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Abstract
Background and purpose The Mynx M5 (AccessClosure, Inc., Mountain View, California, USA), a novel vascular closure device (VCD) utilizing extravascular synthetic sealant, may effectively seal the arteriotomy while reducing the pain associated with arteriotomy closure seen with other VCDs. To date, no studies exist comparing the pain associated with deployment between differing VCDs as a primary end point.
Methods A blinded, randomized controlled trial was performed comparing the Mynx and a popular VCD that utilizes a self-tightening suture, the Angio-Seal Evolution (St Jude Medical, St Paul, Minnesota, USA). Subjects were all adult patients undergoing diagnostic cerebral angiography via femoral access. Local anesthesia and intraprocedural intravenous pain medication were standardized. Pain was assessed using a horizontal visual analog scale both before and after VCD deployment.
Results 64 patients were enrolled with 32 in each treatment arm. Both pain at closure and pain increase from baseline to closure were significantly higher in the Angio-Seal group (p=0.009 and 0.002, respectively). 88% of patients receiving an Angio-Seal reported closure as the most painful part of the procedure compared with only 34% of patients receiving the Mynx (p<0.001). No adverse events were detected in either treatment arm.
Conclusions In a blinded, randomized trial comparing the Mynx with the Angio-Seal Evolution, pain with device deployment at arteriotomy closure was significantly lower with the Mynx. The reason for the large pain gradient between groups is likely due to the presence, and absence, of compression elements within the Angio-Seal and Mynx, respectively.
- Artery
- angiography
- device
- technology
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Introduction
The traditional technique of achieving femoral artery hemostasis following diagnostic and interventional catheterization procedures requires compression methods such as manual pressure or clamps held at the puncture site for 15–30 min. Over the past decade, vascular closure devices (VCDs) have emerged as a means of reducing time to hemostasis and ambulation following catheterization procedures using femoral arterial access.1 Studies have translated the benefits in time to hemostasis, ambulation and discharge into increased patient satisfaction over manual compression.2–7 In addition, VCDs have demonstrated improved patient comfort over manual compression alone.2 3 5
Unfortunately, these devices still tend to subject the patient to a significant amount of pain and discomfort when deployed, as they utilize a compression element that internally exerts pressure upon the femoral artery. However, one of the more recently developed devices, the Mynx M5 (AccessClosure, Inc., Mountain View, California, USA), FDA approved as of April 2009, utilizes extravascular, water-soluble synthetic sealant that expands upon contact with subcutaneous fluids to seal the arteriotomy without the need for a compression element (figure 1). In our clinical experience, we have noted less patient discomfort during use of the Mynx compared with other VCDs, although no studies exist to date to corroborate these findings. Therefore we sought to compare the Mynx M5 with one of the most popular VCDs, the Angio-Seal Evolution (St Jude Medical, St Paul, Minnesota, USA), a VCD that utilizes an intra-arterial, bioabsorbable anchor that occludes the arteriotomy with extravascular compression by a collagen seal held in position by a self-tightening suture (figure 2).
Schematic cartoon demonstrating the mechanism of action of the Mynx VCD.
Schematic cartoon demonstrating the mechanism of action of the Angio-Seal Evolution.
Methods
Patients
Adult patients undergoing diagnostic cerebral angiography via femoral access between 1 January 2010 and 31 July 2010 were eligible for inclusion. Eligible patients provided written informed consent prior to the date of their procedure based on an Institutional Review Board-approved protocol. In addition, patients were trained to use a visual analog scale (VAS) as an assessment for pain at their preprocedure visit. The VAS is a commonly utilized pain scale ranging from 0 (no pain) to 10 (worst possible pain), which has been validated previously in a variety of settings.8–10 Eligible patients undergoing angiography through any non-femoral artery percutaneous access site were excluded. Other exclusion criteria included those with documented psychiatric disorders, those with altered mental status or necessitating conscious sedation during their procedure and those reporting a baseline chronic pain rating of ≥4 on the VAS prior to closure device deployment. VCDs were not placed (patients were excluded) if the manufacturer's instructions for use were violated. These contraindications include: if the puncture is distal to the bifurcation of the superficial femoral and profunda femoris arteries, if the puncture site is proximal to the inguinal ligament, if puncture is through a vascular graft, if multiple punctures are required to obtain arterial access, if patients have clinically significant peripheral vascular disease, if patients have uncontrolled hypertension (systolic blood pressure > 180 mm Hg) or if the femoral artery size is <5 mm.
