1 Department of Medicine, University Health Network, The Toronto General Hospital and 2 Clinical Epidemiology Unit, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada
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Abstract |
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Methods. This 3 year prospective study took advantage of a change in monitoring strategy used in a large dialysis centre to compare the efficacy of two methods used to monitor grafts and fistulas in order to prevent access thrombosis. Accesses were monitored using Duplex ultrasonography in year 1, while the saline ultrasound dilution technique (Transonic) became the primary monitoring strategy in year 3 (year 2 was a transition year). Risk factors for thrombosis were determined using multivariate survival analysis, and the performance of Duplex ultrasonography and Transonic monitoring was assessed.
Results. A total of 303 656 access days at risk were assessed, with 344, 385 and 425 accesses in years 1, 2 and 3, respectively. The total thrombosis rate was 1.01/1000 access days in year 1 compared with 0.66/1000 access days in year 3. This was accomplished despite a reduction in procedure rates of 55% for angiograms, 13% for angioplasties and 31% for thrombolysis.
Conclusion. Low flow rates detected using Transonic monitoring were associated with increased thrombosis, while stenosis detected using Duplex ultrasonography was not a strong predictor of incipient thrombosis; however, these different access characteristics were compared using monitoring techniques that may be ideal in different clinical situations.
Keywords: access monitoring; fistulas; grafts; thrombosis; ultrasound dilution
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Introduction |
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The high cost of access failure demands a closer look at strategies that may prevent vascular access thrombosis. Comparisons of a variety of prospective monitoring tools indicate that measurement of access blood flow (Qa) may provide the best prediction of future thrombosis [3,4]. Recommendations [5,6] have supported such monitoring on the premise that the natural history of the access will be altered by radiological or surgical intervention once access dysfunction is detected. However, there is little clear evidence that such a strategy of prospective monitoring of Qa followed by radiological or surgical intervention significantly improves patency [79].
The primary goal of this study was to compare the efficacy of two established monitoring strategies within our institution in detecting access malfunction and preventing vascular access thrombosis. The first strategy used routine access monitoring by Duplex ultrasonography (Duplex US) followed by radiological or surgical intervention; the second strategy involved routine monitoring of Qa by the saline ultrasound dilution technique (Transonic) followed by radiological or surgical intervention. The secondary goal was to determine patient and access characteristics that predict access thrombosis.
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Subjects and methods |
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All chronic HD patients with a permanent AVG or AVF within this programme were included in the study. Baseline demographic information was collected, including access characteristics such as dates of creation and loss, reason for loss, access type and anatomy (Table 1). The access coordinator prospectively tracked the number of angiograms, angioplasties, surgical revisions, declottings, hospitalizations related to vascular access complications, and the length of stay for such hospitalizations throughout the study. Duplex US and Transonic results were documented at the time of measurement. All information was entered into a centralized vascular access database, specifically created for the study.
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During year 2, Qa monitoring using the ultrasound dilution technique (Transonic Systems, Ithaca, NY, USA) was introduced. The study protocol involved a single trained operator who obtained Transonic measurements monthly for AVG and bimonthly for AVFs as per published guidelines [5,6]. During each Transonic session, a minimum of two flow measurements were obtained in the first hour of dialysis, when the patient was haemodynamically stable with a systolic blood pressure >110 mmHg at a blood flow rate of 300 ml/min. If the measurements were discrepant by 10%, the patients' blood pressure was assessed and another measurement was made if the patient was stable. If the patient was unstable, the attending physician was asked to assess the patient, and the Transonic measurement was delayed until the next time the patient was haemodynamically stable during dialysis. Qa measurements were documented, and the average of that session's measurements was included in the study. If a low or declining flow [defined as <650 ml/min (grafts) or <500 ml/min (AVF) or a drop of >15% compared with the previous measurement] was detected, referral for an angiogram was made. If the interventional radiologist assessed a stenotic lesion as severe (>50% stenosis) and amenable to angioplasty, it was done during the same visit; otherwise, a booking for a surgical revision was made. If the lesion was not severe, routine Transonic monitoring was resumed.
The study protocol for year 3 called for a continuation of the strategy incorporated in year 2. In both years, Doppler monitoring was continued longitudinally, as previously described, to allow for comparison with Transonic monitoring.
