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By Marilyn Hanchett, RN, PhD
Needleless connectors, used today as integral components of aninfusion system, evolved in response to demands for enhanced healthcare workersafety and as part of the continuing development of infusion technology. At thistime, there are three design categories among needleless connectors: splitseptum connectors, luer activated valves, and luer valves with positivedisplacement. Numerous branded products are available within each category.Although needleless connectors offer enhanced safety features, there have beenrecurrent concerns about an increased risk of bacteremia associated with theiruse. This article reviews the development of these devices, examines theavailable evidence base, identifies unresolved issues, and suggests strategiesto facilitate optimum use of needleless connectors within infusion systems.
During the past two years there has been increasing concernexpressed by infection control practitioners, infusion specialists, andepidemiologists that the use of needleless connectors, either generally orspecifically according to design category or brand, is directly responsible forincreased bacteremia inpatients receiving intravenous therapy.
Bacteremia associated with infusion therapies is known toincrease morbidity, prolong inpatient hospitalizations, and significantlyincrease the economic impact of care.1 The incidence of catheter-relatedbloodstream infections is disturbingly high, especially among central catheters,and the mortality risk has been reported as high as 30 percent in ICUs.2 Sinceintravenous therapy is among the most widely used invasive procedures in allhealthcare settings, the risk of complications is often also high. If any partof an intravenous system increases patient risks, then the clinician must beaware of it and be prepared to respond accordingly.
The Evolution of Needleless Connectors
First Generation Products
Priorto the 1980s, intermittent access to an intravenous system was accomplished byinserting a beveled, hollow bore needle into a latex cap positioned either alongthe administration set or at its termination. The needle was often secured withtape and was prone to disconnection. Emerging technology soon combined with engineering controlsrequired under the Occupational Safety and Health Administration (OSHA)Boodborne Pathogens Standard to produce a new generation of connectors.
This first generation of devices featured a split septum thatcould be repeatedly accessed with a blunt cannula. These connectors weredesigned to accommodate the need for intermittent access to the intravenoussystem while simultaneously eliminating the use of needles. The split septumconnectors were used in combination with other emerging technology, includingsafety catheters that typically offered recessed or retractable needles.Although this new technology was neither immediately nor universally adopted andthe costs associated with its use often posed a barrier to implementation, thesefirst generation safety products were successful in reducing the exposureincidents reported by healthcare workers.3 However, the first generationsplit-septum products did not address the problem of catheter occlusion.Split-septum connectors created negative pressure when the blunt cannula waswithdrawn. Any negative pressure at the time of disconnection canjeopardize device patency by allowing retrograde flow into the lumen of thecatheter.
Second Generation Products
Duringthe 1980s, technology continued to evolve. The second generation of needlelessconnectors replaced the split-septum design with an anti-reflux valve activatedby the use of a malefemale luer configuration. The process of joining the luercomponents created a locking action that exceeded the stability of theconnection possible with the splitseptum product. Since female and male luermechanisms were already a well-established concept within medical device design,the integration of a luer into a connector was easily understood and accepted byclinicians.
Like the first generation of connectors, the luer devicespermitted intermittent access and eliminated the use of needles. However, itsunique design was compatible with the use of most syringes and the need for ablunt cannula was eliminated. In addition, the ant-reflux design of the lueractivated valve helped neutralize any negative pressure occurring when thesyringe (or other luer device) was disconnected from the needleless connector.And when used according to manufacturer guidelines, these products did notdemonstrate an increased safety risk.
Unfortunately, the luer compatible design has beendemonstrated to pose other, non-infectious safety risks to patients. The seriousincidents that have been reported have all involved incorrect product use. Forexample, in 1996 and 2002 the Institute for Safe Medicine Practices cautionedthe healthcare industry about the potential to connect a syringe containing oralmedication to an intravenous system by attaching it to a needleless valve.4 In2003, the Food and Drug Administration (FDA) issued a safety alert following apatient death when oxygen was accidentally connected to a needleless luerdevice.5 However, during these years intravenous systems were also evolving.Implanted infusion ports were introduced for patients requiring long-termtherapies.
Tunneled central catheters became a viable option for patientsno longer candidates for peripheral infusions. Peripherally inserted centralcatheters (PICCs) offered a safer alternative when therapy was expected tocontinue for more than several days.
Third Generation Products
Withmore advanced catheter design and the clinical demand for extended catheterdwell times, the need to maintain patency became a growing clinical concern.Replacement of clotted catheters was expensive and traumatic for the patient. Aclotted lumen can also increase the risk of infection. A number of solutionsemerged to address this need, including the development of a valved catheter,the use of fibrinoloytics for catheter clearance, and the introduction of apositive displacement connector.
The third generation of connectors combined the existinglueractivated valve concept with a displacement action. This action expels asmall amount of the solution used to flush the catheter when the syringe usedfor flushing is disconnected from the leur. The displacement is a passivefeature and occurs automatically. Once this action has occurred, the remainingsolution (usually heparin or saline) is retained within the catheter and nofurther positive pressure exists. The positive pressure luer connector isdesigned to reduce retrograde flow into the catheter more effectively thateither split-septum or standard luer connectors.
