Vascular access management after percutaneous transluminal angioplasty using a calcium alginate sheet: a randomized controlled trial

Vascular access management after percutaneous transluminal angioplasty using a calcium alginate... Abstract Background Management of vascular access (VA) is essential in hemodialysis (HD) patients. However, VA often fails and percutaneous transluminal angioplasty (PTA) is required. Conventional hemostasis at the puncture site is associated with complications. This study aimed to analyze the efficacy and safety of a hemostatic wound dressing made of calcium alginate at the puncture site of VA after PTA and evaluate other factors affecting hemostasis. Methods After PTA for VA, 200 HD patients were randomized to a calcium alginate sheet (CA) group (n = 100) or a no drug-eluting sheet (control) group (n = 100). We recorded time to hemostasis at the puncture site every 5 min, noting any complications. Results In the CA group, rates of hemostatic achievement at 5, 10, 15 and >15 min were 57, 25, 8 and 10%, respectively. In the control group, the rates were 39, 28, 14 and 19%, respectively. Rates of hemostatic achievement at 5 min were significantly higher in the CA group (P = 0.01). In logistic regression analysis, factors affecting hemostasis within 5 min were use of the CA sheet [odds ratio (OR) 2.33; 95% confidence interval (CI) 1.26–4.37], platelet count ≤100 000/μL (OR 0.19; 95% CI 0.04–0.69), number of antithrombotic tablets used per day ≥1 tablet (OR 0.50; 95% CI 0.26–0.94) and upper arm VA (OR 0.16; 95% CI 0.03–0.55). Conclusions A CA sheet can safely reduce time to hemostasis at the puncture site after PTA, and should be considered for treating patients with a bleeding tendency. calcium alginate, hemodialysis, hemostasis, percutaneous transluminal angioplasty, vascular access INTRODUCTION Management of vascular access (VA) is essential for the maintenance of appropriate dialysis in hemodialysis (HD) patients [1, 2]. However, as reported previously, in 30–50% of cases, the VA fails to mature or requires an intervention shortly after creation [3–5], and percutaneous transluminal angioplasty (PTA) plays an important role in the management of VA [6, 7]. Hemostasis at the puncture site after PTA is commonly performed using conventional manual compression. However, this technique can be time consuming. Moreover, HD patients tend to be at a higher risk of bleeding compared with healthy individuals [8–10]. In some cases, it is difficult to achieve hemostasis at the puncture site of the VA after PTA. Occasionally, the time to hemostasis is even longer than the PTA time. If we achieve hemostasis in a shorter time and safely, we can relieve the patient of distress and save significant medical resources. Calcium alginate (CA) has a pronounced effect on hemostasis [11] and reduces the amount of bleeding [12–14]. One study reported that CA shortened the time to hemostasis in 54% of patients after dental treatment [15]. Conversely, other studies have reported no hemostatic effect [16, 17]. Moreover, there are no reports evaluating the safety and effectiveness of CA for hemostasis after PTA for VA dysfunction. Herein, we prospectively evaluated the effect of CA on hemostasis at the puncture site after PTA for VA dysfunction. Moreover, we evaluated other factors affecting hemostasis. MATERIALS AND METHODS Study design and patients This was a single-center, prospective, randomized controlled trial. In this study, HD patients were eligible if PTA was performed for VA dysfunction at the Tsuchiya General Hospital between 1 November 2016 and 27 July 2017 (Figure 1). During the study period, 232 HD patients with VA dysfunction underwent PTA 424 times. In patients who underwent PTA two or more times during the study period, only first PTA cases (232 times) were eligible for inclusion in this study. Moreover, the following patients (n = 32) were excluded: patients who did not consent to participate in this study (n = 18), underwent an arterial puncture (n = 4), were punctured by three or more sheaths (n = 0), had a hematoma at the puncture site during PTA (n = 4) and patients for whom the PTA procedure was considered technically unsuccessful (n = 6). Finally, 200 HD patients were enrolled in this study. This study was approved by the local ethics committee (approval number: E161024-2) and was registered with the University Hospital Medical Information Network (UMIN) Center (approval number: 000027022). All patients gave their written informed consent before PTA. The following data were recorded for eligible patients: age, sex, HD vintage, VA vintage, the primary cause of end-stage kidney disease, body mass index (BMI), comorbidities, number of oral antithrombotic tablets (clopidogrel, aspirin, cilostazol, ticlopidine hydrochloride, warfarin) used per day, platelet count, sheath size, use of urokinase, type of VA [arteriovenous fistula (AVF) or arteriovenous graft (AVG)], VA location (forearm or upper arm), blood pressure at the end of PTA, whether PTA was performed before or after HD on the same day, positional relationship between the stenosis site before PTA and the puncture site of the sheath (proximal or distal) and complications after PTA. On the day following PTA, operators conducted a visual inspection of VA (checking whether there was subcutaneous hemorrhage, swelling or exanthema in the extremity with VA) and permitted hospital discharge after confirming that there were no evident complications. In all patients, VA cannulation was performed by the rope-ladder technique with sharp needles during each HD session. FIGURE 1: View largeDownload slide Study flow diagram. FIGURE 1: View largeDownload slide Study flow diagram. VA monitoring and identification of VA dysfunction before PTA In accordance with Japanese Society for Dialysis Therapy Guidelines of Vascular Access Construction and Repair for Chronic Hemodialysis [18], VA monitoring was performed at every HD session. When abnormal physiological findings for thrill, murmur, palpation, venous pressure, extended time for hemostasis, swelling in the fistula limb or pillow condition were detected at HD session, VA scan examinations using ultrasonography were carried out for the patients. The scan protocol included ‘flow volume (FV) and resistance index (RI) of brachial artery’ and ‘minimum internal diameter (MID) of venous stenosis site’ of VA. The critical values of measured FV, RI and MID were defined as the following: FV <300 mL/min; RI >0.60; MID <1.60 mm. When the critical value of FV, RI or MID was detected, VA dysfunction requiring PTA was identified. PTA technique and hemostatic procedures PTA was performed for VA dysfunction (stenosis, n = 164; occlusion, n = 36) during the study period. Occlusion was defined as blood flow interruption by thrombus. PTA for VA dysfunction was executed as follows. VA was punctured with the puncture needles; then, lidocaine 1% was subcutaneously injected at the puncture site before insertion of the sheath. Sheaths of 4, 5, 5.5, 6 or 7 French (F) were inserted, and then 3000 units of heparin were administered. Guide wire (GW) and balloon size were determined according to angiographic findings. After insertion of the GW (0.018 or 0.035 inch in size), balloons (4–6 mm in size) were inflated to a pressure of 2–30 atmospheres for 30–60 s several times. At the end of the PTA, an angiogram was performed, and the PTA procedure was considered technically successful when the residual stenosis was <30%. In all cases of occlusion, urokinase [the mean amount was 59 000 (range 20 000–120 000) units] was scattered to the thrombus using an infusion catheter with multiple side holes to administer therapeutic solutions into the peripheral vasculature (Mistique®, Merit Medical Systems Inc., South Jordan, UT, USA) before the angiogram and balloon inflation. We used a nepcell S® (Alliance Medical Group, Tokyo, Japan) as the hemostatic dressing, which consists of CA extracted from a seaweed called giant kelp. Patients were assigned to either the CA sheet group (n = 100) or the non-drug sheet (control) group (n = 100) using random permuted blocks (block size = 4) with computer-generated random digits (Figure 1). The random digits were generated using R version 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria). Operators performing hemostatic procedures were not informed whether patients