Advertisement

Quantitative assessment of reflux in commercially available needle-free IV connectors

Abstract

Introduction

Blood reflux is caused by changes in pressure within intravascular catheters upon connection or disconnection of a syringe or intravenous tubing from a needle-free connector (NFC). Changes in pressure, differing with each brand of NFC, may result in fluid movement and blood reflux that can contribute to intraluminal catheter occlusions and increase the potential for central-line associated bloodstream infections (CLABSI).

Methods

In this study, 14 NFC brands representing each of the four market-categories of NFCs were selected for evaluation of fluid movement occurring during connection and disconnection of a syringe. Study objectives were to 1)theoretically estimate amount of blood reflux volume in microliters (μL) permitted by each NFC based on exact component measurements, and 2) experimentally measure NFC volume of fluid movement for disconnection reflux of negative, neutral and anti-reflux NFC and fluid movement for connection reflux of positive displacement NFC.

Results

The results demonstrated fluid movement/reflux volumes of 9.73 μL to 50.34 μL for negative displacement, 3.60 μL to 10.80 μL for neutral displacement, and 0.02 μL to 1.73 μL for pressure-activated anti-reflux NFC. Separate experiment was performed measuring connection reflux of 18.23 μL to 38.83 μL for positive displacement NFC connectors.

Conclusions

This study revealed significant differences in reflux volumes for fluid displacement based on NFC design. While more research is needed on effects of blood reflux in catheters and NFCs, results highlight the need to consider NFCs based on performance of individual connector designs, rather than manufacturer designation of positive, negative and neutral marketing categories for NFCs without anti-reflux mechanisms.

Post author correction

Article Type: ORIGINAL RESEARCH ARTICLE

Article Subject: Nursing

DOI:10.5301/jva.5000781

OPEN ACCESS ARTICLE

Authors

Garret J. Hull, Nancy L. Moureau, Shramik Sengupta

Article History

Disclosures

Financial support: This study was funded by a grant to the University of Missouri from Nexus Medical, LLC. Shramik Sengupta PhD, Department of Bioengineering, served as principal investigator on this grant. The funding source played no role in the research results or reporting of the data. The results and conclusions of the research are the work product of the authors. Graphic contributions were received from Nexus Medical.
Conflict of interest: All authors submitted ICMJE Form for Disclosure of Potential Conflicts of Interest. G Hull reported no conflicts of interest, reported no employment and was a full time student. Dr. Sengupta reported serving as a consultant to Fresenius. N Moureau reported employment with PICC Excellence, Inc, Greenville Memorial University and Medical Center, Greenville, South Carolina; educational speaker and consultant to 3M, Angiodynamics, Access Scientific, B Braun, BD Carefusion, Chiesi, Entrotech, Excelsior, Fresenius, Linear Health Sciences, Nexus, Parker Labs, Teleflex, and research grant recipient from 3M, Cook and Entrotech.
This research represents potential limitation and bias due to commercial funding. Experiments and research process was performed independently and exclusively by the University of Missouri research department; the manufacturer had no role in the research results or reporting of the data. The role of the manufacturer was in providing the funding, the product, reviewing the initial objectives and protocol developed by the research department prior to initiation of the study.
Clave, Microclave and Neutron are registered trademarks of ICU Medical, Interlink and One Link are registered trademarks of Baxter Healthcare, Smartsite and MaxPlus are registered trademarks of BD/Carefusion, Q-Syte is a trademark of Becton Dickinson, Ultrasite and Caresite are registered trademarks of B. Braun, Invision Plus is a registered trademark of Rymed, and Nexus TKO-5 and Nexus TKO-6P are registered trademarks of Nexus Medical LLC.

This article is available as full text PDF.

Download any of the following attachments:

Introduction and background

Prior to the advent of needle-free connectors (NFCs), stainless-steel needles were used to access intravenous (IV) y-sites, tubing ports and injection sites. While this process was effective for IV pathway access, needle-stick injuries became a substantial risk to healthcare workers, increasing the potential for occupationally acquired blood-borne diseases (1). In 1992, the Occupational Safety and Health Administration (OSHA) recommended that healthcare facilities incorporate “engineering controls” to prevent such occurrences (2). The use of “engineering controls” included the integration of NFCs into the IV access system both for needle safety and for the prevention of central-line associated bloodstream infections (CLABSI) (3-4-5). NFCs allow for the administration of IV fluids, medications and blood to indwelling venous or arterial catheters without the use of needles. NFCs are also used for the withdrawal of blood samples and for aspiration of blood to check the catheter for patency. While the introduction of NFCs greatly reduced the risk of needle-stick injuries for healthcare workers, their use has been associated with other complications such as an increase in catheter occlusions and CLABSIs (6-7-8-9-10-11).

In response to the increase in CLABSI related to the use of NFCs, medical device companies began designing and developing lower-risk devices (12). Over the past 20 years, 4 categories of NFC designs have emerged (2, 13). While there is no regulatory body that recognizes the categories of NFC as being indicative of function or performance (13), NFCs are typically marketed as being “positive”, “negative”, “neutral” (6, 12-13-14-15-16) or pressure-activated anti-reflux (9, 13, 17). The characteristics of each category of NFC indicate the mechanism and action of the NFC upon connection/disconnection. NFCs are designed as end caps to lock/luer onto the hub of catheters. Efficiency may be measured on the ability of the NFC design to prevent movement of fluids and inadvertent reflux of blood into the catheter (18, 19). The key features and defining characteristics of each NFC design along with manufacturer recommended clamping sequences are summarized in Table I. The specifics of each type of NFC are further explored in the Discussion section of this paper.

