Comparative effects of acetate and bicarbonate hemodialysis on left ventricular function

To assess the comparative effects of hemodialysis with acetate versus bicarbonate base on left ventricular systolic function, we performed M-mode echocardiography on 36 patients prior to and immediately following 4-hr maintenance hemodialysis. Patients were initially dialyzed against either sodium acetate or sodium bicarbonate and 1 week later were dialyzed against the alternate base. The mean velocity of circumferential fiber shortening (mean Vcf, circumferences/s) was used to assess left ventricular systolic function. In patients with normal pre-dialysis mean Vcf hemodialysis with acetate produced no significant change in mean Vcf, whereas hemodialysis with bicarbonate produced a significant increase in mean Vcf. In patients with low pre-dialysis mean Vcf hemodialysis with either base produced a significant increase in mean Vcf. Mean Vcf values obtained after hemodialysis with bicarbonate were significantly higher than those obtained after hemodialysis with acetate, both in patients with normal and low pre-hemodialysis mean Vcf. We conclude that hemodialysis with bicarbonate produces a comparatively greater improvement in left ventricular systolic function than hemodialysis with acetate.     

Effects of acetate during regular hemodialysis

The utilization of acetate and its effects on acid-base balance and on free fatty acid metabolism were investigated during regular hemodialysis (HD). Fourteen patients with chronic renal failure were studied during two successive dialysis treatments for which either acetate or bicarbonate were used as a buffer anion in the dialysate. In the acetate studies the mean plasma acetate concentration in the arterial line rose from 0.16 mM to 4.67 mM, while it rose from 0.17 mM to 0.62 mM during bicarbonate dialysis. There was a linear relationship between acetate utilization and the acetate concentration in the venous line. The increase of the blood pH during bicarbonate HD was due to an immediate increase of HCO3, whereas acetate caused a smaller HCO3 rise and a pronounced fall of the pCO2. The heart rate was higher during acetate than during bicarbonate HD. During both types of dialysis there was a twofold rise of total FFA as well as the individual fatty acids palmitate, palmitoleate, oleate, stearate and linoleate which was of similar magnitude when acetate or bicarbonate were used. The postulated antilipolytic effect of the short-chain fatty acid acetate could not be demonstrated under the circumstances of routine hemodialysis. Pre-dialysis dopamine was elevated in 7 of the 11 patients and remained high during both types of HD; other hormones were normal during acetate and bicarbonate HD.     

Bicarbonate versus acetate hemodialysis in ventilated patients

Hemodynamic tolerance to bicarbonate versus acetate hemodialysis was studied in seven ventilated, critically ill patients, suffering from acute renal failure. Both kinds of hemodialysis were carried out with a recirculating dialysate delivery system and a relatively low blood flow (180 ml/min). Each patient underwent two hemodialysis procedures, one with bicarbonate and one with acetate, lasting for four hours. Ultrafiltration rates were kept below 250 ml/h and only biocompatible membranes with a relatively small surface area (Biospal 2400, Hospal, France) were used. Despite the mild hemodialysis conditions, hypotensive episodes with a mean blood pressure below 70 mmHg were observed in 3 out of 7 bicarbonate sessions and 4 out of 7 acetate sessions. Thus, we could not demonstrate a hemodynamic advantage of bicarbonate hemodialysis in this group of ventilated patients. This contrasts with other studies conducted in non-ventilated patients. Prevention of hypoxemia by mechanical ventilation and control of vascular tone by the use of vasoactive drugs may be of more clinical relevance than the kind of hemodialysis procedure that is used.     

Lithium acetate therapy in a maintenance hemodialysis patient

BACKGROUND/AIMS: Single cases of lithium carbonate dosing in hemodialysis patients have been published. We investigate the dose-serum level relationship after single and multiple lithium acetate dosing in a hemodialysis patient and review the literature. METHODS: Lithium acetate was administered orally over a period of 11 months in a patient with major depressive episodes after being placed on hemodialysis three times a week. The serum trough levels of lithium before and after hemodialysis were analyzed. The data were compared with those reported in the literature, and potential drug interactions and the importance of the residual renal function are discussed. RESULTS: No adverse events due to the lithium therapy were documented. Steady state levels of between 0.6 and 0.8 mmol/l of lithium acetate were achieved 17 days after initiating the therapy, using 24 mmol/l of lithium three times a week, in a patient with a residual diuresis of about 400 ml/day. In contrast, data reported in the literature implicate that only 9.6-14.4 mmol/l of lithium (450-600 mg of lithium carbonate) is sufficient to achieve adequate serum levels. CONCLUSIONS: The residual renal function can be important for lithium clearance. The creatinine clearance does not reflect this point.     