Study design
All patients meeting the criteria were approached for consent. Once informed consent was obtained and no exclusion criteria were encountered during the procedure (access below bifurcation, elevated baseline pain, etc) patients were randomized to undergo femoral arteriotomy closure by either the Angio-Seal Evolution or the Mynx M5 VCD. Randomization was performed utilizing prestudy-created, randomly allotted, sealed envelopes containing the name of the VCD to be used. The patients, nurses administering the VAS questionnaire and study coordinators were blinded to the VCD treatment used. The Institutional Review Board-approved study protocol allowed for accrual of 128 total patients based upon power analyses, with the intention of performing preliminary statistical analyses at 64 patients and terminating the study should statistically significant differences in patient comfort be present.
The primary end point was defined as the change in pain from baseline (pre-closure) to post-closure, assessed by the VAS. Secondary end points included the patient's reporting of the most painful portion of the procedure from a multiple choice selection (1. Lidocaine injection and access; 2. Contrast injection; 3. Closure) and major and minor adverse events associated with device access and closure (table 1).
Reportable adverse events (major and minor complications) as defined by the study protocol
Procedure
All patients underwent diagnostic cerebral angiography according to standard practice. All patients received 10 ml of 1% lidocaine with epinephrine for local anesthesia. All patients received 50 μg of intravenous fentanyl during the procedure in two 25-μg fentanyl doses, the second of which was administered at least 10 min prior to deployment of the VCD. Upon obtaining access, a limited ilio-femoral angiogram was performed per manufacturer instructions prior to VCD deployment. At the termination of the procedure, if the puncture site was deemed appropriate based on the ilio-femoral angiogram, patients received either the Angio-Seal Evolution or Mynx M5 VCD according to the randomization scheme in a blinded fashion. Immediately prior to closure, patients were asked to describe their baseline pain level based on the VAS to a study nurse holding the VAS scale in plain view. Study nurses were given strict, scripted language to use with each patient such that the dialog was consistent among all patients. Patients describing a pain level of ≥4 at this point were excluded from the study. Vascular closure was then performed in a single-blinded fashion. Immediately following closure, patients were once again asked to describe their pain level, in scripted language, on the VAS during the VCD deployment to a study nurse holding the VAS scale in plain view. Following closure, the sites were assessed for hemostasis, defined as the absence of any signs of arterial pulsatile bleeding or signs of expanding or developing hematoma. Oozing of blood easily treated by light manual pressure was considered acceptable hemostasis. Time to ambulation and discharge were recorded. In addition, post-procedure, patients were asked to report the most painful part of the procedure (injection of lidocaine, contrast administration or vascular closure).
Statistical analysis
Analysis of data was performed using SPSS v. 16.0. Primary end points were evaluated using the Mann–Whitney U (Wilcoxon rank-sum) test, Pearson χ2 and linear regression to control for demographic and procedural variables. An α-level of 0.05 was chosen to establish statistical significance.
Results
As prespecified, analysis was performed following enrollment of the first 64 patients. No demographic or procedural factors differed between treatment arms (table 2). Most patients were women who underwent diagnostic angiography via the right femoral artery. The site of access was the common femoral artery at the head of the femur in the majority of patients. No patients received periprocedural aspirin, clopidogrel or heparin. There were also no significant differences in patients' preprocedural (baseline) antiplatelet or anticoagulation regimens (table 2).