Fluid displacement characteristics of negative, neutral displacement, pressure activated anti-reflux, and positive, needle-free connectors

Types of NFCs Negative displacement NFC Neutral displacement NFC Anti-reflux NFC Positive displacement NFC
Fluid movement upon disconnection Blood refluxes into catheter Blood refluxes into catheter Fluid restricted bydiaphragm Fluid moves toward patient
Fluid movement upon connection Fluid moves toward patient Fluids moves toward patient Fluid restricted by diaphragm Blood refluxes in to catheter
Manufacturer recommended clamping sequence Clamp before disconnection No specified clamping No specified clamping Clamp after disconnection of male luer

Unfortunately, the large variety of NFCs, the different designs, performance and instructions for use with each device is a source of confusion among clinicians. In a 2011 survey of 4000 healthcare workers in which 554 responded (9):

21.9% did not know which brand of needle-free IV connector was used with their CVCs (2)

25.4% did not know if their connector was ‘positive’, ‘negative’ or ‘neutral’ (2)

47.2% did not understand the correct way to flush and clamp a catheter with the NFC used by their institution (9).

It is not uncommon for several types or brands of NFCs to be used on peripheral and central venous access devices within a single hospital, such as one category for peripheral catheters and a different category for central catheters (2, 6, 9). Evidence suggests that lack of training for device usage correlates with an increase in CLABSI (20). This was demonstrated in a 2009 study that followed five hospitals adopting new NFCs (12). When switching NFC brands from ‘negative’ to ‘positive’ connectors, which may have different instructions for use, some hospitals reported an increase in bloodstream infections (8). However, hospitals that went back to their original NFC subsequently reported infection rates had returned to previous levels (8, 15, 21). This evidence suggests that NFC design differences, variations in instructions for use and inconsistencies in aseptic technique may contribute to increased incidence of CLABSI associated with NFCs (2, 8, 9, 12).

Central venous access devices (CVAD) have undergone design changes; some of these changes included the elimination of clamps. Despite the instructions for use of many NFC manufactures to use clamps on catheters after disconnection, the option to perform this action is often not present (22).

Given the inconsistencies noted with NFC usage, the aim of the research was to clarify NFC function by quantifying fluid movement and volume of reflux occurring within each NFC after disconnection or connection.

Materials and methods

For this study, 14 commercially available NFCs were selected to quantitatively study the fluid reflux volume in microliters (µL or mm3) of each NFC. Study objectives were to (i) theoretically estimate amount of blood reflux volume in microliters (μL) permitted by each NFC based on exact component measurements, and (ii) experimentally measure amount of fluid movement or reflux. The 14 NFCs are represented in each of the four current marketing categories of NFC (13). The NFCs selected for evaluation in this study included:

Negative displacement

BD Carefusion Smartsite

BD Q-Syte

Baxter Interlink

ICU Medical Clave*

Neutral displacement

ICU Medical Microclave Clear

Baxter One-Link

RyMed Invision

Nexus NIS-6P

Pressure activated anti-reflux

ICU Medical Neutron

Nexus TKO-5

Nexus TKO-6P

*ICU Medical Clave is included in the negative displacement NFC group based on terminology and grouping established in prior publication (13).

Positive displacement*

B. Braun Ultrasite

BD Carefusion MaxPlus

B. Braun Caresite

*As defined in publications as positive pressure mechanical valve with reflux occurring on connection with a final fluid push at disconnection clearing blood from catheter tip, described as a compression/decompression mechanism creating positive (disconnection) and negative pressure (on activation) resulting in fluid displacement fluctuations (2, 16).

To meet the goals of this study, two independent experiments were performed, with experiment 2 separated into 2A and 2B to clearly separate differences of positive displacement devices from negative, neutral and anti-reflux NFC.

Experiment 1: theoretical estimates of NFC reflux volume (Fig. 1)

Experiment 1 - Pictorial model of a needle-free connector (Microclave®) showing its internal mechanism when (A) unaccessed and (B) accessed using a 10-mL BD Syringe. Internal fluid pathway is displayed in red, moving silicone parts in yellow, and the outer housing as translucent. Below the images are the corresponding volumes of the fluid pathway and the differences between them, which yield the expected volume of reflux (reflux volumes for the other NFCs were calculated in a similar manner).

Purpose

To calculate the amount of blood reflux created by suction pressure which occurs in NFC designs.

Materials

Computer with SolidWorks® Professional 2015 software

OGP SmartScope Flash 200 Optical Comparator Measurement System

SolidWorks CAD models of each NFC

Method

To estimate the amount of blood reflux caused by suction pressure during periods of compression and subsequent non-compression from syringe connection and disconnection, dimensions of each component of all NFCs were precisely measured using a computerized optical measuring system (OGP SmartScope Flash 200) by Simplicated Innovation LLC. Each component of the NFC was precisely dimensioned (±0.001”) and built into 3-dimensional (3-D) model using Computer Aided Design (CAD) 3-D software (SolidWorks™ Professional 2015). These dimensions provided the necessary input for the computational study and the elastomeric compression in Experiment 1. Geometrical and mass property calculations were used to generate data measuring the mechanical reflux created during compression of the soft septum during the connection and disconnection of a male luer locking syringe to each NFC septum.

Two pictorial models were created for each NFC using SolidWorks modeling tools: the first was a ‘un-accessed’ or uncompressed “at rest” representation in which the NFC is not connected to a male luer from the syringe or IV tubing set. The second picture demonstrates what happens when the same NFC is ‘accessed’ by a male luer connector, showing compression of the soft septum, the corresponding movement inside the NFC, and the resulting suction pressure and fluid reflux or flow. For this experiment, a 10-mL BD syringe or a blunt cannula was used (Fig. 1). The volume of the “accessed” and “un-accessed” 3-D models were calculated. Subtracting the volume of the “un-accessed” or uncompressed “at rest” area from the “accessed” or compressed area of the NFCs produces the theoretical amount of fluid displacement available to reflux into an IV catheter upon connection or disconnection of the male luer.

Theoretical calculations of reflux values obtained for each of the 14 connectors are listed in Table II.

