Introduction
In patients with kidney failure, the kidney disease outcome and quality initiative (KDOQI) recommends to create an upper extremity–radial cephalic or brachiocephalic–arteriovenous (AV) fistula as the method of choice to carry maintenance hemodialysis (HD).[1] Fistulas have better blood flow and low risk of infection and therefore satisfactory patency rates. When the veins are too small or too weak to support an AV fistula, then the alternative is an AV graft (AVG) using synthetic materials. However, AV grafts have a high rate of thrombosis due to intimal hyperplasia at the anastomotic site, especially in polytetrafluoroethylene grafts.[2,3,4] An ideal HD vascular access (VA) should be durable with low infectious as well as thrombotic risk to provide adequate dialysis dose. Failure to provide patients with one is a common factor leading to significant morbidity and mortality among HD patients with an estimated annual cost around 1 billion US dollars.[5]
A common cause of decreased secondary patency of HD VA is thrombosis stemming from excessive stenosis.[6] It is estimated that roughly 80% of VAs fail due to thrombosis.[7] It is worth noting that the frequency of thrombosis and the need for intervention is significantly lower in AV fistulas as compared to AV grafts.[7,8] Progressive stenosis causes changes in the blood flow and venous pressures (VPs) across VA which is thought to help predicting thrombosis.[9] Dialysis centers, therefore, traditionally use, in addition to clinical examination, the ultrasound dilution method[10,11,12] as a means of surveillance for early detection of access stenosis and thrombosis. The limited data available on this subject vary and do not uniformly confirm the effectiveness of surveillance tools and techniques. In the following, we have attempted to review all the available trials and meta-analysis done to date to assess the true effect of VA blood flow monitoring for the purpose of early detection of thrombosis and over-minimizing the rate of intervention.
Methods
Search strategy
This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A comprehensive literature search was performed in the following databases: PubMed, EMBASE, and Cochrane. The MeSH terms “vascular accesses,” “graft thrombosis,” “Doppler/duplex ultrasound,” and/or “hemodialysis” in combination with “monitoring for stenosis” were used, along with related keywords. Unpublished trials were identified from the ClinicalTrials.gov website.
Study selection
Studies that met the predefined inclusion criteria given in Table 1 were included in this systematic review. Two authors screened the title and abstract of each reference identified by the literature search and excluded references that did not meet the inclusion criteria. Full texts of the remaining references were retrieved and reviewed independently by two authors against the inclusion criteria. Disagreements in the inclusion of studies were settled by a third author.
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Table 1: Synopsis table of the randomized controlled trials.
Data extraction
The following data were extracted from all studies, if available: general data (authors, year of publication, and study type/design), patient characteristics (number, sex, mean age, prior therapies, ultrasound parameters, and presentation), intervention (type of imaging, frequency, and intervals, setting), follow-up periods, and results along with conclusions drawn by individual studies.
Quality assessment
The Newcastle–Ottawa score was used to evaluate the quality of the studies. Funnel plot analysis and Eggers test were used to assess for publication bias.
Literature selection/study characteristics
A total of 6986 abstracts were screened, out of which 10 studies (total n = 1430) were made part of our systematic review article. The details of the study selection are shown in the PRISMA diagram (Figure 1).
Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram for study selection.
Data analysis
A narrative synthesis is presented to identify where the world stands on routine HD surveillance, as a meta-analysis has recently been published.
Results
Studies favoring access surveillance
Aragoncillo et al, performed a prospective, multicenter randomized controlled trial (RCT) over a span of three years enrolling 207 patients divided into two groups: a control group where fistulography was done following classic alarm with subsequent angioplasty based based on the anatomical criteria, and an access blood flow (QA) group in which VA blood flow was measured every four months via a Doppler ultrasound in combination with ultrasound dilution in addition to the classic methods. They observed statistically significant reduction in the rate of thrombosis in the QA group versus the control group and thus concluded that adding access surveillance improves secondary patency and reduces thrombosis.[13] A single-center experience published by Mauro et al in 2014–2015 and studied the long-term secondary patency of AV graft in patients who underwent frequent duplex ultrasound surveillance at three, then followed by every six months postoperatively and compared with another group which was followed a more historical approach where AV malfunction was detected through clinical examination. Their results showed improved secondary patency rates with duplex ultrasound surveillance.[14] Trial done by Sands et al in 1999 showed a rather lower thrombosis rate by measuring monthly access flow rate than after monthly static VP. They had inducted a total of 103 patients with a mean follow-up of 197 days with a study design similar to the above. Their conclusion was that monthly intervention based on access flow rate or static VP decreased dialysis access thrombosis.[15] Smit et al in the year 2000 carried a multicenter RCT comprising 125 patients with a mean follow-up of 80.5 patient years. They were interested in finding outcomes in patients with grafts monitored by frequent VP or access flow (QA) or by the combination of both. They concluded their study by suggesting that either standard monitoring with VP or QA or the combination of both reduces thrombosis risk and grafts and are equal in efficacy.[16] When Scaffaro et al did a trial in 2008 on 108 patients with a mean follow-up of 11 months to assess whether clinical or surveillance by duplex ultrasound of fistulas helped reduce the need for central venous catheters (CVC) and thrombosis incidence by monitoring the intervention group through clinical examination and duplex ultrasound every three months, they found that this type of surveillance program is statistically beneficial.[17]