The primary end point of this study was the cumulative thrombosis rate at 14 and 30 days after access monitoring. Secondary end points were the cumulative procedure rates for angiograms, angioplasties and thrombolysis. Exploratory end points of interest included risk factors for thrombosis, the rate of access-related hospitalizations and the average length of stay of these hospitalizations.
Statistical analysis
The primary and secondary end points of this study were expressed as events/1000 access days. For several reasons, the rates for the three periods were not directly comparable. First, the population consisted of both prevalent and incident dialysis patients; therefore, some patients occurred in the tabulations for all 3 years, resulting in lack of independence in the observations and, secondly, within the study period, a patient could have had more than one access such that an old access would appear earlier in the study and a new one later.
To overcome these analytical problems, a subset of the patients who had the same access in place for the entire 3 year period (1095 days) was identified (n=150 patients). Year 1 and year 3 thrombosis rates were compared in two ways: patients were assigned a binary (yes/no) variable for each year, depending on whether the event of interest did or did not occur, the resulting 2x2 tables were analysed using McNemar's tests and the difference in the number of events was analysed using Wilcoxon sign rank tests. Sensitivity and specificity were calculated to estimate the value of Duplex US and Transonic monitoring in predicting thrombosis. Cox proportional hazard regression analysis was used to identify risk factors for thrombosis. All tests of significance were two-sided with a P-value <0.05. The statistical software used was SAS (version 8.0) (SAS Institute Inc., Cary, NC, USA).
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Results |
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Overall rates of thrombosis and interventions
A total of 333 016 access days at risk were assessed over three 1 year periods. During this time, the thrombosis rate in AVGs fell from 1.66/1000 access days in year 1 to 1.08/1000 in year 3 (Table 2A). Thrombosis rates in AVFs also fell, but less dramatically, from 0.44/1000 access days in year 1 to 0.33/1000 access days in year 3 (Table 2B). In the subset of patients who had retained the same access for the entire 3 year period, AVGs had significantly more episodes of thrombosis in year 1 compared with year 3: of 64 AVGs, 13 had at least one thrombosis in year 1 but none in year 3, compared with four who had at least one thrombosis in year 1 but none in year 3 (P=0.029, McNemar's test). Of 86 AVFs, only one had at least one thrombosis in year 1 but none in year 3, while none of them had a thrombosis in year 3 but not in year 1 (P=0.317, McNemar's test).
Overall, the thrombosis rate fell between year 1 and year 3, despite a decrease in the rate of angiographic procedures (angiograms, angioplasties and thrombolysis) (Table 2). The total rate of angiographic procedures decreased from 2.74/1000 access days in year 1 to 1.96/1000 access days in year 3.
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Finally, there was a total reduction in both vascular access-related hospitalizations and thrombosis-related hospitalizations in year 3 compared with year 1 (Figure 1).
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In order to examine the predictive value of both types of monitoring, we examined the accesses' thrombosis history following monitoring. The findings of the Duplex US studies were categorized as no stenosis (024% lumen reduction), stenosis (2549% lumen reduction) or severe stenosis (50% lumen reduction). Transonic measurements were categorized as a flow rate of <500, 500650 or
650, and were also dichotomized depending on whether or not they showed a decrease of
15% relative to the previous measurement. The outcomes were a thrombotic episode or thrombosis-related access loss within 14 days of the measurement. For AVG, loop and straight subtypes were examined separately. It was not possible to analyse radial and brachial AVF separately due to the small number of events in these accesses. Thrombosis that occurred following 30 days was not included in determining the predictive value of Duplex US or Transonic monitoring. The total thrombosis rate in each study year is presented in Table 2
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Of the Duplex US results for AVG, 148 showed no stenosis, 252 showed stenosis and 205 showed severe stenosis. When appropriate and possible, an intervention was performed following the monitoring (angioplasty, thrombolysis or surgical revision). However, despite a finding of no stenosis, 58 accesses (40%) developed thrombosis. When severe stenosis was detected, 35% of the accesses thrombosed within 14 days. Although AVF were seldom monitored using Duplex US, the only thromboses in these accesses were associated with a finding of severe stenosis (Table 3A).