Results of the theoretical calculations and actual in vitro venous values

NFC category Brand Experiment 1: theoretical calculations (μL) Experiment 2: actual in vitro venous values (μL) SD
For Experiment 1, “theoretical” values are in microliter (μL) volumes mathematically calculated using the method shown in Figure 1. For Experiment 2, actual in vitro venous values in microliter (μL) volumes are the results from fluid reflux obtained upon disconnection of negative, neutral displacement and pressure activated anti-reflux NFCs and upon connection for positive displacement NFC.
NFC = needle-free connector; SD = standard deviation.
Negative Carefusion Smartsite® 27.92 50.37 1.069
BD Q-Syte® 23.20 38.34 0.721
Baxter Interlink® 11.98 13.18 0.134
ICU CLAVE® 8.02 9.73 0.265
Neutral ICU MicroClave® 7.77 10.80 0.458
Baxter One-Link® 15.87 8.05 0.058
Rymed InVision 2.93 6.54 0.375
Nexus NIS®-6P 5.21 3.60 1.487
Anti-reflux ICU NeutronTM 5.21 1.73 2.656
Nexus TKO®-5 4.03 0.34 0.661
Nexus TKO®-6P 5.26 0.02 0.029
Positive B. Braun Ultrasite® 59.69 38.83 2.619
Carefusion MaxPlus® 75.81 23.73 1.872
B. Braun Caresite® 10.65 18.23 4.604

Experiment 2A: Actual venous simulation of negative, neutral and anti-reflux NFC reflux volume (Tab. II)

Purpose

Quantify the amount of fluid movement or reflux associated with the disconnection (negative, neutral and anti-reflux NFC) of a male luer lock to each of the 11 (of 14) NFCs.

To measure blood reflux or fluid movement associated with each NFC upon disconnection of a male luer, an in vitro venous model was created in the laboratory using the following:

Materials (Fig. 2)

In vitro venous model used to measure actual reflux. Consists of the following: (1) Standard 10-mL BD Luer Lock syringe, (2) Needle-free connector, (3) Clear PVC tubing, (4) Glass capillary rod, (5) Metric ruler, (6) 3-way stopcock, (7) Collection bag with dyed water.

An industry standard 10-mL syringe (BD Luer-Lok™ tip syringe)

Needle-free connectors (NFCs)

Clear PVC tubing and stopcock

Glass capillary rod (6 mm OD × 1.2 mm ID × 12”)

Metric ruler

Collection bag with water (green food coloring added).

Needleless connector design Range of reflux
Negative displacement 9.73 μL to 50.37 μL
Neutral displacement 3.60 μL to 10.80 μL
Pressure activated anti-reflux 0.02 μL to 1.73 μL
Positive displacement 18.23 μL to 38.83 μL

Method

The in vitro venous model was designed to replicate the conditions which cause blood reflux into an IV catheter during disconnection of a syringe from an NFC. This venous simulation apparatus was designed to replicate the peripheral venous pressure found in the human vasculature (2, 23). For the purposes of this study, an average venous pressure of 8 mmHg was used. A glass capillary rod was used to allow for visualization as well as accurate measurement of fluid movement.

For the categories of negative displacement, neutral displacement and pressure-activated anti-reflux NFCs (Fig. 2), each of the NFCs was connected to the PVC tubing, which was attached to a stopcock and the vertically positioned glass capillary rod on the model. The following procedure was performed a total of 30 times per NFC type and brand:

A 10-mL syringe was filled with water and attached directly to the NFC.

The stopcock on the model was turned “OFF” to the glass capillary tube.

The 10-mL syringe plunger was depressed and all air was purged from the NFC, PVC tubing and stopcock attached to the model.

The stopcock was turned “ON” to the glass capillary rod.

The syringe plunger was slowly depressed allowing fluid to fill the glass capillary rod until the fluid level reached 108 mm (equal to 8 mmHg of simulated venous pressure) on the metric ruler.

The syringe was disconnected from the NFC and the amount of fluid reflux in the glass capillary tube was recorded.

Three sterile samples of each NFC were tested; steps 1-6 were repeated 10 times for each sample for a total of 30 venous simulations per NFC. All 30 tests were totaled and averaged to obtain a statistically significant total fluid reflux distance into the glass capillary rod. In this study, all experiments were conducted by one person, minimizing user variances, resulting in relatively low standard deviations.

The inside diameter of the glass capillary rod is 0.60 mm. The average distance of fluid reflux volume of each of the 14 NFCs was used to calculate the total reflux volume in microliters (mm3 or µL)

V = π r 2 h

V = volume, r = radius, and Δh = change in height.

Figure 3 provides a visual representation of the venous simulation experimental reflux values as they appear inside a 20-gauge catheter connected to the respective NFC, illustrating the implications of fluid movement and reflux within a catheter.

Visual representation of the consequences of reflux into a 20-gauge catheter lumen using the Experiment 1, theoretical/mathematical calculations and Experiment 2, actual in vitro venous values. The individual pictures of each NFC illustrate the distance in microliters (μL) the amount of blood can reflux into the catheter using both the theoretical/mathematical Experiment 1 (black) and actual in vitro venous value Experiment 2 (red). On each of the cross-sectional views, the volume of blood reflux is depicted in red. Each NFC illustration shows the silicone elastomeric septum in yellow, outer NC housings in blue and fluid pathway in light blue.

Results of disconnection displacement

Four-hundred and twenty NFC fluid displacement measurements were performed in vitro for negative, neutral and anti-reflux NFC (30 actuations for each of the first 11 NFCs, with a total of 14 NFCs for both experiments 2A and 2B). The complete results of theoretical and actual venous simulation of fluid reflux are displayed in Table II. The results for the three categories of negative, neutral and anti-reflux NFC were reported per NFC, per category and in ranges of theoretical and actual. In the negative displacement group fluid displacement volumes were ranging from 9.73 to 50.37 μL for all NFCs. This negative displacement group represented the widest range of values in comparison to the four categories. The theoretical calculations were lower than the actual results by 10%-80%, with standard deviation.

Table III represents the mean results of the top five performing NFCs as predicted by the quantitative analysis versus actual reflux volumes based on the in vitro experiment.

Mean results of the top five performing NFCs

Predicted volumes (μL) Actual volumes (μL)
Model Reflux volume Model Reflux volume
Predictors of quantitative analysis versus actual reflux volumes of in vitro experiments.
Rymed InVision 2.93 Nexus TKO-6P 0.02
Nexus TKO-5 4.03 Nexus TKO-5 0.34
Nexus NIS 6P 5.21 ICU Neutron 1.73
ICU Neutron 5.21 Nexus NIS 6P 3.60
Nexus TKO-6P 5.26 Rymed InVision 6.54

Similarly, Table IV lists the predicted versus actual reflux volumes of the bottom five performers (NFCs allowing the most amount of reflux).