Demographic and procedural comparison of randomized groups
Results of statistical analyses comparing end points are displayed in table 3. Baseline pain scores were not significantly different between those receiving Mynx and those receiving Angio-Seal closure devices (mean±SEM: 0.63±1.01 vs 0.59±1.04, respectively; p=0.72). Pain at closure was significantly lower in the Mynx group (2.94±0.42 vs 5.03±0.56; p=0.009). Similarly, the primary end point, increase in pain from baseline to closure, was significantly lower in the Mynx arm compared with Angio-Seal (2.31±0.35 vs 4.44±0.49; p=0.002). This effect remained highly significant when baseline pain was controlled for in a linear regression model (p=0.001). In addition, when patients were asked to report the most painful part of the procedure, 88% of patients receiving an Angio-Seal reported the deployment of the VCD (closure) as the most painful, compared with only 34% of patients receiving the Mynx (p<0.001). Due to the achievement of a significant difference in the primary end point at 64 patients, enrollment was halted as defined a priori in the study protocol.
Results of statistical analyses
No adverse events (major or minor complications) were recognized in either treatment group. Time to ambulation was not statistically different between groups (p=0.41).
Discussion
The benefits of VCDs over manual compression after angiography are well documented,2–7 11 although some have called into question the necessity of routine use of such VCDs.12 The deployment of VCDs is usually associated with significant local pain secondary to the forceful closure of the arteriotomy. Recently, novel VCD designs using bioabsorbable, extravascular synthetic sealant have emerged as an innovative means to obtain arteriotomy closure without a compressive element. To date, no studies exist comparing pain associated with the deployment of different VCDs as a primary end point. The goal of the present study was to evaluate the differences in pain with deployment of a device lacking a compression element (the Mynx M5) compared with a popular device utilizing a compression element consisting of a self-tightening suture, intra-arterial anchor and collagen seal (Angio-Seal Evolution). Pain was assessed using a horizontal VAS, a well-validated instrument of pain measurement.8–10
The results of this study demonstrate a strongly significant reduction in pain with vascular closure by the Mynx M5 compared with the Angio-Seal Evolution. Baseline pain prior to closure was similar between the two groups; however, both the pain on VAS post-closure and change in pain from baseline to post-closure were clearly lower in the Mynx group. Previous studies evaluating the minimum significant difference in VAS pain scores in a variety of settings ranged from 10 to 16 on a 100-point VAS (1 to 1.6 on a 10-point VAS).8 13–15 Pain scores were >2 points higher in the Angio-Seal group in both of these variables, therefore representing a clinically significant difference in pain. In addition, over twice as many patients undergoing closure by Angio-Seal as those undergoing Mynx closure reported the most painful part of the procedure to be VCD deployment. Unexpectedly, five patients in the Mynx arm (19%) and one patient in the Angio-Seal arm (3%) reported no pain at all during any portion of the procedure, despite this not being a choice offered to them during the protocol-specified questioning. For this reason, the initial three-tiered scale regarding the most painful part of procedure was altered to include a fourth tier of ‘no pain’.
Previously published studies comparing patient comfort with VCD deployment have utilized a variety of scales to assess discomfort. The widespread use of the VAS as well as its ease of use and reproducibility make it an ideal instrument for measuring pain in this setting. Both the VAS11 and a similar 11-point box scale from 0 to 104 have been used previously to assess pain with VCD closure. In addition, a 0 to 5 survey addressing pain and comfort,2 a 1 to 4 scale addressing inconvenience and discomfort5 and a 1 to 5 survey scale regarding procedural and post-procedural pain have been utilized.6 The Angio-Seal has demonstrated superiority to manual compression or other VCDs in recent comparisons of pain or comfort.2 3 5 6 11 The significant reduction in pain associated with the Mynx compared with the Angio-Seal demonstrated in this study, although not directly compared with manual compression or other VCDs, suggests a competitively low pain profile compared with the majority of other means of vascular closure after femoral access.
This reduction in pain associated with vascular closure via VCDs lacking a compression element may have important implications. In this study, a full 10 ml of local anesthesia was given to each patient as well as 50 μg of intravenous fentanyl during the procedure. Even with this standard pain regimen, groin pain was ≥7 in 12 of the 32 patients undergoing closure with the Angio-Seal, compared with 3 of 32 in the Mynx arm. This reduction in pain is likely to improve overall patient satisfaction but also reduce the amount of periprocedural pain medication necessary to facilitate both early ambulation and patient discharge after the procedure. In addition, a reduction in medication that may affect mental status and delay discharge is particularly important in patients undergoing diagnostic angiography as they are generally expected to be discharged from hospital within several hours of their procedure. Multi-center studies evaluating the pain associated with VCD deployment may be of benefit in further elucidating these relationships, as well as confirming the results demonstrated herein.