However, although the third generation of connectors offeredadvantages over previous designs, they cannot prevent occlusion completely orunder all circumstances. Nonetheless, positive displacement connectors are nowwidely used to help reduce complications in central catheters. Today, examplesof split-septum, luer-activated and positive displacement luer connectors arecommercially available and commonly used in intravenous systems (see Table 1).
Emerging Infection Concerns
The gradual introduction of and product diversification withinneedleless connectors was accompanied in the 1990s by concerns regarding theirinfection risks. Studies published during this time period revealed a number ofissues that could potentially lead to increased infections. For example,needleless connectors were not always used according to manufacturer guidelines.Infection risks increased when connectors were changed less frequently thanspecified in protocols.6-8 An increased infection risk was also linked tospecific infusates such as TPN or other independent risk factors such as use of multilumen catheter or recentBMT.9-10
Although a variety of needleless connectors were investigated,no individual products were conclusively associated with either increased riskor national outbreaks. While initial concerns focused on device failure, abetter understanding of device use in conjunction with enhanced product design,helped allay clinician fears and allow needleless connectors to remain anintegral safety component of most, if not all, intravenous systems. In fact in2002 the HICPAC IV Guideline stated that when devices are used according tomanufacturer recommendations, they do not substantially affect the incidence of CRBSI.11
A Limited Base of Evidence
Since the 1990s, concerns have lingered about the relationshipof needleless connectors to bacteremia. Infection control experts have remainedalert to the serious complications that can potentially be associated with theseseemingly innocuous devices. But the need for better device-related scienceremains an elusive goal.
A review of the literature indicates that the studies of the1990s have not been significantly expanded by subsequent experimental research. In fact, although millions of needleless connectors are usedin patient care, the scientific evidence upon which to base their use remainslimited. Current studies vary widely in their scope, design, andscientific rigor.
For example, from 1999 to 2004, three new studies attempted toexamine the efficacy of positive pressure in maintaining the patency of centralvenous catheters. These prospective studies show that positive displacement offluid within central catheters is more effective than negative pressure (ordisplacement) in preventing occlusions. However, these studies also show thatthe positive displacement action accomplished with valve technology cannoteliminate the problem of occlusion in all central venous catheters.12-14
Recent published reports have investigated the issue ofinfection. Two studies, using different products, have reported a reducedpotential for microbial contamination when traditional caps were replaced with aneedle-free, luer valve that was been appropriately disinfected prior to use.15-16
As risks associated with needleless connectors have become aninternational infection control concern, published reports are now available innon-U.S. based clinical journals. For example, an evaluative study conducted inBritain reported inconsistency of use and routine care of all connectors usedwith central catheters prior to staff education and standard implementation of aluer valve.17 A randomized controlled trial conducted in Spain among intensivecare patients requiring central venous catheters found a significant reductionin bacteremia when a needleless connector was used in place of a three-way stopcock.18
In addition to the studies published in scientific,peer-reviewed journals there are also a number of product evaluation studies orreports that have appeared in clinical practice journals, on Web sites, and intrade publications. These articles generally describe an institutionsexperience in using a needleless connector or after changing brands. This levelof evidence is typically presented either as a quasi-experimental study or asdescriptive research and lacks the scientific rigor and control used in theexperimental designs. Their lack of control is especially problematic whenattempting to infer causation and/or generalize the findings to other practicesettings.
Understanding the Current Controversy
Similar to the experiences of a decade ago, reports ofbacteremia have resurfaced. The implied cause of these new or increasedinfection rates appears to be the use of needleless connectors. Concern aboutthe use of needleless connectors has been expressed in presentations, posters,and/or abstracts presented at annual meetings such as the Society of HealthcareEpidemiologists of America (SHEA), the Association for Professionals inInfection Control and Epidemiology (APIC), and other professional organizationssince 2004. Simultaneously, some manufacturers have attempted to leverageinfection concerns to better position their individual brands. For cliniciansstruggling to understand the issue, the result is often a confusing jumble ofgenuine, albeit unanswered, device concerns with product marketing claims, datafrom bench studies, expert speculation, and over-generalization of findings frominstitutional reports.
The dilemma remains, as it did a decade ago, the same for allwho currently attempt to analyze the infectious risk potential of these devices.There is simply not enough scientifically rigorous evidence upon which to make aconclusion. Although there have been sporadic reports of increased infections,there is insufficient evidence to indicate a trend that can be reliablyassociated with a specific type of connector or any particular product.
Potential Risk Factors Requiring Further Investigation
In order to fully understand the risk potential of any type orbrand of needleless connector, several important factors need to be clarified.
1. User Error or Device Failure?
Most published reports have not measured the potential foruser error. Any break in aseptic technique when using a needleless connectorsets the stage for potential infection. At this time, the lack of informationrelated to user error with needleless connectors is a significant barrier inanalyzing the underlying cause of actual or presumed increases in bactermia.Although the devices are mechanically simple and their use intuitive, usererrors can still occur. For example, clinicians may not disinfect the surface ofthe connector before accessing the intravenous system. Connectors may not beflushed completely after use or may not be changed according to establishedprotocols. Luer valves may not fully rebound upon disconnection. Split-septumconnectors may be damaged by incorrect access with a needle or an incorrectlyplaced needle rather than a blunt cannula. Extension sets, attached toconnectors and intended for intermittent IV access, may not be clamped asrequired by the manufacturer.