were in the CA or control group until the end of PTA. At the end of PTA, the nurse gave the operator the CA or control sheet according to the random assignment. If two sheaths were used, only the one closest to the anastomosis was included in the analysis. The operator placed the sheet on the boundary between the sheath and skin, then removed the sheath using manual compression, and, simultaneously, the nurse started to measure the time with a stopwatch. Hemostatic procedures were performed by applying mild, digital direct pressure over the needle sites, using a two-digit technique, one finger at the skin (external) and one finger at the blood vessel wall (internal). Hemostatic achievement was checked every 5 min by removing the sheet. If the bleeding was persistent at the checkpoint, compression was resumed instantly. If bleeding continued for more than 15 min, additional manual compression or sutures were applied. After hemostasis, the puncture site was covered with a sticking plaster without the additional use of a pressure bandage. Outcomes The primary outcome was the rate of hemostatic achievement at 5 , 10 , 15  and >15 min after the start of hemostatic procedure. The secondary outcome was the rate of the following complications: rebleeding, allergic reaction, anaphylactic shock and false aneurysm at the puncture site until patient discharge. Statistical analyses Data were analyzed using JMP® 5.1 (SAS Institute Inc., Cary, NC, USA) and Microsoft Excel 2013 software, and were expressed as either the number of patients or percentage of the study population. The remaining data were expressed as the mean ± SD. The Student’s t-test and chi-square test were used for continuous and categorical variables, respectively. After univariate analysis, a multivariate logistic regression analysis was performed to evaluate factors potentially influencing hemostasis, adjusted for patient age (≥75 years old or <75 years old), sex, HD vintage [≥92 months or <92 months (92 was the mean value of the enrolled patients)], diabetes mellitus, use of urokinase, use of CA, platelet count (≤100 000/μL or >100 000/μL), number of antithrombotic tablets used per day (≥1 tablet or 0), VA location (forearm or upper arm) and sheath size (≥5.5 F or ≤5 F). The results of the regression model were depicted as the odds ratio (OR) and 95% confidence interval (CI). In all analyses, P-values <0.05 were considered statistically significant. RESULTS Demographic data and clinical characteristics before PTA are shown in Table 1. During the study period, 200 patients were randomized (100 in the CA group and 100 in the control group). Of the 200 patients, 164 and 36 underwent PTA for VA stenosis and occlusion, respectively. The mean PTA time in all cases was 59.6 ± 38.3 min (n = 200), and the mean PTA time in occlusion cases (use of urokinase) was 96.7 ± 45.8 min (n = 36). Demographic data and clinical characteristics before PTA were similar between the two groups. Table 1. Patient characteristics Variables CA Control P (n = 100) (n = 100) Age, years 70.2 ± 12.4 71.1 ± 12.0 0.6 Male, n (%) 60 (60) 58 (58) 0.7 BMI, kg/m2 21.7 ± 3.7 21.4 ± 3.7 0.5 HD vintage, months 85.5 ± 77.2 99.4 ± 92.6 0.2 PTA time, min 57.6 ± 39.4 61.7 ± 37.3 0.4 VA vintage, months 60.5 ± 54.4a 66.5 ± 55.6b 0.5 Occlusion (use of urokinase), n (%) 20 (20) 16 (16) 0.5 AVF/AVG, n 95/5 93/7 0.6 Forearm/upper arm VA, n 90/10 90/10 1.0 Sheath diameter, ≤5/≥5.5 F, n 91/9 89/11 0.6 Number of antithrombotic tablets used per day ≥1 tablet, n (%) 63 (63) 55 (55) 0.2 Platelet count, per μL 18.0 ± 5.2 18.4 ± 6.9 0.6 Primary cause of ESKD   Diabetes mellitus, n (%) 47 (47) 49 (49) 0.8   Chronic glomerulonephritis, n (%) 27 (27) 26 (26) 0.9   Nephrosclerosis, n (%) 13 (13) 10 (10) 0.5   Others, n (%) 7 (7) 7 (7) 1.0   Unknown, n (%) 6 (6) 8 (8) 0.6 PTA after HDc, n (%) 3 (3) 6 (6) 0.3 Stenosis proximal to puncture site of sheath before PTA, n (%) 15 (15) 10 (10) 0.3 Residual stenosis of ≥30%, n (%) 0 (0) 0 (0) 1.0 Variables CA Control P (n = 100) (n = 100) Age, years 70.2 ± 12.4 71.1 ± 12.0 0.6 Male, n (%) 60 (60) 58 (58) 0.7 BMI, kg/m2 21.7 ± 3.7 21.4 ± 3.7 0.5 HD vintage, months 85.5 ± 77.2 99.4 ± 92.6 0.2 PTA time, min 57.6 ± 39.4 61.7 ± 37.3 0.4 VA vintage, months 60.5 ± 54.4a 66.5 ± 55.6b 0.5 Occlusion (use of urokinase), n (%) 20 (20) 16 (16) 0.5 AVF/AVG, n 95/5 93/7 0.6 Forearm/upper arm VA, n 90/10 90/10 1.0 Sheath diameter, ≤5/≥5.5 F, n 91/9 89/11 0.6 Number of antithrombotic tablets used per day ≥1 tablet, n (%) 63 (63) 55 (55) 0.2 Platelet count, per μL 18.0 ± 5.2 18.4 ± 6.9 0.6 Primary cause of ESKD   Diabetes mellitus, n (%) 47 (47) 49 (49) 0.8   Chronic glomerulonephritis, n (%) 27 (27) 26 (26) 0.9   Nephrosclerosis, n (%) 13 (13) 10 (10) 0.5   Others, n (%) 7 (7) 7 (7) 1.0   Unknown, n (%) 6 (6) 8 (8) 0.6 PTA after HDc, n (%) 3 (3) 6 (6) 0.3 Stenosis proximal to puncture site of sheath before PTA, n (%) 15 (15) 10 (10) 0.3 Residual stenosis of ≥30%, n (%) 0 (0) 0 (0) 1.0 Data are expressed as the mean ± SD, numbers and percentages for variables. an = 96 (CA group); bn = 96 (control group); cof the 200 patients, 144 underwent PTA on a day without HD, and 9 underwent PTA at 3–4 h after the HD session (CA group = 3, control group = 6; P = 0.3). These nine patients were administered 1000 units of heparin at the start and 500 units of heparin/h during HD. ESKD, end-stage kidney disease. Table 1. Patient characteristics Variables CA Control P (n = 100) (n = 100) Age, years 70.2 ± 12.4 71.1 ± 12.0 0.6 Male, n (%) 60 (60) 58 (58) 0.7 BMI, kg/m2 21.7 ± 3.7 21.4 ± 3.7 0.5 HD vintage, months 85.5 ± 77.2 99.4 ± 92.6 0.2 PTA time, min 57.6 ± 39.4 61.7 ± 37.3 0.4 VA vintage, months 60.5 ± 54.4a 66.5 ± 55.6b 0.5 Occlusion (use of urokinase), n (%) 20 (20) 16 (16) 0.5 AVF/AVG, n 95/5 93/7 0.6 Forearm/upper arm VA, n 90/10 90/10 1.0 Sheath diameter, ≤5/≥5.5 F, n 91/9 89/11 0.6 Number of antithrombotic tablets used per day ≥1 tablet, n (%) 63 (63) 55 (55) 0.2 Platelet count, per μL 18.0 ± 5.2 18.4 ± 6.9 0.6 Primary cause of ESKD   Diabetes mellitus, n (%) 47 (47) 49 (49) 0.8   Chronic glomerulonephritis, n (%) 27 (27) 26 (26) 0.9   Nephrosclerosis, n (%) 13 (13) 10 (10) 0.5   Others, n (%) 7 (7) 7 (7) 1.0   Unknown, n (%) 6 (6) 8 (8) 0.6 PTA after HDc, n (%) 3 (3) 6 (6) 0.3 Stenosis proximal to puncture site of sheath before PTA, n (%) 15 (15) 10 (10) 0.3 Residual stenosis of ≥30%, n (%) 0 (0) 0 (0) 1.0 Variables CA Control P (n = 100) (n = 100) Age, years 70.2 ± 12.4 71.1 ± 12.0 0.6 Male, n (%) 60 (60) 58 (58) 0.7 BMI, kg/m2 21.7 ± 3.7 21.4 ± 3.7 0.5 HD vintage, months 85.5 ± 77.2 99.4 ± 92.6 0.2 PTA time, min 57.6 ± 39.4 61.7 ± 37.3 0.4 VA vintage, months 60.5 ± 54.4a 66.5 ± 55.6b 0.5 Occlusion (use of urokinase), n (%) 20 (20) 16 (16) 0.5 AVF/AVG, n 95/5 93/7 0.6 Forearm/upper arm VA, n 90/10 90/10 1.0 Sheath diameter, ≤5/≥5.5 F, n 91/9 89/11 0.6 Number of antithrombotic tablets used per day ≥1 tablet, n (%) 63 (63) 55 (55) 0.2 Platelet count, per μL 18.0 ± 5.2 18.4 ± 6.9 0.6 Primary cause of ESKD   Diabetes mellitus, n (%) 47 (47) 49 (49) 0.8   Chronic glomerulonephritis, n (%) 27 (27) 26 (26) 0.9   Nephrosclerosis, n (%) 13 (13) 10 (10) 0.5   Others, n (%) 7 (7) 7 (7) 1.0   Unknown, n (%) 6 (6) 8 (8) 0.6 PTA after HDc, n (%) 3 (3) 6 (6) 0.3 Stenosis proximal to puncture site of sheath before PTA, n (%) 15 (15) 10 (10) 0.3 Residual stenosis of ≥30%, n (%) 0 (0) 0 (0) 1.0 Data are expressed as the mean ± SD, numbers and percentages for variables. an = 96 (CA group); bn = 96 (control group); cof the 200 patients, 144 underwent PTA on a day without HD, and 9 underwent PTA at 3–4 h after the HD session (CA group = 3, control group = 6; P = 0.3). These nine patients were administered 1000 units of heparin at the start and 500 units of heparin/h during HD. ESKD, end-stage kidney disease. In the CA group, the proportions of hemostatic achievement at 5, 10, 15 and >15 min after the start of the hemostatic procedure were 57% (n = 57), 25% (n = 25), 8% (n = 8) and 10% (n = 10), respectively. In the control group, the proportions were 39% (n = 39), 28% (n = 28), 14% (n = 14) and 19% (n = 19), respectively (Figure 2). The proportions of hemostatic achievement within 5 min were significantly higher in the CA group compared with the control group (P = 0.01). The rates of rebleeding after hemostasis were similar between the two groups: six (6%) and seven (7%) episodes were