrition or long-term biologics for chronic conditions.
Biofilm is a slime produced by bacteria to protect themselves, it provides shelter under which the bacteria proliferate and transfer information, including resistance to antibiotics (Sharma et al, 2019) (Figure 2). Bacterial biofilms are a serious global health concern due to their abilities to tolerate antibiotics, host defense systems and other external stresses; therefore, biofilms contribute to persistent chronic infections (Sharma et al, 2019). A biofilm can be made up of a single or several species of bacteria and yeast. It coats the internal lumen of the catheter. Biofilm provides a source for near-continuous infection of the bloodstream that is difficult to remove by antibiotic treatment. Pieces of biofilm can break off and be carried to a terminal point in the circulation, causing heart valves, brain, kidneys, and extremities to become particularly vulnerable to seeding with the bacteria emboli (Vestby et al, 2020). The incidence of infective endocarditis associated with biofilms and central line infections is increasing, and an incidence of 7–29% is reported in the literature (Chrissoheris et al, 2009; Alonso et al, 2022). Bioflim can be present on a catheter and be undetected, blood cultures for the catheter may be negative if the biofilm does not migrate into the culture sample, but the risk is still there, preventing the formation of biofilm is a more affective way of maintaining the catheter health, once biofilm has taken hold in the catheter it becomes harder to manage. Prevention is better than cure.
These common vascular access device complications come together to form the ‘triple threat’ to the patient, which combines infection, occlusion and biofilms. Blood reflux at the tip of the catheter can form a clot inside the lumen that promotes and adheres to biofilm, enhancing the environment for micro-organisms to feed and multiply (Casimero et al, 2020). The multiplying micro-organisms increase the creation of biofilm, which in turn promotes clot adherence and so the cycle continues until action is taken to either prevent these threats occurring or disrupts them to break the cycle. Preventing biofilm formation and clot formation will prevent micro-organisms multiplying within the catheter. Add in antiseptic action to eradicate micro-organisms and the triple threat is broken. One catheter-locking solution is designed to offer a solution to the triple threat – KiteLock 4%.
KiteLock 4% catheter-locking solution
KiteLock is a central venous catheter-locking solution that is supplied in a 3 ml plastic vial containing 4% tetrasodium ethylenediaminetetraacetic acid (EDTA) fluid (marketed as KiteLock Sterile Locking Solution™) (Figure 3). KiteLock 4% is non-antibiotic, possesses antimicrobial, anti-biofilm, and anti-coagulant properties. This was first approved by Health Canada as a catheter-locking solution. KiteLock 4% is now CE marked and is available in the UK and other markets worldwide.
EDTA has been used for many decades for intravenous chelation therapy to treat lead poisoning. If the entire vial of KiteLock was completely administered to a patient at one time, the exposure to EDTA would be 30 times less than that to which a patient would be exposed during chelation therapy. In addition, KiteLock has passed the standard toxicity tests to make sure it is not mutagenic or carcinogenic, and that it is biocompatible.
KiteLock 4% and infection control
Vascular access device occlusion can increase the risk of CLABSI because of the complementary interactions of fibrin, thrombus, and biofilms, these organic tissues can provide a medium for microorganisms to attach and multiply on (Rickard and Ullman 2018). KiteLock 4% is an antimicrobial but is not an antibiotic. This means the risk of antimicrobial resistance is eliminated. Its antimicrobial mechanisms of action are related to its chelation properties, which are different from the mechanisms of action of today's antibiotics. In line with this, KiteLock also complies with global antimicrobial stewardship programmes. KiteLock consists of EDTA and water. EDTA is a known chelator. This means it has an affinity for metals and elements such as calcium. Bacterial cell walls are made of calcium so as they are exposed to EDTA, calcium is removed, thereby destroying the wall and killing the bacteria. A similar process happens for biofilm where calcium removed by EDTA destroys the scaffolding of the slime, thereby making holes in the biofilm for EDTA to reach the bacteria. EDTA is effective because of the irreversible and high binding affinity to metals such as calcium, this is what sets this locking solution apart for others such as citrate which is also a chelator but unlike EDTA, citrate has a reversible, low binding affinity meaning it may not be able to remove the calcium, if citrate does remove calcium it can reintroduce it into the cell which means the locking solution efficacy can be mixed and low quality.
Due to KiteLock's chelating abilities, it will impact coagulation and micro-organisms as soon as the CVAD is locked. It has been shown to take 3 to 6 hours to eradicate most common mono-species and mixed species biofilm and is the only catheter lock solution proven to do this. Within 24 hours, KiteLock eradicates Candida species and meticillin-resistant Staphylococcus aureus (MRSA) bacteria and biofilm. KiteLock is indicated for the maintenance of patency and to decrease the risk of bacterial colonisation and biofilm formation within CVADs and is intended to be used as a first-line-of-defense catheter lock solution as soon as the CVAD is inserted.
Occlusion management
KiteLock 4% is an anticoagulant. A study of outcomes in more than 50 000 patients undergoing home infusion demonstrated that occlusions lead to therapy interruption caused by loss of patency (43%), device replacement (29%), device removal (14%), emergency room visits (9%), and unscheduled hospital visits (6%). KiteLock 4% has been shown to reduce occlusions by up to 70% and catheter line replacement by 13%, which translates into improved clinical outcomes and considerable cost savings (Moureau et al, 2002).
