The effect of citrate dialysate on intradialytic heparin dose in haemodialysis patients: study design of a randomised controlled trial.

BACKGROUND: Unfractionated heparin is the most common anticoagulant used in haemodialysis (HD), although it has many potential adverse effects. Citrate dialysate (CD) has an anticoagulant effect which may allow reduction in cumulative heparin dose (CHD) compared to standard acetate dialysate (AD). METHODS: This double-blinded, randomised, cross-over trial of chronic haemodialysis patients determines if CD allows reduction in CHD during HD compared with AD. After enrolment, intradialytic heparin is minimised during a two-week run-in period using a standardised protocol based on a visual clotting score. Patients still requiring intradialytic heparin after the run-in period are randomised to two weeks of HD with AD followed by two weeks of CD (Sequence 1) or two weeks of HD with CD followed by two weeks of AD (Sequence 2). The primary outcome is the change in CHD with CD compared with AD. Secondary outcomes include metabolic and haemodynamic parameters, and dialysis adequacy. DISCUSSION: This randomised controlled trial will determine the impact of CD compared with AD on CHD during HD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01466959.

Associations between hemodialysis access type and clinical outcomes: a systematic review.

Clinical practice guidelines recommend an arteriovenous fistula as the preferred vascular access for hemodialysis, but quantitative associations between vascular access type and various clinical outcomes remain controversial. We performed a systematic review of cohort studies to evaluate the associations between type of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) and risk for death, infection, and major cardiovascular events. We searched MEDLINE, EMBASE, and article reference lists and extracted data describing study design, participants, vascular access type, clinical outcomes, and risk for bias. We identified 3965 citations, of which 67 (62 cohort studies comprising 586,337 participants) met our inclusion criteria. In a random effects meta-analysis, compared with persons with fistulas, those individuals using catheters had higher risks for all-cause mortality (risk ratio=1.53, 95% CI=1.41-1.67), fatal infections (2.12, 1.79-2.52), and cardiovascular events (1.38, 1.24-1.54). Similarly, compared with persons with grafts, those individuals using catheters had higher risks for mortality (1.38, 1.25-1.52), fatal infections (1.49, 1.15-1.93), and cardiovascular events (1.26, 1.11-1.43). Compared with persons with fistulas, those individuals with grafts had increased all-cause mortality (1.18, 1.09-1.27) and fatal infection (1.36, 1.17-1.58), but we did not detect a difference in the risk for cardiovascular events (1.07, 0.95-1.21). The risk for bias, especially selection bias, was high. In conclusion, persons using catheters for hemodialysis seem to have the highest risks for death, infections, and cardiovascular events compared with other vascular access types, and patients with usable fistulas have the lowest risk.

Pneumatic compression devices during hemodialysis: a randomized crossover trial.

BACKGROUND: Maintenance of central blood volume (CBV) is essential for hemodynamic stability during hemodialysis (HD), though preservation of CBV is poorly understood. Pneumatic compression devices (PCDs) during HD may help maintain CBV. METHODS: We performed a randomized, crossover trial to determine the effect of PCDs on CBV during HD. Patients underwent two consecutive mid-week HD sessions, randomized to begin the first session either with or without PCDs [stratified by intradialytic hypotension (IDH)-prone status]. The primary outcome was change in CBV during HD. The secondary outcomes were change in other hemodynamic and volume status parameters. RESULTS: Fifty-one patients (median age 65 years, 75% male, 22% IDH-prone) were randomized; forty-six completed the study. During HD, the median change in CBV for PCD and control sessions was -0.08 versus -0.05 L (P = 0.62). There was no difference in the change in cardiac output (CO) (-0.63 versus -0.49 L/min, P = 0.78) or systemic vascular resistance (SVR) (+1.30 versus +1.55 mmHg/L/min, P = 0.67) for PCDs versus control. Based on the bioimpedance measurements, patients were not volume overloaded pre-dialysis. There was a greater reduction in total body water (TBW) (-2.6 versus -2.3 L, P = 0.05) and intracellular fluid (ICF) volume (-1.3 versus -1.1 L, P = 0.03), and no difference in change in the extracellular fluid (ECF) volume (1.3 versus 1.2 L, P = 0.09) with PCDs versus control. Similar results were observed in IDH-prone patients. CONCLUSIONS: Compared with standard of care, PCDs have no effect on intradialytic hemodynamic parameters, including CBV, although they may allow greater capacity for fluid removal. Further studies are required to better understand physiological and hemodynamic changes in patients during HD.

