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Background Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs). Methods We conducted a cohort study using 2007–2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus <4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case–control study. Results The study included 25   099 patients: 11   107 (44.3%) higher QT-prolonging potential SSRI new users and 13   992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86–1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients <4 mEq/l [weighted HR 2.17 (95% CI 1.16–4.03) versus 0.95 (0.78–1.16)]. Nested case–control analyses yielded analogous results. Conclusions The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted. [ABSTRACT FROM AUTHOR]

Purpose: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug–drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT‐prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions. Methods: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007–2017) and a new‐user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1‐year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11–1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06–1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85–1.26]). Conclusions: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients. [ABSTRACT FROM AUTHOR]

Nephrologists are faced with a difficult dilemma in choosing the ideal dialysis prescription to maintain neutral potassium mass balance. Should potassium mass balance goals prioritize the normalization of serum potassium levels using low potassium dialysate at the expense of provoking intradialytic arrhythmias, or should mass balance goals favor permissive hyperkalemia using higher dialysate potassium to avoid rapid intradialytic fluxes at the risk of more interdialytic arrhythmias? This review examines the factors that determine potassium mass balance among HD patients, the relationships between serum and dialysate potassium levels and outcomes, and concludes by examining currently available approaches to reducing risk of arrhythmias while managing potassium mass balance. [ABSTRACT FROM AUTHOR]

Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events ( EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient. [ABSTRACT FROM AUTHOR]

Background. Sudden cardiac death is the leading cause of death among end-stage kidney disease patients (ESKD) on dialysis, but the benefit of primary prevention implantable cardioverter defibrillators (ICDs) in this population is uncertain. | We conducted this investigation to compare the mortality of dialysis patients receiving a primary prevention ICD with matched controls. Methods. We used data from the National Cardiovascular Data Registry's ICD Registry to select dialysis patients who received a primary prevention ICD, and the Get with the Guidelines-Heart Failure Registry to select a comparator cohort. We matched ICD recipients and no-ICD patients using propensity score techniques to reduce confounding, and overall survival was compared between groups. Results. We identified 108 dialysis patients receiving primary prevention ICDs and 195 comparable dialysis patients without ICDs. One year (3-year) mortality was 42.2% (68.8%) in the ICD registry cohort compared with 38.1% (75.7%) in the control cohort. There was no significant survival advantage associated with ICD [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.66-1.13, log-rank P = 0.29]. After propensity matching, our analysis included 86 ICD patients and 86 matched controls. Comparing the propensity-matched cohorts, 1 year (3 years) mortality was 43.4% (74.0%) in the ICD cohort and 39.7% (76.6%) in the control cohort; there was no significant difference in mortality outcome between groups (HR = 0.94, 95% CI: 0.67-1.31, log-rank P = 0.71). Conclusions. We did not observe a significant association between primary prevention ICDs and reduced mortality among ESKD patients receiving dialysis. Consideration of the potential risks and benefits of ICD implantation in these patients should be undertaken while awaiting the results of definitive clinical trials. [ABSTRACT FROM AUTHOR]

Background: Cardiac arrest is the leading cause of death among patients receiving hemodialysis. Despite guidelines recommending CPR training and AED presence in dialysis clinics, rates of CPR and AED use by dialysis staff are suboptimal. Given that racial disparities exist in bystander CPR administration in non-healthcare settings, we examined the relationship between patient race/ethnicity and staff-initiated CPR and AED application within dialysis clinics.Methods: We analyzed data prospectively collected in the Cardiac Arrest Registry to Enhance Survival across the U.S. from 2013 to 2017 and the Centers for Medicare & Medicaid Services dialysis facility database to identify outpatient dialysis clinic cardiac arrest events. Using multivariable logistic regression models, we examined relationships between patient race/ethnicity and dialysis staff-initiated CPR and AED application.Results: We identified 1568 cardiac arrests occurring in 809 hemodialysis clinics. The racial/ethnic composition of patients was 31.3% white, 32.9% Black, 10.7% Hispanic/Latinx, 2.7% Asian, and 22.5% other/unknown. Overall, 88.0% of patients received CPR initiated by dialysis staff, but rates differed by race: 91% of white patients, 85% of black patients, and 77% of Asian patients (p = 0.005). After adjusting for differences in patient and clinic characteristics, black (OR = 0.41, 95% CI 0.25-0.68) and Asian patients (OR = 0.28, 95% CI 0.12-0.65) were significantly less likely than white patients to receive staff-initiated CPR. No significant difference between staff-initiated CPR rates among white, Hispanic/Latinx, and other/unknown patients was observed. An AED was applied by dialysis staff in 62% of patients. In adjusted models, there was no relationship between patient race/ethnicity and staff AED application.Conclusions: Black and Asian patients are significantly less likely than white patients to receive CPR from dialysis staff. Further understanding of practices in dialysis clinics and increased awareness of this disparity are necessary to improve resuscitation practices. [ABSTRACT FROM AUTHOR]

Cardiac arrest is the leading cause of death among patients receiving hemodialysis, and major deficiencies exist in hemodialysis staff-provided cardiopulmonary resuscitation (CPR). Our study aimed to identify factors influencing CPR delivery in the outpatient hemodialysis clinic. Through content analysis of in-depth interviews with 10 staff members of a hemodialysis clinic, we identified three broad themes regarding barriers and facilitators to performing CPR in the hemodialysis clinic: 1) physical and environmental challenges regarding the layout of the clinic; 2) uncertainty about optimal in-clinic CPR procedures, particularly concerning patient positioning and dealing with the hemodialysis machine; and 3) benefit of continuous improvement programs, including hemodialysis-specific protocols, hands-on training, and pre-defined team roles. Our findings call for further investigation of optimal in-clinic resuscitation procedures to inform hemodialysis clinic CPR protocols and hemodialysis staff training. [ABSTRACT FROM AUTHOR]