Abstract
Objective
To collect real-world data to demonstrate the safety and performance of Arrowg+ard Blue® /Arrowg+ard Blue Plus® (AGB/AGB+) central venous catheters (CVCs).
Methods
This observational, retrospective study involved patients who required AGB/AGB+ CVCs at designated general hospitals in USA (22), UK (19) and Germany (2). Data were extracted from electronic medical records. There were no specific inclusion/exclusion criteria. Primary endpoint was successful treatment without an adverse event (AE). Secondary endpoint was rate of AEs.
Results
In total, 384 cases were included from 43 centres and most patients (74%) were >35 years of age. A success rate of 99%, and an overall AE rate of 0.8% were observed. Moreover, the overall infection rate was lower than typically reported for standard catheters. In addition, power injection of contrast media was successful in all 51 cases.
Conclusions
This study indicates the AGB/AGB+ CVCs perform as intended with a high success rate and few AEs. Further large-scale, controlled studies are required to confirm our findings.
Introduction
Central venous catheters (CVCs) are widely used across many medical specialties, including cardiology, oncology, emergency care and intensive care. While it is widely recognized that CVCs are essential for acutely ill patients, bloodstream infections are a major concern. 1 Antimicrobial-impregnated CVCs (e.g., Arrowg+ard Blue® (AGB) and Arrowg+ard Blue Plus® (AGB+; Arrow/Teleflex, Wayne PA, USA) have potential as infection control measures. The AGB CVC is externally treated with chlorhexidine and silver sulfadiazine. The AGB+ catheter contains the same antimicrobial agents as AGB CVC but has an increased concentration of chlorohexidine on the external surface and an additional coating on the internal lumen The CVCs are indicated for short-term (<30 days) central venous access for several procedures including: central venous pressure (CVP) monitoring; frequent blood sampling; infusion of total parenteral nutrition solutions; administration of routine IV fluids, medications, blood products and/or chemotherapeutic agents. The devices have several configurations and are available in a variety of sizes, lengths, and lumens, in both pressure-injectable and non-pressure injectable presentations.
According to the EU Medical Device Regulation (MDR), manufacturers of CE (Conformité Européenne)-marked medical devices are required to conduct post-marketing follow-up to substantiate clinical safety and performance of the device. 2 To that end, an observational, retrospective study was conducted from 2021–2022 with the purpose of collecting real-world data to demonstrate the safety and performance of the AGB/AGB+ CVCs.
Methods
For this observational, retrospective study, patients who required AGB/AGB+ CVCs at designated general hospitals in USA, UK and Germany from 01 April to 20 September 2021 were identified by healthcare professionals at those sites. Data were collected from consecutive patients who had received either the AGB or AGB+ CVC in the 30 days prior to the start of study. Other than a clinical need for a CVC, there were no specific inclusion/exclusion criteria for a case to be included in the study. An objective was to collect data from a representative number of cases at each site. While, there was no mandate for image-guidance placement, an assumption was made that image-guidance had been used for most catheters.
The following data were extracted from patients’ electronic medical records: specific use of the device; placement site; duration of use; incidence of adverse events (AEs). The primary endpoint was the absence of device-related AEs during device placement, use, and removal. Secondary endpoints were rates of AEs experienced during use of the device.
The reporting of this study conforms to STROBE guidelines. 3 The study protocol was reviewed by independent Advarra institutional review board (Pro00073689, Advarra, Columbia, MD, USA). Written informed consent was not required due to the retrospective design of the study and patient data were anonymized.
Statistical analysis
All analyses were conducted using the R statistical software (version 4.1.2). Continuous variables were described as mean ± standard deviation (SD) or median (interquartile range [IQR]). Categorical variables were described as absolute counts and frequencies (%).
Initially, a literature search was performed of PubMed and EMBASE for all studies that provided data on AGB/AGB+ CVCs. In addition, an internet search was conducted for additional information regarding guidelines relevant to the devices. Overall, eight studies were identified. Based on results from these studies, the expected performance criterion for successful treatment using the AGB/AGB+ CVC without a device-related adverse event (AE) was estimated to be 82%. This value, based on 90% CIs was calculated using the Cochrane formula. 4 Using these data, and estimating an 80% likelihood of meeting the acceptance criterion, the sample size was approximated to be 384 cases.