Calcium acetate control of serum phosphorus in hemodialysis patients

Calcium acetate has many characteristics of an ideal phosphorus binder. It is a readily soluble salt that avidly binds phosphorus in vitro at pH 5 and above. One-dose/one-meal balance studies show it to be more potent than calcium carbonate or calcium citrate. We studied chronic (3-month) phosphorus binding with calcium acetate in 91 hyperphosphatemic dialysis patients at four different centers. All phosphorus binders were stopped for 2 weeks. Calcium acetate at an initial dose of 8.11 mmol (325 mg Ca2+) per meal was then used as the only phosphorus binder. Dose was adjusted to attempt control of predialysis phosphorus level less than 1.78 mmol/L (5.5 mg/100 mL). Final calcium acetate dose was 14.6 mmol (586 mg) Ca2+ per meal. Sixteen patients developed mild transient hypercalcemia (mean, 2.84 mmol/L [11.4 mg/dL]. Initial phosphorus values in mmol/L (mg/dL) were 2.39 (7.4); at 1 month, 1.91 (5.9); and at 3 months, 1.68 (5.2). Initial calcium values in mmol/L (mg/dL) were 2.22 (8.9); at 1 month, 2.37 (9.5); and at 3 months, 2.42 (9.7). Initial aluminum values in mumol/L (micrograms/L) were 2.99 (80.7); and at 3 months were 2.54 (68.4). Initial C-terminal parathyroid hormone (C-PTH) values in ng/mL were 14.6; at 1 month, 11.9; and at 3 months, 13.2. Sixty-nine patients then entered a double-blind study. Phosphorus binders were stopped for 1 week. Calcium acetate (at a dose established in a prior study) or placebo was then administered for 2 weeks. Next, patients were crossed to the opposite regimen for 2 weeks. Initial phosphorus was 2.36 mmol/L (7.3 mg/100 mL) and calcium 2.22 mmol/L (8.9 mg/100 mL).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients

BACKGROUND: We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. METHODS: To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. RESULTS: The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. CONCLUSION: Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.     

Comparisons of the effects of calcium carbonate and calcium acetate on zinc tolerance test in hemodialysis patients.

Because aluminum hydroxide, as a phosphate binder, lowered intestinal zinc absorption, we studied the effects of calcium carbonate (CaCO3) and calcium acetate (CaAc), two other phosphate binders, on intestinal Zn absorption in nine patients on hemodialysis and in 11 controls by measuring 1- and 2-hour serum Zn levels after oral administration of 50 mg of elemental Zn as Zn gluconate with or without concomitant administration of 2 g CaCO3 (800 mg elemental Ca) or 3 g CaAc (750 mg elemental Ca). Fasting serum Zn levels were not different between patients and controls (14.0 +/- 2.3 v 14.1 +/- 1.2 mumol/L [91.8 +/- 14.9 v 92.3 +/- 8.0 micrograms/dL]), but the area under the curve of serum Zn increment (AUC) 2 hours after an oral Zn challenge without or with either of two of phosphate binders used was significantly smaller in patients than in controls (P less than 0.05). The AUC after concomitant administration of Zn with CaCO3 did not differ from that of Zn alone in either patients or controls, but it was significantly less in Zn with CaAc than in Zn alone or in Zn with CaCO3 in both groups. The results demonstrate that intestinal Zn absorption after an oral Zn challenge decreased in patients on hemodialysis and concomitant administration of CaAc, but CaCO3 did not decrease intestinal Zn absorption in either group.     

高通量血液透析与低通量血液透析的透析效果比较

目的 比较高通量血液透析(HFHD)、低通量血液透析(LFHD)对维持性血液透析患者的综合疗效.方法 32例维持性血透患者,随机分为高通量血液透析组(n=16)和低通量血液透析组(n=16),分别每2周透析5次,每次4.5h.分别于首次透析前、透析后取血检测患者血清BUN、Cr、K+、Na+、Ca2+、P3++、β2-MG、Alb及iPTH.同时观察患者的临床症状变化情况.治疗1年后复查并比较上述指标.结果 高通量透析组对iPTH及β2-MG的清除高于低通量血液透析组(p＜0.05).两组Urea、Cr清除率及KT/V值无统计学差异(p＞0.05),透析前后两组K+、Na+、Ca2+、P3+无统计学差异(p＞0.05).高通量透析组患者的临床症状较低通量透析组明显改善,血清白蛋白变化无明显差异(p＞0.05).结论 高通量血液透析对中大分子物质的清除明显优于低通量血液透析,并能改善患者的临床症状,不会引起蛋白质过多的丢失,对小分子物质清除与低通量血液透析具有同样的效果.     