Predicted versus actual reflux volumes of the lowest five performers

Predicted volumes (μL) Actual volumes (μL)
Model Reflux volume Model Reflux volume
Predictors of quantitative analysis versus actual reflux volumes of in vitro experiments with NFCs allowing the most reflux.
BD Carefusion MaxPlus 75.81 BD Carefusion Smartsite 50.37
B. Braun Ultrasite 59.69 B.Braun Ultrasite 38.83
BD Carefusion Smartsite 27.92 BD Q-Syte 38.34
BD Q-Syte 23.20 BD Carefusion MaxPlus 23.73
Baxter One-Link 11.98 B. Braun Caresite 18.23

Figure 4 lists the reflux volume range per NFC design category from Table II.

Reflux volume range per needle-free connector (NFC) design category from Table II.

Experiment 2B: actual venous simulation of positive pressure NFC reflux volume (Tab. II)

Purpose

Quantify the amount of fluid movement or reflux associated with the connection of a male luer lock to each of three positive pressure NFC connectors.

To measure blood reflux or fluid movement associated with each positive displacement NFC upon connection of a male luer, an in vitro venous model was created in the laboratory using the following:

Materials (Fig. 2)

An industry standard 10-mL syringe (BD Luer-Lok™ tip syringe)

Needle-free connectors (NFCs)

Clear PVC tubing and stopcock

Glass capillary rod (6 mm OD × 1.2 mm ID × 12”)

Metric ruler

Collection bag with water (green food coloring added).

Method

The in vitro venous pressure model was designed to replicate the conditions that cause blood reflux into an IV catheter during connection of a syringe from each NFC. This venous simulation apparatus/model was designed to replicate the peripheral venous pressure found in the human vasculature (2, 23). For the purposes of this study, an average venous pressure of 8 mmHg was used. A glass capillary rod was used to allow for visualization as well as accurate measurement of fluid movement.

For the category of positive displacement NFCs:

To effectively test reflux, due to the design and functionality of the positive displacement NFCs, the testing was reversed from the test steps above to measure connection reflux (16). Each of the positive displacement NFCs were connected to the PVC tubing attached to a stopcock and the vertical glass capillary rod on the model. The following procedure was performed a total of 30 times per NFC brand:

A 10-mL syringe was filled with water and attached directly to the NFC.

The stopcock on the model was turned “OFF” to the glass capillary tube.

The 10-mL syringe plunger was depressed and all air was purged from the NFC, tubing and stopcock on the model.

The stopcock was turned “ON” to the glass capillary rod.

The syringe plunger was slowly depressed allowing fluid to fill the glass capillary rod until the fluid level reached 108 mm (equal to 8 mmHg of simulated venous pressure) on the metric ruler.

The syringe was disconnected from the NFC and the amount of fluid in the glass capillary tube was recorded.

The syringe was again connected to the positive displacement NFC and the amount of fluid reflux in the glass capillary tube was recorded.

Three samples of each NFC were tested; steps 1-7 were repeated 10 times for each sample for a total of 30 venous simulations per NFC.

All 30 tests were totaled and averaged to obtain a statistically significant total fluid reflux distance into the glass capillary rod. In this study, all experiments were conducted by one person, minimizing user variances, resulting in relatively low standard deviations.

The inside diameter of the glass capillary rod is 0.60 mm. The average distance of fluid reflux volume of each of the 14 NFCs was used to calculate the total reflux volume in microliters (mm3 or µL)

V = π r 2 h

V = volume, r = radius, and Δh = change in height.

Figure 3 provides a visual representation of the venous simulation experimental reflux values as they appear inside a 20-gauge catheter connected to the respective NFC, illustrating the implications of fluid movement and reflux within a catheter.

Results of positive displacement

Four-hundred and twenty NFC fluid displacement measurements were performed in vitro (30 for each of the 3 positive pressure NFCs). The complete results of theoretical and actual venous simulation of fluid reflux are displayed in Table II. The results for the last category of positive NFC were reported in ranges of theoretical and actual. In the positive displacement group were fluid displacement volumes ranging from 18.23-38.83 μL with displacement reflux occurring upon connection. This positive displacement group represented a narrow range of values in comparison to the other three categories. The theoretical calculations were generally higher for this group than the actual results by approximately 35%, apart from the B. Braun Caresite where the theoretical calculation was approximately 41% lower than the actual (Tab. II).

Table III represents the mean results of the top five performing NFCs as predicted by the quantitative analysis versus actual reflux volumes based on the in vitro experiment.

Similarly, Table IV lists the predicted versus actual reflux volumes of the bottom five performers (NFC allowing the most amount of reflux).

Figure 4 lists the reflux volume range per NFC design category from Table II.

Discussion

All NFCs have some fluid movement/reflux either on connection, disconnection or both (16). In this study, we chose to measure the fluid movement for each category of connector to provide comparison of potential blood reflux. It is not known how long it takes for undisturbed blood in an NFC or catheter to coagulate. It is not known the minimum blood volume that will occlude an intravenous catheter. These issues are the subject of future study. The function of negative, neutral and anti-reflux NFC is consistent with the fluid shift occurring primarily at discontinuation. Positive displacement NFCs have a different function with a mechanical valve that required measurement of the fluid movement at a different stage. In the positive displacement NFC, the fluid shift upon disconnection is offset by the outward displacement of fluid, different from negative and neutral NFCs. This difference in the positive displacement NFC required the fluid displacement measurements to be performed at the time of connection, rather than disconnection. Since intravenous devices with positive displacement NFCs continue to have an incidence of occlusion with the catheters, the hypothesis was that significant reflux occurred at some point of connection or disconnection, or even after the positive pressure push of fluid, justifying the measurement and comparison with another NFC. The researchers recognize that this created a variation, which should be considered as a significant variable in comparisons between each of the NFC categories represented in this study. Since all NFCs have some fluid shift that may result in blood reflux upon connection and/or disconnection these measurements do provide value in comparison, but require an understanding of the distinction between the categories and NFC functions which may not facilitate an exact correlation.