Citrate vs. acetate dialysate on intradialytic heparin dose: A double blind randomized crossover study.

Introduction Citrate containing dialysate has a calcium-binding anticoagulant effect compared to standard acetic acid containing dialysate. We performed a randomized, double-blind, crossover trial in maintenance HD patients to determine if citrate dialysate ("citrate") safely allows for a lower cumulative heparin dose ("heparin dose"). Methods Intradialytic heparin was adjusted to the minimum during a 2-week run-in phase. Patients remaining on heparin at the end of the run-in phase were then randomized to two weeks of HD with acetate dialysate ("acetate") followed by two weeks of citrate (sequence 1) or two weeks of citrate followed by two weeks of acetate (sequence 2). We estimated a minimum of 14 patients are required to show a 30% reduction in heparin dose per HD session with citrate compared with acetate. Twenty-five patients entered the run-in phase, 20 were randomized, and 19 completed the study. Findings The mean heparin dose was reduced by 19% (656 units, 95% CI -174 to -1139 units, P = 0.011) in the acetate group, and 30% (1046 units 95% CI -498 to 1594 units, P < 0.001) in the citrate group. There was no difference in the mean heparin dose reduction between the two dialysates (P > 0.05). The intradialytic ionized calcium in the citrate group was lowered by 0.10 mmol/L (95% CI 0.07 to 0.14 mmol/L, P < 0.001), and remained unchanged in the acetate group. Discussion Although citrate is a safe alternative to acetate, it does not result in additional heparin dose reduction.

Hemodialysis prescription education decreases intradialytic hypotension.

BACKGROUND: Intradialytic hypotension (IDH) is associated with increased morbidity and mortality. We studied the impact of an education program and hemodialysis (HD) prescription optimization on the frequency of IDH. METHODS: We compared chronic HD patients during 2 retrospective time periods: a control period and the study period which occurred after 2 months of physician education and HD prescription optimization. Primary study outcomes were the frequency of HD sessions complicated by IDH, and the prevalence of IDH-prone patients. RESULTS: There were 91 and 82 patients in the control and study periods, respectively. In the study period, 11% (115/1107) of HD sessions were complicated by IDH vs. 17% (189/1103) in the control period (p = 0.0002). There was a decreased odds ratio for IDH in the study period compared with control (odds ratio [OR] = 0.59; 95% confidence interval [95% CI], 0.40-0.86; p = 0.007). Compared with control, more patients in the study period were prescribed at least 2 preventative strategies (42% vs. 61%, p = 0.02), including increased use of cool dialysate (55% vs. 89%, p<0.001). Cool dialysate reduced the odds of IDH by 50% (OR = 0.50; 95% CI, 0.30-0.86; p = 0.012). CONCLUSION: HD prescription education with concurrent use of multiple preventative strategies is associated with a significant decrease in IDH.

Cardiovascular effects of angiotensin converting enzyme inhibition or angiotensin receptor blockade in hemodialysis: a meta-analysis.

BACKGROUND AND OBJECTIVES: Cardiovascular (CV) disease causes significant morbidity and mortality among the hemodialysis (HD) population. This meta-analysis was performed to determine whether angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) reduce fatal and nonfatal CV events and left ventricular (LV) mass in patients receiving HD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Studies were identified by searching electronic databases, bibliographies, and conference proceedings. Two reviewers independently selected randomized controlled trials using ACEIs or ARBs compared with control among patients receiving HD. Studies were independently assessed for inclusion, quality, and data extraction. Random-effects models were used to estimate the pooled relative risk (RR) for CV outcomes and the weighted mean difference (WMD) for pooled change-from-baseline comparisons for LV mass for ACEI or ARB treated patients compared with control. RESULTS: Compared with control, the RR of CV events associated with ACEI or ARB use was 0.66 [95% confidence interval (CI) 0.35 to 1.25; P = 0.20]. ACEI or ARB use resulted in a statistically significant reduction in LV mass, with a WMD of 15.4 g/m(2) (95% CI 7.4 to 23.3; P < 0.001). CONCLUSIONS: Treatment with an ACEI or ARB reduced LV mass in patients receiving HD. However, their use was not associated with a statistically significant reduction in the risk of fatal and nonfatal CV events. Larger, high-quality trials in the HD population are required to determine if the effects of ACEI or ARB therapy on LV mass translate into decreased CV morbidity and mortality.