identified in the CA and control groups, respectively (P = 0.7). In all rebleeding cases, complete hemostasis was achieved using further manual compression. No serious complications, such as anaphylactic shock, bleeding refractory to manual compression, cutaneous allergy or false aneurysm at the puncture site were identified in the two groups. FIGURE 2: View largeDownload slide Distributions of time to hemostasis at the puncture site after PTA in the CA and control groups. *P = 0.01. FIGURE 2: View largeDownload slide Distributions of time to hemostasis at the puncture site after PTA in the CA and control groups. *P = 0.01. In the univariate analysis (Table 2), the OR for use of the CA sheet for hemostasis within 5 min was significantly high (OR 2.07; 95% CI 1.18–3.66; P = 0.01). On the other hand, ORs of the following variables for hemostasis within 5 min were significantly low: platelet count  ≤100 000/μL (OR 0.22; 95% CI 0.05–0.72; P = 0.02), sheath size ≥5.5 F (OR 0.32; 95% CI 0.10–0.88; P = 0.04) and upper arm VA (OR 0.16; 95% CI 0.03–0.51; P = 0.01). The other variables were not determinant. Table 2. Univariate analysis of predictors for hemostasis of sheath puncture site after PTA Variables OR 95% CI P Age ≥75 years 0.66 0.37–1.17 0.2 Male 1.32 0.75–2.33 0.3 HD vintage ≥92 months 1.13 0.63–2.02 0.7 Primary cause of ESKD   Diabetes mellitus 1.26 0.72–2.21 0.4   CGN 0.81 0.33–1.94 0.6 Occlusion (use of urokinase) 1.08 0.35–3.30 0.9 Use of CA sheet 2.07 1.18–3.66 0.01 PTA time ≥60 min 0.89 0.50–1.57 0.7 Platelet count ≤100 000/μL 0.22 0.05–0.72 0.02 Number of antithrombotic  tablets used per day ≥1 tablet 0.57 0.32–1.01 0.06 Upper arm VA 0.16 0.03–0.51 0.01 Sheath diameter ≥ 5.5 F 0.32 0.10–0.88 0.04 Systolic blood pressure after  PTA ≥180 mmHg 1.22 0.47–3.22 0.7 PTA after HD 0.86 0.20–3.34 0.8 Stenosis proximal to puncture  site of sheath 0.46 0.18–1.10 0.09 Variables OR 95% CI P Age ≥75 years 0.66 0.37–1.17 0.2 Male 1.32 0.75–2.33 0.3 HD vintage ≥92 months 1.13 0.63–2.02 0.7 Primary cause of ESKD   Diabetes mellitus 1.26 0.72–2.21 0.4   CGN 0.81 0.33–1.94 0.6 Occlusion (use of urokinase) 1.08 0.35–3.30 0.9 Use of CA sheet 2.07 1.18–3.66 0.01 PTA time ≥60 min 0.89 0.50–1.57 0.7 Platelet count ≤100 000/μL 0.22 0.05–0.72 0.02 Number of antithrombotic  tablets used per day ≥1 tablet 0.57 0.32–1.01 0.06 Upper arm VA 0.16 0.03–0.51 0.01 Sheath diameter ≥ 5.5 F 0.32 0.10–0.88 0.04 Systolic blood pressure after  PTA ≥180 mmHg 1.22 0.47–3.22 0.7 PTA after HD 0.86 0.20–3.34 0.8 Stenosis proximal to puncture  site of sheath 0.46 0.18–1.10 0.09 ESKD, end-stage kidney disease; CGN, chronic glomerulonephritis. Table 2. Univariate analysis of predictors for hemostasis of sheath puncture site after PTA Variables OR 95% CI P Age ≥75 years 0.66 0.37–1.17 0.2 Male 1.32 0.75–2.33 0.3 HD vintage ≥92 months 1.13 0.63–2.02 0.7 Primary cause of ESKD   Diabetes mellitus 1.26 0.72–2.21 0.4   CGN 0.81 0.33–1.94 0.6 Occlusion (use of urokinase) 1.08 0.35–3.30 0.9 Use of CA sheet 2.07 1.18–3.66 0.01 PTA time ≥60 min 0.89 0.50–1.57 0.7 Platelet count ≤100 000/μL 0.22 0.05–0.72 0.02 Number of antithrombotic  tablets used per day ≥1 tablet 0.57 0.32–1.01 0.06 Upper arm VA 0.16 0.03–0.51 0.01 Sheath diameter ≥ 5.5 F 0.32 0.10–0.88 0.04 Systolic blood pressure after  PTA ≥180 mmHg 1.22 0.47–3.22 0.7 PTA after HD 0.86 0.20–3.34 0.8 Stenosis proximal to puncture  site of sheath 0.46 0.18–1.10 0.09 Variables OR 95% CI P Age ≥75 years 0.66 0.37–1.17 0.2 Male 1.32 0.75–2.33 0.3 HD vintage ≥92 months 1.13 0.63–2.02 0.7 Primary cause of ESKD   Diabetes mellitus 1.26 0.72–2.21 0.4   CGN 0.81 0.33–1.94 0.6 Occlusion (use of urokinase) 1.08 0.35–3.30 0.9 Use of CA sheet 2.07 1.18–3.66 0.01 PTA time ≥60 min 0.89 0.50–1.57 0.7 Platelet count ≤100 000/μL 0.22 0.05–0.72 0.02 Number of antithrombotic  tablets used per day ≥1 tablet 0.57 0.32–1.01 0.06 Upper arm VA 0.16 0.03–0.51 0.01 Sheath diameter ≥ 5.5 F 0.32 0.10–0.88 0.04 Systolic blood pressure after  PTA ≥180 mmHg 1.22 0.47–3.22 0.7 PTA after HD 0.86 0.20–3.34 0.8 Stenosis proximal to puncture  site of sheath 0.46 0.18–1.10 0.09 ESKD, end-stage kidney disease; CGN, chronic glomerulonephritis. In the multivariate logistic regression analysis (Table 3), use of the CA sheet (OR 2.33; 95% CI 1.26–4.37; P = 0.007), platelet count  ≤100 000/μL (OR 0.19; 95% CI 0.04–0.69; P = 0.02), number of antithrombotic tablets used per day  ≥1 tablet (OR 0.50; 95% CI 0.26–0.94; P = 0.03) and VA location (OR for upper arm VA 0.16; 95% CI 0.03–0.55; P = 0.008) were independent predictors of time to hemostasis within 5 min. The other variables were not determinant. Table 3. Multivariate analysis of predictors for hemostasis of sheath puncture site after PTA Variables OR 95% CI P Age ≥75 years 0.78 0.41–1.49 0.5 Male 1.56 0.83–2.96 0.2 HD vintage ≥92 months 1.53 0.79–3.02 0.2 Diabetes mellitus 1.11 0.59–2.09 0.7 Occlusion (use of urokinase) 1.01 0.28–3.69 0.97 Use of CA sheet 2.33 1.26–4.37 0.007 Platelet count ≤100 000/μL 0.19 0.04–0.69 0.02 Number of antithrombotic tablets  used per day ≥1 tablet 0.50 0.26–0.94 0.03 Upper arm VA 0.16 0.03–0.55 0.008 Sheath diameter ≥5.5 F 0.51 0.15–1.54 0.3 Variables OR 95% CI P Age ≥75 years 0.78 0.41–1.49 0.5 Male 1.56 0.83–2.96 0.2 HD vintage ≥92 months 1.53 0.79–3.02 0.2 Diabetes mellitus 1.11 0.59–2.09 0.7 Occlusion (use of urokinase) 1.01 0.28–3.69 0.97 Use of CA sheet 2.33 1.26–4.37 0.007 Platelet count ≤100 000/μL 0.19 0.04–0.69 0.02 Number of antithrombotic tablets  used per day ≥1 tablet 0.50 0.26–0.94 0.03 Upper arm VA 0.16 0.03–0.55 0.008 Sheath diameter ≥5.5 F 0.51 0.15–1.54 0.3 Table 3. Multivariate analysis of predictors for hemostasis of sheath puncture site after PTA Variables OR 95% CI P Age ≥75 years 0.78 0.41–1.49 0.5 Male 1.56 0.83–2.96 0.2 HD vintage ≥92 months 1.53 0.79–3.02 0.2 Diabetes mellitus 1.11 0.59–2.09 0.7 Occlusion (use of urokinase) 1.01 0.28–3.69 0.97 Use of CA sheet 2.33 1.26–4.37 0.007 Platelet count ≤100 000/μL 0.19 0.04–0.69 0.02 Number of antithrombotic tablets  used per day ≥1 tablet 0.50 0.26–0.94 0.03 Upper arm VA 0.16 0.03–0.55 0.008 Sheath diameter ≥5.5 F 0.51 0.15–1.54 0.3 Variables OR 95% CI P Age ≥75 years 0.78 0.41–1.49 0.5 Male 1.56 0.83–2.96 0.2 HD vintage ≥92 months 1.53 0.79–3.02 0.2 Diabetes mellitus 1.11 0.59–2.09 0.7 Occlusion (use of urokinase) 1.01 0.28–3.69 0.97 Use of CA sheet 2.33 1.26–4.37 0.007 Platelet count ≤100 000/μL 0.19 0.04–0.69 0.02 Number of antithrombotic tablets  used per day ≥1 tablet 0.50 0.26–0.94 0.03 Upper arm VA 0.16 0.03–0.55 0.008 Sheath diameter ≥5.5 F 0.51 0.15–1.54 0.3 Furthermore, in the multivariate analysis including only the determinants identified in the univariate analysis, the results were similar to those found in the multivariate analysis including all 10 factors (Supplementary data, Table S1). DISCUSSION Maintenance of VA function is essential for keeping adequate doses of dialysis in HD patients. PTA is the most common treatment for VA dysfunction. A high percentage of HD patients are elderly, take several types of antithrombotic drugs and have a tendency to bleed [19]. Shortening time to hemostasis after PTA can reduce the medical resources needed and relieve patients of their distress promptly. In this study, we proved that CA shortened the time to hemostasis after PTA. CA, a kind of alginic acid, is used as a hemostatic agent in the medical field, e.g. as a hemostatic material after endoscopic biopsy and as a wound dressing material. In this study, after multivariate adjustment for factors potentially influencing hemostasis, only the use of a CA sheet promoted hemostasis after PTA. Our findings support the hemostatic effect of CA reported in a previous study [20]. Conversely, platelet count  ≤100 000/μL, number of antithrombotic tablets used per day  ≥1 tablet and upper arm VA were independently associated with increased time to hemostasis. In two previous studies, low platelet count and antithrombotic drugs were both associated with bleeding after intra-vascular treatment and intra-arterial treatment, respectively [21, 22]. Previous studies showed that upper arm VA was associated with greater FV than forearm access [23, 24], and this may be the reason why hemostasis was more difficult to achieve with upper arm VA. Unexpectedly, there was no relationship between use of urokinase and time to hemostasis at the puncture site after PTA. This finding may be