The design of NFC has a significant impact on the ability to clear blood and control reflux. Blood provides many of the nutrients to support the growth of bacteria. Residual blood inside the fluid pathway of an NFC has the potential to increase the risk of occlusion of the device and may promote bacterial growth (2, 24, 25). Each of the NFCs tested in this study was designed to function in a specific way, leading it to be classified as negative, positive, neutral or anti-reflux. For the purposes of this study, the NFCs were categorized based on design and function. A brief description follows:

Negative displacement NFCs allow fluid displacement into the catheter lumen during disconnection from a male luer syringe or IV tubing. This displacement occurs when fluid (blood) is mechanically pulled away from the patient and into the catheter or NFC lumen based on pressure changes (9, 13). Because blood is pulled toward the NFC through the catheter upon disconnection, protocol states the catheter be clamped prior to luer-lock disconnection (2, 6, 14). Apart from blunt cannulas entering a split-septum, the general mechanism consists of a plunger depressing a pre-slit septum facilitating fluid flow through the center of the device (6, 26).

Positive displacement NFCs allow fluid displacement into the catheter lumen during connection of a male luer syringe or IV tubing. Fluid movement or reflux occurs upon connection with suction created as the syringe is pushed into the NFC. Upon disconnection of the syringe from the NFC a final fluid push/displacement or fluid movement occurs out as a function of the positive displacement NFC (27). Several functional characteristics of positive NFCs differ from other NFCs. For example, while an elastic or deformable plunger is still depressed during luer-lock connection, the fluid flow occurs around the plunger (6, 26). This space between the plunger and outer housing creates a reservoir where fluid is gathered; when the NFC is disconnected from a syringe or IV tubing, fluid movement occurs and is pushed outward, toward the patient (13). This design is created to overcome potential blood reflux that occurs upon disconnection, but does not prevent fluid displacement associated with connection (13). Theoretically, reflux in positive NFCs may also occur after the fluid push occurs on disconnection, first shifting fluid out and then retracting fluid back. The method to prevent the potential fluid movement after the outward push of fluid with disconnection is through clamping (6, 14, 15). Measurement of pressure variations of positive displacement NFCs was only performed in this study upon connection, not after positive fluid disconnection.

Neutral displacement NFCs suggest the absence of fluid movement upon connection or disconnection. The marketing term neutral indicates prevention of blood reflux that is not substantiated in other research (18). The name ‘neutral NFC’ inherently suggests that these devices eliminate movement of fluid typically observed in negative and positive NFCs (13, 26). However, the internal mechanisms that govern function of when and how fluid movement and flow is established appear to be like those of other negative NFCs (13, 18).

Anti-reflux NFCs suggest minimal fluid movement upon connection or disconnection. The function of an anti-reflux NFC is through a 3-position silicone diaphragm, which opens and closes based upon fluid or infusion pressure. The anti-reflux diaphragm opens or closes based on fluid pressure changes from sources such as IV pump, IV bag, when flushing with a syringe or from physiologic body pressure changes (13, 17). Fluid movement and blood reflux is minimized with connection or disconnection of a male luer syringe or IV tubing. The diaphragm within the anti-reflux NFC supports continuous bi-directional fluid pressure control when attached to the hub of a catheter. When the fluid pressure drops, the anti-reflux diaphragm closes preventing blood reflux into the catheters. NFCs designed with an anti-reflux diaphragm provide continuous fluid control while attached to the catheter.

This study sought to quantitatively evaluate fluid reflux within NFCs. The results demonstrate a wide range of displacement in different NFCs ranging from 10-50 µL for ‘negative’ NFCs, 3-10 µL for ‘neutral’ NFCs, and displacement that approaches 0 with a range of 0.02-1.73 with pressure activated anti-reflux NFCs. Recent research validates the results with similar findings on some of the included NFCs (20). Of the commercially available NFCs tested in Experiment 2, pressure-activated anti-reflux NFCs performed best in terms of minimizing fluid displacement. The results suggest NFC designs and functional variations represent potential clotting risk associated with blood reflux.

Data shown in Table II and Figure 3 demonstrate the following:

All needless connectors have a measurable volume of reflux on connection or disconnection, however small.

The amount of reflux within a catheter is dependent on the individual design of the NFC.

The type of NFC device (negative, positive and neutral) does not inherently guarantee against unintended or uncontrolled fluid movement or reflux of blood.

Anti-reflux connector had the lowest measurable volume of fluid movement.

Clinical implications

Blood reflux volumes as small as 4-30 µL may result in fibrin formation adequate to occlude the function of a catheter (28). Body movements, muscle flexing, respirations, coughing, vomiting, crying, clamping, unclamping, syringe plunger rebound, and connection/disconnection of syringes all cause mechanical and physiological pressure changes within a catheter that typically pulls blood into the catheter tip (11, 29). Short peripheral catheters, PICCs and midlines are particularly affected by blood reflux due to their small lumen diameter and high surface area. Complications such as sluggish flow, inability to aspirate blood, loss of patency, fibrin sheath formation, catheter dysfunction and even catheter-related infections are all complications which may be related to blood reflux (30, 31).

NFCs that permit a blood reflux volume >10 μL allow blood to move beyond the smooth-bore of the distal end of a 20-gauge catheter and into the wider lumen. Any amount of blood moving into the lumen of a catheter may create the opportunity for partial or complete occlusion (13, 32); however, as illustrated in Figure 3 reflux volumes >10 μL provide greater risk due to the shape of the lumen. While the exact volume of blood reflux into each catheter resulting in occlusion is unknown, greater blood reflux volume and longer time in situ will cause coagulation within a catheter lumen. Smaller lumen catheters, such as PICCs and midlines have higher incidence of occlusion and may have greater impact from any amount of blood reflux. Catheter dysfunction with loss of patency is the most common complication of intravascular catheters resulting in significant impact on continued catheter use with added cost associated with treatment or replacement (33-34-35-36-37-38-39-40-41-42).