Compartment effects in hemodialysis

Compartment effects in hemodialysis are important because they reduce the efficiency of removal of the compartmentalized solute during dialysis. The dialyzer can only remove those waste products that are presented to it, and then only in proportion to the concentration of the solute in the blood. Classically a two-compartment system has been modeled, with the compartments arranged in series. Because modeling suggests that the sequestered compartment is larger than the accessible compartment, an assumption has been made that the sequestered compartment is the intracellular space. For urea and other solutes that move easily across many cell membranes, compartmentalization may be flow related, that is, related to sequestration in organs (muscle, skin, bone). Although mathematically urea rebound and mass balance can be described with either model, the flow-related model best explains data showing that urea rebound after dialysis is increased during ultrafiltration, diminished during high cardiac output states, and also reduced during exercise. Whether compartmentalization is increased in vasoconstricted intensive care unit patients receiving acute dialysis remains an open question.     

The ocular effects of etomidate

Etomidate, a new intravenous hypnotic agent, significantly lowered the mean intraocular pressure (IOP) of fifty patients within 30 s of an intravenous injection from 15.7 to 9.5 mmHg. This effect was present even during the administration (to twenty patients) of low doses (0.25 mg/kg) when the mean reduction was from 15.6 to 7.6 mmHg. The reduction in IOP was unaffected by the presence of muscle movement. Low frequency pendular nystagmus was observed in five patients.     

Calcium acetate as a phosphorus binder in hemodialysis patients.

Much interest is currently centered on the use of calcium acetate as a phosphorus binder in patients with renal failure. Therefore, this compound in subjects previously stable on calcium carbonate and undergoing high-efficiency hemodialysis with a dialysate calcium of 2.5 mEq/L was evaluated. Twenty subjects were switched from generic calcium carbonate to a single calcium carbonate preparation for a period of 2 months. This was followed by a phase (1 month) in which calcium acetate was substituted for calcium carbonate at a dose containing half the amount of elemental calcium. Subjects then continued calcium acetate for 6 months. It was found that calcium acetate allowed comparable control of immunoreactive parathyroid hormone, calcium, and phosphorus levels compared with calcium carbonate. This occurred with half the amount of elemental calcium ingested in the form of calcium acetate (349 +/- 25 versus 699 +/- 75 mmol/day; P less than 0.001). With this lower dose, the overall incidence of hypercalcemia was the same with each formulation. In the eight subjects concurrently receiving i.v. calcitriol, the incidence of hypercalcemia was significantly higher during the first month of calcium acetate compared with that in those not receiving this compound (P less than 0.05). Of those four subjects receiving the high dose of calcitriol (2 micrograms thrice weekly), all required either reduction in the dose or discontinuation of the drug. Thus, mineral metabolism could be controlled adequately with calcium acetate despite using half as much elemental calcium compared with calcium carbonate. This, however, did not result in a lower incidence of hypercalcemia, particularly in those receiving i.v. calcitriol.     

Serum calcium increases the incidence of arrhythmias during acetate hemodialysis.

We investigated the occurrence of arrhythmias during maintenance acetate hemodialysis (HD) using a 24-hour continuous electrocardiogram recording system. Three of 22 patients showed augmented increases in both ventricular premature beats and supraventricular premature beats during HD. When we changed the dialysate from one with a Ca2+ concentration of 1.75 mmol/L (3.5 mEq/L), to one with a Ca2+ concentration of 1.25 mmol/L (2.5 mEq/L), the elevation of serum Ca2+ concentration during HD was abolished and the increases in both ventricular premature beats and supraventricular premature beats were significantly decreased. The elevation of serum Ca2+ concentration during HD might induce either extracellular or intracellular increase in Ca2+ concentration in the heart and elicit either reentry- or triggered-activity types of arrhythmias during HD. The present results indicate that the dialysate with a lower Ca2+ concentration is advisable to use in patients with underlying cardiac diseases.     

Incidence and significance of rising blood acetate levels during hemodialysis.

Recent work suggests that rising arterial acetate levels occur in some patients undergoing hemodialysis and that they may be responsible for some dialysis problems, particularly cardiovascular instability. Blood acetate levels and acetate flux rates have been determined in 20 adult and 4 pediatric patients during hemodialysis as well as in 4 patients with combined renal and hepatic failure. Rising acetate levels occurred in 25% of the adult patients, although they were stable in the children and the patients with renal and hepatic failure. The occurrence of hypotension during dialysis was unrelated to a high blood acetate level.     