explained by the fact that the half-life time of urokinase is 3–26 min, whereas mean PTA time in cases with VA occlusion (with use of urokinase) was 96.7 min. Moreover, most of the urokinase was used during the early phase of PTA. Therefore, the thrombolytic function of urokinase may have been attenuated by the end of PTA. To summarize the above analysis, preventing factors for hemostasis were platelet count  ≤100 000/μL, number of antithrombotic tablets used per day  ≥1 tablet and upper arm VA. Therefore, we recommend that CA should be used after PTA in patients with these risk factors. This study had many strengths. It was a prospective, randomized controlled trial for hemostasis after PTA. Because the analysis took place in a single hospital, it enabled us to advocate for changes that should be implemented to the policies that surround VA management strategies. In addition, use of a CA sheet, which was evaluated to determine its efficacy and safety for hemostasis, is a simple procedure. Moreover, we also evaluated other factors affecting hemostasis. Therefore, the current study can guide clinical management practices for achievement of hemostasis after PTA. This study had several limitations. First, this study was based on a group of patients being treated at a single center and the sample size was small. However, this study was a randomized trial, and the baseline characteristics between the two groups were similar (Table 1). Second, the operators who performed hemostasis after PTA may have known whether a CA sheet or control sheet was used, because this study was open label. Therefore, we assessed the achievement of hemostasis every 5 min in both groups. If the operators were allowed to check the hemostasis at any time, this may have resulted in different hemostasis checking times in the two groups. Third, we did not identify the exact time to hemostasis in cases where time to hemostasis was >15 min. Therefore, we did not identify the actual time to hemostasis after PTA. Fourth, evaluation of false aneurysm at the puncture site of VA was not performed by ultrasonography. The operators visually evaluated the puncture site on the day following PTA. The search for false aneurysms may, thus, not have been performed accurately. Finally, we did not measure laboratory coagulation parameters, such as prothrombin time, activated partial thromboplastin time and activated clotting time. Despite these limitations, there are no previous reports that examine the effect of the CA after PTA for VA dysfunction; therefore, this study is valuable relative to the existing information in the field. In conclusion, CA safely reduced time to hemostasis at the VA puncture site after PTA for VA dysfunction. Other factors affecting hemostasis were platelet count, antithrombotic drugs and VA location. Our findings can guide clinical management practices for achievement of hemostasis at the VA puncture site after PTA in HD patients. SUPPLEMENTARY DATA Supplementary data are available at ndt online. CONFLICT OF INTEREST STATEMENT None declared. REFERENCES 1 Ethier J , Mendelssohn DC , Elder SJ. Vascular access use and outcomes: an international perspective from the Dialysis Outcomes and Practice Patterns Study . Nephrol Dial Transplant 2008 ; 23 : 3219 – 3226 Google Scholar CrossRef Search ADS PubMed 2 Windus DW. Permanent vascular access: a nephrologist’s view . Am J Kidney Dis 1993 ; 21 : 457 – 471 Google Scholar CrossRef Search ADS PubMed 3 Schinstock CA , Albright RC , Williams AW et al. Outcomes of arteriovenous fistula creation after the Fistula First Initiative . Clin J Am Soc Nephrol 2011 ; 6 : 1996 – 2002 Google Scholar CrossRef Search ADS PubMed 4 Bashar K , Zafar A , Elsheikh S et al. Predictive parameters of arteriovenous fistula functional maturation in a population of patients with end-stage renal disease . Plos One 2015 ; 10 : e0119958 Google Scholar CrossRef Search ADS PubMed 5 Pisoni R , Barker-Finkel J , Allo M. Statin therapy is not associated with improved vascular access outcomes . Clin J Am Soc Nephrol 2010 ; 5 : 1447 – 1450 Google Scholar CrossRef Search ADS PubMed 6 Burger H , Zijlstra JJ , Kluchert SA et al. Percutaneous transluminal angioplasty improves longevity in fistulae and shunts for haemodialysis . Nephrol Dial Transplant 1990 ; 5 : 608 – 611 Google Scholar CrossRef Search ADS PubMed 7 Kumano S , Itatani K , Shiota J et al. Strategies for the creation and maintenance of reconstructed arteriovenous fistulas using the forearm basilic vein . Ther Apher Dial 2013 ; 17 : 504 – 509 Google Scholar PubMed 8 Kuo CC , Kuo HW , Lee IM et al. The risk of upper gastrointestinal bleeding in patients treated with hemodialysis: a population-based cohort study . BMC Nephrol 2013 ; 14 : 15 Google Scholar CrossRef Search ADS PubMed 9 Wakasugi M , Matsuo K , Kazama JJ et al. Higher mortality due to intracerebral hemorrhage in dialysis patients: a comparison with the general population in Japan . Ther Apher Dial 2015 ; 19 : 45 – 49 Google Scholar CrossRef Search ADS PubMed 10 Numasawa Y , Kohsaka S , Ueda I et al. Incidence and predictors of bleeding complications after percutaneous coronary intervention . J Cardiol 2017 ; 69 : 272 – 279 Google Scholar CrossRef Search ADS PubMed 11 Blair SD , Backhouse CM , Harper R et al. Comparison of absorbable materials for surgical haemostasis . Br J Surg 1988 ; 75 : 969 – 971 Google Scholar CrossRef Search ADS PubMed 12 Blair SD , Jarvis P , Salmon M et al. Clinical trial of calcium alginate haemostatic swabs . Br J Surg 1990 ; 77 : 568 – 570 Google Scholar CrossRef Search ADS PubMed 13 Taskin AK , Yasar M , Ozaydin I et al. The hemostatic effect of calcium alginate in experimental splenic injury model . Ulus Travma Acil Cerrahi Derg 2013 ; 19 : 195 – 199 Google Scholar CrossRef Search ADS PubMed 14 Davies MS , Flannery MC , McCollum CN. Calcium alginate as haemostatic swabs in hip fracture surgery . J R Coll Surg Edinb 1997 ; 42 : 31 – 32 Google Scholar PubMed 15 Kaneda K , Kuroda S , Goto N et al. Is sodium alginate an alternative haemostatic material in the tooth extraction socket? J Oral Tissue Engin 2008 ; 5 : 127 – 133 16 Sharp JF , Rogers MJ , Riad M et al. Combined study to assess the role of calcium alginate swabs and ligation of the inferior tonsillar pole in the control of intra-operative blood loss during tonsillectomy . J Laryngol Otol 1991 ; 105 : 191 – 194 Google Scholar CrossRef Search ADS PubMed 17 Ingram M , Wright TA , Ingoldby CJ. A prospective randomized study of calcium alginate (Sorbsan) versus standard gauze packing following haemorrhoidectomy . J R Coll Surg Edinb 1998 ; 43 : 308 – 309 Google Scholar PubMed 18 Kukita K , Ohira S , Amano I et al. 2011 update Japanese Society for Dialysis Therapy Guidelines of Vascular Access Construction and Repair for Chronic Hemodialysis . Ther Apher Dial 2015 ; 19 : 1 – 39 Google Scholar CrossRef Search ADS PubMed 19 Misgav M , Lubetszki A , Brutman-Barazani T et al. The hemostatic efficacy of chitosan-pads in hemodialysis patients with significant bleeding tendency . J Vasc Access 2017 ; 18 : 220 – 224 Google Scholar CrossRef Search ADS PubMed 20 Blaine G. Experimental observations on absorbable alginate products in surgery . Ann Surg 1947 ; 125 : 102 – 114 Google Scholar CrossRef Search ADS PubMed 21 Mumtaz H , Williams V , Hauer-Jensen M et al. Central venous catheter placement in patients with disorders of hemostasis . Am J Surg 2000 ; 180 : 503 – 506 Google Scholar CrossRef Search ADS PubMed 22 Stone PA , Campbell JE. Complications related to femoral artery access for transcatheter procedures . Vasc Endovascular Surg 2012 ; 46 : 617 – 623 Google Scholar CrossRef Search ADS PubMed 23 Back MR , Maynard M , Winkler A et al. Expected flow parameters within hemodialysis access and selection for remedial intervention of nonmaturing conduits . Vasc Endovascular Surg 2008 ; 42 : 150 – 158 Google Scholar CrossRef Search ADS PubMed 24 Wijnen E , Keuter XH , Planken NR et al. The relation between vascular access flow and different types of vascular access with systemic hemodynamics in hemodialysis patients . Artif Organs 2005 ; 29 : 960 – 964 Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nephrology Dialysis Transplantation Oxford University Press

Vascular access management after percutaneous transluminal angioplasty using a calcium alginate sheet: a randomized controlled trial