In any study that attempts to identify causation, it isessential that all reasonable contributing variables be identified andcontrolled. Without this essential step, it is easy to draw the wrongconclusion. Allegations of device failure are often the initial andpresumptive cause attributed to sudden increases in bloodstream infections.While concern over device failure is a possibility that must always beconsidered, it cannot be presumed to the primary cause when insufficientevidence exists to support the claim. At the same time, designing a clinicalstudy that can achieve the necessary level of control is very challenging andcan be cost prohibitive for the sponsoring institution. This is particularly problematic when studying needlelessconnectors since both the number of potential users and opportunities forintentional or accidental misuse is high in all practice settings where infusiontherapies are administered.
The potential impact of incorrect use cannot be ignored,especially since the study by Cookson et al. reported that only 60 percent to 70percent of nurses maintained needleless connectors correctly.6 While proceduralcompliance by clinicians performing infusion therapy has not been thoroughlystudied, other aspects of infection control have been. Perhaps the best-known focuses on hand washing where, nomatter how frequent or extensive the education provided, clinician compliance rarely exceeds 40 percent.22 If compliance with the use of needleless connectors is similar to compliance with handwashing, user errorcould emerge as the most important contributing factor in device-relatedinfections. At this time, however, it remains an unknown variable.
2. Device Design In spite of marketing claims to the contrary,the superiority of one type of design for needleless connectors has not beenproven. In fact, the impact of residual volumes, dead spaces, and flow rates oninfection risk has not been extensively analyzed. Manufacturers will inoculatethe access surface and/or the fluid pathway of their device with bacteria totest, under strict laboratory conditions, the efficacy of surfacedecontamination with an approved disinfectant as well as the possibility ofbacterial growth and transfer along the fluid pathway. Such testing is usuallylimited to seven or eight consecutive days. Longer-term outcomes, especially inless rigidly controlled environments, have not been discussed in the literature.
Part of the current controversy focuses on determining whethersplit septum or luer-activated valve technology represents the safest approachin preventing catheter-related bloodstream infections. Until more evidenceexists regarding the impact of mechanical design aspects on infection risk, noneof the three currently available categories of needleless connectors can claimsuperiority.
3. The Impact of Biofilm Microbial biofilm is the accumulationof polymers excreted by bacterial cells adhering to a device surface. Theaccumulation of biofilm on medical devices, including intravenous catheters,cannot be prevented and creates clinical management challenges for long-term,indwelling devices. Biofilm accumulates rapidly on central venous catheters andonce in place, is difficult to eradicate. Biofilm-related infections often require removal of the device.19
There has been minimal investigation on the role that biofilmmay play in the needleless connector controversy. A study published in 2001examined needleless connectors used at a bone marrow transplant center. The results of this analysis showed that 63 percent of the 24needleless connectors tested contained biofilms comprised predominantly ofcoagulase-negative staphylococci.20-21 These results suggest additionalquestions. If biofilm has been detected on central venous catheters is less than72 hours after placement, is development within needleless connectors equally asrapid? Is the accumulation of biofilm facilitated by mechanical design aspectsof these devices? Does biofilm demonstrate an affinity for split-septumproducts, luer-activated valves, or is there no difference? Answers to these andmany other questions will remain unanswered until more research is done.
Taking Action When Evidence is Lacking
The lack of reliable evidence, although highly problematic, isnot an insurmountable obstacle for ICPs urgently seeking to prevent bacteremiain patients receiving infusion therapies. Awareness of a limited evidence basehelps direct decisions and actions along lines of the best available data andobjective reasoning. The following list summarizes steps that infection controlpractitioners can take now.
Needleless connectors, initially designed to reduceneedlestick exposures among clinicians, have contributed to a safer workplaceand helped reduce the injury risks associated with performing infusionprocedures. Whether or not needleless connectors increase the risk ofbacteremia or prevent catheter occlusion is less certain.
Effectiveness of intraluminal fluid displacement triggered byspecific valved connectors is suggested by current studies but has not beenextensively examined in the literature. At the same time, as needlelessconnectors have been the alleged cause of infection outbreaks, studies havefailed to conclusively demonstrate the link or identify any product trends. Manyproducts have been investigated but none have shown greater or lesser risk forpotential infections. Many important variables in the infection equation,including user error, mechanical design, and the role of biofilm, remainunknown.
Like all medical products, needleless connectors present theclinicians with both advantages and disadvantages. And like other products, theyare only as safe and reliable as the individuals using them. Until conclusiveevidence becomes available to differentiate among existing products or as partof a new generation of products, clinicians must continue to include monitorneedleless connectors, evaluate device-related outcomes, and seek to betterunderstand the potential for user error within all practice settings. ICT MarilynHanchett, RN, PhD, is director of clinical affairs for IgG America.
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