According to Rupp, Jarvis and others, design features and complexities of NFCs create higher or lower risk for vascular access device infection. Vascular access device infection rates have increased in some facilities with the advent of luer-activated mechanical valve NFCs (12, 23, 43, 44). The ability to effectively disinfect the surface area, gaps and hub designs of each connector are listed by Jarvis as characteristics affecting risk of infection (8). Ease of flushing and complete clearance of all blood products and medications within the NFC is another design feature contributing to infection risk. CLABSIs impact patient safety and financial risk. To reduce CLABSIs and complications of occlusion, it is crucial that all blood be adequately flushed from NFCs and the reflux of blood be minimized.

Methods to maintain patency and function of catheters include consistent flushing, standardization of NFCs throughout the facility and frequent education with competency validation on use of NFCs per manufacturer’s recommendations. The relationship between blood reflux and occlusion is not clarified in the research, although theoretically NFC pressure control preventing reflux and minimizing blood within the catheter would reduce occlusions while maintaining catheter patency (18, 45, 46). In the Canadian Vascular Access Association (CVAA http://cvaa.info/PUBLICATIONS/OcclusionManagementGuideline(OMG)/tabid/229/Default.aspx) OcclusionManagement Guidelines, prevention strategies note the need for education to: prevent reflux of blood into the tip of the catheter by avoiding syringe rebound, keeping the infusion rate at a level to avoid pressure changes or stasis, flushing with at least twice the volume of the device and more after blood administration or draws, and consideration for using technology designed to prevent catheter occlusions (39).

For those NFC manufacturers who indicate clamping upon disconnection within the instructions for use, the NFCs are not intended to be used without a clamping sequence. The significance of microliter reflux volumes on each catheter remains speculation; results are currently unknown and are the subject of research to follow this investigation.

Limitations

While the theoretical/mathematical calculations were useful in identifying best and worst fluid reflux in this in vitro investigation, several limitations prevented the exact prediction of expected reflux with a greater degree of accuracy. The theoretical calculations were based purely on the 3-D model changes in volume and fluid displacement created when the soft silicone septum was compressed by the male luer-lock connector. Additional variables influencing the actual amount of fluid-movement/reflux into the catheter included:

Amount of pressure or distortion of the soft silicone material within each NFC

Amount of deflection and speed of contraction of the soft silicone material when engaging luer-lock or cannula to the needle-free IV connector

The opening and closing of the split septum seals in the soft silicone septum

The potential for mechanically created fluid movement in and out of the system at different rates due to internal mechanisms, pressures and freely moving bi-directional flow

Manner in which some irregularly shaped compressible parts fold, and the amounts of residual fluids these parts trap as they fold.

Research performed with theoretic calculations and in vitro testing is a limitation where clinical implications are difficult to define. Clinical relevance of reflux volume in intravascular catheters has yet to be determined. The venous simulation experiments yield insight into the amount of reflux likely to occur with a standard venous pressure of 8 mmHg; however, actual reflux in the clinical setting is influenced by a variety of other factors. Patients are likely to have conditions resulting in abnormal blood pressures (both high and low) (47), abnormal blood viscosity (usually higher) (48) and are likely to experience temporary, often acute, changes in bloodstream pressure due to factors such as bodily movement, coughing, sneezing, etc.

The experimental values of reflux also have their own limitations. First, these values are for unclamped operation. Surprisingly, the clamping sequence in some manufacturer information for use is not specified or not clearly described, whereas others are clear in the instructions for clamping after disconnection (13, 22, 49, 50). In addition, we have compared the reflux upon disconnection for negative, neutral and anti-reflux connectors to the reflux upon connection for positive connectors. In doing so, we chose to compare the maximum inward movement of fluid into the catheter at any point during the usage of the NFC, which (as highlighted in Tab. I) functionally occurs during connection of a syringe for positive displacement NFCs, and during disconnection for all other NFC types. This difference in functional fluid movement establishes a variable and limitation in direct correlation of results from negative, neutral, anti-reflux and positive displacement NFCs. Surfaces that contact blood (especially surfaces in irregularly shaped regions from which blood may not be completely expelled upon flushing) serve as zones where adverse events such as occlusion formation and bacterial colonization can occur. Thus, our work identifies the way in which NFCs may be expected to perform best, in relation to fluid movement, through both theoretical and actual quantitative measurement methods.

Conclusion

In conclusion, this study serves as a necessary stepping stone to quantitatively inspect and evaluate commercially available NFCs, while also establishing evidence for education of healthcare providers regarding risk associated with NFCs. These results indicate incorporation of NFC designs with pressure activated anti-reflux diaphragm, which may minimize blood reflux and potentially contribute to the reduction of lumen occlusion. Overall, the results demonstrated significant differences in the volume of fluid reflux based on NFC design. More comparative research on the impact of blood reflux and associated outcomes in intravascular catheters is needed.