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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0931-0509
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1460-2385
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10.1093/ndt/gfy143
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Abstract

Abstract Background Management of vascular access (VA) is essential in hemodialysis (HD) patients. However, VA often fails and percutaneous transluminal angioplasty (PTA) is required. Conventional hemostasis at the puncture site is associated with complications. This study aimed to analyze the efficacy and safety of a hemostatic wound dressing made of calcium alginate at the puncture site of VA after PTA and evaluate other factors affecting hemostasis. Methods After PTA for VA, 200 HD patients were randomized to a calcium alginate sheet (CA) group (n = 100) or a no drug-eluting sheet (control) group (n = 100). We recorded time to hemostasis at the puncture site every 5 min, noting any complications. Results In the CA group, rates of hemostatic achievement at 5, 10, 15 and >15 min were 57, 25, 8 and 10%, respectively. In the control group, the rates were 39, 28, 14 and 19%, respectively. Rates of hemostatic achievement at 5 min were significantly higher in the CA group (P = 0.01). In logistic regression analysis, factors affecting hemostasis within 5 min were use of the CA sheet [odds ratio (OR) 2.33; 95% confidence interval (CI) 1.26–4.37], platelet count ≤100 000/μL (OR 0.19; 95% CI 0.04–0.69), number of antithrombotic tablets used per day ≥1 tablet (OR 0.50; 95% CI 0.26–0.94) and upper arm VA (OR 0.16; 95% CI 0.03–0.55). Conclusions A CA sheet can safely reduce time to hemostasis at the puncture site after PTA, and should be considered for treating patients with a bleeding tendency. calcium alginate, hemodialysis, hemostasis, percutaneous transluminal angioplasty, vascular access INTRODUCTION Management of vascular access (VA) is essential for the maintenance of appropriate dialysis in hemodialysis (HD) patients [1, 2]. However, as reported previously, in 30–50% of cases, the VA fails to mature or requires an intervention shortly after creation [3–5], and percutaneous transluminal angioplasty (PTA) plays an important role in the management of VA [6, 7]. Hemostasis at the puncture site after PTA is commonly performed using conventional manual compression. However, this technique can be time consuming. Moreover, HD patients tend to be at a higher risk of bleeding compared with healthy individuals [8–10]. In some cases, it is difficult to achieve hemostasis at the puncture site of the VA after PTA. Occasionally, the time to hemostasis is even longer than the PTA time. If we achieve hemostasis in a shorter time and safely, we can relieve the patient of distress and save significant medical resources. Calcium alginate (CA) has a pronounced effect on hemostasis [11] and reduces the amount of bleeding [12–14]. One study reported that CA shortened the time to hemostasis in 54% of patients after dental treatment [15]. Conversely, other studies have reported no hemostatic effect [16, 17]. Moreover, there are no reports evaluating the safety and effectiveness of CA for hemostasis after PTA for VA dysfunction. Herein, we prospectively evaluated the effect of CA on hemostasis at the puncture site after PTA for VA dysfunction. Moreover, we evaluated other factors affecting hemostasis. MATERIALS AND METHODS Study design and patients This was a single-center, prospective, randomized controlled trial. In this study, HD patients were eligible if PTA was performed for VA dysfunction at the Tsuchiya General Hospital between 1 November 2016 and 27 July 2017 (Figure 1). During the study period, 232 HD patients with VA dysfunction underwent PTA 424 times. In patients who underwent PTA two or more times during the study period, only first PTA cases (232 times) were eligible for inclusion in this study. Moreover, the following patients (n = 32) were excluded: patients who did not consent to participate in this study (n = 18), underwent an arterial puncture (n = 4), were punctured by three or more sheaths (n = 0), had a hematoma at the puncture site during PTA (n = 4) and patients for whom the PTA procedure was considered technically unsuccessful (n = 6). Finally, 200 HD patients were enrolled in this study. This study was approved by the local ethics committee (approval number: E161024-2) and was registered with the University Hospital Medical Information Network (UMIN) Center (approval number: 000027022). All patients gave their written informed consent before PTA. The following data were recorded for eligible patients: age, sex, HD vintage, VA vintage, the primary cause of end-stage kidney disease, body mass index (BMI), comorbidities, number of oral antithrombotic tablets (clopidogrel, aspirin, cilostazol, ticlopidine hydrochloride, warfarin) used per day, platelet count, sheath size, use of urokinase, type of VA [arteriovenous fistula (AVF) or arteriovenous graft (AVG)], VA location (forearm or upper arm), blood pressure at the end of PTA, whether PTA was performed before or after HD on the same day, positional relationship between the stenosis site before PTA and the puncture site of the sheath (proximal or distal) and complications after PTA. On the day following PTA, operators conducted a visual inspection of VA (checking whether there was subcutaneous hemorrhage, swelling or exanthema in the extremity with VA) and permitted hospital discharge after confirming that there were no evident complications. In all patients, VA cannulation was performed by the rope-ladder technique with sharp needles during each HD session. FIGURE 1: View largeDownload slide Study flow diagram. FIGURE 1: View largeDownload slide Study flow diagram. VA monitoring and identification of VA dysfunction before PTA In accordance with Japanese Society for Dialysis Therapy Guidelines of Vascular Access Construction and Repair for Chronic Hemodialysis [18], VA monitoring was performed at every HD session. When abnormal physiological findings for thrill, murmur, palpation, venous pressure, extended time for hemostasis, swelling in the fistula limb or pillow condition were detected at HD session, VA scan examinations using ultrasonography were carried out for the patients. The scan protocol included ‘flow volume (FV) and resistance index (RI) of brachial artery’ and ‘minimum internal diameter (MID) of venous stenosis site’ of VA. The critical values of measured FV, RI and MID were defined as the following: FV <300 mL/min; RI >0.60; MID <1.60 mm. When the critical value of FV, RI or MID was detected, VA dysfunction requiring PTA was identified. PTA technique and hemostatic procedures PTA was performed for VA dysfunction (stenosis, n = 164; occlusion, n = 36) during the study period. Occlusion was defined as blood flow interruption by thrombus. PTA for VA dysfunction was executed as follows. VA was punctured with the puncture needles; then, lidocaine 1% was subcutaneously injected at the puncture site before insertion of the sheath. Sheaths of 4, 5, 5.5, 6 or 7 French (F) were inserted, and then 3000 units of heparin were administered. Guide wire (GW) and balloon size were determined according to angiographic findings. After insertion of the GW (0.018 or 0.035 inch in size), balloons (4–6 mm in size) were inflated to a pressure of 2–30 atmospheres for 30–60 s several times. At the end of the PTA, an angiogram was performed, and the PTA procedure was considered technically successful when the residual stenosis was <30%. In all cases of occlusion, urokinase [the mean amount was 59 000 (range 20 000–120 000) units] was scattered to the thrombus using an infusion catheter with multiple side holes to administer therapeutic solutions into the peripheral vasculature (Mistique®, Merit Medical Systems Inc., South Jordan, UT, USA) before the angiogram and balloon inflation. We used a nepcell S® (Alliance Medical Group, Tokyo, Japan) as the hemostatic dressing, which consists of CA extracted from a seaweed called giant kelp. Patients were assigned to either the CA sheet group (n = 100) or the non-drug sheet (control) group (n = 100) using random permuted blocks (block size = 4) with computer-generated random digits (Figure 1). The random digits were generated using R version 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria). Operators