Evidence from studies
KiteLock 4% was first approved by Health Canada in 2016 as a Class II Medical Device, with Canada being the first market in the world to use it. Since that time there have been numerous successful clinical studies in adults. It was approved for use in children (not neonates) in Canada in July 2019, and in Europe in January 2020, based on a long-term quality improvement study conducted by Toronto Sick Kids (Quirt et al, 2021).
A study by Gattini et al (2023) showed a 63% reduction in cost when 4% tetrasodium EDTA (T-EDTA) is used for 24 months compared to using 0.9% sodium chloride, heparin, or taurolidine.
A study by Hill and Garner (2021) looked at the efficacy of 4% T-EDTA catheter lock solution in home parenteral nutrition and showed a 100% reduction in occlusions following 24 months of using KiteLock 4% in parenteral nutrition patients and a 71% reduction in CLABSI incidence in the same 24 months period when using the KiteLock 4% catheter locking solution.
Quirt et al (2021) published evidence concerning the reduction of central line-associated bloodstream infections and line occlusions in paediatric intestinal failure patients on long-term parenteral nutrition using 4% T-EDTA and demonstrated a 100% reduction in CLABSI incidence following KiteLock 4% use for 12 months in those paediatric patients on long-term parenteral nutrition. The study also showed a 90% reduction in occlusions following KiteLock 4% use over the same 12-month period in those paediatric patients on long-term parenteral nutrition with previous occlusions requiring alteplase.
KiteLock 4% in the UK
The first clinical trial and phase one integration of KiteLock 4% is under way in Frimley Health NHS Foundation Trust. The trial was started in August 2023, based on the clinical evidence from Canada, the positive safety profile and the triple action of the solution. This trial was approved to be undertaken in the infusion unit and the vascular access service which are both part of the Department of Intravenous and Vascular Access Services (IVAS). So far, KiteLock has been used to protect all the oncology PICCs placed in the unit, as well as the Hickman catheter patients having home parenteral nutrition and the IVAS patients who have ports for biologic infusions.
As the trial continues, as of October 2023, there have been no noted complications associated with KiteLock 4% locking solution and no occlusions or catheter infection in patients with catheters including KiteLock.
Phase two of the integration will be to use KiteLock 4% in renal patients and within the paediatric units.
Application in clinical practice
The application and benefits of KiteLock in clinical practice, including paediatrics, oncology, nutrition support and renal care are outstanding. Its effectiveness is well published and the benefits clearly include reduced catheter occlusion, and catheter infections. This will help prevent missed doses of intravenous medication, which in turn can avoid extended admissions due to suboptimal intravenous treatments, better patient outcomes associated with reduced catheter associated blood stream infections and a reduction in the use of antibiotic catheter locks, which can increase the risk of antibiotic resistance. Kitelock 4% locking solutions can be implemented in clinical practice by including the locking process in the care and maintenance bundle and protocols for PICC and long term vascular access device use when the patient is an outpatient having day case IV treatment. Weekly flushes of these devices can then include final lock with Kitelock. This practice is already established in many centres who already use line locking.
Case study
KiteLock has been introduced into the author's oncology PICCs with the aim of maintaining patency and reducing the risk of CRBSI. This case study decribes the use of KiteLock in a 39-year old patient with Crohn's disease. The patient has had previous catheter-related infections which have been compounded by her immunosuppressed state. She also has extremely complex vascular access needs.
On admission the patient needed a laparotomy for a small bowel obstruction and required intravenous parenteral nutrition. The patient has had multiple upper body vascular access devices in the past with extensive stenosis of their brachial, axillary and subclavian vein bilaterally. Taurolidine locks had previously been used to maintain patency for the catheter and reduce the risk of CRBSI with poor results. The patient has had multiple replacement catheters which in turn have caused vessel stenosis. On this admission, the vascular access team placed a cuffed tunnelled catheter in the right internal jugular, which was the only patent vessel available. This was then locked with KiteLock during the 4-hour rest period between the parenteral nutrition infusions. The catheter was a double lumen, and the additional lumen was locked with KiteLock overnight. Since locking the catheter daily in this way (since August 2023), the patient has not had any associated catheter complications and the catheter has remained patent with constant blood aspiration.
Conclusion
The triple action of KiteLock 4% locking solution makes this system superior to other locking solutions on the market. The action against biofilm and its ability to eradicate fungus, MRSA and other pathogens is well evidenced and the anticoagulation actions means that using other locking solutions to unblock catheters such as urokinase and alteplase will be reduced, saving time and money, especially when these unblocking solutions seem to be in short supply.
Changing the care and maintenance process to include catheter locking with KiteLock 4% is key to ensuring we get the maximum benefit from the device for our patients.
Key Points
- Locking solutions should be adopted as part of the care and maintenance protocol for central venous access devices (CVADs)
- KiteLock 4% is a central venous catheter-locking solution that possesses an antimicrobial that breaks down bacteria and biofilm
- KiteLock 4% has a triple action on infection, occlusion and biofilm
- KiteLock 4% is claimed to be the only locking solution that eradicates biofilm
CPD reflective questions
- Consider what flushing regimes are used in your clinical practice and what could be introduced
- How could you incorporate catheter locking into your local CVAD care bundles and care and maintenance?
- Could KiteLock be used to reduce the number of PICC occlusions in your facility as a strategy to cope with reduction in catheter unblocking solution?