Results
In total, 384 patients were included in the study from 43 hospital/centres in USA (22, 51%), UK (19, 44%) and Germany (2, 5%). On average, each center contributed 9 cases (range 3–22). Data were collected by 43 health care professionals (i.e., 27 [63%] physicians; 12 [28%] nurses; 4 [9%] nurse practitioners).
Most patients (74%) were >35 years of age (Table 1). Twenty-one patients (6%) were ≤18 years old, but none were <12 months. In most cases (73%) the device was used for infusion of fluids, medication or chemotherapy (Table 2). Other uses of the device included: parenteral nutrition (32%); blood sampling (34%); blood transfusion (29%); CVP monitoring (30%). Power injection of contrast media was successful in all 51 cases. Most devices were placed in the right internal jugular vein (Table 3). Among the various types of image-guided technologies used for device insertion and placement, ultrasound was the most common (55%; Table 4). Devices were used from 1 to 35 days (mean ± SD, 9.8 ± 6.8 days). Most devices (370, 96%) remained in place for 1 to 15 days, 13 (3%) for <1 day and one (1%) was used for >30 days.
Age ranges.
Data are expressed as n (%).
Clinical indication for device usage.
Data are expressed as n, or n (%).
Placement of device.
Data are expressed as n (%).
Type of image-guided technology used for device insertion/placement.
Data are expressed as n (%).
In terms of the primary endpoint, the overall success rate (i.e., device placement, use, and removal without occurrence of specific AEs) was 99% (95% CI, 98–100%) success. Therefore, the performance success criterion of >82% was met. Three (0.8%) device-related AEs were reported: cardiac tamponade (during device placement); vessel erosion (during device use); dysrhythmia (during device use). None of these AEs required additional treatment.
While infection was not reported as a device related AE, four (1%) catheters were removed because of infection. Of these, three occurred with the AGB catheter and one with the AGB+ catheter. Considering these reports as potentially non-recognized central line-associated bloodstream infections (CLABSI), the rate for AGB was estimated to be 1.35/1,000 catheter days and for AGB+ was 0.65/1,000 catheter days. This equated to a 52% lower CLABSI rate with the AGB+ compared to the AGB. The overall CLABSI rate was 1.07/1,000 catheter days.
Discussion
The use of CVCs is often crucial to the improvement and recovery of critically ill patients. Estimates on the number of CVCs placed every year in the USA vary from 3.5 to 15 million.5,6 CVCs are used worldwide with global placements estimated to be approximately 27 million.7,8 However, serious complications, including death, are known to occur with use of CVCs, with >15% of patients experiencing one or more complication. 9
The main purpose of this study was to collect real-world data to demonstrate the safety and performance of the AGB/AGB+ CVCs according to EU MDR requirements. Although the sample size was relatively small, we collected data from 43 hospitals across USA (22), UK (19) and Germany (2). We found that, among the 384 patient participants, the devices were used successfully in 99% of cases. The secondary endpoint was the rate of AEs potentially related to the AGB/AGB+ CVCs. Three AEs were reported; one report of dysrhythmia, one report of cardiac tamponade and one report of vessel erosion. Therefore, the overall rate of AEs associated with these CVCs was 0.8%. Consistent with previous reports, these AEs are known complications of CVCs. 10 Other complications include, pneumothorax, chylothorax, bleeding, catheter occlusion, deep venous thrombosis, pulmonary embolism, venous air embolism, catheter malposition, arterial injury, nerve injury, infection and death.