performing hemostatic procedures were not informed whether patients were in the CA or control group until the end of PTA. At the end of PTA, the nurse gave the operator the CA or control sheet according to the random assignment. If two sheaths were used, only the one closest to the anastomosis was included in the analysis. The operator placed the sheet on the boundary between the sheath and skin, then removed the sheath using manual compression, and, simultaneously, the nurse started to measure the time with a stopwatch. Hemostatic procedures were performed by applying mild, digital direct pressure over the needle sites, using a two-digit technique, one finger at the skin (external) and one finger at the blood vessel wall (internal). Hemostatic achievement was checked every 5 min by removing the sheet. If the bleeding was persistent at the checkpoint, compression was resumed instantly. If bleeding continued for more than 15 min, additional manual compression or sutures were applied. After hemostasis, the puncture site was covered with a sticking plaster without the additional use of a pressure bandage. Outcomes The primary outcome was the rate of hemostatic achievement at 5 , 10 , 15  and >15 min after the start of hemostatic procedure. The secondary outcome was the rate of the following complications: rebleeding, allergic reaction, anaphylactic shock and false aneurysm at the puncture site until patient discharge. Statistical analyses Data were analyzed using JMP® 5.1 (SAS Institute Inc., Cary, NC, USA) and Microsoft Excel 2013 software, and were expressed as either the number of patients or percentage of the study population. The remaining data were expressed as the mean ± SD. The Student’s t-test and chi-square test were used for continuous and categorical variables, respectively. After univariate analysis, a multivariate logistic regression analysis was performed to evaluate factors potentially influencing hemostasis, adjusted for patient age (≥75 years old or <75 years old), sex, HD vintage [≥92 months or <92 months (92 was the mean value of the enrolled patients)], diabetes mellitus, use of urokinase, use of CA, platelet count (≤100 000/μL or >100 000/μL), number of antithrombotic tablets used per day (≥1 tablet or 0), VA location (forearm or upper arm) and sheath size (≥5.5 F or ≤5 F). The results of the regression model were depicted as the odds ratio (OR) and 95% confidence interval (CI). In all analyses, P-values <0.05 were considered statistically significant. RESULTS Demographic data and clinical characteristics before PTA are shown in Table 1. During the study period, 200 patients were randomized (100 in the CA group and 100 in the control group). Of the 200 patients, 164 and 36 underwent PTA for VA stenosis and occlusion, respectively. The mean PTA time in all cases was 59.6 ± 38.3 min (n = 200), and the mean PTA time in occlusion cases (use of urokinase) was 96.7 ± 45.8 min (n = 36). Demographic data and clinical characteristics before PTA were similar between the two groups. Table 1. Patient characteristics Variables CA Control P (n = 100) (n = 100) Age, years 70.2 ± 12.4 71.1 ± 12.0 0.6 Male, n (%) 60 (60) 58 (58) 0.7 BMI, kg/m2 21.7 ± 3.7 21.4 ± 3.7 0.5 HD vintage, months 85.5 ± 77.2 99.4 ± 92.6 0.2 PTA time, min 57.6 ± 39.4 61.7 ± 37.3 0.4 VA vintage, months 60.5 ± 54.4a 66.5 ± 55.6b 0.5 Occlusion (use of urokinase), n (%) 20 (20) 16 (16) 0.5 AVF/AVG, n 95/5 93/7 0.6 Forearm/upper arm VA, n 90/10 90/10 1.0 Sheath diameter, ≤5/≥5.5 F, n 91/9 89/11 0.6 Number of antithrombotic tablets used per day ≥1 tablet, n (%) 63 (63) 55 (55) 0.2 Platelet count, per μL 18.0 ± 5.2 18.4 ± 6.9 0.6 Primary cause of ESKD   Diabetes mellitus, n (%) 47 (47) 49 (49) 0.8   Chronic glomerulonephritis, n (%) 27 (27) 26 (26) 0.9   Nephrosclerosis, n (%) 13 (13) 10 (10) 0.5   Others, n (%) 7 (7) 7 (7) 1.0   Unknown, n (%) 6 (6) 8 (8) 0.6 PTA after HDc, n (%) 3 (3) 6 (6) 0.3 Stenosis proximal to puncture site of sheath before PTA, n (%) 15 (15) 10 (10) 0.3 Residual stenosis of ≥30%, n (%) 0 (0) 0 (0) 1.0 Variables CA Control P (n = 100) (n = 100) Age, years 70.2 ± 12.4 71.1 ± 12.0 0.6 Male, n (%) 60 (60) 58 (58) 0.7 BMI, kg/m2 21.7 ± 3.7 21.4 ± 3.7 0.5 HD vintage, months 85.5 ± 77.2 99.4 ± 92.6 0.2 PTA time, min 57.6 ± 39.4 61.7 ± 37.3 0.4 VA vintage, months 60.5 ± 54.4a 66.5 ± 55.6b 0.5 Occlusion (use of urokinase), n (%) 20 (20) 16 (16) 0.5 AVF/AVG, n 95/5 93/7 0.6 Forearm/upper arm VA, n 90/10 90/10 1.0 Sheath diameter, ≤5/≥5.5 F, n 91/9 89/11 0.6 Number of antithrombotic tablets used per day ≥1 tablet, n (%) 63 (63) 55 (55) 0.2 Platelet count, per μL 18.0 ± 5.2 18.4 ± 6.9 0.6 Primary cause of ESKD   Diabetes mellitus, n (%) 47 (47) 49 (49) 0.8   Chronic glomerulonephritis, n (%) 27 (27) 26 (26) 0.9   Nephrosclerosis, n (%) 13 (13) 10 (10) 0.5   Others, n (%) 7 (7) 7 (7) 1.0   Unknown, n (%) 6 (6) 8 (8) 0.6 PTA after HDc, n (%) 3 (3) 6 (6) 0.3 Stenosis proximal to puncture site of sheath before PTA, n (%) 15 (15) 10 (10) 0.3 Residual stenosis of ≥30%, n (%) 0 (0) 0 (0) 1.0 Data are expressed as the mean ± SD, numbers and percentages for variables. an = 96 (CA group); bn = 96 (control group); cof the 200 patients, 144 underwent PTA on a day without HD, and 9 underwent PTA at 3–4 h after the HD session (CA group = 3, control group = 6; P = 0.3). These nine patients were administered 1000 units of heparin at the start and 500 units of heparin/h during HD. ESKD, end-stage kidney disease. Table 1. Patient characteristics Variables CA Control P (n = 100) (n = 100) Age, years 70.2 ± 12.4 71.1 ± 12.0 0.6 Male, n (%) 60 (60) 58 (58) 0.7 BMI, kg/m2 21.7 ± 3.7 21.4 ± 3.7 0.5 HD vintage, months 85.5 ± 77.2 99.4 ± 92.6 0.2 PTA time, min 57.6 ± 39.4 61.7 ± 37.3 0.4 VA vintage, months 60.5 ± 54.4a 66.5 ± 55.6b 0.5 Occlusion (use of urokinase), n (%) 20 (20) 16 (16) 0.5 AVF/AVG, n 95/5 93/7 0.6 Forearm/upper arm VA, n 90/10 90/10 1.0 Sheath diameter, ≤5/≥5.5 F, n 91/9 89/11 0.6 Number of antithrombotic tablets used per day ≥1 tablet, n (%) 63 (63) 55 (55) 0.2 Platelet count, per μL 18.0 ± 5.2 18.4 ± 6.9 0.6 Primary cause of ESKD   Diabetes mellitus, n (%) 47 (47) 49 (49) 0.8   Chronic glomerulonephritis, n (%) 27 (27) 26 (26) 0.9   Nephrosclerosis, n (%) 13 (13) 10 (10) 0.5   Others, n (%) 7 (7) 7 (7) 1.0   Unknown, n (%) 6 (6) 8 (8) 0.6 PTA after HDc, n (%) 3 (3) 6 (6) 0.3 Stenosis proximal to puncture site of sheath before PTA, n (%) 15 (15) 10 (10) 0.3 Residual stenosis of ≥30%, n (%) 0 (0) 0 (0) 1.0 Variables CA Control P (n = 100) (n = 100) Age, years 70.2 ± 12.4 71.1 ± 12.0 0.6 Male, n (%) 60 (60) 58 (58) 0.7 BMI, kg/m2 21.7 ± 3.7 21.4 ± 3.7 0.5 HD vintage, months 85.5 ± 77.2 99.4 ± 92.6 0.2 PTA time, min 57.6 ± 39.4 61.7 ± 37.3 0.4 VA vintage, months 60.5 ± 54.4a 66.5 ± 55.6b 0.5 Occlusion (use of urokinase), n (%) 20 (20) 16 (16) 0.5 AVF/AVG, n 95/5 93/7 0.6 Forearm/upper arm VA, n 90/10 90/10 1.0 Sheath diameter, ≤5/≥5.5 F, n 91/9 89/11 0.6 Number of antithrombotic tablets used per day ≥1 tablet, n (%) 63 (63) 55 (55) 0.2 Platelet count, per μL 18.0 ± 5.2 18.4 ± 6.9 0.6 Primary cause of ESKD   Diabetes mellitus, n (%) 47 (47) 49 (49) 0.8   Chronic glomerulonephritis, n (%) 27 (27) 26 (26) 0.9   Nephrosclerosis, n (%) 13 (13) 10 (10) 0.5   Others, n (%) 7 (7) 7 (7) 1.0   Unknown, n (%) 6 (6) 8 (8) 0.6 PTA after HDc, n (%) 3 (3) 6 (6) 0.3 Stenosis proximal to puncture site of sheath before PTA, n (%) 15 (15) 10 (10) 0.3 Residual stenosis of ≥30%, n (%) 0 (0) 0 (0) 1.0 Data are expressed as the mean ± SD, numbers and percentages for variables. an = 96 (CA group); bn = 96 (control group); cof the 200 patients, 144 underwent PTA on a day without HD, and 9 underwent PTA at 3–4 h after the HD session (CA group = 3, control group = 6; P = 0.3). These nine patients were administered 1000 units of heparin at the start and 500 units of heparin/h during HD. ESKD, end-stage kidney disease. In the CA group, the proportions of hemostatic achievement at 5, 10, 15 and >15 min after the start of the hemostatic procedure were 57% (n = 57), 25% (n = 25), 8% (n = 8) and 10% (n = 10), respectively. In the control group, the proportions were 39% (n = 39), 28% (n = 28), 14% (n = 14) and 19% (n = 19), respectively (Figure 2). The proportions of hemostatic achievement within 5 min were significantly higher in the CA group compared with the control group (P = 0.01). The rates of rebleeding after hemostasis were similar