Disclosures

Financial support: This study was funded by a grant to the University of Missouri from Nexus Medical, LLC. Shramik Sengupta PhD, Department of Bioengineering, served as principal investigator on this grant. The funding source played no role in the research results or reporting of the data. The results and conclusions of the research are the work product of the authors. Graphic contributions were received from Nexus Medical.
Conflict of interest: All authors submitted ICMJE Form for Disclosure of Potential Conflicts of Interest. G Hull reported no conflicts of interest, reported no employment and was a full time student. Dr. Sengupta reported serving as a consultant to Fresenius. N Moureau reported employment with PICC Excellence, Inc, Greenville Memorial University and Medical Center, Greenville, South Carolina; educational speaker and consultant to 3M, Angiodynamics, Access Scientific, B Braun, BD Carefusion, Chiesi, Entrotech, Excelsior, Fresenius, Linear Health Sciences, Nexus, Parker Labs, Teleflex, and research grant recipient from 3M, Cook and Entrotech.
This research represents potential limitation and bias due to commercial funding. Experiments and research process was performed independently and exclusively by the University of Missouri research department; the manufacturer had no role in the research results or reporting of the data. The role of the manufacturer was in providing the funding, the product, reviewing the initial objectives and protocol developed by the research department prior to initiation of the study.
Clave, Microclave and Neutron are registered trademarks of ICU Medical, Interlink and One Link are registered trademarks of Baxter Healthcare, Smartsite and MaxPlus are registered trademarks of BD/Carefusion, Q-Syte is a trademark of Becton Dickinson, Ultrasite and Caresite are registered trademarks of B. Braun, Invision Plus is a registered trademark of Rymed, and Nexus TKO-5 and Nexus TKO-6P are registered trademarks of Nexus Medical LLC.
References
  • 1. Hadaway L Needlestick injuries, short peripheral catheters, and health care worker risks. J Infus Nurs 2012 35 3 164 178 Google Scholar
  • 2. Jarvis W Choosing the best design for intravenous needlefree connectors to prevent healthcare-associated bloodstream infections. Infection Control Today 2010 14 8 30 31 Available from: http://www.infectioncontroltoday.com/articles/2010/07/choosing-the-best-design-for-intravenous-needleless-connectors-to-prevent-bloodstream-infections.aspx?pg=2#. Accessed July 12, 2017. Google Scholar
  • 3. US Congress Needlestick Safety and Prevention Act. 2000 HR 5178 p. 4 Available from: https://www.govtrack.us/congress/bills/106/hr5178. Accessed July 12, 2017. Google Scholar
  • 4. O’Grady NP Alexander M Burns LA et al. Guidelines for the prevention of intravascular catheter-related infections 2011. Centers for Disease Control 2011: 1 83 Available from: https://www.cdc.gov/hai/pdfs/bsi-guidelines-2011.pdf. Accessed July 12, 2017. Google Scholar
  • 5. Yébenes JC Serra-Prat M Clinical use of disinfectable needle-free connectors. Am J Infect Control 2008 36 10 36(10):S175.e1-4. Google Scholar
  • 6. Hadaway L Needleless connectors for IV catheters. Am J Nurs 2012 112 11 32 44 quiz 45. Google Scholar
  • 7. Btaiche IF Kovacevich DS Khalidi N Papke LF The effects of needleless connectors on catheter-related bloodstream infections. Am J Infect Control 2011 39 4 277 283 Google Scholar
  • 8. Jarvis W Needlefree connectors and the improvement of patient and healthcare professional safety. Infection Control Today 2013 17 12). Available from: http://www.infectioncontroltoday.com/articles/2013/12/needleless-connectors-and-the-improvement-of-patient-and-healthcare-professional-safety.aspx.  Accessed July 12, 2017. Google Scholar
  • 9. Hadaway L Needlefree Connectors: Improving Practice, Reducing Risks. J Assoc Vasc Access 2011 16 1 20 33 Google Scholar
  • 10. Cookson ST Ihrig M OMara EM et al. Increased bloodstream infection rates in surgical patients associated with variation from recommended use and care following implementation of a needleless device. Infect Control Hosp Epidemiol 1998 19 1 23 27 Google Scholar
  • 11. Schilling S Doellman D Hutchinson N Jacobs BR The impact of needleless connector device design on central venous catheter occlusion in children: a prospective, controlled trial. JPEN J Parenter Enteral Nutr 2006 30 2 85 90 Google Scholar
  • 12. Jarvis WR Murphy C Hall KK et al. Health care-associated bloodstream infections associated with negative- or positive-pressure or displacement mechanical valve needleless connectors. Clin Infect Dis 2009 49 12 1821 1827 Google Scholar
  • 13. Hadaway L Richardson D Needleless connectors: a primer on terminology. J Infus Nurs 2010 33 1 22 31 Google Scholar
  • 14. Chernecky C Macklin D Casella L Jarvis E Caring for patients with cancer through nursing knowledge of IV connectors. Clin J Oncol Nurs 2009 13 6 630 633 Google Scholar
  • 15. Logan R Neutral displacement intravenous connectors: Evaluating new technology. JAVA 2013 18 1 31 36 Google Scholar
  • 16. Macklin D The impact of IV connectors on clinical practice and patient outcomes. JAVA 2014 15 3 139 Google Scholar
  • 17. Jasinsky LM Wurster J Occlusion reduction and heparin elimination trial using an antireflux device on peripheral and central venous catheters. J Infus Nurs 2009 32 1 33 39 Google Scholar
  • 18. Elli S Abbruzzese C Cannizzo L Lucchini A In vitro evaluation of fluid reflux after flushing different types of needlefree connectors. J Vasc Access 2016 17 5 429 434 Google Scholar
  • 19. Hadaway LC Major thrombotic and nonthrombotic complications. Loss of patency. J Intraven Nurs 1998 21 5 Suppl S143 S160 Google Scholar
  • 20. McGee WT Central venous catheterization: better and worse. J Intensive Care Med 2006 21 1 51 53 Google Scholar
  • 21. Jarvis WR Murphy C Hall KK et al. Health care-associated bloodstream infections associated with negative- or positive-pressure or displacement mechanical valve needleless connectors. Clin Infect Dis 2009 49 12 1821 1827 Google Scholar
  • 22. Carefusion BD MaxPlus clear needlefree connector - Instructions for use. Available from: http://www.carefusion.com/our-products/infusion/iv-therapy/needlefree-connectors/maxplus-clear-needlefree-connector. Accessed July 17, 2017. Google Scholar