While CLABSI was not reported as a device-related AE in our study, ‘infection’ was recorded as the reason for device removal in four cases. CLABSIs are rare but can be life-threatening and are difficult and expensive to treat. For this reason, CLABSI ‘prevention bundles’ were adopted in 2009. These practices include use of antimicrobial-impregnated CVCs. 11 However, despite widespread adoption of these measures, rates of CLABSI continue to be significant. For example, in 2016 the global incidence of CLABSI was reported to be as 3.73/1,000 central line days. 12 Data from a retrospective study conducted in 2020, found a CLABSI rate of 1.7/1,000 central line days in intensive care and 2.8/1,000 central line days in medical-surgical units. 13 In addition, a multinational study conducted from 1998 to 2022 across 41 countries involving 278,241 patients followed during >1.8 million patient days, found CLABSI rates of 4.82/1,000 central line days. 14 In our present study involving 384 patients that used chlorhexidine and silver sulfadiazine coated CVCs, the overall suspected CLABSI rate was 1% and rate per catheter day was 1.07/1,000 days. This relatively low incidence of infection may be attributed to the antimicrobial properties of the AGB/AGB+ CVCs, and adherence to the CLABSI ‘prevention bundles’ basic practices that have been adopted by many institutions since 2009. Indeed, a prospective, randomized study conducted among 680 intensive care patients, compared catheter colonization and blood stream infections between antimicrobial-coated CVCs and standard CVCs and found coated CVCs had a lower infection rate (2.0% vs. 6.5%). 15 Similarly, there was a lower mean incidence of BSI per 1000 catheter days in the coated CVC group compared with the standard CVC group (3.2 vs. 8.3). Subset analysis showed, among our four cases of infection, three were associated with AGB catheters, which were in place for 2,216 days, resulting in an estimate of 1.35 infections/1,000 catheter days. The remaining case was in one of 120 patients for whom an AGB+ catheter was in place for 1,525 days, equating to 0.65 infections/1,000 catheter days. Therefore, the additional antimicrobial properties present in the AGB+ catheters may have contributed to the 52% reduction in CLABSI compared with the AGB catheters. With caution, these results may justify the use of the AGB+ catheters to prevent infection, particularly for high-risk patients, such as intraoperative and oncology patients. 16
Arrythmias associated with CVC placement are often caused by irritation of the endocardium by the metallic guidewire, particularly when the guidewire is inserted too far into the superior vena cava. For instance, in a study of 1,303 patients, the incidence of arrhythmias during and following central line placement was 1.6%. 17 However, in another study, up to 41% of CVC procedures resulted in atrial arrhythmias and 25% produced some degree of ventricular ectopy. 18 We only observed one report of dysrhythmia among the 384 patients. We believe that this low rate may be partially attributable to the depth markers on the AGB/AGB+ catheter guidewires, that assist practitioners by visually informing them of how much of the guidewire has been inserted at any point.
Chlorhexidine is a key ingredient in the antimicrobial coating of the AGB/AGB+ catheters. The agent is believed to be instrumental in reducing the rate of many types of infections due to its antiseptic abilities compared with the long-used povidone-iodine or alcohol solutions. 19 However, its pervasive use in numerous medical and surgical interventions, as well as common household uses, has raised the possibility of sensitization in the general population. 20 Importantly, cases of anaphylaxis attributed to coated CVCs have been reported. 21 Nevertheless, in this study of 384 patients in which coated catheters were used for 3,741 catheter days, there were no reports of anaphylaxis.
Arterial puncture during CVC placement has been reported to be high as 25%. 22 One study reported that arterial puncture was the most common mechanical complication associated with CVC insertion into the internal jugular vein. 23 However, in the present study, where the internal jugular vein was used in 277 (72%) cases, there were no incidences of arterial puncture.
The AGB/AGB+ CVCs are specifically indicated for infusion of fluids, medication or chemotherapy, administration of total parental nutrition, frequent blood sampling, blood transfusion, CVP monitoring and pressure injection of contrast media (for pressure injectable labelled devices). In this study, the devices were used for all these aforementioned indications with a frequency ranging from >73% for infusion of fluids/medications/chemotherapy to 29% for blood transfusions. This finding could perhaps demonstrate the clinicians’ general awareness of the multiple indications and intended uses of the devices. Of particular note was the successful use of the AGB/AGB+ CVCs for pressure injection of contrast media in 51 cases, without extravasation or other adverse events. To our knowledge, this is the first report of the use of the AGB/AGB+ CVCs for injection of contrast media.
The study had several limitations. For example, it was an observational, retrospective study, involving a relatively small number of patients, with no control group. In addition, data were collected from patients’ charts that had been recorded by a variety of medical health professionals at several hospital sites in three different countries, and so may have been subjected to bias. Therefore, data from a large, controlled, prospective study and/or registry are needed to verify the performance and safety of the AGB/AGB+ CVCs reported here.
Nevertheless, data from this observational, retrospective study of AGB/AGB+ CVCs in 384 patients, found a success rate of 99% and an overall AE rate of 0.8%. Moreover, the overall infection rate was lower than typically reported for standard catheters. Significantly, the suspected infection rate was 52% lower for patients treated with the AGB+ catheters compared with those treated with AGB catheters. In addition, catheters indicated for pressure injection demonstrated safe use for contrast media without occurrence of extravasation or any other AE. Overall, this real-world evidence study indicated that the AGB/AGB+ CVCs may perform as intended with a high level of success and relatively few AEs or complications.