between the two groups: six (6%) and seven (7%) episodes were identified in the CA and control groups, respectively (P = 0.7). In all rebleeding cases, complete hemostasis was achieved using further manual compression. No serious complications, such as anaphylactic shock, bleeding refractory to manual compression, cutaneous allergy or false aneurysm at the puncture site were identified in the two groups. FIGURE 2: View largeDownload slide Distributions of time to hemostasis at the puncture site after PTA in the CA and control groups. *P = 0.01. FIGURE 2: View largeDownload slide Distributions of time to hemostasis at the puncture site after PTA in the CA and control groups. *P = 0.01. In the univariate analysis (Table 2), the OR for use of the CA sheet for hemostasis within 5 min was significantly high (OR 2.07; 95% CI 1.18–3.66; P = 0.01). On the other hand, ORs of the following variables for hemostasis within 5 min were significantly low: platelet count  ≤100 000/μL (OR 0.22; 95% CI 0.05–0.72; P = 0.02), sheath size ≥5.5 F (OR 0.32; 95% CI 0.10–0.88; P = 0.04) and upper arm VA (OR 0.16; 95% CI 0.03–0.51; P = 0.01). The other variables were not determinant. Table 2. Univariate analysis of predictors for hemostasis of sheath puncture site after PTA Variables OR 95% CI P Age ≥75 years 0.66 0.37–1.17 0.2 Male 1.32 0.75–2.33 0.3 HD vintage ≥92 months 1.13 0.63–2.02 0.7 Primary cause of ESKD   Diabetes mellitus 1.26 0.72–2.21 0.4   CGN 0.81 0.33–1.94 0.6 Occlusion (use of urokinase) 1.08 0.35–3.30 0.9 Use of CA sheet 2.07 1.18–3.66 0.01 PTA time ≥60 min 0.89 0.50–1.57 0.7 Platelet count ≤100 000/μL 0.22 0.05–0.72 0.02 Number of antithrombotic  tablets used per day ≥1 tablet 0.57 0.32–1.01 0.06 Upper arm VA 0.16 0.03–0.51 0.01 Sheath diameter ≥ 5.5 F 0.32 0.10–0.88 0.04 Systolic blood pressure after  PTA ≥180 mmHg 1.22 0.47–3.22 0.7 PTA after HD 0.86 0.20–3.34 0.8 Stenosis proximal to puncture  site of sheath 0.46 0.18–1.10 0.09 Variables OR 95% CI P Age ≥75 years 0.66 0.37–1.17 0.2 Male 1.32 0.75–2.33 0.3 HD vintage ≥92 months 1.13 0.63–2.02 0.7 Primary cause of ESKD   Diabetes mellitus 1.26 0.72–2.21 0.4   CGN 0.81 0.33–1.94 0.6 Occlusion (use of urokinase) 1.08 0.35–3.30 0.9 Use of CA sheet 2.07 1.18–3.66 0.01 PTA time ≥60 min 0.89 0.50–1.57 0.7 Platelet count ≤100 000/μL 0.22 0.05–0.72 0.02 Number of antithrombotic  tablets used per day ≥1 tablet 0.57 0.32–1.01 0.06 Upper arm VA 0.16 0.03–0.51 0.01 Sheath diameter ≥ 5.5 F 0.32 0.10–0.88 0.04 Systolic blood pressure after  PTA ≥180 mmHg 1.22 0.47–3.22 0.7 PTA after HD 0.86 0.20–3.34 0.8 Stenosis proximal to puncture  site of sheath 0.46 0.18–1.10 0.09 ESKD, end-stage kidney disease; CGN, chronic glomerulonephritis. Table 2. Univariate analysis of predictors for hemostasis of sheath puncture site after PTA Variables OR 95% CI P Age ≥75 years 0.66 0.37–1.17 0.2 Male 1.32 0.75–2.33 0.3 HD vintage ≥92 months 1.13 0.63–2.02 0.7 Primary cause of ESKD   Diabetes mellitus 1.26 0.72–2.21 0.4   CGN 0.81 0.33–1.94 0.6 Occlusion (use of urokinase) 1.08 0.35–3.30 0.9 Use of CA sheet 2.07 1.18–3.66 0.01 PTA time ≥60 min 0.89 0.50–1.57 0.7 Platelet count ≤100 000/μL 0.22 0.05–0.72 0.02 Number of antithrombotic  tablets used per day ≥1 tablet 0.57 0.32–1.01 0.06 Upper arm VA 0.16 0.03–0.51 0.01 Sheath diameter ≥ 5.5 F 0.32 0.10–0.88 0.04 Systolic blood pressure after  PTA ≥180 mmHg 1.22 0.47–3.22 0.7 PTA after HD 0.86 0.20–3.34 0.8 Stenosis proximal to puncture  site of sheath 0.46 0.18–1.10 0.09 Variables OR 95% CI P Age ≥75 years 0.66 0.37–1.17 0.2 Male 1.32 0.75–2.33 0.3 HD vintage ≥92 months 1.13 0.63–2.02 0.7 Primary cause of ESKD   Diabetes mellitus 1.26 0.72–2.21 0.4   CGN 0.81 0.33–1.94 0.6 Occlusion (use of urokinase) 1.08 0.35–3.30 0.9 Use of CA sheet 2.07 1.18–3.66 0.01 PTA time ≥60 min 0.89 0.50–1.57 0.7 Platelet count ≤100 000/μL 0.22 0.05–0.72 0.02 Number of antithrombotic  tablets used per day ≥1 tablet 0.57 0.32–1.01 0.06 Upper arm VA 0.16 0.03–0.51 0.01 Sheath diameter ≥ 5.5 F 0.32 0.10–0.88 0.04 Systolic blood pressure after  PTA ≥180 mmHg 1.22 0.47–3.22 0.7 PTA after HD 0.86 0.20–3.34 0.8 Stenosis proximal to puncture  site of sheath 0.46 0.18–1.10 0.09 ESKD, end-stage kidney disease; CGN, chronic glomerulonephritis. In the multivariate logistic regression analysis (Table 3), use of the CA sheet (OR 2.33; 95% CI 1.26–4.37; P = 0.007), platelet count  ≤100 000/μL (OR 0.19; 95% CI 0.04–0.69; P = 0.02), number of antithrombotic tablets used per day  ≥1 tablet (OR 0.50; 95% CI 0.26–0.94; P = 0.03) and VA location (OR for upper arm VA 0.16; 95% CI 0.03–0.55; P = 0.008) were independent predictors of time to hemostasis within 5 min. The other variables were not determinant. Table 3. Multivariate analysis of predictors for hemostasis of sheath puncture site after PTA Variables OR 95% CI P Age ≥75 years 0.78 0.41–1.49 0.5 Male 1.56 0.83–2.96 0.2 HD vintage ≥92 months 1.53 0.79–3.02 0.2 Diabetes mellitus 1.11 0.59–2.09 0.7 Occlusion (use of urokinase) 1.01 0.28–3.69 0.97 Use of CA sheet 2.33 1.26–4.37 0.007 Platelet count ≤100 000/μL 0.19 0.04–0.69 0.02 Number of antithrombotic tablets  used per day ≥1 tablet 0.50 0.26–0.94 0.03 Upper arm VA 0.16 0.03–0.55 0.008 Sheath diameter ≥5.5 F 0.51 0.15–1.54 0.3 Variables OR 95% CI P Age ≥75 years 0.78 0.41–1.49 0.5 Male 1.56 0.83–2.96 0.2 HD vintage ≥92 months 1.53 0.79–3.02 0.2 Diabetes mellitus 1.11 0.59–2.09 0.7 Occlusion (use of urokinase) 1.01 0.28–3.69 0.97 Use of CA sheet 2.33 1.26–4.37 0.007 Platelet count ≤100 000/μL 0.19 0.04–0.69 0.02 Number of antithrombotic tablets  used per day ≥1 tablet 0.50 0.26–0.94 0.03 Upper arm VA 0.16 0.03–0.55 0.008 Sheath diameter ≥5.5 F 0.51 0.15–1.54 0.3 Table 3. Multivariate analysis of predictors for hemostasis of sheath puncture site after PTA Variables OR 95% CI P Age ≥75 years 0.78 0.41–1.49 0.5 Male 1.56 0.83–2.96 0.2 HD vintage ≥92 months 1.53 0.79–3.02 0.2 Diabetes mellitus 1.11 0.59–2.09 0.7 Occlusion (use of urokinase) 1.01 0.28–3.69 0.97 Use of CA sheet 2.33 1.26–4.37 0.007 Platelet count ≤100 000/μL 0.19 0.04–0.69 0.02 Number of antithrombotic tablets  used per day ≥1 tablet 0.50 0.26–0.94 0.03 Upper arm VA 0.16 0.03–0.55 0.008 Sheath diameter ≥5.5 F 0.51 0.15–1.54 0.3 Variables OR 95% CI P Age ≥75 years 0.78 0.41–1.49 0.5 Male 1.56 0.83–2.96 0.2 HD vintage ≥92 months 1.53 0.79–3.02 0.2 Diabetes mellitus 1.11 0.59–2.09 0.7 Occlusion (use of urokinase) 1.01 0.28–3.69 0.97 Use of CA sheet 2.33 1.26–4.37 0.007 Platelet count ≤100 000/μL 0.19 0.04–0.69 0.02 Number of antithrombotic tablets  used per day ≥1 tablet 0.50 0.26–0.94 0.03 Upper arm VA 0.16 0.03–0.55 0.008 Sheath diameter ≥5.5 F 0.51 0.15–1.54 0.3 Furthermore, in the multivariate analysis including only the determinants identified in the univariate analysis, the results were similar to those found in the multivariate analysis including all 10 factors (Supplementary data, Table S1). DISCUSSION Maintenance of VA function is essential for keeping adequate doses of dialysis in HD patients. PTA is the most common treatment for VA dysfunction. A high percentage of HD patients are elderly, take several types of antithrombotic drugs and have a tendency to bleed [19]. Shortening time to hemostasis after PTA can reduce the medical resources needed and relieve patients of their distress promptly. In this study, we proved that CA shortened the time to hemostasis after PTA. CA, a kind of alginic acid, is used as a hemostatic agent in the medical field, e.g. as a hemostatic material after endoscopic biopsy and as a wound dressing material. In this study, after multivariate adjustment for factors potentially influencing hemostasis, only the use of a CA sheet promoted hemostasis after PTA. Our findings support the hemostatic effect of CA reported in a previous study [20]. Conversely, platelet count  ≤100 000/μL, number of antithrombotic tablets used per day  ≥1 tablet and upper arm VA were independently associated with increased time to hemostasis. In two previous studies, low platelet count and antithrombotic drugs were both associated with bleeding after intra-vascular treatment and intra-arterial treatment, respectively [21, 22]. Previous studies showed that upper arm VA was associated with greater FV than forearm access [23, 24], and this may be the reason why hemostasis was more difficult to achieve with upper arm VA. Unexpectedly, there was no relationship between use of urokinase and time