Estimates of the sensitivity and specificity of Duplex US measurements can be made in various ways. For example, the stenosis' column can be combined with either the no stenosis' or the severe stenosis' column. The best case scenario assumes that all patients with stenosis who received an intervention would otherwise have thrombosed, whereas none of the patients with no stenosis would have gone on to thrombose. This best case interpretation provided a sensitivity of 0.78, specificity of 0.26 and the positive predictive value of 0.44. For AVG, 40% of loop grafts had a thrombosis vs 29% of straight grafts if a stenosis was detected.
Transonic measurements were examined similarly (Table 3B). In AVG, there was a clear gradient: thrombosis occurred within 14 days in 45% of the accesses with a low reading, in 33% of those with an intermediate reading and in 30% of those with a high flow. The gradient appeared to be stronger in AVG straight grafts, where the thrombosis rates within 14 days were 42, 31 and 27%, while in AVG loop grafts, the thrombosis rate was 52% in grafts with low flow, but was similar (35%) in grafts with intermediate and high flow rates. There were few thrombotic episodes within 14 days in AVF, regardless of the flow rate (5, 3 and 8% of the accesses with low, intermediate and high flow rates). Change from the previous reading, dichotomized into a decrease of at least 15% or not, was not predictive of thrombosis. The conclusion did not change with dichotomization using a 20% change. In AVG, 33% of those with a large drop and 31% of those without a large drop developed thrombosis within 14 days. In AVF, 7 and 8% thrombosed, respectively.
For robustness, the analysis was repeated using a cut-off of 30 days. The results (Table 3) show that few thromboses formed and few interventions occurred after day 14.
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Additional risk factors
Cox proportional hazards regression using stepwise selection identified the type of access, a diagnosis of diabetes and race to be significant predictors of risk of thrombosis. Adjusted for the other variables, AVG had an estimated hazard ratio of 2.8 [P<0.0001, 95% confidence interval (CI) 2.04.0], while a diagnosis of diabetes as the aetiology of end-stage renal disease conferred a hazard ratio of 1.7 (P=0.006, 95% CI 1.22.5). The risk of thrombosis was found to be highest for blacks, followed by Caucasians. The overall P-value for race was 0.003, and individual estimates of risk ratio were: black vs other, risk ratio 2.4 (P=0.002, 95% CI 1.44.2); black vs Caucasian, risk ratio 1.7 (P=0.028, 95% CI 1.12.6); and Caucasian vs other, risk ratio 1.4 (P=0.117, 95% CI 0.92.3). Figure 2 depicts the risk of first thrombosis, by type of access, for accesses created on or after 1 November, 1997. The estimated time until 25% of AVF experienced their first thrombosis was 2.4 years (95% CI 1.54.2 years), whereas for AVG it was estimated that 25% would experience a first thrombosis within 0.6 years (95% CI 0.50.9 years), and 50% would experience a first thrombosis by 1.9 years (95% CI 1.32.8 years). When analysed further according to subtype of accesses, there was no difference between loop and straight AVG (P=0.157), nor a difference between radial vs brachial AVF accesses (P=0.507).
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Discussion |
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A variety of assessment tools [14,15] have been used in the attempts to detect vascular stenosis and to intervene before thrombosis develops. Access thrombosis is a result of a process involving progressive vascular stenosis due to intimal hyperplasia, myointimal proliferation and matrix deposition. Unfortunately, there are few proven medical therapies to inhibit this process. For this reason, the nephrologist must maximize access patency by detecting lesions early and intervening with angioplasty or surgical revision. Previous studies comparing different access monitoring techniques have concluded that access flow [4,8] and, in particular, Transonic monitoring [8,16] appeared to be superior in detecting access malfunction. The results of this study are consistent with this view and demonstrate a reduction by 35% in the total thrombosis rate associated with the use of Transonic monitoring as the primary strategy, compared with a strategy which used only Duplex US monitoring. In AVG, the results of the Duplex US monitoring correlated very poorly with the prognosis of thrombosis formation within 14 or 30 days, whereas lower flow rates detected by Transonic monitoring were associated with a greater probability of thrombosis. This is consistent with previous studies demonstrating the Transonic device's ability to predict thrombosis based on a declining Qa [4,17]. Neither strategy appeared to be useful in predicting the small number of thromboses in AVF accesses.