  • 23. Field K McFarlane C Cheng AC et al. Incidence of catheter-related bloodstream infection among patients with a needleless, mechanical valve-based intravenous connector in an Australian hematology-oncology unit. Infect Control Hosp Epidemiol 2007 28 5 610 613 Google Scholar
  • 24. Hanchett M Visualizing the IV fluid path as an emerging concept in infection control. Infection Control Today 2004 1 2 Available from: http://www.infectioncontroltoday.com/articles/2015/05/expanding-intravascular-catheter-surveillance-issues-and-obstacles.aspx. Accessed July 12, 2017. Google Scholar
  • 25. Maki DG Kluger DM Crnich CJ The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc 2006 81 9 1159 1171 Google Scholar
  • 26. Richardson D Vascular Access Nursing Practice: Standards of Care and Strategies to Prevent Infection: A Review of Flushing Solutions and Injection Caps (Part 3 of a 3-Part Series). Journal of the Association for Vascular Access 2007 12 2 74 84 Google Scholar
  • 27. Chernecky CC Macklin D Jarvis WR Joshua TV Comparison of central line-associated bloodstream infection rates when changing to a zero fluid displacement intravenous needleless connector in acute care settings. Am J Infect Control 2014 42 2 200 202 Google Scholar
  • 28. Faintuch S Salazar GM Malfunction of dialysis catheters: management of fibrin sheath and related problems. Tech Vasc Interv Radiol 2008 11 3 195 200 Google Scholar
  • 29. Jacobs BR Schilling S Doellman D Hutchinson N Rickey M Nelson S Central venous catheter occlusion: a prospective, controlled trial examining the impact of a positive-pressure valve device. JPEN J Parenter Enteral Nutr 2004 28 2 113 118 Google Scholar
  • 30. Mayo D Catheter-related thrombosis. J Infus Nurs 2001 24 3S S13 S22 Available from: http://journals.lww.com/journalofinfusionnursing/Abstract/2001/05001/Catheter_Related_Thrombosis.5.aspx. Accessed July 12, 2017. Google Scholar
  • 31. Steiger E Dysfunction and thrombotic complications of vascular access devices. JPEN J Parenter Enteral Nutr 2006 30 1 Suppl S70 S72 Google Scholar
  • 32. Hadaway LC Reopen the pipeline for I. V. therapy. Nursing 2005 35 8 54 61 quiz, 61-63. Google Scholar
  • 33. Hadaway L Loss of catheter patency. Thrombotic and nonthrombotic occlusions. 1999: p. 1-8 Google Scholar
  • 34. Moureau N Poole S Murdock MA Gray SM Semba CP Central venous catheters in home infusion care: outcomes analysis in 50,470 patients. J Vasc Interv Radiol 2002 13 10 1009 1016 Google Scholar
  • 35. Tripathi S Kaushik V Singh V Peripheral IVs: factors affecting complications and patencya randomized controlled trial. J Infus Nurs 2008 31 3 182 188 Google Scholar
  • 36. Keogh S Flynn J Maintenance of intravascular device patency: a survey of nursing and midwifery flushing practice. Qld Nurse 2014 33 2 30 31 Google Scholar
  • 37. van Miert C Hill R Jones L Interventions for restoring patency of occluded central venous catheter lumens (Review). [Review]. Evid Based Child Health 2013 8 2 695 749 Google Scholar
  • 38. Ernst FR Chen E Lipkin C Tayama D Amin AN Comparison of hospital length of stay, costs, and readmissions of alteplase versus catheter replacement among patients with occluded central venous catheters. J Hosp Med 2014 9 8 490 496 Google Scholar
  • 39. Hill J Broadhurst D Miller K et al. Occlusion management guidelines for CVAD. Vascular Access 2013 7 Suppl. 1 1 34 Available from: http://www.cvaa.info/Portals/0/documents/OMG 2013 Final Revised.pdf. Accessed July 12, 2017. Google Scholar
  • 40. Wallis MC McGrail M Webster J et al. Risk factors for peripheral intravenous catheter failure: a multivariate analysis of data from a randomized controlled trial. Infect Control Hosp Epidemiol 2014 35 1 63 68 Google Scholar
  • 41. Baskin JL Reiss U Wilimas JA et al. Thrombolytic therapy for central venous catheter occlusion. Haematologica 2012 97 5 641 650 Google Scholar
  • 42. Hadaway LC Managing vascular access device occlusions, part 2. Nursing 2009 39 3 13 14 Google Scholar
  • 43. Rupp ME Sholtz LA Jourdan DR et al. Outbreak of bloodstream infection temporally associated with the use of an intravascular needleless valve. Clin Infect Dis 2007 44 11 1408 1414 Google Scholar
  • 44. Salgado CD Chinnes L Paczesny TH Cantey JR Increased rate of catheter-related bloodstream infection associated with use of a needleless mechanical valve device at a long-term acute care hospital. Infect Control Hosp Epidemiol 2007 28 6 684 688 Google Scholar
  • 45. Hadaway L Technology of flushing vascular access devices. J Infus Nurs 2006 29 3 137 145 Google Scholar
  • 46. Khalidi N Kovacevich DS Papke-ODonnell LF Btaiche I Impact of the Positive Pressure Valve on Vascular Access Device Occlusions and Bloodstream Infections. Journal of the Association for Vascular Access 2009 14 2 84 91 Google Scholar
  • 47. Mayo Clinic High and low blood pressure (hyper/hypotension). 2015 Available from: http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/basics/definition/con-20019580?reDate=16032016. Accessed July 12, 2017. Google Scholar
  • 48. Kwaan HC Bongu A The hyperviscosity syndromes. Semin Thromb Hemost 1999 25 2 199 208 Google Scholar
  • 49. ICU Medical Inc. Neutron and MaxPlus comparative matrix. 2012, ICU Medical Inc Available from: http://www.icumed.com/media/155735/M1-1372 Neutron vs MaxPlus Combat Rev.01_email.pdf. Accessed July 12, 2017. Google Scholar
  • 50. Nexus Medical LLC Nexus TKO®-6P Luer Activated Anti-Reflux Device. Available from: http://www.nexusmedical.com/tko-6p.htm. Accessed July 12, 2017. Google Scholar

Authors

Affiliations

  • Cook Medical, Bloomington, Indiana - USA
  • PICC Excellence, Inc, Hartwell, GA; Greenville Memorial Hospital, Greenville, SC; Adjunct Associate Professor, Alliance for Vascular Access Teaching and Research (AVATAR) Group, Centre for Health Practice Innovation, Menzies Health Institute Queensland, Griffith University, Brisbane - Australia
  • Department of Biomedical Engineering, University of Missouri, Columbia, MO - USA

Article usage statistics

The blue line displays unique views in the time frame indicated.
The yellow line displays unique downloads.
Views and downloads are counted only once per session.

No supplementary material is available for this article.