to hemostasis at the puncture site after PTA. This finding may be explained by the fact that the half-life time of urokinase is 3–26 min, whereas mean PTA time in cases with VA occlusion (with use of urokinase) was 96.7 min. Moreover, most of the urokinase was used during the early phase of PTA. Therefore, the thrombolytic function of urokinase may have been attenuated by the end of PTA. To summarize the above analysis, preventing factors for hemostasis were platelet count  ≤100 000/μL, number of antithrombotic tablets used per day  ≥1 tablet and upper arm VA. Therefore, we recommend that CA should be used after PTA in patients with these risk factors. This study had many strengths. It was a prospective, randomized controlled trial for hemostasis after PTA. Because the analysis took place in a single hospital, it enabled us to advocate for changes that should be implemented to the policies that surround VA management strategies. In addition, use of a CA sheet, which was evaluated to determine its efficacy and safety for hemostasis, is a simple procedure. Moreover, we also evaluated other factors affecting hemostasis. Therefore, the current study can guide clinical management practices for achievement of hemostasis after PTA. This study had several limitations. First, this study was based on a group of patients being treated at a single center and the sample size was small. However, this study was a randomized trial, and the baseline characteristics between the two groups were similar (Table 1). Second, the operators who performed hemostasis after PTA may have known whether a CA sheet or control sheet was used, because this study was open label. Therefore, we assessed the achievement of hemostasis every 5 min in both groups. If the operators were allowed to check the hemostasis at any time, this may have resulted in different hemostasis checking times in the two groups. Third, we did not identify the exact time to hemostasis in cases where time to hemostasis was >15 min. Therefore, we did not identify the actual time to hemostasis after PTA. Fourth, evaluation of false aneurysm at the puncture site of VA was not performed by ultrasonography. The operators visually evaluated the puncture site on the day following PTA. The search for false aneurysms may, thus, not have been performed accurately. Finally, we did not measure laboratory coagulation parameters, such as prothrombin time, activated partial thromboplastin time and activated clotting time. Despite these limitations, there are no previous reports that examine the effect of the CA after PTA for VA dysfunction; therefore, this study is valuable relative to the existing information in the field. In conclusion, CA safely reduced time to hemostasis at the VA puncture site after PTA for VA dysfunction. Other factors affecting hemostasis were platelet count, antithrombotic drugs and VA location. Our findings can guide clinical management practices for achievement of hemostasis at the VA puncture site after PTA in HD patients. SUPPLEMENTARY DATA Supplementary data are available at ndt online. CONFLICT OF INTEREST STATEMENT None declared. REFERENCES 1 Ethier J , Mendelssohn DC , Elder SJ. Vascular access use and outcomes: an international perspective from the Dialysis Outcomes and Practice Patterns Study . Nephrol Dial Transplant 2008 ; 23 : 3219 – 3226 Google Scholar CrossRef Search ADS PubMed 2 Windus DW. Permanent vascular access: a nephrologist’s view . Am J Kidney Dis 1993 ; 21 : 457 – 471 Google Scholar CrossRef Search ADS PubMed 3 Schinstock CA , Albright RC , Williams AW et al. Outcomes of arteriovenous fistula creation after the Fistula First Initiative . Clin J Am Soc Nephrol 2011 ; 6 : 1996 – 2002 Google Scholar CrossRef Search ADS PubMed 4 Bashar K , Zafar A , Elsheikh S et al. Predictive parameters of arteriovenous fistula functional maturation in a population of patients with end-stage renal disease . Plos One 2015 ; 10 : e0119958 Google Scholar CrossRef Search ADS PubMed 5 Pisoni R , Barker-Finkel J , Allo M. Statin therapy is not associated with improved vascular access outcomes . Clin J Am Soc Nephrol 2010 ; 5 : 1447 – 1450 Google Scholar CrossRef Search ADS PubMed 6 Burger H , Zijlstra JJ , Kluchert SA et al. Percutaneous transluminal angioplasty improves longevity in fistulae and shunts for haemodialysis . Nephrol Dial Transplant 1990 ; 5 : 608 – 611 Google Scholar CrossRef Search ADS PubMed 7 Kumano S , Itatani K , Shiota J et al. Strategies for the creation and maintenance of reconstructed arteriovenous fistulas using the forearm basilic vein . Ther Apher Dial 2013 ; 17 : 504 – 509 Google Scholar PubMed 8 Kuo CC , Kuo HW , Lee IM et al. The risk of upper gastrointestinal bleeding in patients treated with hemodialysis: a population-based cohort study . BMC Nephrol 2013 ; 14 : 15 Google Scholar CrossRef Search ADS PubMed 9 Wakasugi M , Matsuo K , Kazama JJ et al. Higher mortality due to intracerebral hemorrhage in dialysis patients: a comparison with the general population in Japan . Ther Apher Dial 2015 ; 19 : 45 – 49 Google Scholar CrossRef Search ADS PubMed 10 Numasawa Y , Kohsaka S , Ueda I et al. Incidence and predictors of bleeding complications after percutaneous coronary intervention . J Cardiol 2017 ; 69 : 272 – 279 Google Scholar CrossRef Search ADS PubMed 11 Blair SD , Backhouse CM , Harper R et al. Comparison of absorbable materials for surgical haemostasis . Br J Surg 1988 ; 75 : 969 – 971 Google Scholar CrossRef Search ADS PubMed 12 Blair SD , Jarvis P , Salmon M et al. Clinical trial of calcium alginate haemostatic swabs . Br J Surg 1990 ; 77 : 568 – 570 Google Scholar CrossRef Search ADS PubMed 13 Taskin AK , Yasar M , Ozaydin I et al. The hemostatic effect of calcium alginate in experimental splenic injury model . Ulus Travma Acil Cerrahi Derg 2013 ; 19 : 195 – 199 Google Scholar CrossRef Search ADS PubMed 14 Davies MS , Flannery MC , McCollum CN. Calcium alginate as haemostatic swabs in hip fracture surgery . J R Coll Surg Edinb 1997 ; 42 : 31 – 32 Google Scholar PubMed 15 Kaneda K , Kuroda S , Goto N et al. Is sodium alginate an alternative haemostatic material in the tooth extraction socket? J Oral Tissue Engin 2008 ; 5 : 127 – 133 16 Sharp JF , Rogers MJ , Riad M et al. Combined study to assess the role of calcium alginate swabs and ligation of the inferior tonsillar pole in the control of intra-operative blood loss during tonsillectomy . J Laryngol Otol 1991 ; 105 : 191 – 194 Google Scholar CrossRef Search ADS PubMed 17 Ingram M , Wright TA , Ingoldby CJ. A prospective randomized study of calcium alginate (Sorbsan) versus standard gauze packing following haemorrhoidectomy . J R Coll Surg Edinb 1998 ; 43 : 308 – 309 Google Scholar PubMed 18 Kukita K , Ohira S , Amano I et al. 2011 update Japanese Society for Dialysis Therapy Guidelines of Vascular Access Construction and Repair for Chronic Hemodialysis . Ther Apher Dial 2015 ; 19 : 1 – 39 Google Scholar CrossRef Search ADS PubMed 19 Misgav M , Lubetszki A , Brutman-Barazani T et al. The hemostatic efficacy of chitosan-pads in hemodialysis patients with significant bleeding tendency . J Vasc Access 2017 ; 18 : 220 – 224 Google Scholar CrossRef Search ADS PubMed 20 Blaine G. Experimental observations on absorbable alginate products in surgery . Ann Surg 1947 ; 125 : 102 – 114 Google Scholar CrossRef Search ADS PubMed 21 Mumtaz H , Williams V , Hauer-Jensen M et al. Central venous catheter placement in patients with disorders of hemostasis . Am J Surg 2000 ; 180 : 503 – 506 Google Scholar CrossRef Search ADS PubMed 22 Stone PA , Campbell JE. Complications related to femoral artery access for transcatheter procedures . Vasc Endovascular Surg 2012 ; 46 : 617 – 623 Google Scholar CrossRef Search ADS PubMed 23 Back MR , Maynard M , Winkler A et al. Expected flow parameters within hemodialysis access and selection for remedial intervention of nonmaturing conduits . Vasc Endovascular Surg 2008 ; 42 : 150 – 158 Google Scholar CrossRef Search ADS PubMed 24 Wijnen E , Keuter XH , Planken NR et al. The relation between vascular access flow and different types of vascular access with systemic hemodynamics in hemodialysis patients . Artif Organs 2005 ; 29 : 960 – 964 Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Nephrology Dialysis TransplantationOxford University Press

Published: May 28, 2018

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