Our study supports the results of a recent pilot study [8] of 42 HD patients that demonstrated that intervention with angioplasty or surgical revision improved flows and reduced thrombosis rates. However, that study compared Transonic monitoring with venous pressure monitoring instead of Duplex US.
Also consistent with the literature was an increase in total angioplasty rates (9%) in the first year of Transonic monitoring in order to achieve a reduction in total thrombosis rate. This increase in intervention rate was small compared with previous studies that had up to a 13-fold increase in intervention rate [15]. However, the intervention rate and, in particular, the angioplasty rate fell below baseline by the end of the second year of Transonic monitoring, while maintaining a lower thrombosis rate. Possible explanations for the rise and fall in procedure rates, and the accompanying decrease in thrombosis rate, include the possibility that once old, previously unidentified lesions were corrected, fewer subsequent stenoses would require intervention. Within the first year of Transonic monitoring, as more confidence was gained in performing and interpreting the results of the technique, more interventions occurred. Finally, the single trained operator may have later become more familiar with the patients' accesses and their flow readings, providing a more reliable estimation of the urgency for intervention of the remaining fewer and/or possibly newer stenoses, leading to more appropriate and timely referrals. Thus, the long-term benefit was mediated through fixed stenosis and became apparent when improved information from routine Transonic monitoring allowed those who needed intervention to receive it.
Although previous studies have shown that Duplex US may be useful in detecting stenosis, studies on the efficacy of intervention-based Duplex US monitoring are conflicting [7,9]. This study provides further support for exploring alternative monitoring techniques. Although Duplex US assessments provide anatomical details of the access, it is operator-dependent and expensive, inconvenient for the patient, with variable waiting times from bookings to appointments, a situation that may leave the patient at a higher risk of thrombosis. In contrast, Transonic surveillance is much more convenient for the patient and can be done more frequently and regularly, and may improve compliance with the monitoring strategy. It is because of these practical differences and difficulties that we were unable to compare US Duplex and Transonic monitoring methods directly. The disparity in the frequency of the two monitoring methods reflects our institution's practices and may account for some of the differences observed in the outcomes of this study. Also, the effect of increasing experience of the dialysis staff in access surveillance could not be controlled in this study. In the absence of a randomized controlled trial design, we could not eliminate all bias. However, our study is the first prospective study comparing these two monitoring strategiesone of intermittent off-site surveillance of access patency and the other of more frequent evaluation of intradialytic access function.
To our knowledge, this is the largest prospective study with the longest follow-up of both AVG and AVF that describes the efficacy of intervention based on Transonic monitoring in preventing thrombosis. This study supports published guidelines [5,6] for investigation and intervention based on a cut-off Qa determined by Transonic monitoring to prevent thrombosis for AVG (<650 ml/min) but not for AVF (<500 ml/min). Using a change in Qa of 15 or 20% as an indicator to investigate cannot be supported based on this study.
Recognizing the impracticality of solely depending on monitoring strategies to predict thrombosis, we analysed patient and access characteristics for risk factors for thrombosis. Our study confirms the longevity and superior thrombosis risk profile of AVF compared with AVG [18]. Of the first 25% of accesses that had a thrombosis, AVF had a 4.0 times longer thrombosis-free survival compared with AVG, with the average time from access creation to first thrombosis being 2.4 years in AVF compared with 0.6 years in AVG. Our finding of increased thrombosis in loop grafts compared with straight grafts is consistent with another report [19]. In loop grafts, the risk of thrombosis increases when Qa is <650 ml/min, while a more graded relationship exists between flow and risk of thrombosis in straight grafts. Also consistent with the literature is our finding that race and the presence of diabetes are risk factors for thrombosis. In contrast to the literature, age and gender were not statistically significant risk factors [10,19,20].
Finally, the economic benefits of this strategy have not been formally assessed but, based on a reduction in the rate of procedures, thrombosis-related hospitalizations and length of stays, it seems likely that Transonic monitoring has the potential to reduce overall costs.
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Conclusion |
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Acknowledgments |
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Conflict of interest statement. None declared.
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Notes |
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References |
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