Studies with inconclusive results
Han et al carried a prospective RCT on routine duplex ultrasound surveillance on AV fistula maturation and studied whether aggressive surveillance and intervention can have an impact on the maturation rate of AV fistulas. From a total of 150 patients enrolled, the first group received clinical as well as a duplex ultrasound on regular intervals postoperatively for eight weeks while in the other group, duplex ultrasound was performed only when the clinical examination revealed an abnormality. They did not find a statistically significant benefit from routine duplex ultrasound.[18] Moist et al, did a blinded RCT in 2003 comprising 112 patients. They also compared the two groups, one undergoing monthly VA blood flow surveillance by ultrasound velocity dilution technique combined with standard surveillance (by VP and clinical examination) and the control group received standard surveillance only. They monitored patients for time to graft thrombosis and graft loss. Only the patients in the treatment group received angiography ± angioplasty (for stenosis >50%). Their conclusion was that even though frequent sonographic surveillance detected stenosis earlier, there was no difference in the time to graft thrombosis or time to graft loss following intervention with angioplasty.[19] Polkinghorne et al showed that even though monthly AV fistula blood flow surveillance detects angiographically significant stenosis twice as likely compared to historical clinically criteria but the result was found statistically nonsignificant.[20] Another RCT done by Ram et al compared the control group with flow and stenosis groups (monthly flow measured by ultrasound dilution and four monthly by duplex ultrasound in percent stenosis). Patients were referred for angiography based on set criteria while those grafts showing stenosis >50% underwent angioplasty. Based on their results, they did not support the idea that QA or stenosis surveillance was improving graft survival albeit reduced thrombotic events in the stenosis group.[21]
Meta-analysis
Finally, a meta-analysis done and published by Muchayi et al looked through seven eligible studies and did not reach a certain result, further adding to the un-clarity on any real benefit from access to blood flow surveillance.[22] While a recently published meta-analysis done by Ali et al who had included a total of 10 studies concluded that frequent monitoring of excess blood flow can reduce thrombosis risk in patients with fistulas but not with grafts.[23] A summary of these is given in Table 2).
Table 2: Synopsis table of the meta-analyses.
Discussion
The 2019 KDOQI published guidelines do not favor routine HD access surveillance by monitoring the access blood flow.[1] We also reviewed the available randomized control trials and meta-analysis done on this subject so far, and the results have a variable outcome as described above. Table 1 provides a synopsis of all the studies for readers.
There is number of studies that showed that regular HD access surveillance using non-invasive ultrasound techniques is beneficial in decreasing the risk of AV fistula thrombosis. Aragoncillo et al who favored adding access surveillance to improve secondary patency rates and thrombosis incidence, combining the use of Doppler ultrasound and ultrasound dilution methods enabled the authors to perform early intervention reducing the rate of thrombosis in the surveillance group.[13] Similarly, Scaffaro et al combined duplex ultrasound with clinical examination and had similar results, however, low frequency of surveillance, i.e., every three months, small size and a shorter follow-up may have been the limitations of the study.[17] Another study done by Tessitore et al had a long mean follow-up of five years and they reached the same conclusion. Their main point was a limited access blood flow of 350 mL/min.4 Their monitoring frequency was higher compared to other studies and may have added to early detection and therefore better outcomes. The study done by Sands et al carries the criticism of being an old study and was underpowered and that may have limited its white-scale acceptability.[15] On the contrary, many studies have reported a not-so-favorable outcome with regular access surveillance. Among them, the one performed by Polkinghorne et al had quite a few limitations: Incidence of access thrombosis was not their primary end-point, and the other one was an underpowered study due to less number of patients recruited.[20] The recently published meta-analysis too concluded in favor of doing regular HD access surveillance, while the same was not seen to be for AV grafts and as such regular surveillance for graft was not recommended.[23] Many patients have their AV fistulas created as a last resort access, and therefore, a noninvasive access surveillance methods as cheap and effective as an ultrasound are very useful in averting HD access thrombosis.
Conclusion
Periodic monitoring of the blood flow of the AVF is considered a cost-effective method in reducing the frequency of thrombosis and in improving the VA outcome. Nevertheless, multicenter randomized control trials with a large number of patients and longer follow-up period are needed to address the true effect of AV blood flow monitoring as a vital and cost-effect method of surveillance in improving AVF and AVG outcomes
Conflict of interest:
None declared.
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