靶向治疗的不良反应及处理

近年来,肿瘤的靶向治疗取得了飞速发展,但是对于靶向治疗药物的毒性和安全性方面的信息还知之甚少。高血压是血管内皮生长因子抑制剂常见的不良反应,而曲妥珠单抗最主要的不良反应为心脏毒性。其他的不良反应有出血、伤口愈合延迟、胃肠道穿孔、皮肤不良反应、手足综合征、黏膜炎、腹泻、蛋白尿等;此外血栓、可逆性后脑白质病综合征少见但十分严重。早期快速诊断、及时停药是决定病人预后的关键。     

Cardiovascular effects of frequent intensive hemodialysis

Cardiovascular disease remains the leading cause of morbidity and mortality for patients with end-stage renal disease (ESRD). Frequent intensive hemodialysis (short daily hemodialysis [2 hours per session, six sessions per week] and nocturnal home hemodialysis [6 hours per session, five to six sessions per week]) has recently gained increasing popularity as an alternative to conventional hemodialysis (4 hours per session, three sessions per week). There is an emerging body of evidence that frequent intensive hemodialysis offers superior uremic toxin clearance, blood pressure control, and other cardiovascular outcomes. The goals of the present review are to systematically evaluate the available evidence in blood pressure control and cardiovascular outcomes in ESRD and the achievable changes after converting from conventional dialysis to frequent intensive hemodialysis, and to provide possible physiological explanations to account for these important changes of potent markers of adverse events in this patient population.     

Effects of acetate versus bicarbonate hemodialysis on left ventricular size and function

To investigate the effects of different types of hemodialysis on hemodynamics, left ventricular size and function, 10 patients with uremia due to chronic renal failure were examined using echocardiography and measurement of systolic time intervals before and after both acetate and bicarbonate hemodialysis. Both caused decreases in left ventricular end diastolic (acetate -3.2 vs. bicarbonate -5.1 mm, p less than 0.01 for both) and end systolic (-3.2 vs. -3.7 mm, p less than 0.01 for both) diameters, and increases in mVCF (+0.24 vs. +0.23 circ/s, p less than 0.005 for both) and fractional shortening (+2.7%, p less than 0.05 vs. +0.9%, NS). In systolic time intervals, the LVETI decreased (-28 vs. -38 ms, p less than 0.001 for both) and the PEP/LVET ratio increased (+0.04, NS vs. 0.09, p less than 0.01). There were no significant differences between the changes in any of the measured parameters caused by acetate or bicarbonate hemodialysis, except in blood bicarbonate concentration (+1.9 vs. +5.4 mmol/l, difference p less than 0.01). Thus hemodialysis with acetate or bicarbonate base causes similar decreases in left ventricular size apparently because of decreased diastolic filling, but in spite of this, there is an increase in left ventricular systolic function, apparently partially due to increased myocardial contractility.     

Efficacy and safety of calcium acetate on hyperphosphatemia in patients undergoing hemodialysis

Objective To evaluate the efficacy and safety of calcium acetate in treating hemodialysis(HD) patients with hyperphosphatemia. Methods A randomized, controlled multicenter study was performed. Phosphate binders were discontinued during a two-week washout period． A total of 171 hemodialysis patients from 10 sites with serum phosphorus during 1.94-2.75 mmol/L after two-week washout period were randomized to calcium acetate or calcium carbonate for 8 - week treatment period. Patients with serum phosphorus between 1.94-2.26 mmol/L were given elemental calcium 1000 mg/d and between 2.27- 2.75 mmol/L were given elemental calcium 1500 mg/d. The dose was constant during the 8 - week treatment period. Results All of 171 patients entered the safety analysis set, including 123 cases who completed the study into effect analysis set. In terms of efficacy: compared with the baseline, serum phosphorus, calcium - phosphorus products, parathyroid hormone (iPTH) levels were significantly decreased (all P＜0.05) and serum calcium levels increased slightly in both groups; compared with the calcium carbonate group, calcium acetate group had a significant advantage in the change of serum phosphorus content [(1.73 ± 1.85) vs (0.99 ± 1.60) mmol/L, P＜0.05] and drug response ratio (compared with the baseline serum phosphorus level fell more than 25%) (51.6% vs 32.8%, P＜0.05). In safety aspects, calcium acetate group and the control group had no significant differences in the incidence of adverse events (19.8% vs 18.8%) and adverse reactions (8.1% vs 4.7%), all P＞0.05. The main adverse reactions of calcium acetate were mild to moderate gastrointestinal reactions, including nausea, vomiting. Conclusions In hemodialysis patients with hyperphosphatemia, calcium acetate can decrease serum phosphorus and reduce the levels of calcium - phosphorus product and iPTH. In the phosphate binding capacity, calcium acetate is superior to calcium carbonate. Mild to moderate gastrointestinal reactions are most common after administration.