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      Sudden Death in Hemodialysis: An Update

      a , b , c , d

      Blood Purification

      S. Karger AG

      Sudden death, Hemodialysis

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          Cardiovascular disease including sudden death, myocardial infarction, cardiac arrest, malignant arrhythmias and other cardiac causes is the major cause of death accounting for 43% of all-cause mortality among hemodialysis patients. In addition to increased traditional risk factors, hemodialysis patients also have a number of nontraditional cardiovascular risk factors, which may play a prominent role in the development of sudden death such as left ventricular hypertrophy, coronary artery disease, rapid electrolyte shifts, QT dispersion, sympathetic overactivity, calcium-phosphate deposition. The purpose of the present review was to critically review the current literature to summarize the following aspects: (1) the pathophysiological mechanism responsible for sudden death in hemodialysis patients, and (2) the prevention and management of sudden death in hemodialysis patients.

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          Most cited references 57

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          Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease.

          Sympathetic tone is consistently raised in patients with end-stage renal disease (ESRD). We therefore tested the hypothesis that sympathetic activation is associated with mortality and cardiovascular events in a cohort of 228 patients undergoing chronic hemodialysis who did not have congestive heart failure at baseline and who had left ventricular ejection fraction >35%. The plasma concentration of norepinephrine (NE) was used as a measure of sympathetic activity. Plasma NE exceeded the upper limit of the normal range (cutoff 3.54 nmol/L) in 102 dialysis patients (45%). In a multivariate Cox regression model that included all univariate predictors of death as well as the use of sympathicoplegic agents and beta-blockers, plasma NE proved to be an independent predictor of this outcome (hazard ratio [1-nmol/L increase in plasma NE]: 1.07, 95% CI 1.01 to 1.14, P=0.03). Similarly, plasma NE emerged as an independent predictor of fatal and nonfatal cardiovascular events (hazard ratio [1-nmol/L increase in plasma NE] 1.08, 95% CI 1.02 to 1.15, P=0.01) in a model that included previous cardiovascular events, pulse pressure, age, diabetes, smoking, and use of sympathicoplegic agents and beta-blockers. The adjusted relative risk for cardiovascular complications in patients with plasma NE >75th percentile was 1.92 (95% CI 1.20 to 3.07) times higher than in those below this threshold (P=0.006). Sympathetic nerve overactivity is associated with mortality and cardiovascular outcomes in ESRD. Controlled trials with antiadrenergic drugs are needed to determine whether interference with the sympathetic system could reduce the high cardiovascular morbidity and mortality in dialysis patients.
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            Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study.

            Cardiovascular mortality is extremely high in end-stage renal disease. Cardiovascular mortality risk also is increased in selected (high-risk) individuals with mild to moderate impairment of renal function. It is not clear whether a similar association exists in the general population and, if so, through what mechanisms. We investigated the association of renal function with all-cause and cardiovascular mortality in a population-based cohort and explored potential mechanisms underlying any such relationship. An age-, sex-, and glucose-tolerance-stratified sample (N = 631) of a population-based cohort aged 50 to 75 years was followed prospectively. After up to 10.2 years of follow-up, 117 subjects had died (50 of cardiovascular causes). At baseline, renal function was estimated by the serum creatinine level, the Cockcroft-Gault formula and Levey's equation. At baseline, the mean age was 64 +/- 7 years, 48% were men, 55% had hypertension, and 27% (by design) had type 2 diabetes. Serum creatinine was 91.7 +/- 19.0 micromol/L; creatinine clearance as estimated by the Cockroft-Gault formula was 72.5 +/- 13.7 mL/min/1.73 m(2), and the glomerular filtration rate (GFR) estimated by Levey's equation was 67.8 +/- 12.1 mL/min/1.73 m(2). Renal function was inversely associated with all-cause and with cardiovascular mortality. Relative risks (95% confidence intervals) were 1.08 (1.04 to 1.13) and 1.11 (1.07 to 1.16) per 5 micromol/L increase of serum creatinine; 1.07 (0.98 to 1.17) and 1.15 (1.01 to 1.31) for each decrease of 5 mL/min/1.73 m(2) creatinine clearance; and 1.15 (1.05 to 1.26) and 1.26 (1.12 to 1.42) for each decrease of 5 mL/min/1.73 m(2) of GFR. These associations remained after adjusting for age, sex, glucose tolerance status, hypertension, prior cardiovascular disease, low-density lipoprotein cholesterol, homocysteine, (micro)albuminuria, von Willebrand factor, soluble vascular adhesion molecule-1 and C-reactive protein. Analyses in diabetic and hypertensive subjects gave similar results. Mild to moderate loss of renal function is strongly associated with an increased risk of cardiovascular mortality. The mechanism behind this association is unclear but does not appear to involve common risk factors such as hypertension, diabetes or hyperhomocysteinemia. Estimation of renal function by relatively simple methods therefore may be a valuable tool for cardiovascular risk assessment over and above that provided by conventional risk factors. Our results were obtained in a general middle-aged to elderly population, and thus have broad applicability.
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              Characteristics of sudden death in hemodialysis patients.

              Hemodialysis (HD) is an intermittent procedure during which large fluid and electrolyte shifts occur. We hypothesized that sudden death occurrences in HD patients are related to the timing of HD, and that they occur more frequently in the 12 h period starting with dialysis and in the 12 h period at the end of the dialysis-free weekend interval. In a retrospective study, 228 patient deaths were screened to determine if they met the criteria for sudden death. Information was obtained from clinic charts, dialysis center records, and interview of witnesses of the death event. There were 80 HD patients who met the criteria for sudden death. A bimodal distribution of death occurrences was present, with a 1.7-fold increased death risk occurring in the 12 h period starting with the dialysis procedure and a threefold increased risk of death in the 12 h before HD at the end of the weekend interval (P=0.011). Patients with sudden death had a high prevalence of congestive heart failure and coronary artery disease. Only 40% of patients experiencing sudden death were receiving beta-blockers, and the prior monthly serum potassium value was less than 4 mEq/l in 25%. Sudden death is temporally related to the HD procedure. Every other day HD could be beneficial in preventing sudden death. Careful attention to the usage of beta-blockers and to the maintenance of normal serum potassium values is indicated in HD patients at risk for sudden death.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                September 2010
                26 August 2010
                : 30
                : 2
                : 135-145
                Department of Internal Medicine, Section of Nephrology, aFatih University School of Medicine and bGulhane Military School of Medicine, Ankara, Turkey; cDepartment of Internal Medicine, Renal Unit, Guy’s Hospital, London, UK; dDepartment of Nephrology Clinic and Dialysis and Transplantation Center, ‘C.I. Parhon’ University Hospital, Iasi, Romania
                320370 Blood Purif 2010;30:135–145
                © 2010 S. Karger AG, Basel

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                Page count
                Figures: 2, References: 86, Pages: 11
                In-Depth Review

                Cardiovascular Medicine, Nephrology

                Hemodialysis, Sudden death


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