Prior studies have indicated similar major complication rates when comparing extravascular synthetic sealant VCDs with other VCDs,16 17 although the devices lacking a compression element may be associated with more device failures than Angio-Seal.17 In addition, one observational study by Fields and colleagues18 reported pseudoaneurysm formation in 11% of patients after Mynx deployment. No adverse events, either minor or major, occurred in any of the 64 patients undergoing Angio-Seal or Mynx closure. However, the study was not powered to compare adverse events between VCDs as a primary outcome, nor was routine ultrasound used to evaluate possible pseudoaneurysm formation. No patients were observed to have any complications or clinically identifiable negative occurrences. These findings leave in question the clinical relevance of any unidentified potential adverse sequelae such as asymptomatic pseudoaneurysms that are only diagnosed on ultrasonography.
There are several other important limitations. Although patients and study personnel were blinded to the device used, the proceduralist could not be blinded to the VCD deployed. This is a potential source of significant bias. To minimize this effect, a standardized anesthesia protocol and regimented pain questionnaire were used such that all patients were asked about their pain in a consistent, scripted manner. Secondly, the Angio-Seal Evolution is only one of a variety of potential VCDs available on the market that would be suitable for comparison with the Mynx in this study; however, this study was limited to just one of such alternative devices. For this reason, a popular and effective VCD was chosen. It is likely that other VCDs on the market have different degrees of pain with deployment and therefore the Angio-Seal is not necessarily representative of all VCDs with a compression element. Furthermore, manual compression was not directly evaluated as an alternative to the VCDs in this study. Finally, the results presented herein are those of a single-center trial; multi-center studies may be of assistance in confirming these findings.
Conclusions
In a blinded, randomized trial comparing the Mynx with the Angio-Seal Evolution, pain with device deployment at arteriotomy closure was significantly lower with the Mynx. The reason for the large pain gradient between groups is likely due to the presence, and absence, of compression elements within the Angio-Seal and Mynx, respectively. No adverse events were seen in either group.
Key messages
Vascular closure devices (VCDs) utilizing extravascular synthetic sealant may reduce the pain associated with arteriotomy closure compared with those VCDs using suture.
Pain with closure of different VCDs has not previously been evaluated as a primary end point.
Patients undergoing closure with the Mynx M5 (extravascular sealant VCD) reported less pain during closure than those treated with Angio-Seal Evolution (suture VCD), with no adverse events detected in either group.
The Mynx M5 is an effective VCD that reduces pain associated with arteriotomy closure.
References
Footnotes
Disclosures All authors (Fargen, Hoh, Mocco) participated in manuscript composition, data collection/analysis, clinical care and/or critical review of the manuscript. All ethical guidelines have been adhered to in the composition of this work. It is not under consideration for publication in any other journal. The University of Florida receives an educational grant and consulting fees from Codman Neurovascular. Dr Mocco serves on the Clinical Events Committee Adjudication Board for the Conscious-2 and Conscious-3 International Studies (Actelion, Inc). He is a consultant for Nfocus and Lazarus Effect and receives honoraria from Edge Therapeutics. Dr Hoh receives honoraria from Codman Neurovascular and Actelion Inc. as well as non-financial research support from Micrus Endovascular. This study was funded in part by a scientific research grant from Access Closure, Inc., however, this was an independently run physician-initiated study, and Access Closure, Inc. had no input into data collection, analysis or presentation.
Funding This study was funded in part by a scientific research grant from Access Closure, Inc., however, this was an independently run physician-initiated study, and Access Closure, Inc. had no input into data collection, analysis or presentation.
Competing interests None.
Ethics approval This study was conducted with the approval of the University of Florida Institutional Review Board, as stated in the article.
Provenance and peer review Not commissioned; externally peer reviewed.